Peng Guan

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Anopheles gambiae is the principal vector of malaria, a disease that afflicts more than 500 million people and causes more than 1 million deaths each year. Tenfold shotgun sequence coverage was obtained from the PEST strain of A. gambiae and assembled into scaffolds that span 278 million base pairs. A total of 91% of the genome was organized in 303 scaffolds; the largest scaffold was 23.1 million base pairs. There was substantial genetic variation within this strain, and the apparent existence of two haplotypes of approximately equal frequency ("dual haplotypes") in a substantial fraction of the genome likely reflects the outbred nature of the PEST strain. The sequence produced a conservative inference of more than 400,000 single-nucleotide polymorphisms that showed a markedly bimodal density distribution. Analysis of the genome sequence revealed strong evidence for about 14,000 protein-encoding transcripts. Prominent expansions in specific families of proteins likely involved in cell adhesion and immunity were noted. An expressed sequence tag analysis of genes regulated by blood feeding provided insights into the physiological adaptations of a hematophagous insect.

A comparative analysis of the genomes of Drosophila melanogaster , Caenorhabditis elegans , and Saccharomyces cerevisiae —and the proteins they are predicted to encode—was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease.

Genotyping may improve risk stratification of high-risk (HR) human papillomavirus (HPV)-positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta-analysis of cross-sectional HR HPV-type distribution in 115,789 HPV-positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low-grade squamous intraepithelial lesions (LSIL) and 6,616 high-grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR-based studies worldwide. No strong differences in HPV-type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20-28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV-positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV-based screening programs.

The Genotype-Tissue Expression (GTEx) project, sponsored by the NIH Common Fund, was established to study the correlation between human genetic variation and tissue-specific gene expression in non-diseased individuals. A significant challenge was the collection of high-quality biospecimens for extensive genomic analyses. Here we describe how a successful infrastructure for biospecimen procurement was developed and implemented by multiple research partners to support the prospective collection, annotation, and distribution of blood, tissues, and cell lines for the GTEx project. Other research projects can follow this model and form beneficial partnerships with rapid autopsy and organ procurement organizations to collect high quality biospecimens and associated clinical data for genomic studies. Biospecimens, clinical and genomic data, and Standard Operating Procedures guiding biospecimen collection for the GTEx project are available to the research community.

The high degree of similarity between the mouse and human genomes is demonstrated through analysis of the sequence of mouse chromosome 16 (Mmu 16), which was obtained as part of a whole-genome shotgun assembly of the mouse genome. The mouse genome is about 10% smaller than the human genome, owing to a lower repetitive DNA content. Comparison of the structure and protein-coding potential of Mmu 16 with that of the homologous segments of the human genome identifies regions of conserved synteny with human chromosomes (Hsa) 3, 8, 12, 16, 21, and 22. Gene content and order are highly conserved between Mmu 16 and the syntenic blocks of the human genome. Of the 731 predicted genes on Mmu 16, 509 align with orthologs on the corresponding portions of the human genome, 44 are likely paralogous to these genes, and 164 genes have homologs elsewhere in the human genome; there are 14 genes for which we could find no human counterpart.

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

Systematic reviews of the prevalence of different types of Human Papillomavirus (HPV) across a broad range of disease grades from normal to cancer are essential to gain basic knowledge of how widespread infections with the different HPV types are, and to provide information on the possible carcinogenicity of different HPV types. For HPV types that infect human mucosa, of which 12 are established causes of cervical cancer, we present the results of a systematic review and meta-analysis of 47 HPV types in cervical samples across the entire range of cervical diagnoses from normal to cervical cancer, restricted to studies using a number of well characterized PCR assays. For the cutaneous HPV types, which have been linked to the development of squamous cell carcinoma of the skin, their presence has been measured in a variety of different sample types and by assays with variable performance. Therefore, we restricted a systematic review of their prevalence to studies that assayed for cutaneous HPV infection in a case-control format.

Abstract There has been conflicting evidence concerning the possible association between tuberculosis (TB) and subsequent risk of lung cancer. To investigate whether currently published epidemiological studies can clarify this association, we performed a systematic review of 37 case‐control and 4 cohort studies (published between January 1966 and January 2009) and a meta‐analysis of risk estimates, with particular attention to the role of smoking, passive smoking and the timing of diagnosis of TB on this relationship. Data for the review show a significantly increased lung cancer risk associated with preexisting TB. Importantly, the association was not due to confounding by the effects of tobacco use (RR = 1.8, 95% confidence interval (CI) = 1.4–2.2, among never smoking individuals), lifetime environmental tobacco smoke exposure (RR = 2.9, 95%CI = 1.6–5.3, after controlling) or the timing of diagnosis of TB (the increased lung cancer risk remained 2‐fold elevated for more than 20 years after TB diagnosis). Interestingly, the association was significant with adenocarcinoma (RR = 1.6, 95%CI = 1.2–2.1), but no significant associations with squamous and small cell type of lung cancer were observed. Although no causal mechanism has been demonstrated for such an association, present study supports a direct relation between TB and lung cancer, especially adenocarcinomas. © 2009 UICC

Abstract Background Lung cancer is the major cause of cancer death globally, it is often diagnosed at an advanced stage and has one of the lowest survival rates of any type of cancer. The common interest in the field of lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence to suggest that microRNAs play important and complex roles in lung cancer. Methods A meta-analysis was conducted to review the published microRNA expression profiling studies that compared the microRNAs expression profiles in lung cancer tissues with those in normal lung tissues. A vote-counting strategy that considers the total number of studies reporting its differential expression, the total number of tissue samples used in the studies and the average fold change was employed. Results A total of 184 differentially expressed microRNAs were reported in the fourteen microRNA expression profiling studies that compared lung cancer tissues with normal tissues, with 61 microRNAs were reported in at least two studies. In the panel of consistently reported up-regulated microRNAs, miR-210 was reported in nine studies and miR-21 was reported in seven studies. In the consistently reported down-regulated microRNAs, miR-126 was reported in ten studies and miR-30a was reported in eight studies. Four up-regulated microRNAs (miR-210, miR-21, miR-31 and miR-182) and two down-regulated mcroiRNAs (miR-126 and miR-145) were consistently reported both in squamous carcinoma and adenocarcinoma-based subgroup analysis, with the other 14 microRNAs solely reported in one or the other subset. Conclusions In conclusion, the top two most consistently reported up-regulated microRNAs were miR-210 and miR-21. The results of this meta-analysis of human lung cancer microRNA expression profiling studies might provide some clues of the potential biomarkers in lung cancer. Further mechanistic and external validation studies are needed for their clinical significance and role in the development of lung cancer.

The Internet has become an established source of health information for people seeking health information. In recent years, research on the health information seeking behavior of Internet users has become an increasingly important scholarly focus. However, there have been no long-term bibliometric studies to date on Internet health information seeking behavior.The purpose of this study was to map publication trends and explore research hot spots of Internet health information seeking behavior.A bibliometric analysis based on PubMed was conducted to investigate the publication trends of research on Internet health information seeking behavior. For the included publications, the annual publication number, the distribution of countries, authors, languages, journals, and annual distribution of highly frequent major MeSH (Medical Subject Headings) terms were determined. Furthermore, co-word biclustering analysis of highly frequent major MeSH terms was utilized to detect the hot spots in this field.A total of 533 publications were included. The research output was gradually increasing. There were five authors who published four or more articles individually. A total of 271 included publications (50.8%) were written by authors from the United States, and 516 of the 533 articles (96.8%) were published in English. The eight most active journals published 34.1% (182/533) of the publications on this topic. Ten research hot spots were found: (1) behavior of Internet health information seeking about HIV infection or sexually transmitted diseases, (2) Internet health information seeking behavior of students, (3) behavior of Internet health information seeking via mobile phone and its apps, (4) physicians' utilization of Internet medical resources, (5) utilization of social media by parents, (6) Internet health information seeking behavior of patients with cancer (mainly breast cancer), (7) trust in or satisfaction with Web-based health information by consumers, (8) interaction between Internet utilization and physician-patient communication or relationship, (9) preference and computer literacy of people using search engines or other Web-based systems, and (10) attitude of people (especially adolescents) when seeking health information via the Internet.The 10 major research hot spots could provide some hints for researchers when launching new projects. The output of research on Internet health information seeking behavior is gradually increasing. Compared to the United States, the relatively small number of publications indexed by PubMed from other developed and developing countries indicates to some extent that the field might be still underdeveloped in many countries. More studies on Internet health information seeking behavior could give some references for health information providers.

To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.

Brucellosis is one of the most common zoonoses worldwide, causing huge economic losses in the animal industry and posing a serious threat to human health. Although the World Health Organization (WHO) and World Organization for Animal Health (OIE) has recommended strategies or measures to control or eradicate brucellosis, only some developed countries have achieved freedom from animal brucellosis. In developing countries, brucellosis remains a serious problem, and the importance of its control has attracted little attention. The strategies and measures are difficult to implement effectively in countries with limited resources because the eradication of brucellosis is an expensive, time-consuming and labor-intensive project. Therefore, more effort is needed to explore the appropriate strategies and measures in developing countries. In this study, we collected the available publications regarding brucellosis control or eradication programs in different countries and areas, and summarized the main strategies and measures, supplementary measures, effects, and lessons learned during their implementation. Results showed that the freedom from animal brucellosis was only achieved in three countries among the 23 included countries and areas after the implementation of the programs, which had lasted several decades. Either alone or together, vaccination and test-and-slaughter programs can effectively reduce brucellosis prevalence. Supplementary measures involve a number of aspects, and their effective implementation is crucial to the success of disease control and cannot be ignored. While disease control or eradication requires extensive resources, some studies have shown that a well-designed and well-implemented disease control or eradication program is economically effective. Experience has revealed that even if significant results have been achieved, the project could not be terminated without careful consideration due to the potential for recurrence.

Unraveling the growth of northern Tibet is crucial to understanding the geodynamic processes of the India-Eurasia collision, evaluating plateau uplift models and reconstructing associated paleoclimate history. However, pre-middle Miocene deformation history of northern Tibet remains poorly understood. We use detrital apatite fission track (detrital AFT) thermochronology of Mesozoic and Cenozoic sedimentary rocks from northern Qaidam basin to constrain the early growth of northern Tibet. Detrital AFT ages of the Mesozoic samples are younger than their depositional ages, indicating that the Mesozoic succession underwent two stages of exhumation after deep burial during 80–61 Ma and 54–47 Ma. Detrital AFT ages of the Cenozoic samples are older than their depositional ages and reveal that their source region experienced two periods of exhumation (peak ages in 86–59 Ma and 54–36 Ma). These results suggest that the northern Tibet successively experienced Late Cretaceous–early Paleocene and early–middle Eocene deformation. The Late Cretaceous–early Paleocene deformation implies that the extent of pre-collisional (India-Eurasia) deformation region in the plateau were much larger than previously known. The static detrital AFT peak ages (54–51 Ma) based on lag-time analysis for the Paleogene samples demonstrate the early Eocene deformation was a rapid and short-lived event, which was a far-field response to the India-Eurasia collision. Hence, we advocate synchronous deformation throughout the northern plateau at the collision time. Lag-time analysis results also demonstrate absence of Oligocene to early Miocene cooling ages and post-Eocene decreasing exhumation rates in the Cenozoic source regions. This suggests relatively quiescent tectonic settings in the Qilian Mountains during the Oligocene–early Miocene and agrees that the lateral strike-slip movement of the Altyn Tagh Fault was accommodated out of the plateau by the end of the early Miocene.

Background Brucellosis is regarded as a major zoonotic infection worldwide. Awareness and knowledge of brucellosis among occupational workers is considered an important aspect of brucellosis control in both humans and animals. The aim of this study was to explore the distributions of the pooled awareness level and the knowledge level of the disease worldwide. Methods A meta-analysis was carried out to obtain pooled brucellosis awareness levels and knowledge levels of respondents regarding the zoonotic nature of brucellosis, mode of brucellosis transmission, and brucellosis symptoms in animals and humans. The analysis was conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Results A total of seventy-nine original articles reporting the brucellosis awareness levels of in populations from 22 countries were assessed. The total pooled awareness level of brucellosis was 55.5%, and the pooled awareness levels regarding the zoonotic nature of brucellosis, mode of brucellosis transmission, signs of human brucellosis and signs of animal brucellosis were 37.6%, 35.9%, 41.6%, and 28.4% respectively. The pooled awareness level was higher than the brucellosis-related knowledge level. Subgroup analyses showed that no obvious differences in brucellosis awareness levels between high-risk populations in Asia and Africa. Health workers (including human health workers and veterinarians) had the greatest overall awareness and knowledge of human brucellosis. The overall awareness levels and knowledge levels of livestock owners (farmers) and herders were higher than those of dairy farmers and abattoir workers. In addition, awareness and knowledge levels were higher among people who were involved in bovine, caprine and ovine animal production or in caprine and ovine animal production than among people who were involved in only bovine animal production. Conclusions Insufficient awareness and knowledge of brucellosis were observed in the original studies conducted mainly in Asia and Africa. Interventions to improve public knowledge about brucellosis are urgently needed.

At present, there is a lack of research on the structural changes of lacustrine Type-II kerogen, which is regionally distributed but has significant potential for hydrocarbon resources. In our previous work, a series of non-hydrous, temperature-based semi-open pyrolysis experiments have been performed on the Chang 7 oil shale to simulate the thermal maturation (from 0.53 %Ro to 1.68 %Ro) of lacustrine Type-II kerogen. In that work, the parallel reaction pathway for kerogen decomposition was supported. The aim of this work is to reveal the structural changes of the post-pyrolysis kerogen. Integrated analysis including elemental analysis, programmed pyrolysis (Rock-Eval), Fourier transform infrared (FT-IR) spectroscopy, and solid-state 13C nuclear magnetic resonance (13C NMR) spectroscopy were conducted on the native unheated and post-pyrolysis rocks and kerogens. Based on the compositional features of the hydrocarbon products, structural changes of the post-pyrolysis kerogen were investigated, and insights on the initial chemical structure of the kerogen were also obtained. Before the peak hydrocarbon-generating stage (Ro < 0.6%), defunctionalization of oxygen-containing functional groups, which leads to the generation of water, CO2 and NSOs, occurs simultaneously with the detachment of short aliphatic side chains and small aromatic rings, which leads to the generation of volatile fractions (C6–C14, C15+ sat and C15+ aro). This process suggests that the Chang7 kerogen is highly branched. During the peak hydrocarbon-generating stage (0.6–1.09 %Ro), the concurrent breakage of weak cross-link bonds and long aliphatic chains lead to the simultaneous peak generation of liquid hydrocarbons and NSOs. This reflects the highly cross-linked features of the Chang7 kerogen. After the peak hydrocarbon-generating stage (Ro > 1.09%), the reactions in the previous two stages produce a highly aromatic kerogen. The increased aromaticity of the highly matured kerogen is most likely to be caused by aromatization or dehydrogenation of hydroaromatics and coking of aromatic bitumen, not by fusing or condensation of aromatic rings.

There is a substantial amount of oil shale resources in the seventh member of the Triassic Yanchang Formation (abbreviated as Chang 7) in the Ordos Basin, and its geological and geochemical characteristics are highly suitable for in-situ conversion process (ICP). A comprehensive characterization of its hydrocarbon generation, expulsion and retention features will help determine the optimum conditions for future field tests. However, typical thermal simulation experiments based on either open-system or closed-system are not applicable to provide data to construct the models. Therefore, in this study, eight parallel thermal simulation experiments, which were based on the newly designed temperature-based semi-open pyrolysis experiments were performed on the Chang 7 oil shale. The yields (including cumulative yields and net incremental yields) and compositional characteristics of the expelled oil, expelled gas, and retained oil were analyzed. Results show that the hydrocarbon expulsion has a coupling relationship with hydrocarbon generation that can be divided into four stages: (1) Slow hydrocarbon generation stage (300–320 °C, 0.53–0.55 %Ro). Minimal amounts of oil and gas are generated in this stage. The hydrocarbon expulsion efficiency increases rapidly. (2) Quick oil-generation stage (320–380 °C, 0.55–1.09 %Ro). The fast cracking of kerogen and thermal bitumen generates a large amount of oil. The hydrocarbon expulsion efficiency remains relatively stable. (3) The secondary oil cracking and quick gas-generation stage (380–420 °C, 1.09–1.66 %Ro). The oil yield begins to decrease after reaching its maximum and a large amount of hydrocarbon gas is generated. The oil generation capability of kerogen is basically exhausted. The hydrocarbon expulsion efficiency and gas/oil ratio increase rapidly at this stage. (4) The heavy hydrocarbon gas cracking stage (after 420 °C, 1.66 %Ro). The oil yield continues to decline, accompanied by the onset decline in the gas yield (except methane). At this time, the hydrocarbon expulsion efficiency continues to increase but at a rather low speed. Under the experimental conditions in this study, 1.24–1.66% Ro is considered a favorable thermal maturity interval, in which maximum oil production with relatively light components can be obtained and the hydrocarbon gas is abundant.

Plant diseases may threaten the safety of crops around the world, and timely detection of crop diseases and accurate determination of disease species are important to protect crop safety and control the spread of diseases. Recent studies have proposed the application of modern automatic recognition systems based on convolutional neural networks to the identification tasks of multiple crops and diseases. Although some research results have been achieved, studies have shown that these models are not optimal because they are susceptible to features unrelated to crop diseases, and have poor application ability in real-world environments. Therefore, this paper proposes a more concise method that separating the crop and disease identification and classify them independently, and demonstrates that it is more effective than the traditional crop-disease pairs approach. Meanwhile, we constructed a trilinear convolutional neural networks model using bilinear pooling and used images obtained in a real-world environment for the study of crop disease identification. The crop and disease identification accuracies achieved 99.99% and 99.7% on the test set in a controlled laboratory environment, and 84.11% and 75.58% on the test set in a real-world environment, respectively. The work in this paper improves the application value of crop disease identification research in the real-world.

Whole-rock geochemical data of the Mesozoic and Cenozoic sediments in the northern Qaidam basin were used to reconstruct the provenance and chemical weathering history. Based on the fairly uniform REE patterns and trace element ratios, both the Mesozoic (LaCN/YbCN = 10.37 ± 1.75; Eu/Eu* = 0.68 ± 0.07; Th/Sc = 1.11 ± 0.38) and Cenozoic (LaCN/YbCN = 9.77 ± 0.62; Eu/Eu* = 0.69 ± 0.03; Th/Sc = 0.97 ± 0.14) mudstones were derived from a similar source area with acidic-intermediate rocks as dominant contributors, and two modeled mixtures composed of 60% granite, 35% quartzdiorite and 5% mafic rocks, and 55% granite, 40% quartzdiorite and 5% mafic rocks can be deduced as the potential source compositions for the Mesozoic and Cenozoic sediments, respectively. This conclusion is reinforced by the mudstone major element composition and sandstone petrography. The Early–Middle Jurassic mudstones have relatively high K-corrected CIA (84–93) and PIA (88–99) values, indicating intense chemical weathering conditions; while the Late Jurassic to Cenozoic sediments have variable corrected CIA (51–85) and PIA (50–92) values, implying predominantly mild to moderate weathering conditions. The chemical weathering history suggests that a warm and humid climate prevailed during the Early–Middle Jurassic, whereas a cool and semiarid to arid climate prevailed from the Late Jurassic up to now. This dramatic transition of climate may be attributed to multiple likely factors, including the restructuring of global atmospheric circulation patterns in response to the breakup of Pangea since Late Jurassic, and the orogenic rejuvenation and high elevation of the Qilian Mountains, northeastern Tibetan Plateau. Furthermore, the decreasing chemical weathering intensity over time indicates the increase of aridification and cooling of the climate culminating in the Late Cenozoic.

Recent evidence from several relatively small nested case‐control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere‐length associated genetic variants in a large study of 5,457 never‐smoking female Asian lung cancer cases and 4,493 never‐smoking female Asian controls using data from a previously reported genome‐wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere‐length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34–1.69) for upper vs . lower quartile of the weighted GRS, p value = 4.54 × 10 −14 ) even after removing rs2736100 ( p value = 4.81 × 10 −3 ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere‐associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

An exceptionally thick Cenozoic sedimentary succession has developed in the Qaidam basin of the northeastern Tibetan Plateau. The provenance remains enigmatic; thus, more precise investigations are needed. An integrated study of sandstone framework petrography, heavy mineral analysis and mineral chemistry was adopted to perform provenance analysis of the Tertiary sandstones in the northern Qaidam basin. No individual method exists that can provide comprehensive provenance interpretations on spatial and temporal variations. Based on three types of data, three depositional areas can be distinguished. Sandstones of Area A exhibit relatively high abundances of quartz, garnet and zircon, as well as relatively high textural maturity, implying long-distance sources. Multi-composition garnets and tourmalines reveal derivations of metasedimentary rocks and intermediate-acidic igneous rocks. Sandstones of Area B are rich in metamorphic lithic fragments, epidote and garnet. A dominance of Fe-rich garnets with low Mg, low Mn and variable Ca contents and dravites demonstrates predominant derivation of metasedimentary rocks. Therefore, the North Qaidam and South Qilian terranes are potential source areas for these two depositional areas. Additionally, high metamorphic heavy mineral abundances in the upper formations imply increasing contributions of these two metamorphic belts during the Tertiary tectonic uplift. However, sandstones of Area C are characterized by relatively high abundances of feldspar, igneous heavy minerals and high-Fe + Mn garnet, which suggest a main source of igneous rocks. The Altun and Qilian Mountains are potential source regions. Furthermore, increasing amounts of feldspar and igneous heavy minerals in the upper formations indicate a significant presence of igneous parent rocks, which are most likely a response to the multi-stage uplift events in the Altun Mountains since the early Eocene.

The importance of circulating free DNA (cfDNA) in cancer clinical research was recognized in 1994 when a mutated RAS gene fragment was detected in a patient's blood sample. Up to 1% of the total circulating DNA in patients with cancer is circulating tumor DNA (ctDNA) that originates from tumor cells. As ctDNA is rapidly cleared from the blood stream and can be obtained by minimally invasive methods, it can be used as a dynamic cancer biomarker for cancer early detection, diagnosis, and treatment monitoring. Despite the potential for clinical use, few ctDNA assays have been cleared or approved by the US Food and Drug Administration. As tools for clinical and translational research, current ctDNA assays face some challenges, and more research is needed to advance use of these assays. On September 29–30, 2016, the Division of Cancer Treatment and Diagnosis at the National Cancer Institute convened a workshop entitled "Circulating Tumor DNA Assays in Clinical Cancer Research" to garner input from industry experts, academia, and government research and regulatory agencies to understand and promote the translation of ctDNA assays to clinical research, with potential to advance to use in clinical practice. This Commentary presents the topics of the workshop covered in the presentations and points made in the discussions that followed: 1) background on ctDNA, 2) potential clinical utility of ctDNA assays, 3) assay technology, 4) assay clinical and analytical validation, and 5) industry perspectives. Additional relevant information that has come to light since the workshop has been included.

Resveratrol is a polyphenolic compound that has received much attention for its use in ameliorating various systemic pathological conditions. The present study was performed to investigate whether the resveratrol alleviated cardiac hypertrophy and functional remodelling by regulating autophagy. Male rats were exposed to CIH 8 h/day for five weeks and/or intragastric administration of resveratrol daily. The morphological and echocardiography were used to evaluate the cardiac protective effects. The apoptosis was detected by TUNEL staining. The biochemical assessments were used to evaluate oxidative stress. Further, the effect of resveratrol on autophagy and PI3K/AKT/mTOR pathway was investigated. The CIH group exhibited increased heart weight/body weight and left ventricle weight/body weight ratios, which was accompanied by left ventricular remodelling. Echocardiography analysis showed that CIH-treated rats had significantly higher left ventricular posterior wall thickness, ejection fraction and fractional shortening than those of controls. In addition, the apoptosis index and oxidative markers were significantly elevated in the CIH group versus the control. The autophagy marker Beclin-1 was elevated, while p62 was decreased by CIH treatment. Resveratrol treatment significantly improved cardiac function and alleviated cardiac hypertrophy, oxidative stress, and apoptosis in CIH rats. Further results indicated that PI3K/AKT pathway-mediated inhibition of the mammalian target of rapamycin (mTOR) pathway played a role in the activation of autophagy by resveratrol after CIH stimulation. In conclusion, resveratrol supplementation during CIH upregulates autophagy by targeting the PI3K/AKT/mTOR pathway, which appears to be beneficial for resisting cardiac hypertrophy.

The main objective of this study was to describe the temporal distribution of monthly reported human brucellosis cases in mainland China and develop an appropriate time series model for short-term extrapolation forecast.Surveillance data of the monthly reported human brucellosis cases occurring from April 1, 2007, to March 31, 2017, in mainland China were obtained. The spectrum analysis was first adopted to find the cyclic and seasonal features, the existence of the seasonality and trend was determined by exponential smoothing method and the seasonal-trend decomposition. The candidate models of exponential smoothing included the additive model and multiplicative model; R2 was selected as the indicator for the selection of candidate model, and the stability of the model was verified by adjusting the training data and test data set. Finally, the extrapolations of monthly incident human brucellosis cases in 2017 were made.From April 1, 2007, to March 31, 2017, a total of 435,108 cases of Brucellosis occurred in mainland China were reported, with an average of 3626 cases per month and a standard deviation of 1834 cases. The R2 of the exponential smoothing method that based on additive model increased steadily from 0.927 to 0.949 with the increase of the data volume. Ten of 12 actual values fell in the confidence interval of predicted value.Human brucellosis cases peaked during the months from March to August in mainland China, with clear seasonality. The exponential smoothing based on the additive model method could be effectively used in the time series analysis of human brucellosis in China. Control methods, such as vaccination, quarantine, elimination of infected animals, and good hygiene within the production cycle, should be strengthened with paying more attention to the seasonality. Further research is warranted to explore the drivers behind the seasonality.

Obstructive sleep apnea (OSA) can cause intermittent changes in blood oxygen saturation, resulting in the generation of many reactive oxygen species (ROS). To discover new antioxidants and clarify the endoplasmic reticulum (ER) stress involved in cardiac injury in OSA, we established a chronic intermittent hypoxia (CIH) rat model with a fraction of inspired O 2 (FiO 2 ) ranging from 21% to 9%, 20 times/h for 8 h/day, and the rats were treated with H 2 -O 2 mixture (67% hydrogen and 33% oxygen) for 2 h/day for 35 days. Our results showed that H 2 -O 2 mixture remarkably improved cardiac dysfunction and myocardial fibrosis. We found that H 2 -O 2 mixture inhalation declined ER stress-induced apoptosis via three major response pathways: PERK-eIF2 α -ATF4, IRE 1-XBP1, and ATF 6. Furthermore, we revealed that H 2 -O 2 mixture blocked c-Jun N-terminal kinase- (JNK-) MAPK activation, increased the ratio of Bcl-2/Bax, and inhibited caspase 3 cleavage to protect against CIH-induced cardiac apoptosis. In addition, H 2 -O 2 mixture considerably decreased ROS levels via upregulating superoxide dismutase (SOD) and glutathione (GSH) as well as downregulating NADPH oxidase (NOX 2) expression in the hearts of CIH rats. All the results demonstrated that H 2 -O 2 mixture significantly reduced ER stress and apoptosis and that H 2 might be an efficient antioxidant against the oxidative stress injury induced by CIH.

Objectives Human brucellosis is a public health problem endangering health and property in China. Predicting the trend and the seasonality of human brucellosis is of great significance for its prevention. In this study, a comparison between the autoregressive integrated moving average (ARIMA) model and the eXtreme Gradient Boosting (XGBoost) model was conducted to determine which was more suitable for predicting the occurrence of brucellosis in mainland China. Design Time-series study. Setting Mainland China. Methods Data on human brucellosis in mainland China were provided by the National Health and Family Planning Commission of China. The data were divided into a training set and a test set. The training set was composed of the monthly incidence of human brucellosis in mainland China from January 2008 to June 2018, and the test set was composed of the monthly incidence from July 2018 to June 2019. The mean absolute error (MAE), root mean square error (RMSE) and mean absolute percentage error (MAPE) were used to evaluate the effects of model fitting and prediction. Results The number of human brucellosis patients in mainland China increased from 30 002 in 2008 to 40 328 in 2018. There was an increasing trend and obvious seasonal distribution in the original time series. For the training set, the MAE, RSME and MAPE of the ARIMA(0,1,1)×(0,1,1) 12 model were 338.867, 450.223 and 10.323, respectively, and the MAE, RSME and MAPE of the XGBoost model were 189.332, 262.458 and 4.475, respectively. For the test set, the MAE, RSME and MAPE of the ARIMA(0,1,1)×(0,1,1) 12 model were 529.406, 586.059 and 17.676, respectively, and the MAE, RSME and MAPE of the XGBoost model were 249.307, 280.645 and 7.643, respectively. Conclusions The performance of the XGBoost model was better than that of the ARIMA model. The XGBoost model is more suitable for prediction cases of human brucellosis in mainland China.

Abstract The National Cancer Institute conducted the Biospecimen Pre-analytical Variables (BPV) study to determine the effects of formalin fixation and delay to fixation (DTF) on the analysis of nucleic acids. By performing whole transcriptome sequencing and small RNA profiling on matched snap-frozen and FFPE specimens exposed to different delays to fixation, this study aimed to determine acceptable delays to fixation and proper workflow for accurate and reliable Next-Generation Sequencing (NGS) analysis of FFPE specimens. In comparison to snap-freezing, formalin fixation changed the relative proportions of intronic/exonic/untranslated RNA captured by RNA-seq for most genes. The effects of DTF on NGS analysis were negligible. In 80% of specimens, a subset of RNAs was found to differ between snap-frozen and FFPE specimens in a consistent manner across tissue groups; this subset was unaffected in the remaining 20% of specimens. In contrast, miRNA expression was generally stable across various formalin fixation protocols, but displayed increased variability following a 12 h delay to fixation.

The prominent feature of obstructive sleep apnea (OSA) is chronic intermittent hypoxia (CIH). Given the strong antioxidant ability of resveratrol against oxidative stress, we evaluated the potential protective effects of resveratrol on myocardial injury induced by CIH. Twenty-four rats were divided into normal control group, CIH group, CIH plus resveratrol treated (CIH + Res) group, and resveratrol treated control (Res) group. We proved that CIH impaired cardiac structure and function with an increase in oxidative stress, endoplasmic reticulum (ER) stress and NOD-like receptors (NLRP3) inflammasome induction in heart, which was attenuated after resveratrol administration. NLRP3 inflammasome blockade by resveratrol appeared to be mediated by activating AMP-activated Protein Kinase (AMPK), which could restrain mTOR/TTP/NLRP3 mRNA signalling. Furthermore, resveratrol attenuated CIH-induced oxidative stress through elevation antioxidant molecules expression via NF-E2-related factor-2 (Nrf2). Moreover, AMPK may play a role in Nrf2/HO-1 signalling by resveratrol. These results expand our understanding of the myocardial protective mechanism of resveratrol during CIH and suggest that resveratrol treatment may be useful to counteract OSA-associated cardiac injury.

The purpose of this work is to investigate the generation characteristics of bitumen, NSO compounds, oil, and HC compounds during the artificial maturation of a lacustrine Type-II kerogen (which has not been given enough attention before) in order to determine its decomposition process. The analysis is based on the data itself, on the premise of jumping out of the generally accepted sequential reaction model. By taking the kerogen of the Chang 7 shale as an example, seven parallel experiments, in the temperature range from 300 °C to 420 °C were conducted on newly designed temperature-based semi-open pyrolysis system. The overall products are classified into oil and bitumen according to their phase, the C15+ fractions are classified into C15+sat, C15+aro and NSOs based on chemical compositions, and the NSOs are further classified into n-pentane NSOs and DCM NSOs according to Behar et al., (2008) and (2010). Results show that large proportion of oil is not merely a result of thermal cracking of bitumen, but also directly from the decomposition of kerogen itself. Both C15+sat and C15+aro are generated as soon as kerogen starts to decompose. It is not until the initial productivity of kerogen is basically exhausted that NSOs become the main precursor of hydrocarbons. The comparison with Behar et al. [2008, organic geochemistry 39, 1–22] further reveals that, for Chang 7 kerogen, initial decomposition of kerogen generates much more HCs than DCM NSOs. These results contradict the sequential reaction model described as: kerogen → bitumen → oil or kerogen → NSOs → hydrocarbons. Instead, they confirm the “alternate pathway” mechanism proposed by Burnham et al. [ACS symposium, 1989] in which hydrocarbons can be formed immediately from kerogen in parallel with NSOs and the formation of the two species are controlled by bond-breaking reactions that are independent of each other. This study adds geochemical insights into the decomposition mechanism of lacustrine Type-II kerogen.

Arrhythmia (ARR) is the defective origin and conduction of heart activity leading to an abnormal frequency and rhythm of heartbeats. ARR can cause chest tightness, weakness, sinoatrial node blockages, tachycardia and even sudden death. ARR, therefore, seriously affects the safety of human life. An electrocardiogram (ECG) can record the changes in electrical activity produced in each heartbeat cycle. Due to its simplicity and noninvasiveness, ECGs are used clinically to diagnose ARRs. However, the diagnosis of ARR by experts is an inefficient diagnostic method. Heart rate variability (HRV) analysis is a common method for analyzing heart-related diseases, especially for the automatic diagnosis of ARR based on RR intervals. In this article, we extracted the linear and nonlinear characteristics collected from the 5G-enabled Medical Internet of Things to construct a time-frequency spectrogram from HRV sequences and used a deep learning model based on the combination of a deep convolutional neural network (CNN) and a long short-term memory (LSTM) network in order to classify normal sinus intervals and ARR intervals. The average accuracy, sensitivity and specificity of this model were 99.06%, 98.29%, and 99.73%, respectively, using a tenfold cross validation strategy. The united CNN-LSTM model can accurately detect ARR and has potential value in clinical applications.

An increasing number of detrital zircon U–Pb geochronological data have been reported to trace sediment provenance for the Cenozoic Qaidam basin, which is crucial to understanding crustal deformation, paleoclimate change and basin development in northern Tibetan Plateau and to assessing geodynamic models of plateau growth. However, the existing provenance interpretations are highly diverse and how the northern Tibet has evolved remains controversial. This contribution presents new detrital zircon dating results from Cenozoic outcrop and borehole samples and compiles published data from the whole Qaidam basin, adjacent small Cenozoic basins and the surrounding mountains. Our new synthesis indicates that, Paleoproterozoic signals (1800–2000 Ma and 2350–2500 Ma), rather than the Permian–Triassic ages, can be applied effectively to distinguish the Qilian, Altun and Eastern Kunlun-sourced detrital zircons. The Cenozoic Qaidam basin exhibits spatiotemporally variable detrital zircon age populations. Most sandstones from the western and southern basin are characterized by Phanerozoic bimodal age spectra (i.e., 400–480 Ma and 220–280 Ma) with minor Precambrian signals, indicating major contributions from the neighboring Altun and Eastern Kunlun ranges. By contrast, almost all the northern and eastern basin sandstones display prominent early Paleozoic detrital zircon ages; but Paleoproterozoic, Neoproterozoic (750–950 Ma) and Permian–Triassic signals only appear as dominant age clusters in some samples. Different temporal variation trends are observed from the investigated sections in this region, revealing variable zircon supply from different micro-terranes in the Qilian Mountains. This implies that using detrital zircon provenance data from a single section or from a local area of the Qaidam basin to address regional tectonic and climatic issues of the northern Tibetan Plateau unlikely provide useful results. We propose that the Cenozoic Qaidam basin deposits were derived from localized, adjacent source regions, rather than cross-basinal, distant mountains. Our conclusions support models with synchronous deformation throughout most of northern Tibet in the Cenozoic. The observed spatiotemporal variations in detrital zircon populations are not only attributed to tectonic deformation-induced source changes, but can also be due to heterogeneity of the source terranes (e.g., durability and zircon fertility) and variable factors (e.g., hydrodynamic sorting, recycling and sedimentary microenvironment) in transport-deposition processes. This study also highlights the importance of involving detrital zircon textural and sedimentological parameters to zircon provenance interpretations. An integrated provenance analysis combining other detritus components is helpful to comprehensively characterize source-to-sink systems for sedimentary basins.

X-ray repair cross-complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the base excision repair (BER) and single-strand break repair (SSBR) pathway. Single nucleotide polymorphisms (SNPs) in XRCC1 may alter protein function and repair capacity, thus lead to genetic instability and carcinogenesis. To establish our understanding of possible relationships between XRCC1 polymorphisms (5′UTR -77T>C, Arg194Trp, Arg280His and Arg399Gln) and the susceptibility to lung cancer among women nonsmokers, we performed a hospital-based case-control study of 350 patients with newly diagnosed lung cancer and 350 cancer-free controls, frequency matched by age. Our results showed that exposure to cooking oil fume was associated with increased risk of lung cancer in Chinese women nonsmokers [odds ratio (OR) = 2.51, 95% confidence interval (CI) [1.80–3.51], P < 0.001]. Individuals with homozygous XRCC1 399Gln/Gln genotype (OR = 1.75, 95% CI [1.02–3.01]) and XRCC1 -77 combined TC and CC genotype (OR = 1.66, 95% CI [1.13–2.42]) showed a slightly higher risk for lung cancer overall. In the subgroup of adenocarcinoma cases, adjusted ORs were increased for individuals with homozygous XRCC1 399Gln/Gln genotype (OR = 2.62, 95% CI [1.44–4.79]) and XRCC1 -77 combined TC and CC genotype (OR = 1.85, 95% CI [1.19–2.86]). Haplotype analysis showed that T–Trp–Arg–Gln haplotypes were associated with an increased risk of lung cancer among women nonsmokers (OR = 2.26, 95% CI [1.38–3.68]), however, we did not observe a statistically significant joint effect of cooking oil fume and 399Gln or -77C variant allele on lung cancer among women nonsmokers. In conclusion, XRCC1 Arg399Gln and T-77C polymorphisms may alter the risk of lung cancer in women nonsmokers in China.

Summary Shenyang in Northern China has one of the highest reported prevalence rates of oral clefts in the world. To explore the risk factors for oral clefts in Shenyang, we carried out a population‐based case‐control study. A total of 360 990 births in 2000 to 2007 were screened for oral clefts; the overall prevalence was 1.76 per 1000. The ratio of cleft lip with or without cleft palate (CL ± P) : cleft palate only (CP) was 5.60:1. The overall male : female ratio was 2.02:1. CLP and CL were more common in males than in females with a sex ratio (SR) of 2.88:1 and 1.86:1 respectively, whereas CP was more common in females with an SR of 0.71:1. Using a multivariable conditional logistic regression model, 586 oral clefts cases were compared with 1172 control mothers. Maternal factors significantly associated with increased risk for oral clefts were history of a fever or cold (adjusted OR 2.34, 95% CI 1.06, 5.60); use of analgesic and antipyretic drugs (adjusted OR 3.10, 95% CI 1.41, 6.86); poor ventilation during heating (adjusted OR 2.25, 95% CI 1.10, 4.60); and consumption of pickled vegetables &gt;6 per week (adjusted OR 3.86, 95% CI 1.11, 13.47) during pregnancy. Factors which appeared to be protective were meat consumption ≥4 times per week (adjusted OR 0.43, 95% CI 0.28, 0.67); and legume consumption &gt;6 times per week (adjusted OR 0.60, 95% CI 0.41, 0.89). Differences in risk were found between the two most common phenotypes, CL ± P and CP only. Most of the environmental factors had stronger associations with risk for CL ± P rather than CP, whereas history of oral clefts, as well as legume consumption, were more strongly associated with the risk for CP than for CL ± P. The findings suggest that aetiological heterogeneity may exist between CL ± P and CP.

The shortage of qualified nurses is one of the critical challenges in the field of healthcare. Among the contributing factors, job burnout has been indicated as a risk factor for the intention to leave. The purpose of this study was to provide a better understanding of the local status and reference data for coping strategies for intensive care unit (ICU)-nurse burnout among Liaoning ICU nurses.Observational study.17 ICUs from 10 tertiary-level hospitals in Liaoning, China.431 ICU nurses from 14 ICUs nested in 10 tertiary-level hospitals in Liaoning, China, were invited during October and November 2010.Burnout was measured using the 22-item Chinese version of Maslach Burnout Inventory-Health Service Survey (MBI-HSS) questionnaires.14 ICUs responded actively and were included; the response rate was 87.7% among the 486 invited participants from these 17 ICUs. The study population was a young population, with the median age 25 years, IQR 23-28 years and female nurses accounted for the major part (88.5%). 68 nurses (16%) were found to have a high degree of burnout, earning high emotional exhaustion and depersonalisation scores together with a low personal accomplishment score.The present study indicated a moderate distribution of burnout among ICU nurses in Liaoning, China. An investigation into the burnout levels of this population could bring more attention to ICU caregivers.

Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10−13), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10−10) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10−9). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.

Both genetic polymorphisms and environmental risk factors play important roles in the development of human chronic diseases including lung cancer. This is the first case-control study of interaction between polymorphisms in pre-miRNA genes and cooking oil fume exposure on the risk of lung cancer.A hospital-based case-control study of 258 cases and 310 controls was conducted. Six polymorphisms in miRNAs were determined by Taqman allelic discrimination method. The gene-environment interactions were assessed on both additive and multiplicative scale. The statistical analyses were performed mostly with SPSS.The combination of the risk genotypes of five miRNA SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-608 rs4919510, miR-27a rs895819 and miR-423 rs6505162) with risk factor (cooking oil fume exposure) contributed to a significantly higher risk of lung cancer, and the corresponding ORs (95% confidence intervals) were 1.91(1.04-3.52), 1.94 (1.16-3.25), 2.06 (1.22-3.49), 1.76 (1.03-2.98) and 2.13 (1.29-3.51). The individuals with both risk genotypes of miRNA SNPs and exposure to risk factor (cooking oil fumes) were in a higher risk of lung cancer than persons with only one of the two risk factors (ORs were 1.91, 1.05 and 1.41 for miR-146a rs2910164, ORs were 1.94, 1.23 and 1.34 for miR-196a2 rs11614913, ORs were 2.06, 1.41 and 1.68 for miR-608 rs4919510, ORs were 1.76, 0.82 and 1.07 for miR-27a rs895819, and ORs were 2.13, 1.15 and 1.02 for miR-423 rs6505162, respectively). All the measures of biological interaction indicate that there were not indeed biological interactions between the six SNPs of miRNAs and exposure to cooking oil fumes on an additive scale. Logistic models suggested that the gene-environment interactions were not statistically significant on a multiplicative scale.The interactions between miRNA SNPs and cooking oil fume exposure suggested by ORs of different combination were not statistically significant.

Increasing attention has been paid to differences in the prevalence of perinatal depression by HIV status, although inconsistent results have been reported. The aim of this systematic review and meta-analysis was to assess the relationship between perinatal depression and HIV infection. A comprehensive meta-analysis of comparative studies comparing the prevalence of antenatal or postnatal depression between HIV-infected women and HIV-negative controls was conducted.Studies were identified through PubMed/Medline, Scopus, Web of Science, Cochrane Library, Embase and PsycINFO, and the reading of complementary references in August 2019. Subgroup analyses were performed for anticipated explanation of heterogeneity using methodological quality and pre-defined study characteristics, including study design, geographical location and depression screening tools for depression. The overall odds ratio (OR) and mean prevalence of each group were calculated.Twenty-three studies (from 21 publications), thirteen regarding antenatal depression and ten regarding postnatal depression were included, comprising 3165 subjects with HIV infection and 6518 controls. The mean prevalence of antenatal depressive symptoms in thirteen included studies was 36% (95% CI: 27, 45%) in the HIV-positive group and 26% (95% CI: 20, 32%) in the control group. The mean prevalence of postnatal depressive symptoms in ten included studies was 21% (95% CI: 14, 27%) in the HIV-positive group and 16% (95% CI: 10, 22%) in the control group. Women living with HIV have higher odds of antenatal (OR: 1.42; 95% CI: 1.12, 1.80) and postnatal depressive symptoms (OR: 1.58; 95% CI: 1.08, 2.32) compared with controls. Publication bias and moderate heterogeneity existed in the overall meta-analysis, and heterogeneity was partly explained by the subgroup analyses.Women with HIV infection exhibit a significantly higher OR of antenatal and postnatal depressive symptoms compared with controls. For the health of both mother and child, clinicians should be aware of the significance of depression screening before and after delivery in this particular population and take effective measures to address depression among these women.

Establishing epidemiological models and conducting predictions seems to be useful for the prevention and control of human brucellosis. Autoregressive integrated moving average (ARIMA) models can capture the long-term trends and the periodic variations in time series. However, these models cannot handle the nonlinear trends correctly. Recurrent neural networks can address problems that involve nonlinear time series data. In this study, we intended to build prediction models for human brucellosis in mainland China with Elman and Jordan neural networks. The fitting and forecasting accuracy of the neural networks were compared with a traditional seasonal ARIMA model. The reported human brucellosis cases were obtained from the website of the National Health and Family Planning Commission of China. The human brucellosis cases from January 2004 to December 2017 were assembled as monthly counts. The training set observed from January 2004 to December 2016 was used to build the seasonal ARIMA model, Elman and Jordan neural networks. The test set from January 2017 to December 2017 was used to test the forecast results. The root mean squared error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) were used to assess the fitting and forecasting accuracy of the three models. There were 52,868 cases of human brucellosis in Mainland China from January 2004 to December 2017. We observed a long-term upward trend and seasonal variance in the original time series. In the training set, the RMSE and MAE of Elman and Jordan neural networks were lower than those in the ARIMA model, whereas the MAPE of Elman and Jordan neural networks was slightly higher than that in the ARIMA model. In the test set, the RMSE, MAE and MAPE of Elman and Jordan neural networks were far lower than those in the ARIMA model. The Elman and Jordan recurrent neural networks achieved much higher forecasting accuracy. These models are more suitable for forecasting nonlinear time series data, such as human brucellosis than the traditional ARIMA model.

Abstract Background This study aimed to describe the changing distribution of human brucellosis between 2004 and 2017 in mainland China and seek scientific evidence of the relationship between socio-economic, environmental, and ecological factors and human brucellosis incidence. Methods The annual numbers of brucellosis cases and incidence rates from 31 provinces in mainland China between 2004 and 2017 were obtained from the Data-Center for China Public Health Science. The number of monthly brucellosis cases in 2018 was obtained from the Chinese Center for Disease Control and Prevention. The electronic map of the People’s Republic of China was downloaded from the National Earth System Science Data Sharing Platform. Human population density, gross domestic product (GDP), and an inventory of cattle and sheep at the end of each year from 2004 to 2017 were obtained from the National Bureau of Statistics of China. Annual rainfall data from 31 provinces in the People’s Republic of China from 2004 to 2017 were collected from the China Meteorological Data Service Center. The risk distribution and changing trends of human brucellosis were mapped with ArcGIS. A cluster analysis was employed to identify geographical areas and periods with statistically significant incidence rates. Multivariate linear regression was used to determine possible factors that were significantly correlated with the presence of human brucellosis cases. Results Human brucellosis cases have spread throughout the whole country. Human brucellosis cases occurred mostly from March to August and were concentrated from April to July. The inventory of sheep, GDP, and climate were significantly correlated with the presence of brucellosis cases in mainland China. Conclusions The geographical expansion of human brucellosis in mainland China was observed, so did the high-incidence clusters between 2004 and 2017. Most of the cases were reported during the early spring to early summer (February–August). Results from the multivariate linear regression suggested that the inventory of sheep, GDP, and climate were significantly associated with the incidence of human brucellosis in mainland China.

Abstract Pyroptosis has been implicated in the pathophysiology of myocardial infarction (MI) in rodents, but its contribution to reperfusion injury in MI patients is unclear. Here, we evaluated pyroptosis in MI patients in vitro and in vivo models of myocardial ischemia/reperfusion (I/R) injury. We also investigated the molecular mechanisms that regulate pyroptosis and myocardial I/R injury in these in vitro and in vivo models. The study showed that MI patients exhibited elevated serum concentrations of the pyroptosis-related pro-inflammatory cytokines IL-1β and IL-18. Increased levels of IL-1β and IL-18 as well as the pyroptosis-related inflammatory caspases (caspase-1 and 11) were detected in cultured cardiomyocytes after anoxia/reoxygenation (A/R) and in cardiac tissues after I/R. Circ-NNT and USP46 were upregulated while miR-33a-5p was downregulated in MI patients, as well as in cultured cardiomyocytes after A/R and cardiac tissues after I/R. Circ-NNT or USP46 knockdown or miR-33a-5p overexpression inhibited the expression of pro-caspase-1, cleaved caspase-1, pro-caspase-11, cleaved caspase-11, IL-1β, and IL-18 in A/R cardiomyocytes and attenuated myocardial infarction in I/R mice. The results from luciferase reporter assays and gene overexpression/knockdown studies indicated that miR-33a-5p directly targets USP46, and circ-NNT regulates USP46 by acting as a miR-33a-5p sponge. Direct association between circ-NNT and miR-33a-5p in cardiomyocytes was confirmed by pull-down assays. In summary, pyroptosis is activated during myocardial I/R and contributes to reperfusion injury. Circ-NNT promotes pyroptosis and myocardial I/R injury by acting as a miR-33a-5p sponge to regulate USP46. This circ-NNT→miR-33a-5p→USP46 signaling axis may serve as a potential target for the development of cardio-protective agents to improve the clinical outcome of reperfusion therapy.

Adriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstrated that ASIV significantly ameliorated kidney injury, improved renal dysfunction, reduced oxidative stress, alleviated iron accumulation, and inhibited the induction of ferroptosis by ADR. ASIV also rescued the intracellular levels of nuclear factor-erythroid-2-related factor 2 (Nrf2) and promoted nuclear translocation of Nrf2. These protective effects of ASIV on renal injury might be attained through the ASIV-induced activation of the Pi3K/Akt signaling pathway. In vitro, the treatment of the HK-2 cells with fer-1 or deferoxamine mesylate obviously improved cell viability during Adriamycin administration. On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent. Moreover, ASIV lowered the expression of transferrin receptor 1 and divalent metal transporter 1 while enhancing the expression of ferropotin 1 and glutathione peroxidase 4 in ADR administrated cells, the effects of which were akin to those of deferoxamine mesylate. Furthermore, ASIV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.

To prevent and control agricultural diseases and insect pests, the timely detection and accurate identification of crop diseases and insect pests are significant. Studies have shown that pests on plant surfaces are challenging to detect because of their small size and strong camouflage. Therefore, to better detect pests on citrus leaves, a citrus disease and insect pest detection method based on a double backbone network is proposed. The double backbone network-improved Single Shot MultiBox Detector (SSD) model was used to detect citrus images. The accuracy and recall rate of the neural network target detection were evaluated, and the robustness was verified by analyzing the detection results. The experimental results showed that the trained network’s mean average precision (mAP) on the test dataset was 72.54%. In addition, the model showed high robustness on citrus pest datasets, with mAP reaching 86.01%. The results showed that the method was accurate and efficient compared with other target detection methods and could be applied to detect and control citrus pests and diseases.

Sensitive, simple, and rapid nucleic acid testing used for pathogen detection are crucial for preventing outbreaks and transmission of infectious diseases. In this study, we present a fluorogenic RNA aptamer Output Sensors via transcription Activated by Recombinase polymerase amplification (RPA), termed ROSAR, for highly sensitive detection of DNA and RNA from pathogenic bacteria or viruses in clinical samples. The promoter primer and reporter primer facilitate the integration of the transcriptional promoter with the fluorogenic RNA aptamer transcription templates through the RPA of target DNA. Subsequently, the amplification products are transcribed by T7 RNA polymerase, producing RNA aptamer that binds to a fluorogenic dye. The assay, which can be completed within 50 min and can allow a limit of detection of level aM nucleic acid concentration, owning to the dual amplification effects of RPA and in vitro transcription. Furthermore, we develop a paper-based ROSAR by freeze-drying the reaction components, which is compatible with visual detection based on mobile phone fluorescent reader and suitable for point-of-care (POC) applications. The assay can detect various viral and bacterial nucleic acids, making it a highly promising tool for large-scale epidemic screening and rapid POC testing in home healthcare settings.

Abstract Background The effects of climate variations on bacillary dysentery incidence have gained more recent concern. However, the multi-collinearity among meteorological factors affects the accuracy of correlation with bacillary dysentery incidence. Methods As a remedy, a modified method to combine ridge regression and hierarchical cluster analysis was proposed for investigating the effects of climate variations on bacillary dysentery incidence in northeast China. Results All weather indicators, temperatures, precipitation, evaporation and relative humidity have shown positive correlation with the monthly incidence of bacillary dysentery, while air pressure had a negative correlation with the incidence. Ridge regression and hierarchical cluster analysis showed that during 1987–1996, relative humidity, temperatures and air pressure affected the transmission of the bacillary dysentery. During this period, all meteorological factors were divided into three categories. Relative humidity and precipitation belonged to one class, temperature indexes and evaporation belonged to another class, and air pressure was the third class. Conclusion Meteorological factors have affected the transmission of bacillary dysentery in northeast China. Bacillary dysentery prevention and control would benefit from by giving more consideration to local climate variations.

HFRS is a serious public health problem in China and the study on HFRS is important in China for its large population. The present study aimed to explore the impact of climatic variables and reservoir on the incidence of HFRS in Huludao City, an epidemic focus of the disease in northeastern China.Structure Equation Model (SEM), a statistical technique for testing and estimating causal relationships, was conducted based on climatic variables, virus-carrying index among rodents, and incidence of HFRS in the city during the period 1990 to 2006. The linear structural relationships (LISREL) software (Scientific Software International, Lincolnwood, IL) was used to fit SEMs.Temperature, precipitation, relative humidity and virus-carrying index among rodents have shown positive correlations with the monthly incidence of HFRS, while air pressure had a negative correlation with the incidence. The best-fit SEM model fitted well with the data-based correlation matrix, P value was more than 0.56, root mean square error of approximation (RMSEA) equaled to 0, goodness-of-fit index (GFI) was more than 0.99.Climate and reservoirs have affected the incidence of HFRS in Huludao City, located in northeastern China. Climate affects HFRS incidence mainly through the effect on reservoir in the study area. HFRS prevention and control should give more consideration to rodent control and climate variations.

The tumor suppressor gene p53 is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the p53 gene is associated with the risk for development of various neoplasms. MDM2 SNP309 is a single nucleotide T to G polymorphism located in the MDM2 gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between MDM2 SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory.To investigate whether currently published epidemiological studies can clarify the potential interaction between MDM2 SNP309 and the functional genetic variant in p53 codon72 (Arg72Pro) and p53 mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls.The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17). We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively). In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively). However, no association was seen between MDM2 SNP309 and tumor susceptibility in the stratified analysis by p53 mutation status (GG vs TT: OR = 1.17, 95% CI = 0.75-1.82 and TG vs TT: OR = 1.09, 95% CI = 0.89-1.34 for positive p53 mutation status; GG vs TT: OR = 0.95, 95% CI = 0.72-1.25 and TG vs TT: OR = 1.06, 95% CI = 0.85-1.30 for negative p53 mutation status).The analyses indicate that MDM2 SNP309 serves as a tumor susceptibility marker, and that there is an association between MDM2 SNP309 and p53 Arg72Pro regarding tumor susceptibility. Further studies that take into consideration environmental stresses and functional genetic variants in the p53-MDM2-related genes are warranted.

X-ray repair cross-complementing group 1 (XRCC1) protein plays an important role in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of XRCC1 are suspected to have some relationship with response to chemotherapy and overall survival of lung cancer. This meta-analysis aimed to summarize published data on the association between the commonest SNPs of XRCC1 (Arg194Trp, C > T, rs1799782 and Arg399Gln, G > A, rs25487) and clinical outcome of lung cancer patients.We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) databases. Studies were selected using specific inclusion and exclusion criteria. Primary outcomes included objective response (i.e., complete response + partial response vs. progressive disease + stable disease) and overall survival (OS). Odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) were estimated. All analyses were performed using the Stata software.Twenty-two articles were included in the present analysis. XRCC1 Arg194Trp and Arg399Gln polymorphisms were significantly associated with response to treatment in lung cancer patients. Patients with C/T genotype, T/T genotype and minor variant T allele at Arg194Trp were more likely to respond to platinum-based chemotherapy compared with those with C/C genotype (C/T vs. C/C: OR, 2.54; 95%CI, 1.95-3.31; T/T vs. C/C: OR, 2.06; 95%CI, 1.39-3.06; C/T+T/T vs. C/C: OR, 2.42; 95% CI, 1.88-3.10). For XRCC1 Arg399Gln, G/A genotype, A/A genotype and minor variant A allele were associated with objective response in all patients (G/A vs. G/G: OR, 0.67; 95%CI, 0.50-0.90; A/A vs. G/G: OR, 0.43; 95%CI, 0.25-0.73; A/A+G/A vs. G/G: OR, 0.63; 95%CI, 0.49-0.83). Both G/A and A/A genotypes of XRCC1 Arg399Gln could influence overall survival of lung cancer patients (G/A vs. G/G: HR, 1.23; 95%CI, 1.06-1.44; A/A vs. G/G: HR, 2.03; 95%CI, 1.20-3.45). Interaction analysis suggested that compared with the patients carrying C/T+T/T genotype at XRCC1 194 and G/G genotype at XRCC1 399, the patients carrying 194 C/C and 399 G/A+A/A or 194 C/C and 399 G/G genotype showed much worse objective response.Genetic polymorphisms in XRCC1 gene might be associated with overall survival and response to platinum-based chemotherapy in lung cancer patients.

Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19×10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.

Facies, biomarker and stable isotopic records from the Miocene lacustrine sediments in the northwestern Qaidam basin were investigated to reconstruct the Miocene sedimentary environment and climatic history. Three distinct facies can be recognized. These include the following: (1) gray–black laminated mudstone and marlstone, which represent a semi-deep fresh to semi-brackish lake environment; (2) gray, yellowish massive mudstone, marlstone and siltstone; and (3) yellowish massive sandstone, which imply a shallow brackish lake environment. The decreasing C27/C31 and (C27 + C29)/(C31 + C33) values, the increasing ACL (mean chain length) values of n-alkanes and the vertical evolution of sedimentary environments indicate the overall intensified aridity, which is considered to be an integrated result of high elevation of the Himalaya–Tibetan system, retreat of the Paratethys and global cooling. High fluctuations of the δ18O values and primary dolomite contents reveal the hydrologically closed paleolake with intermittently open conditions in the study area during middle–late Miocene. The Qaidam basin is suggested to be hydrologically segmented, based on the stable isotopic data comparison between the study area and the northeastern area. The most negative end of the oscillations of the δ18O values (indicating the minimal evaporation), which likely represents the isotopic ratio of the meteoric water, surprisingly conveys stability in the Shang Youshashan and Shizigou Formations and displays a positive ~ 2.5‰ shift. This significant shift was probably due to the climatic aridification and air mass changes around 10–8 Ma rather than the global cooling.

Cases of hemorrhagic fever with renal syndrome (HFRS) are widely distributed in eastern Asia, especially in China, Russia, and Korea. It is proved to be a difficult task to eliminate HFRS completely because of the diverse animal reservoirs and effects of global warming. Reliable forecasting is useful for the prevention and control of HFRS.Two hybrid models, one composed of nonlinear autoregressive neural network (NARNN) and autoregressive integrated moving average (ARIMA) the other composed of generalized regression neural network (GRNN) and ARIMA were constructed to predict the incidence of HFRS in the future one year. Performances of the two hybrid models were compared with ARIMA model.The ARIMA, ARIMA-NARNN ARIMA-GRNN model fitted and predicted the seasonal fluctuation well. Among the three models, the mean square error (MSE), mean absolute error (MAE) and mean absolute percentage error (MAPE) of ARIMA-NARNN hybrid model was the lowest both in modeling stage and forecasting stage. As for the ARIMA-GRNN hybrid model, the MSE, MAE and MAPE of modeling performance and the MSE and MAE of forecasting performance were less than the ARIMA model, but the MAPE of forecasting performance did not improve.Developing and applying the ARIMA-NARNN hybrid model is an effective method to make us better understand the epidemic characteristics of HFRS and could be helpful to the prevention and control of HFRS.

We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene–HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30 % increased risk of lung cancer (OR 1.3, 95 % CI 1.0–1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.

Abstract The RhoA/Rho‐kinase cascade plays an important role in many aspects of cardiovascular function. This study aims to investigate the protective effects of fasudil, a Rho‐kinase inhibitor, on pressure overload induced heart failure in rats. Pressure overload induced heart failure was induced in SD rats by banding the abdominal aorta for 8 weeks. The rats were divided into four groups: Sham, TAC, TAC plus low dose of fasudil, and TAC plus high dose of fasudil group. Low dose and high dose fasudil were 5 and 10 mg/kg/day, respectively. Rats in the Sham and TAC groups were treated with vehicle. Fasudil effectively inhibited TAC‐induced heart failure, as evaluated by echocardiography and transmission electron microscopy. Fasudil could significantly promote superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity and significantly decrease malondialdehyde (MDA) content in a dose‐dependent maner in TAC rats. Consistently, fasudil evoked significant nuclear translocation of Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) with increased DNA/promoter binding and transactivation of Nrf2 targets. In addition, fasudil increased the content of iron as well as transferrin receptor 1 (TfR1) in TAC rats. A mild oxidative stress induced by iron may activate the antioxidant enzymes by feedback response. Taken together, these results indicate that the protective effect of fasudil may be due to its strong antioxidative activities which related with the activated Nrf2 and its down‐regulated genes. These findings provide a new treatment concept and support the benefit of fasudil treatment in heart failure.

Weathering, as an important process in the earth surface system, can be significantly influenced by tectonics and climates over long time scales. Here, we use mineralogical, petrographic and geochemical data of a paleoweathering profile developed on basement granodioritic rocks of northern Qaidam basin, northern Tibet, to reconstruct early Eocene weathering conditions and to discuss how paleoclimates and tectonics dominated the weathering process. The results indicate that neoformed mineral phases in weathering products are dominated by smectite, and the profile has overwhelmingly low chemical index of alteration values (ca. 51–59) and significantly decreasing micropetrographic index values (from 25.0 to 0.2) from bottom to top. These findings suggest that the basement rocks experienced mild chemical weathering but relatively intensive physical weathering. We favor that non-steady-state weathering, in which mechanical erosion rates compare favorably with rates of chemical weathering, prevailed in northern Tibet during the early Eocene. The weathering conditions were likely an integrated response to active tectonism and dry climates at that time. Furthermore, chemical element mobility evaluation demonstrates that most of large ion lithophile elements and light rare earth elements (LREEs) of granodioritic rocks are quite active during weathering and can be easily leached even under mild chemical weathering conditions. Significant mass loss of Al and LREEs in upper weathered samples probably reflects acidic weathering conditions, which were likely due to extremely high atmospheric CO2 level during the early Eocene. This study, from the unique perspective of weathering process, suggests that intensive deformation and rapid tectonic erosion occurred in northern Tibet during the early Eocene, as a far-field response to the India-Eurasia collision. It also agrees with warm and relatively dry climates, which were likely attributed to the global greenhouse climates and the Paleogene planetary-wind-dominant climate system in Asia, respectively.

Hydrogen gas (H2) has a diversity of effects such as anti-apoptotic, anti-inflammatory and anti-oxidative properties. However, molecular mechanism underlying the potential effect of H2 on chronic intermittent hypoxia (CIH) induced renal injury remains obscure.In the present study, adult male Sprague-Dawley rats were randomly allocated into four groups: control (CON) group, CIH group, CIH with H2 treatment (CIH + H2) group, and control with H2 treatment (CON + H2) group. Oxidative stress, autophagy and endoplasmic reticulum (ER) stress were detected to determine how H2 affected the renal function of CIH exposed rats.We demonstrated that rats who inhale hydrogen gas showed improved renal function, alleviated pathological damage, oxidative stress and apoptosis in CIH rats. Meanwhile, CIH-induced endoplasmic reticulum stress was decreased by H2 as the expressions of CHOP, caspase-12, and GRP78 were down-regulated. Furthermore, relative higher levels of LC3-II/I ratio and Beclin-1, with decreased expression of p62, were found after H2 administrated. Inhibition of mTOR may be involved in the upregulation of autophagy by H2. Finally, increased phosphorylation of p38 and JNK was involved in the CIH-induced pathological process. H2 could inhibit the activation of p38 and JNK, suggesting H2 played an active part in resisting renal injury via MAPK.Taken together, our study reveals that H2 can ameliorate CIH-induced kidney injury by decreasing endoplasmic reticulum stress and activating autophagy through inhibiting oxidative stress-dependent p38 and JNK MAPK activation.

Objective To analyze the maternal and fetal factors affecting emergency cesarean section (EmCS) and establish a risk scoring system to quantitatively predict the risk of EmCS. Design A total of 10,295 pregnant women were enrolled in this study. The influence of maternal and fetal factors on the risk of EmCS was analyzed. Results 991 (9.63%) cases of failed vaginal delivery received EmCS. The two main causes of EmCS were fetal distress (67.21%) and abnormal fetal position (14.93%). There were significant differences in 17 maternal and fetal factors between the normal vaginal delivery (NVD) and EmCS groups (p&lt;0.05 for all). Univariate and multivariate regression analyses showed that nine maternal and infant factors were independent risk factors (p&lt;0.05 for all). The major factors were abnormal quantity of amniotic fluid (OR 6.867, 95% CI 4.442 to 10.618), nulliparous (OR 4.336, 95% CI 3.074 to 6.115), induction of labor (OR 5.300, 95% CI 4.514 to 6.224) and abnormal characters of amniotic fluid (OR 3.126, 95% CI 2.708 to 3.608). A risk scoring system (six grades) was established based on those factors which showed high discriminative power. The rate of EmCS was 1.30%, 2.57%, 5.83%, 13.94%, 21.75% and 39.71% in grades 1, 2, 3, 4, 5 and 6, respectively. The area under the curve of the risk scoring system was 0.787, indicating that the regression model of the risk factors had a good predictive ability. Conclusion An effective risk scoring system has been developed to quantitatively assess the risk of EmCS based on measurable maternal and fetal factors. The system is simple, easy to operate and has good repeatability in clinical practice.

Myocardial dysfunction is a frequent complication in patients with severe sepsis. However, effective drugs for the prevention of myocardial dysfunction and the molecular mechanisms of the disease remain elusive. The present study demonstrated that Cyclovirobuxine D (CVB-D) could improve cardiac dysfunction in a cecal ligation and puncture (CLP) model in rodents and in a lipopolysaccharide (LPS) model in vitro. Echocardiography and histopathological examination were used to detect changes in cardiac structure and function. Kits were used to detect indicators of cardiac injury, transmission electron microscopy to detect structural changes in mitochondria and reverse transcription-quantitative PCR to detect prostaglandin-endoperoxide synthase 2 and hamp expression levels. L-Glutathione and malondialdehyde levels and superoxide dismutase activity were measured using kits. Cell viability was measured with the Cell Counting Kit-8. Iron metabolism-related proteins, inflammatory factor levels and related pathway proteins were detected using western blot analysis. Changes in L-type calcium currents were detected by membrane clamp, and contractility of cardiomyocytes was measured by Ion Optix. CVB-D attenuated CLP-induced cardiac malfunction in septic rats, with changes observed in myocardial pathological structure, creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTnI). CVB-D attenuated sepsis-induced lipid peroxidation and iron overload. In addition, CVB-D decreased the expression of CK-MB, LDH and cTnI, suppressed oxidative stress index levels and reduced the production of reactive oxygen species. CVB-D decreased LPS-induced cytoplasmic iron overload by increasing upregulation of iron uptake molecules. Conversely, CVB-D significantly increased the upregulation of ferroportin 1. CVB-D pretreatment significantly reduced the levels of hamp mRNA compared with the LPS-treated group. CVB-D pretreatment significantly reduced inflammatory factor levels and the ratio of phosphorylated vs. total signal transducer and activator of transcription 3. The expression of SLC7A11 and GPX4 was upregulated in septic cells pretreated with CVB-D, however treatment with ML385 largely decreased this upregulation. Of note, CVB-D inhibited the inward flow of calcium ions through the LTCC. In conclusion, these findings suggest that CVB-D alleviated sepsis-induced cardiac iron toxicity by alleviating iron metabolism.

Weathering mechanisms of volcanic and granitic rocks in Hong Kong have been studied by chemical analysis, optical microscopy on thin sections and magnetic susceptibility measurements. The mobility of elements of calcium, sodium, iron, potassium, magnesium, silicon, aluminium and constitutional water is investigated in detail using the Mobility Index. Chemical weathering processes in Hong Kong are dominated by decomposition of feldspars and biotite, leaching of alkali and alkaline earth metals, and enrichment of ferric oxide under prolonged subtropical climate conditions. Data for some granitic residual soils from five neighbouring regions in Southern China are also gathered and examined. It is found that the residual soils in Hong Kong are abnormal and immature with respect to its latitude. By examining various quantitative chemical indices and comparing them with the current six-grade material classification scheme, WPI , LOI and I mob are found to be good indicators of the degree of weathering for both volcanic and granitic rocks in Hong Kong. Regarding the optical microscopy, the micropetrographic index ( I p ) is only suitable for granitic rock but not for volcanic rock due to the presence of fine-grained minerals and small voids. For the magnetic susceptibility measurements, consistent results with weathering grades for volcanic rocks are obtained by applying a moving average technique. However, due to the low content of Al 2 O 3 and Fe 2 O 3 in granitic rock, SOC and the magnetic susceptibility index, which are appropriate for quantifying the degree of weathering of volcanic rock, are not quite suitable for the granitic rock.

To study the application of artificial neural network (ANN) in forecasting the incidence of hepatitis A, which had an autoregression phenomenon.The data of the incidence of hepatitis A in Liaoning Province from 1981 to 2001 were obtained from Liaoning Disease Control and Prevention Center. We used the autoregressive integrated moving average (ARIMA) model of time series analysis to determine whether there was any autoregression phenomenon in the data. Then the data of the incidence were switched into [0,1] intervals as the network theoretical output. The data from 1981 to 1997 were used as the training and verifying sets and the data from 1998 to 2001 were made up into the test set. STATISTICA neural network (ST NN) was used to construct, train and simulate the artificial neural network.Twenty-four networks were tested and seven were retained. The best network we found had excellent performance, its regression ratio was 0.73, and its correlation was 0.69. There were 2 input variables in the network, one was AR(1), and the other was time. The number of units in hidden layer was 3. In ARIMA time series analysis results, the best model was first order autoregression without difference and smoothness. The total sum square error of the ANN model was 9 090.21, the sum square error of the training set and testing set was 8 377.52 and 712.69, respectively, they were all less than that of ARIMA model. The corresponding value of ARIMA was 12 291.79, 8 944.95 and 3 346.84, respectively. The correlation coefficient of nonlinear regression (R(NL)) of ANN was 0.71, while the R(NL) of ARIMA linear autoregression model was 0.66.ANN is superior to conventional methods in forecasting the incidence of hepatitis A which has an autoregression phenomenon.

Abstract Background Excision repair cross-complementing group 1 (ERCC1) and group 2 (ERCC2), and X-ray repair cross-complementing group 1 (XRCC1) proteins play important roles in the repair of DNA damage and adducts. Single nucleotide polymorphisms (SNPs) of DNA repair genes are suspected to influence treatment effect and survival of cancer patients. This study aimed to investigate the relationship between polymorphisms in ERCC2 , ERCC1 and XRCC1 genes and survival of non-smoking female patients with lung adenocarcinoma. Methods We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to evaluate SNPs in ERCC2 , ERCC1 and XRCC1 genes among 257 patients. Results The overall median survival time (MST) was 13.07 months. Increasing numbers of either ERCC1 118 or XRCC1 399 variant alleles were associated with shorter survival of non-smoking female lung adenocarcinoma patients (Log-rank P &lt; 0.001). The adjusted hazard ratios (HRs) for individuals with CT or TT genotype at ERCC1 Asn118Asn were 1.48 and 2.67 compared with those with CC genotype. For polymorphism of XRCC1 399, the HRs were 1.28 and 2.68 for GA and AA genotype. When variant alleles across both polymorphisms were combined to analysis, the increasing number of variant alleles was associated with decreasing overall survival. Using the stepwise Cox regression analysis, we found that the polymorphisms in ERCC1 and XRCC1 , tumor stage and chemotherapy or radiotherapy status independently predicted overall survival of non-smoking female patients with lung adenocarcinoma. Conclusions Genetic polymorphisms in ERCC1 and XRCC1 genes might be prognostic factors in non-smoking female patients with lung adenocarcinoma.

Danshen (Salvia miltiorrhiza) has been widely prescribed in traditional folk medicine for treatment of hepatic and cardiovascular diseases in China and other Asian countries for several hundred years.Sixty male mice were randomly divided into five groups: control, iron overload, low-dose Danshen (L-Danshen, 3g/kg/day), high-dose Danshen (H-Danshen, 6g/kg/day) and deferoxamine (DFO) groups (n=12 per group). Iron dextran was injected intraperitoneally (i.p.) at 50mg/kg body weight/day to establish the iron overload model. While control mice received saline, mice of the treated groups simultaneously received (i.p.) injections of L-Danshen, H-Danshen or DFO daily for 2 weeks. At the end of the experiment, changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), glutathione peroxidase (GSH-Px), superoxide desmutase (SOD) and malondialdehyde (MDA) were measured, and histological changes were observed by Prussian blue or hematoxylin and eosin staining of the liver. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling.Treatment of iron overloaded mice with either low or high doses of Danshen not only significantly attenuated the hepatic dysfunction (ALT/AST levels), decreased the content of MDA and increased the activities of GSH-Px and SOD, it also suppressed apoptosis in hepatocytes. Histopathological examination showed that treatment with Danshen reduced iron deposition and ameliorated pathological changes in the liver of iron overloaded mice.Danshen demonstrated significant protective effects in the liver of iron overloaded mice, which were at least partly due to the decrease of iron deposition and inhibition of lipid peroxidation and hepatocyte apoptosis.

Abstract Lower Paleozoic sedimentary rocks in the northwestern Tarim basin were strongly altered by complicated geofluids, which resulted in the occurrence of various diagenetic minerals (e.g., dolomite). Here, in situ major, trace, and rare earth element geochemistry of Lower Ordovician diagenetic dolomite grains as well as petrography were performed to unravel the geochemical features, the nature, and origin of the diagenetic fluids. The results indicate that different geochemical information can be detected within a single sample, even within a single dolomite grain. Five generations of diagenetic dolomite have been identified based on geochemical signatures, resulting from four distinct types of diagenetic fluids: (1) HREE enrichment (PAAS‐normalized), low ΣREE, no Eu anomaly, low Mn, Ba, moderate Fe, and high Sr contents are probably due to early burial dolomitizing fluids; (2) MREE enrichment, high ΣREE, high Mn, Fe, and low Sr content are likely to be associated with Devonian deep‐circulating crustal hydrothermal fluids; (3) flat or LREE enrichment pattern with obviously positive Eu anomaly is inferred to be linked to Permian magmatic hydrothermal fluids; and (4) flat REE pattern, moderate ΣREE, no Eu anomaly, low Mn, Ba, moderate Fe, and high Sr contents are probably due to late burial dolomitizing fluids. The significances of in situ method demonstrated in this study, compared with the whole rock analysis, include not only contamination‐free analysis but also unraveling the internal geochemical variation within a single sample or a mineral grain. Thus, for the geochemical study of complicated diagenetic process, in situ method should be preferentially considered.

Biospecimens are essential resources for advancing basic and translational research. However, there are little data available regarding the costs associated with operating a biobank, and few resources to enable their long-term sustainability. To support the research community in this effort, the National Institutes of Health, National Cancer Institute's Biorepositories and Biospecimen Research Branch has developed the Biobank Economic Modeling Tool (BEMT). The tool is accessible at http://biospecimens.cancer.gov/resources/bemt.asp.To obtain market-based cost information and to inform the development of the tool, a survey was designed and sent to 423 biobank managers and directors across the world. The survey contained questions regarding infrastructure investments, salary costs, funding options, types of biospecimen resources and services offered, as well as biospecimen pricing and service-related costs.A total of 106 responses were received. The data were anonymized, aggregated, and used to create a comprehensive database of cost and pricing information that was integrated into the web-based tool, the BEMT. The BEMT was built to allow the user to input cost and pricing data through a seven-step process to build a cost profile for their biobank, define direct and indirect costs, determine cost recovery fees, perform financial forecasting, and query the anonymized survey data from comparable biobanks.A survey was conducted to obtain a greater understanding of the costs involved in operating a biobank. The anonymized survey data was then used to develop the BEMT, a cost modeling tool for biobanks. Users of the tool will be able to create a cost profile for their biobanks' specimens, products and services, establish pricing, and allocate costs for biospecimens based on percent cost recovered, and perform project-specific cost analyses and financial forecasting.

Both iron deficiency and excess are relatively common health concerns. Maintaining the body's levels of iron within precise boundaries is critical for cell functions. However, the difference between iron deficiency and overload is often a question of a scant few milligrams of iron. The mammalian target of rapamycin (mTOR), an atypical Ser/Thr protein kinase, is attracting significant amounts of interest due to its recently described role in iron homeostasis. Despite extensive study, a complete understanding of mTOR function has remained elusive. mTOR can form two multiprotein complexes that consist of mTOR complex 1 (mTORC1) and mTOR complex 2. Recent advances clearly demonstrate that mTORC1 can phosphorylate iron-sulfur cluster assembly enzyme ISCU and affect iron-sulfur clusters assembly. Moreover, mTOR is reported to control iron metabolism through modulation of tristetraprolin expression. It is now well appreciated that the hormonal hepcidin-ferroportin system and the cellular iron-responsive element/iron-regulatory protein regulatory network play important regulatory roles for systemic iron metabolism. Sustained ISCU protein levels enhanced by mTORC1 can inhibit iron-responsive element and iron-regulatory protein binding activities. In this study, hepcidin gene and protein expression in the livers of tristetraprolin knockout mice were dramatically reduced. Here, we highlight and summarize the current understanding of how mTOR pathways serve to modulate iron metabolism and homeostasis as the third iron-regulatory system.

Background Influenza epidemics pose significant social and economic challenges in China. Internet search query data have been identified as a valuable source for the detection of emerging influenza epidemics. However, the selection of the search queries and the adoption of prediction methods are crucial challenges when it comes to improving predictions. The purpose of this study was to explore the application of the Support Vector Machine (SVM) regression model in merging search engine query data and traditional influenza data. Methods The official monthly reported number of influenza cases in Liaoning province in China was acquired from the China National Scientific Data Center for Public Health from January 2011 to December 2015. Based on Baidu Index, a publicly available search engine database, search queries potentially related to influenza over the corresponding period were identified. An SVM regression model was built to be used for predictions, and the choice of three parameters ( C , γ, ε) in the SVM regression model was determined by leave-one-out cross-validation (LOOCV) during the model construction process. The model’s performance was evaluated by the evaluation metrics including Root Mean Square Error, Root Mean Square Percentage Error and Mean Absolute Percentage Error. Results In total, 17 search queries related to influenza were generated through the initial query selection approach and were adopted to construct the SVM regression model, including nine queries in the same month, three queries at a lag of one month, one query at a lag of two months and four queries at a lag of three months. The SVM model performed well when with the parameters ( C = 2, γ = 0.005, ɛ = 0.0001), based on the ensemble data integrating the influenza surveillance data and Baidu search query data. Conclusions The results demonstrated the feasibility of using internet search engine query data as the complementary data source for influenza surveillance and the efficiency of SVM regression model in tracking the influenza epidemics in Liaoning.

Despite widespread use of formalin-fixed, paraffin-embedded (FFPE) tissue in clinical and research settings, potential effects of variable tissue processing remain largely unknown.To elucidate molecular effects associated with clinically relevant preanalytical variability, the National Cancer Institute initiated the Biospecimen Preanalytical Variables (BPV) program.The BPV program, a well-controlled series of systematic, blind and randomized studies, investigated whether a delay to fixation (DTF) or time in fixative (TIF) affects the quantity and quality of DNA and RNA isolated from FFPE colon, kidney, and ovarian tumors in comparison to case-matched snap-frozen controls.DNA and RNA yields were comparable among FFPE biospecimens subjected to different DTF and TIF time points. DNA and RNA quality metrics revealed assay- and time point-specific effects of DTF and TIF. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay was superior when assessing RNA quality, consistently detecting differences between FFPE and snap-frozen biospecimens and among DTF and TIF time points. RNA Integrity Number and DV200 (representing the percentage of RNA fragments longer than 200 nucleotides) displayed more limited sensitivity. Differences in DNA quality (Q-ratio) between FFPE and snap-frozen biospecimens and among DTF and TIF time points were detected with a qPCR-based assay.DNA and RNA quality may be adversely affected in some tumor types by a 12-hour DTF or a TIF of 72 hours. Results presented here as well as those of additional BPV molecular analyses underway will aid in the identification of acceptable delays and optimal fixation times, and quality assays that are suitable predictors of an FFPE biospecimen's fit-for-purpose.

Monitoring and prediction of diabetic retinopathy (DR) is necessary in patients with diabetes for early discovery and timely treatment of disease. We aimed to analyze the association between DR and biochemical and metabolic parameters, and develop a predictive model for DR.A total of 530 Chinese residents including 423 with type 2 diabetes (T2D) aged 18 years or older participated in this study. The association between DR and biochemical and metabolic parameters was analyzed by the univariate and multivariable logistic regression (MLR). According to the MLR results, we developed a back propagation artificial neural network (BP-ANN) model by selecting tan-sigmoid as the transfer function of the hidden layers nodes, and pure-line of the output layer nodes, with training goal of 0.5×10-5.There were 51 (9.6%) diabetic participants with DR. After univariate and MLR analysis, duration of diabetes, waist to hip ratio, HbA1c and family history of diabetes were independently associated with the presence of DR (all P < 0.05). Based on these parameters, the area under the receiver operating characteristic (ROC) curve for the BP-ANN model was significantly higher than that by MLR (0.84 vs. 0.77, P < 0.001).Our evaluation demonstrated the potential role of BP-ANN model to identify DR in screening practice. The presence of DR was well predictable using the proposed BP-ANN model based on four related parameters (duration of diabetes, waist to hip ratio, HbA1c and family history of diabetes).

Understanding how blood lipid levels change with age in the general population is a precondition to defining dyslipidemia.To explore age-related trends in LDL-C and non-HDL-C levels in the general population, a large-scale cross-sectional study with 49,201 males and 35,084 females was adopted.Trends of non-HDL-C and LDL-C levels were plotted against each age (18 to 85 years old, one-year increments); the trends, as well as the influence of confounding factors on the trends, were validated and adjusted by linear regression modeling.The trajectory of LDL-C and non-HDL-C levels by age displayed a nonlinear correlation trend.Further multivariate linear regression modeling that incorporated sex-specific age phases showed that age was positively associated with LDL-C and non-HDL-C levels, with coefficients of 0.018 and 0.031, respectively, in females aged ≥18 to ≤56 years and negatively associated with LDL-C and non-HDL-C levels, with coefficients of -0•013 and -0.015, respectively, in females aged ≥57 years.The LDL-C and non-HDL-C levels increased with age in males ≥18 to ≤33 years of age, with coefficients of 0.025 and 0.053, respectively; the lipid levels plateaued at ≥34 to ≤56 years of age and subsequently decreased in those ≥57 years of age, with coefficients of -0.008 and -0.018, respectively.In contrast, pooled analyses without age stratification concealed these details.In conclusion, fluctuating increasing and decreasing lipid levels occurred with phases of aging in both sexes.Well-grounded age stratification is necessary to improve lipid-related pathophysiological studies.

This study aimed to investigate the association between the triglyceride-glucose (TyG) index and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.In this nested case-control study, all diabetic participants were registered hospitalizations during 2012-2018, including 596 with DR as cases and three matching controls per case. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. The TyG index was calculated: Ln (fasting blood glucose [mg/dL] × fasting triglycerides [mg/dL] ÷ 2). Multivariate logistic regression, a receiver-operating characteristic (ROC) curve, linear regression models, and mediation analysis were used to explore associations.The TyG index was lower in DR and decreased as its severity advanced among 2,112 subjects (P=0.005). After confounders (sex, duration of diabetes, use of antidiabetic agents, heart rate, systolic blood pressure, pulse pressure, height, weight, body-mass index, and glycated hemoglobin) had been accounted for, there were significant associations between the TyG index and any-severity DR (OR 0.83, 95% CI 0.73-0.95; P=0.006), as well as vision-threatening DR (VTDR; OR 0.53, 95% CI 0.36-0.76; P=0.001). ROC analysis indicated that the TyG index showed significant discriminatory ability in any-severity DR (area under curve [AUC] 0.534, P=0.015) and VTDR (AUC 0.624, P=0.001).The TyG index was associated with the presence and severity of DR. Our findings suggest that the TyG index may become a useful biomarker in evaluating and following the presence of DR and VTDR.

A series of chemical analyses and dry density tests of rhyolitic tuff and granitic samples have been carried out. The test results have been interpreted using a newly developed theoretical weathering model for calculating a mobility index of major elements in rock and soil. It is found that this index is useful for describing changes of rock and soil during weathering and classifying the degrees of weathering. Based on the theoretical model, a new parameter called the volume index, which combines chemical and physical data, is suggested. This index appears to be a good indicator for classifying the degree of weathering in Hong Kong. A quantitative classification scheme is suggested.

The relationship between the incidence of bacillary dysentery and meteorological factors was investigated. Data on bacillary dysentery incidence in Shenyang from 1990 to 1996 were obtained from Liaoning Provincial Center for Disease Control and Prevention, and meteorological data such as atmospheric pressure, air temperature, precipitation, evaporation, wind speed, and the amount of solar radiation were obtained from Shenyang Meteorological Bureau. Kendall and Spearman correlations were used to analyze the relationship between bacillary dysentery and meteorological factors. The incidence of bacillary dysentery was treated as a response variable, and meteorological factors were treated as predictable variables. Software R 2.3.1 was used to execute the classification and regression trees (CART). The model improved the accuracy of the fitting results. The residual sum square error of the regression tree model was 53.9, while the residual sum square error of the multivariate linear regression model was 107.2. Among all the meteorological indexes, relative humidity, minimum temperature, and pressure one month prior were statistically influential factors in the multivariate regression tree model. CART may be a useful tool for dealing with heterogeneous data, as it can serve as a decision support tool and is notable for its simplicity and ease.

The interaction between the karyoplast and cytoplast plays an important role in the efficiency of somatic cell nuclear transfer (SCNT), but the underlying mechanism remains unclear. It is generally accepted that in nuclear transfer embryos, the reprogramming of gene expression is induced by epigenetic mechanisms and does not involve modifications of DNA sequences. In cattle, oocytes with various mitochondrial DNA (mtDNA) haplotypes usually have different ATP content and can further affect the efficiency of in vitro production of embryos. As mtDNA comes from the recipient oocyte during SCNT and is regulated by genes in the donor nucleus, it is a perfect model to investigate the interaction between donor nuclei and host oocytes in SCNT.We investigated whether the in vitro development of reconstructed bovine embryos produced by SCNT would be influenced by mtDNA haplotype compatibility between the oocytes and donor cells. Embryos from homotype A-A or B-B showed significantly higher developmental ability at blastocyst stages than the heterotype A-B or B-A combinations. Post-implantation development ability, pregnancy rate up to day 90 of gestation, as well as percent of term births were higher in the homotype SCNT groups than in the heterotype groups. In addition, homotype and heterotype SCNT embryos showed different methylation patterns of histone 3-lysine 9 (H3K9) genome-wide and at pluripotency-related genes (Oct-4, Sox-2, Nanog).Both histone and DNA methylation show that homotype SCNT blastocysts have a more successful epigenetic asymmetry pattern than heterotype SCNT blastocysts, which indicates more complete nuclear reprogramming. This may result from variability in their epigenetic patterns and responses to nuclear reprogramming. This suggests that the compatibility of mtDNA haplotypes between donor cells and host oocytes can significantly affect the developmental competence of reconstructed embryos in SCNT, and may include an epigenetic mechanism.

A reliable and precise classification is essential for successful diagnosis and treatment of cancer. Gene expression microarrays have provided the high-throughput platform to discover genomic biomarkers for cancer diagnosis and prognosis. Rational use of the available bioinformation can not only effectively remove or suppress noise in gene chips, but also avoid one-sided results of separate experiment. However, only some studies have been aware of the importance of prior information in cancer classification.Together with the application of support vector machine as the discriminant approach, we proposed one modified method that incorporated prior knowledge into cancer classification based on gene expression data to improve accuracy. A public well-known dataset, Malignant pleural mesothelioma and lung adenocarcinoma gene expression database, was used in this study. Prior knowledge is viewed here as a means of directing the classifier using known lung adenocarcinoma related genes. The procedures were performed by software R 2.80.The modified method performed better after incorporating prior knowledge. Accuracy of the modified method improved from 98.86% to 100% in training set and from 98.51% to 99.06% in test set. The standard deviations of the modified method decreased from 0.26% to 0 in training set and from 3.04% to 2.10% in test set.The method that incorporates prior knowledge into discriminant analysis could effectively improve the capacity and reduce the impact of noise. This idea may have good future not only in practice but also in methodology.

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease caused by Hantavirus, with characteristics of fever, hemorrhage, kidney damage, and hypotension. HFRS is recognized as a notifiable public health problem in China, and Liaoning Province is one of the most seriously affected areas with the most cases in China. It is necessary to investigate the spatial, temporal, and space-time distribution of confirmed cases of HFRS in Liaoning Province, China for future research into risk factors. Methods A cartogram map was constructed; spatial autocorrelation analysis and spatial, temporal, and space-time cluster analysis were conducted in Liaoning Province, China over the period 1988-2001. Results When the number of permutation test was set to 999, Moran's I was 0.3854, and was significant at significance level of 0.001. Spatial cluster analysis identified one most likely cluster and four secondary likely clusters. Temporal cluster analysis identified 1998-2001 as the most likely cluster. Space-time cluster analysis identified one most likely cluster and two secondary likely clusters. Conclusions Spatial, temporal, and space-time scan statistics may be useful in supervising the occurrence of HFRS in Liaoning Province, China. The result of this study can not only assist health departments to develop a better prevention strategy but also potentially increase the public health intervention's effectiveness.

This work investigates the performance of dispersed particle gel (DPG) by core flow tests including injectivity, selective plugging, thermal stability, and improved oil recovery (IOR). Results showed that the resistance factor is small when DPG was injected, but obviously became larger while turning into brine water flooding. Both the oil and water relative permeability were reduced and greater reduction appeared in water relative permeability. DPG could block water flow without affecting oil flow, and oil–water segregated flow mechanism was proposed to explain this selective plugging. The injection pressure increases, caused by strong plugging due to the DPG aggregation aging in high temperature, which was consistent with the observation of atomic force microscope (AFM) photos. The DPG could effectively block high permeability zone and produce oil from low permeability zone, which could provide a practical way to enhance hydrocarbon recovery while reducing water production for extremely heterogeneous reservoirs.

The aim of this study was to investigate the involvement of the RhoA/Rho kinase (ROCK) signaling pathway in the progression of ADR-induced heart failure. Rats were administered captopril or fasudil over a period of 6 days, and the ADR was injected intraperitoneally on day 4. Similar to the effect of captopril, fasudil treatment significantly protected against ADR-induced hemodynamic, histopathologic and ultra-structural changes and decreased plasma lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) in a dose-dependent manner in the left ventricle of the heart. While ADR treatment induced ROCKI mRNA expression, fasudil significantly and dose-dependently reduced the incidence of apoptosis and the ratio of bax/bcl-2 protein expression. Moreover, a dose-related decrease in c-jun mRNA expression and an increase in c-FLIP (L) expression were observed in the fasudil groups. Fasudil also downregulated NF-κB activity in a dose-dependent manner. These data indicated that the RhoA/ROCK signaling pathway plays an important role in the progression of heart failure induced by ADR, while fasudil increased resistance to cardiac cell injury. The mechanisms of fasudil-mediated protection against ADR-induced apoptosis may be related to higher c-FLIP (L) and bcl-2 expression, lower c-jun expression and inhibition of NF-κB activation in the heart.

Sichuan basin, situated in the west of China, is the fourth biggest basin in China. In order to describe a systematic study of the cry2-type genes resources from Bacillus thuringiensis strains of Sichuan basin, a total of 791 Bacillus thuringiensis strains have been screened from 2650 soil samples in different ecological regions. The method of PCR-restriction fragment length polymorphism (PCR-RFLP) was used to identify the type of cry2 genes. The results showed that 322 Bacillus thuringiensis strains harbored cry2-type genes and four different RFLP patterns were found. The combination of cry2Aa/cry2Ab genes was the most frequent (90.4%), followed by cry2Aa (6.8%) and cry2Ab alone (2.5%), and only one novel type of cry2 gene was cloned from one isolate (JF19-2). The full-length of this novel gene was obtained by the method of thermal asymmetric interlaced PCR (Tail-PCR), which was designated as cry2Ag1 (GenBank No. ACH91610) by the Bt Pesticide Crystal Protein Nomenclature Committee. In addition, the result of scanning electron microscopic (SEM) observation showed that these strains had erose, spherical, bipyramidal, and square crystal. And the results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that these strains harbored about one to three major proteins. These strains exhibited a wide range of insecticidal spectrum toxic to Aedes aegypti (Diptera) and Pieris rapae Linnaeus, 1758 (Lepidoptera). Particularly, JF19-2 contained cry2Ag gene had the highest insecticidal activity. All these researches mentioned above revealed the diversity and particularity of cry2-type gene resources from Bacillus thuringiensis strains in Sichuan basin.

Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer.We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non- smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay.The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles.P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.

Background: MicroRNAs (miRNAs) are suggested to be very important in the development of lung cancer. This study assesses the association between polymorphisms in miRNA-related (miR)-26a-1, miR-605, and miR-16-1 genes and risk of lung cancer, as well as the effect of gene–environment interaction between miRNA polymorphisms and cooking fume exposure on lung cancer. Methods: A case–control study including 268 diagnosed nonsmoking female lung cancer patients and 266 nonsmoking female controls was carried out. Three miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) were analyzed. Both additive and multiplicative interactions were assessed. Results: MiR-16-1 rs1022960 may be associated with the risk of lung cancer. Carriers with TT genotype of miR-16-1 rs1022960 were observed to have a decreased risk of lung cancer compared with CC and CT genotype carriers (odds ratio =0.550, 95% confidence interval =0.308–0.983, P =0.044). MiR-26a-1 rs7372209 and miR-605 rs2043556 showed no statistically significant associations with lung cancer risk. There were no significant associations between the three single nucleotide polymorphisms and lung adenocarcinoma. People with exposure to both risk genotypes of miR-26a-1 rs7372209 and cooking oil fumes were more likely to develop lung cancer than those with only genetic risk factor or cooking oil fumes (odds ratios were 2.136, 1.255, and 1.730, respectively). The measures of biological interaction and logistic models indicate that gene–environment interactions were not statistically significant on additive scale or multiplicative scale. Conclusion: MiR-16-1 rs1022960 may be associated with the risk of lung cancer in a Chinese nonsmoking female population. The interactions between miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) and cooking oil fumes were not statistically significant. Keywords: lung cancer, microRNA, single nucleotide polymorphism, cooking oil fume, interaction

Late Cenozoic lacustrine mixed carbonate-siliciclastic sequences in the northwestern Qaidam basin (NW China) are mainly composed of high porosity and low permeability fine-grained rocks but have big potentials of oil-gas commercial production. However, how these fine-grained rocks generate high-quality reservoirs and accumulate hydrocarbons, remains poorly known. This study focuses on shallow-buried Shang Youshashan Formation (Middle–Late Miocene, N22) and Shizigou Formation (Late Miocene–Pliocene, N23) reservoirs and hydrocarbons in Xiaoliangshan area of the northwestern Qaidam basin. We conduct mineralogy, petrography and porosity and permeability analysis for reservoir rocks and biomarker analysis for hydrocarbons and potential source rocks. The results indicate that the N22 high-quality reservoirs are dominated by fractured marlstones and lime mudstones and constitute structural traps, whereas the N23 hydrocarbon reservoirs are mainly composed of siliciclastic-dominantly rocks and form stratigraphic-lithologic traps. Similar biomarker ratios between crude oil samples and Paleogene organic matter-rich rocks reveal that hydrocarbons in the shallow system were likely derived from deep-buried source rocks, rather than late Cenozoic lacustrine fine-grained rocks themselves. In this case, large-scale vertical fractures created by kink band structures in the northwestern Qaidam basin are supposed to facilitate hydrocarbon migration and accumulation. Preliminary production data and exploration well oil-gas test results demonstrate highest yields and thus large hydrocarbon potentials in the N22 marlstone and lime mudstone reservoirs. Collectively, we suggest that relatively high-permeability, fractured and carbonate-rich reservoirs on structural highs are favorable targets for future oil-gas exploration in the northwestern Qaidam basin. This petroleum system provides a typical and significant example for hydrocarbon exploration and development in mixed carbonate-siliciclastic fine-grained rocks of nonmarine petroliferous basins.

Gentianella acuta (Michx.) Hulten (G. acuta) has been widely used in Mongolian medicines for the treatment of cardiovascular diseases in Ewenki and Oroqen, Inner Mongolia autonomous region, China. The aim of this study was to investigate the effects and related mechanism of G. acuta on isoproterenol (ISO)-induced oxidative stress, fibrosis, and myocardial damage in rats. Male Sprague Dawley rats were randomly divided into the normal control group, ISO induced group and ISO+G. acuta treatment group. Rats were administered with ISO subcutaneously (5 mg/kg/day) for 7 days, and were orally administered simultaneously with aqueous extracts of G. acuta for 21 days. This investigation showed G. acuta treatment ameliorated cardiac structural disorder, excessive collagenous fiber accumulation and cardiac malfunction. Compared with the ISO induced model group, G. acuta treatment increased superoxide dismutase (SOD) activities and glutathione (GSH) level, prevented the rise of malondialdehyde (MDA), and decreased hydroxyproline contents in the heart tissues. Moreover, G. acuta reduced the expression of transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF), and inhibited the expression and activation of NF-κB-P65 in myocardial tissues. These results suggested that G. acuta protects against ISO-induced cardiac malfunction probably by preventing oxidative stress, and fibrosis, and the mechanism might be through inhibiting NF-κB pathway.

Changes in climate and environmental conditions could be the driving factors for the transmission of hantavirus. Thus, a thorough collection and analysis of data related to the epidemic status of hemorrhagic fever with renal syndrome (HFRS) and the association between HFRS incidence and meteorological factors, such as air temperature, is necessary for the disease control and prevention.Journal articles and theses in both English and Chinese from Jan 2014 to Feb 2019 were identified from PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Data and VIP Info. All identified studies were subject to the six criteria established to ensure the consistency with research objectives, (i) they provided the data of the incidence of HFRS in mainland China; (ii) they provided the type of air temperature indexes; (iii) they indicated the underlying geographical scale information, temporal data aggregation unit, and the data sources; (iv) they provided the statistical analysis method that had been used; (v) from peer-reviewed journals or dissertation; (vi) the time range for the inclusion of data exceeded two consecutive calendar years.A total of 27 publications were included in the systematic review, among them, the correlation between HFRS activity and air temperature was explored in 12 provinces and autonomous regions and also at national level. The study period ranged from 3 years to 54 years with a median of 10 years, 70.4% of the studies were based on the monthly HFRS incidence data, 21 studies considered the lagged effect of air temperature factors on the HFRS activity and the longest lag period considered in the included studies was 34 weeks. The correlation between HFRS activity and air temperature varied widely, and the effect of temperature on the HFRS epidemic was seasonal.The present systematic review described the heterogeneity of geographical scale, data aggregation unit and study period chosen in the ecological studies that seeking the correlation between air temperature indexes and the incidence of HFRS in mainland China during the period from January 2014 to February 2019. The appropriate adoption of geographical scale, data aggregation unit, the length of lag period and the length of incidence collection period should be considered when exploring the relationship between HFRS incidence and meteorological factors such as air temperature. Further investigation is warranted to detect the thresholds of meteorological factors for the HFRS early warning purposes, to measure the duration of lagged effects and determine the timing of maximum effects for reducing the effects of meteorological factors on HFRS via continuous interventions and to identify the vulnerable populations for target protection.

Chronic intermittent hypoxia (CIH) is a consequence of obstructive sleep apnea (OSA), which increases reactive oxygen species (ROS) generation, resulting in oxidative damage and neurocognitive impairment. This study was designed to determine whether abnormal iron metabolism occurs in the brain under conditions of CIH and whether Huperzine A (HuA) could improve abnormal iron metabolism and neurological damage. The mouse model of CIH was established by reducing the percentage of inspired O2 (FiO2) from 21% to 9% 20 times/h for 8 h/day, and Huperzine A (HuA, 0.1 mg/kg, i.p.) was administered during CIH exposure for 21 days. HuA significantly improved cognitive impairment and neuronal damage in the hippocampus of CIH mice via increasing the ratio of Bcl-2/Bax and inhibiting caspase-3 cleavage. HuA considerably decreased ROS levels by downregulating the high levels of NADPH oxidase (NOX 2, NOX 4) mediated by CIH. There was an overload of iron, which was characterized by high levels of ferritin (FTL and FTH) and transferrin receptor 1 (TfR1) and low levels of ferroportin 1 (FPN1) in the hippocampus of CIH mice. Decreased levels of TfR1 and FTL proteins observed in HuA treated CIH group, could reduce iron overload in hippocampus. HuA increased PSD 95 protein expression, CREB activation and BDNF protein expression to protect against synaptic plasticity impairment induced by CIH. HuA acts as an effective iron chelator to attenuate apoptosis, oxidative stress and synaptic plasticity mediated by CIH.

Astragaloside IV (ASIV) is the main active component of Astragalus , and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups ( n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway.

Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with I/R injury as cardiomyocytes are abundant in mitochondria. SOCS6 is known to participate in mitochondrial fragmentation, but its exact involvement and the pathways associated are uncertain.The expression of SOCS6 was analyzed by western blot in cardiomyocytes under a hypoxia and reoxygenation (H/R) model. A dual-luciferase reporter assay was used to confirm the direct interaction between miR-19b and the 3'-UTR of Socs6. In the present study, we found that Socs6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that Socs6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro. Moreover, the presence of miR-19b reduced the level of SOCS6 and the injury caused by I/R in vivo. There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, Quaking (QK), participates in the regulation of miR-19b expression.Our results indicate that the inhibition of mitochondrial fission through downregulating Socs6 via the QK/miR-19b/Socs6 pathway attenuated the damage sustained by I/R. The QK/miR-19b/Socs6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.

Ophthalmic epidemiology is concerned with the prevalence, distribution and other factors relating to human eye disease. While observational studies cannot avoid confounding factors from interventions, human eye composition and structure are unique, thus, eye disease pathogenesis, which greatly impairs quality of life and visual health, remains to be fully explored. Notwithstanding, inheritance has had a vital role in ophthalmic disease. Mendelian randomization (MR) is an emerging method that uses genetic variations as instrumental variables (IVs) to avoid confounders and reverse causality issues; it reveals causal relationships between exposure and a range of eyes disorders. Thus far, many MR studies have identified potentially causal associations between lifestyles or biological exposures and eye diseases, thus providing opportunities for further mechanistic research, and interventional development. However, MR results/data must be interpreted based on comprehensive evidence, whereas MR applications in ophthalmic epidemiology have some limitations worth exploring. Here, we review key principles, assumptions and MR methods, summarise contemporary evidence from MR studies on eye disease and provide new ideas uncovering aetiology in ophthalmology.

Abstract There has been conflicting evidence concerning the best sequence of radiotherapy (RT) and chemotherapy (CT) for advanced non‐small‐cell‐lung‐cancer (NSCLC). To investigate whether current clinical trials can clarify this schedule and offer further bases for clinical decision making, we performed a systematic review of 11 trials (2,043 patients; concurrent–1,019, sequential–1,024) that compared concurrent RT‐CT with sequential arm in advanced NSCLC patients. Primary end point was overall survival (OS). Pooled median ratios (MRs) and progression‐free‐survival ratios (FRs) for median survival and progression‐free survival (PFS) were calculated using the weighted sum of the log ratio of MR and FR of individual study. Pooled odds ratios (ORs) for the objective response rate, relapse control rate, and toxic events were calculated using the Mantel‐Haenszel estimate. Results confirmed that concurrent RT‐CT determined a statistically significant increase in median survival time (16.3 vs . 13.9 months; MR = 1.17,95%CI:1.09–1.26), response rate (64.0% vs . 56.3%; OR = 1.38,95%CI:1.10–1.72), and tumor‐relapse control (OR = 0.82,95%CI:0.69–0.97), though at the expense of increased hematological toxicity (neutropenia and thrombocytopenia) and non‐hematological toxicity (nausea/vomiting, stomatitis, and esophagitis). Similar results were obtained from the sensitivity analysis of all Phase‐III/trials designed to evaluate the primary end point of OS. Subgroup analysis revealed that concurrent strategy was mainly associated with improved loco‐regional control (OR = 0.68,95%CI:0.52–0.87). However, no difference in PFS is shown. While careful interpretation of our conclusions is required because of potential bias, the present study, to some extent, exhibits the superiority of the concurrent arm over the sequential in the treatment of advanced NSCLC. Further improvements will be obtained by optimizing the conditions for a concurrent regimen.

Dear Editor, Glandular preinvasive lesions of the cervix (i.e., atypical glandular cells, AGC and adenocarcinoma in situ, AIS) are more likely to be missed in cytological cervical screening than their squamous-cell equivalents, owing to their location in the endocervical canal and difficulties in their cytological and colposcopical assessment.1, 2 Hence, in well-screened populations, although the incidence of cervical cancer has been decreasing over the last three decades, the ratio of adeno/adenosquamous (ADC) to squamous cell carcinoma (SCC) has been rising.1, 3 Screening using high-risk (HR) HPV rather than cytology can improve prevention of ADC.4 ADC: adeno/adenosquamous cell carcinoma; AGC: atypical glandular cells; AIS: adenocarcinoma in situ; ASCUS: atypical squamous cells of undetermined significance; CIN: cervical intra-epithelial neoplasia; HPV: human papillomavirus; HR: high-risk; HSIL: high-grade squamous intraepithelial lesions; LSIL: low-grade squamous intraepithelial lesions; SCC: squamous cell carcinoma Human papillomavirus (HPV) 18 is more frequently detected in ADC than in SCC and this tendency may also apply to other types (e.g., HPV45) that belong to the same alpha-7 species as HPV18.5 However, in contrast to the extensive information about HPV types across the complete spectrum of squamous cervical lesions,6 little is known about the pattern of HPV types in glandular preinvasive lesions, and how it compares to that in ADC. With the aim to improve our understanding of the carcinogenic process for individual HR types from infection of glandular tissue to adenocarcinoma, we performed a systematic literature review of HPV type-specific prevalence data in preinvasive glandular neoplastic lesions, and compared to similar data on women with normal cytology and ADC reported in a recently published meta-analysis.6 Methods have been reported previously.6 In brief, Medline was used to search for publications from January 1990 to November 2011 using combinations of the MeSH terms: “cervical cancer,” “cervical intraepithelial neoplasia,” “HPV,” “human,” “female” and “polymerase chain reaction.” Eligible studies met the following criteria: (i) use of broad-spectrum consensus PCR-assays based on the primers MY09/11, PGMY09/11, GP5+/6+, SPF10, SPF1/GP6 or L1C1/L1C2, and (ii) reporting of overall and type-specific HPV prevalence, by strata of cyto- and/or histo-pathological cervical diagnoses. Overall HPV prevalence is reported as a percentage of all women tested by consensus PCR. Type-specific HPV positivity is presented among HPV-positive women only, for each of the 13 HR HPV types judged to be carcinogenic or probably carcinogenic (i.e., HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 68),1 in the order of their frequency of detection in ADC.7 Type-specific positivity includes that contributed by single and multiple HPV infections. Standard errors of type-specific positivity estimates were computed assuming the nonindependence of cases within the same study using cluster-correlated robust variance estimates.8 We identified 12 studies reporting relevant data on AGC and/or AIS from Europe (n = 4, Belgium, Italy and two studies from The Netherlands), North America (n = 5, all from the United States), Eastern Asia (n = 1, Thailand), Western Asia (n = 1, Kuwait) and South/Central America (n = 1, Brazil). As data on both AGC and AIS were available only for Europe and North America, comparisons of HPV-type distribution with that in women with normal cytology and ADC are restricted to studies from these two regions. Table 1a summarizes the prevalence of any HPV type, and, among HPV-positive women, of 13 HR HPV types, in normal cytology and in different glandular lesions. HPV infection was detected in 10.5, 57.5, 99.1 and 84.6% of women with normal cytology, AGC, AIS and ADC, respectively. Among HPV-positive women, HPV16 positivity was similar in normal cytology (23.4%) and AGC (23.4%) but it increased to 48.7% in AIS and 45.7% in ADC (Table 1a). HPV18 positivity increased slightly between normal cytology (8.9%) and AGC (15.6%), but rose to 51.8% in AIS and 43.9% in ADC. HPV45 positivity was approximately 7% in all glandular lesions. ADC:normal cytology ratio was, therefore, higher for HPV18 (4.93) than HPV16 (1.95) and HPV45 (1.24). All HR HPV types other than HPV16, 18 and 45 showed steep declines in prevalence between AGC and AIS. There were no substantial changes in prevalence between AIS and ADC for any HR HPV type. Table 1b is an adaptation of the findings from Guan et al.6 restricted to lesions of cervical squamous-cell epithelium from Europe and North America. It highlights the much less frequent detection of HPV18 in high-grade lesions of the squamous-cell epithelium (i.e., high-grade intraepithelial squamous lesions, HSIL and cervical intra-epithelial neoplasia, CIN, grades 2 and 3) compared to that in high-grade lesions of the glandular epithelium (i.e., AIS). In conclusion, HPV16 and 18 were highly enriched in ADC and AIS compared to lower grades of diagnosis, confirming their higher potential to cause ADC than other HR-HPV types. The HPV-type distribution was similar in HPV-positive AIS and ADC (of which more than 90% were positive for HPV16 and/or 18). Our present findings support, therefore, the role of AIS as a true ADC precursor and suggest that findings from vaccination trials on prevention of AIS2 can be expected to hold for ADC. The HPV-type distribution in AGC, on the other hand, resembled that in normal cytology, suggesting that, like its squamous-cell equivalent low-grade intraepithelial lesion and CIN1, these lesions are more of a proxy of HPV infection than cancer precursors. The greater importance of HPV18 in ADC in comparison to SCC has been well described.7 However, we were able to show that this is also the case for AIS, which is in contrast with the relatively rare detection of HPV18 in HSIL or CIN2/3 in comparison to SCC. Restriction to European and North-American studies was unavoidable, but it probably allowed better quality and consistency in cytological and histological classification. It did not overcome, however, the paradox of lower HPV positivity in ADC (84.6%) than in AIS (99.1%) and SCC (92.0%). Some misclassification of extra-uterine adenocarcinoma as ADC9 and the existence of some rare varieties of ADC that are not related to HPV infection10 cannot be ruled out. Yours sincerely, The authors thank Dr. Silvia de Sanjosé and Dr. Laia Bruni (Institut Catalan d'Oncologia, Barcelona, Spain), for helping to provide information on HPV prevalence in women with normal cytology. Peng Guan* , Gary M. Clifford*, Silvia Franceschi*, * International Agency for Research on Cancer, Lyon, France, China Medical University, Shenyang, People's Republic of China.

ABSTRACT Bacillus thuringiensis is an important microbial insecticide used in the control of agricultural pests. Here we report the finished, annotated genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28, which can form parasporal crystals consisting of Cry4Cc1, Cry30Fa1, Cry53Ab1, Cry54Aa1, Cry54Ab1, Cry68Aa1, Cry69Aa1, Cry69Aa2, Cry70Ba1, Cyt1Da1, and Cyt2Aa3. It is also highly toxic to lepidopterous and dipterous insects.

The morbidity and mortality of cancer increase remarkably every year. It's a heavy burden for family and society. The detection of prognostic biomarkers can help to improve the theraputic effect and prolong the lifetime of patients. microRNAs have an influential role in cancer prognosis. The results of articles discussing the relationship between microRNA polymorphisms and cancer prognosis are inconsistent.We conduct a meta-analysis of 19 publications concerning the association of four common polymorphisms, mir-146a rs2910164, mir-149 rs2292832, mir-196a2 rs11614913 and mir-499 rs3746444, with cancer prognosis. Pooled Hazard Ratios with 95% Confidence Intervals for the relationship between four genetic polymorphisms and Overall Survival, Recurrence-free Survival, Disease-free survival, recurrence are calculated. Subgroup analysis by population and type of tumor are conducted.GG genotype of mir-146a may be the protective factor for overall survival, especially in Caucasian population. C-containing genotypes of mir-196a2 act as a risk role for overall survival. The same result exists in Asian population, in Non-Small Cell Lung Cancer and digestive cancer. The patients with C allele of mir-149 have a better overall survival, especially in Non-Small Cell Lung Cancer. No significant results are obtained for mir-499 polymorphisms.Genetic polymorphisms in mir-146a, mir-196a2 and mir-149 may be associated with overall survival. This effect varies with different types of cancer. Genetic polymorphism in mir-499 may have nothing to do with cancer prognosis.

Previous pharmacological studies have indicated that AC11 (a standardized aqueous extract of Uncaria tomentosa) has beneficial effects on DNA repair and immune function. However, its benefits go beyond this. The present study utilized electron spin resonance (ESR) and spin trapping technique, as well as the 6-OHDA-induced cell damage and transgenic Caenorhabditis elegans models, towards exploring the antioxidant and neuroprotective ability of AC11. Our results showed that AC11 could scavenge several types of free radicals, especially hydroxyl radicals (60% of hydroxyl radicals were scavenged by 30 μg/ml of AC11). In SH-SY5Y cells, we found that AC11 could dose dependently protect 6-OHDA induced cell damage by increase cell viability and mitochondrial membrane potential. AC11 pretreatment also significantly decreased the level of lipid peroxidation, intracellular reactive oxygen species and nitric oxide in 6-OHDA treated cells. In NL5901 C. elegans, 10 μg/ml AC11 could reduce the aggregation of α-synuclein by 40%. These findings encourage further investigation on AC11 and its active constituent compounds, as possible therapeutic intervention against Parkinson's disease.

Iron-induced oxidative stress has been found to be a central player in the pathogenesis of kidney injury. Recent studies have indicated H₂ can be used as a novel antioxidant to protect cells. The present study was designed to investigate the protective effects of H₂ against chronic intermittent hypoxia (CIH)-induced renal injury and its correlation mechanism involved in iron metabolism. We found that CIH-induced renal iron overloaded along with increased apoptosis and oxidative stress. Iron accumulates mainly occurred in the proximal tubule epithelial cells of rats as showed by Perl's stain. Moreover, we found that CIH could promote renal transferrin receptor and divalent metal transporter-1 expression, inhibit ceruloplasmin expression. Renal injury, apoptosis and oxidative stress induced by CIH were strikingly attenuated in H₂ treated rats. In conclusion, hydrogen may attenuate CIH-induced renal injury at least partially via inhibiting renal iron overload.

Climate change is a challenge for the sustainable development of an international economy and society. The impact of climate change on infectious diseases has been regarded as one of the most urgent research topics. In this paper, an analysis of the bibliometrics, co-word biclustering, and strategic diagram was performed to evaluate global scientific production, hotspots, and developing trends regarding climate change and infectious diseases, based on the data of two decades (1999-2008 and 2009-2018) from PubMed. According to the search strategy and inclusion criteria, a total of 1443 publications were found on the topic of climate change and infectious diseases. There has been increasing research productivity in this field, which has been supported by a wide range of subject categories. The top highly-frequent major MeSH (medical subject headings)/subheading combination terms could be divided into four clusters for the first decade and five for the second decade using a biclustering analysis. At present, some significant public health challenges (global health, and travel and tropical climate, etc.) are at the center of the whole target research network. In the last ten years, "Statistical model", "Diarrhea", "Dengue", "Ecosystem and biodiversity", and "Zoonoses" have been considered as emerging hotspots, but they still need more attention for further development.

Sedimentary records of the North China Craton (NCC) between 1.8–0.8 Ga are indispensable for studying the evolution of the Earth’s surface ecosystem in the middle Proterozoic. Continuous late Paleoproterozoic successions (1.8–1.6 Ga) were found in the Xiong’er and Yanliao basins, which are located in the southern and northern margins of present NCC. The formation and evolution of these two basins were likely related to the breakup of Columbia supercontinent. With the deepening of research in recent years, the rifting and filling processes of these two basins are getting increasing attentions and controversies. Among them, a crucial controversy is the distribution of isochronous strata in these two basins, which is related to whether these two basins have ever been connected. In this study, we scrutinized the Paleoproterozoic successions in the Taihang Mountain area, which is located in the junction of the Xiong’er and Yanliao basins. The sedimentary distributions and overlaps indicated gradually transgression and northward extension of the Xiong’er Basin during 1.75–1.65 Ga, and demonstrated a temporary connection of the Xiong’er and Yanliao basins, at least during 1.67–1.64 Ga. We further estimated the maximum depositional ranges of the isochronous stratigraphic units and drew the evolutionary history of the Xiong’er and Yanliao basins in 1.8–1.6 Ga. These results will be helpful in further understanding the habitats of early life and predicting the distribution of mineral-containing sediments, such as iron ore and source rocks.

Abstract Unravelling early Cenozoic basin development in northern Tibetan Plateau remains crucial to understanding continental deformation mechanisms and to assessing models of plateau growth. We target coarse‐grained red beds from the Cenozoic basal Lulehe Formation in the Qaidam basin by combining conglomerate clast compositions, paleocurrent determinations, sandstone petrography, heavy mineral analysis and detrital zircon U–Pb geochronology to characterize sediment provenance and the relationship between deformation and deposition. The red beds are dominated by matrix‐supported, poorly sorted clastic rocks, implying low compositional and textural maturity and short transport distances. Although most sandstones have high (meta)sedimentary lithic fragment contents and abundant heavy minerals of metamorphic origin (e.g., garnet, epidote and chlorite), spatiotemporal differences in detrital compositions are evident. Detrital zircon grains mainly have Phanerozoic ages (210–280 Ma and 390–480 Ma), but Proterozoic ages (750–1000 Ma, 1700–2000 Ma and 2300–2500 Ma) are also prominent in some samples. Analysed strata display dissimilar (including south‐, north‐ and west‐directed) paleocurrent orientations. These results demonstrate that the Cenozoic basal deposits were derived from localized, spatially diverse sources with small drainage networks. We advocate that initial sedimentary filling in the northern Qaidam basin was fed by parent‐rocks from the North Qaidam‐South Qilian belts and the pre‐Cenozoic basement within the Qaidam terrane interior, rather than southern distant Eastern Kunlun regions. Seismic and drilling well stratigraphic data indicate the presence of paleohighs and syn‐sedimentary reverse faults and noteworthy diversity in sediment thickness of the Lulehe Formation, revealing that the Qaidam terrane exhibited as several isolated depocenters, rather than a coherent basin, in the early stage of the Cenozoic deposition. We suggest the Cenozoic Qaidam basin to have developed in a contractional deformation regime, which supports models with synchronous deformation throughout most of Tibet shortly after the India‐Eurasia collision.