Jie Chen

The effects of high pressure homogenization processing (HPHP), thermal treatment (TT) and milk matrix (soy, skimmed and whole milk) on the phenolic bioaccessibility and the ABTS scavenging activity of apple, grape and orange juice (AJ, GJ and OJ) were investigated. HPHP and soy milk diminished AJ's total phenolic bioaccessibility 29.3%, 26.3%, respectively, whereas TT and bovine milk hardly affected it. HPHP had little effect on GJ's and OJ's total phenolic bioaccessibility, while TT enhanced them 27.3-33.9%, 19.0-29.2%, respectively, and milk matrix increased them 26.6-31.1%, 13.3-43.4%, respectively. Furthermore, TT (80 °C/30 min) and TT (90 °C/30 s) presented the similar influences on GJ's and OJ's phenolic bioaccessibility. Skimmed milk showed a better enhancing effect on OJ's total phenolic bioaccessibility than soy and whole milk, but had a similar effect on GJ's as whole milk. These results contribute to promoting the health benefits of fruit juices by optimizing the processing and formulas in the food industry.

Similar to other local therapeutic methods, local interstitial radiotherapy (IRT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis.Mn-based IRT radiosensitizers consisting of 131I, MnO2 and bovine serum albumin (BSA) (131I-MnO2-BSA) were engineered. Such Mn-based IRT radiosensitizers successfully unlocked radiogenetics to magnify systematic immune responses of local IRT via remodeling hypoxic and immunosuppressive microenvironments and resist tumor metastasis. The MnO2 in 131I-MnO2-BSA caused decomposition of H2O2 enriched in tumors to generate O2 for alleviating hypoxic microenvironment and removing tumor resistances to IRT. Concurrently, hypoxia mitigation by such radiosensitizers-unlocked radiogenetics can effectively remodel immunosuppressive microenvironment associated with regulatory T (Treg) cells and tumor-associated macrophages (TAMs) infiltration inhibition to induce immunogenic cell death (ICD), which, along with hypoxia mitigation, activates systematic immune responses. More intriguingly, 131I-MnO2-BSA-enabled radiogenetics can upregulate PD-L1 expression, which allows anti-PD-L1-combined therapy to exert a robust antitumor effect on primary tumors and elicit memory effects to suppress metastatic tumors in both tumor models (4T1 and CT26).IRT radiosensitizer-unlocked radiogenetics and the corresponding design principle provide a general pathway to address the insufficient systematic immune responses of local IRT.

Wedelolactone (WEL), a major coumestan ingredient in Wedelia chinensis, has been used to treat septic shock, hepatitis and venom poisoning in traditional Chinese medicines. The objective of the study was to elucidate the anti-inflammatory effects and mechanism of WEL with a cellular model of lipopolysaccharide (LPS)-induced RAW 264.7 cells.To study the role of WEL in pro-inflammation, we measured key inflammation mediators and end products including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) by using the Griess method, enzyme linked immunosorbent assay (ELISA) and Western blotting. Nuclear factor-kappaB (NF-κB) transcription activity was detected by luciferase reporter assay. The important pro-inflammatory transcription factors, NF-κB p65 and inhibitory kappaB alpha (IκB-α); and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) were analyzed by Western blotting. Our study showed that WEL (0.1, 1, 10 μM) significantly inhibited the protein expression levels of iNOS and COX-2 in LPS-stimulated cells, as well as the downstream products, including NO, PGE2 and TNF-α. Moreover, WEL also inhibited LPS-induced NF-κB p65 activation via the degradation and phosphorylation of IκB-α and subsequent translocation of the NF-κB p65 subunit to the nucleus.Our results revealed that WEL has a potential to be a novel anti-inflammatory agent targeting on the NF-κB signaling pathway.

This study quantified the overall effects of aortic valve disease (AVD) and mitral valve disease (MVD) by disease severity on direct health-care costs to insurers and patients.Based on 1996-2011 data from the Medical Expenditure Panel Survey (MEPS), a large, nationally representative US database, multivariate analyses were performed to assess the relationship between AVD and MVD and direct annual health-care costs to insurers and patients, at individual and US-aggregate levels. Adults aged 18 years and over with diagnosis codes for AVD or MVD based on International Classification of Diseases (ninth revision) diagnosis codes were identified. Subjects were further classified as symptomatic AVD, asymptomatic AVD, symptomatic MVD, and asymptomatic MVD. These classifications were determined with clinical assistance and based in part on data availability in the MEPS.The MEPS database included 148 patients with AVD: 53 patients with symptomatic AVD, 95 patients with asymptomatic AVD, and 1,051 with MVD, including 315 patients with symptomatic MVD and 736 patients with asymptomatic MVD. Symptomatic AVD had the largest incremental effect on annual per patient health-care expenditure: $12,789 for symptomatic AVD, $10,816 for asymptomatic AVD, $5,163 for symptomatic MVD, and $1,755 for asymptomatic MVD. When aggregated to the US population, heart-valve disease accounted for an incremental annual cost of $23.4 billion. The largest aggregate annual costs were incurred by patients with symptomatic MVD ($7.6 billion), followed by symptomatic AVD ($5.6 billion), asymptomatic MVD ($5.6 billion), and asymptomatic AVD ($4.6 billion).The annualized incremental costs of heart-valve disease were substantial for all groups examined, and greatest for patients with symptomatic MVD. This reflects the relatively high prevalence associated with this group. With a growing and aging population, the prevalence of heart-valve disease is expected to rise, increasing the burden on public health.

Silica exposure can cause lung inflammation and fibrosis, known as silicosis. Interleukin-17A (IL-17A) and Th17 cells play a pivotal role in controlling inflammatory diseases. However, the roles of IL-17A and Th17 cells in the progress of silica-induced inflammation and fibrosis are poorly understood. This study explored the effects of IL-17A on silica-induced inflammation and fibrosis. We used an anti-mouse IL-17A antibody to establish an IL-17A-neutralized mice model, and mice were exposed to silica to establish an experimental silicosis model. We showed that IL-17A neutralization delayed neutrophil accumulation and progression of silica-induced lung inflammation and fibrosis. IL-17A neutralization reduced the percentage of Th17 in CD4 + T cells, decreased IL-6 and IL-1β expression, and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A delayed silica-induced Th1/Th2 immune and autoimmune responses. These results suggest that IL-17A neutralization alleviates early stage silica-induced lung inflammation and delays progression of silica-induced lung inflammation and fibrosis. Neutralization of IL-17A suppressed Th17 cell development by decreasing IL-6 and/or IL-1β and increased Tregs at an early phase of silica-induced inflammation. Neutralization of IL-17A also delayed the Th1/Th2 immune response during silica-induced lung inflammation and fibrosis. IL-17A may play a pivotal role in the early phase of silica-induced inflammation and may mediate the Th immune response to influence silica-induced lung inflammation and fibrosis in mice.

The mitochondrial pathway of apoptosis is controlled by the ratio of anti- and pro-apoptotic members of the Bcl-2 family of proteins. The molecular events underlying how a given physiological stimulus changes this ratio to trigger apoptosis remains unclear. We report here that human 17-β-estradiol (E2) and its related steroid hormones induce apoptosis by binding directly to phosphodiesterase 3A, which in turn recruits and stabilizes an otherwise fast-turnover protein Schlafen 12 (SLFN12). The elevated SLFN12 binds to ribosomes to exclude the recruitment of signal recognition particles (SRPs), thereby blocking the continuous protein translation occurring on the endoplasmic reticulum of E2-treated cells. These proteins include Bcl-2 and Mcl-1, whose ensuing decrease triggers apoptosis. The SLFN12 protein and an apoptosis activation marker were co-localized in syncytiotrophoblast of human placentas, where levels of estrogen-related hormones are high, and dynamic cell turnover by apoptosis is critical for successful implantation and placenta development.

Summary How cadmium (Cd) tolerance in rice is regulated remains poorly understood. We used a forward genetic approach to investigate Cd tolerance in rice. Using a root elongation assay, we isolated a rice mutant with enhanced Cd tolerance, cadt1 , from an ethyl methanesulphonate (EMS)‐mutagenized population of a widely grown Indica cultivar. The mutant accumulated more Cd in roots but not in shoots and grains. Using genomic resequencing and complementation, we identified OsCADT1 as the causal gene for the mutant phenotype, which encodes a putative serine hydroxymethyltransferase. OsCADT1 protein was localized to the nucleus and the OsCADT1 gene was expressed in both roots and shoots. OsCADT1 mutation resulted in higher sulphur and selenium accumulation in the shoots and grains. Selenate influx in cadt1 was 2.4 times that of the wild‐type. The mutant showed higher expression of the sulphate/selenate transporter gene OsSULTR1;1 and the sulphur‐deficiency‐inducible gene OsSDI1 . Thiol compounds including cysteine, glutathione and phytochelatins were significantly increased in the mutant, underlying its increased Cd tolerance. Growth and grain biomass were little affected. The results suggest that OsCADT1 acts as a negative regulator of sulphate/selenate uptake and assimilation. OsCADT1 mutation increases Cd tolerance and enriches selenium in rice grains, providing a novel solution for selenium biofortification.

Convolutional neural networks (CNNs) have recently been widely used in remote-sensing scene classification. Additionally, it is becoming very popular to automatically learn specific CNN architectures for specific data sets. The rich contextual information in high-resolution remote-sensing images (RSIs) is critical to remote-sensing intelligent understanding tasks. However, architecture learning approaches tend to simplify the original data (i.e., resizing images to smaller resolution) for efficiency, yet result in contextual information loss of RSIs. In this article, we proposed a contextual information-preserved architecture learning (CIPAL) framework for remote-sensing scene classification to utilize the contextual information in RSIs as much as possible during the architecture learning process. We introduce channel compression into CIPAL, which can reduce the memory and time consumption of architecture learning and make it possible to construct a larger architecture space. We add potential operators that are rarely used for scene classification tasks (i.e., atrous convolution) into the architecture space to explore unknown architectures that are more suitable for remote-sensing scenes. The experimental results on four remote-sensing scene classification benchmarks indicate that CIPAL learns architectures with less time consumption than similar works, and the newly found architectures outperform popular hand-designed architectures for better use of contextual information in RSIs. Different architectures are good at learning different representations, and our proposed architecture learning method potentially helps us understand which types of representations are crucial for RSI intelligent understanding.

Objective Mild cognitive impairment (MCI) is a preclinical and transitional stage between healthy ageing and dementia. The purpose of our study was to investigate the recent pooled global prevalence of MCI. Methods This meta-analysis was in line with the recommendations of Cochrane’s Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. We conducted a comprehensive search using the PubMed, Embase, Web of Science, CNKI, WFD, VIP, and CBM from their inception to March 1, 2023. Quality assessment was guided by the Agency for Healthcare Research and Quality (AHRQ) methodology checklist. The pooled global prevalence of MCI was synthesized using meta-analysis via random effect model. Subgroup analyses were performed to examine considered factors potentially associated with MCI prevalence. Results We identified 233 studies involving 676,974 individuals aged above 50 years. All the studies rated as moderated-to-high quality. The overall prevalence of MCI was 19.7% [95% confidence interval (95% CI): 18.3–21.1%]. Subgroup analyses revealed that the global prevalence of MCI increased over time, with a significant rise [32.1% (95% CI: 22.6–41.6%)] after 2019. Additionally, MCI prevalence in hospitals [34.0% (95% CI: 22.2–45.7%)] was higher than in nursing homes [22.6% (95% CI: 15.5–29.8%)] and communities [17.9% (95% CI: 16.6–19.2%)], particularly after the epidemic of coronavirus disease 2019 (COVID-19). Conclusion The global prevalence of MCI was 19.7% and mainly correlated with beginning year of survey and sample source. The MCI prevalence increased largely in hospitals after 2019 may be related to the outbreak of COVID-19. Further attention to MCI is necessary in the future to inform allocation of health resources for at-risk populations.

Mulberry anthocyanin extract (MAE) is a valuable natural pigment with potential applications in the food industry. However, its storage stability remains a challenge, as it is prone to degradation over time. To tackle this issue, the present study focuses on investigating the efficacy of utilizing whey protein isolate (WPI) and ferulic acid (FA) in combination at pH 6.3. The addition of FA reduced the ΔE values and the degradation of anthocyanin within MAE solution in the presence of WPI. Notably, the combination of WPI and FA exhibited a remarkable stabilizing effect on the MAE solution. Multi-spectroscopic analysis revealed the occurrence of non-covalent interactions mediated by hydrophobic interaction between β-lactoglobulin (β-LG) and cyanidin-3-O-glucoside (C3G) in the presence of FA, with improved binding affinity. While FA did not exhibit a copigmentation effect on the C3G solution, it enhanced the protective action of β-LG on the chromophoric structural form of C3G. Moreover, although the introduction of FA to the β-LG complex with C3G resulted in minor modifications to the secondary structure, in contrast to the binary complexes, its particle size increased. The molecular dynamics simulations also revealed that FA enhances the binding affinity between β-LG and C3G. These findings provide a foundation for enhancing the storage stability of anthocyanins and expanding the utilization of MAE pigment in the food industry.

Abstract Conditionally replicating adenoviruses (CRAd) can replicate specifically in cancer cells and lyse them. The CRAds were widely used in the preclinical and clinical studies of cancer therapy. We hypothesize that more precisely regulated replication of CRAds may further improve the vector safety profile and enhance its antitumor efficacy. Here, a triple-regulated CRAd carrying p53 gene expression cassette, SG600-p53, was engineered. In SG600-p53, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the p53 gene is controlled by the cytomegalovirus promoter. The precise triple-regulation endows SG600-p53 with enhanced antitumor potential and improved safety profile. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human non-small cell lung cancer in nude mice. With the selective replication and oncolysis, it was found by ELISA assay that SG600-p53 expressed p53 efficiently in cancer cells. In NCI-H1299 tumor xenograft models, SG600-p53 displayed a tumor-selective killing capacity. At a dose of 2 × 109 plaque-forming units, SG600-p53 could completely inhibit the tumor growth and more effective than replication-defective Ad-p53. Histopathologic examination revealed that SG600-p53 administration resulted in cancer cell apoptosis. We concluded that the triple-regulated SG600-p53, as a more potent and safer antitumor therapeutic, could provide a new strategy for cancer biotherapy. [Mol Cancer Ther 2008;7(6):1598–603]

Silicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored.To evaluate the role of Th17 and IL-17 in the development of silicosis and their interaction with Tregs, Treg-depleted mice model was generated and exposed to silica to establish experimental model of silica-induced lung fibrosis. Here we showed that silica increased Th17 response in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein results showed that Tregs exerted its modulatory function on Th17 cells and IL-17 by regulating TGF-β1 and IL-1β.Our study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-β1 and IL-1β in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation.

The sine oculis homeobox 1 (Six1) gene encodes an evolutionarily conserved transcription factor. In the past two decades, much research has indicated that Six1 is a powerful regulator participating in skeletal muscle development. In this review, we summarized the discovery and structural characteristics of Six1 gene, and discussed the functional roles and molecular mechanisms of Six1 in myogenesis and in the formation of skeletal muscle fibers. Finally, we proposed areas of future interest for understanding Six1 gene function.

We examine changes in health insurance coverage and access to and utilization of health care before and after the national implementation of the Patient Protection and Affordable Care Act (ACA) among the U.S. adult immigrant population. Data from the 2011–2016 National Health Interview Survey are used to compare adult respondents in 2011–2013 (before the ACA implementation) and 2014–2016 (after the ACA implementation). Multivariable logistic regression analyses are used to compare changes over time. This study shows that the ACA has closed the coverage gap that previously existed between U.S. citizens and non-citizen immigrants. We find that naturalized citizens, non-citizens with more than 5 years of U.S. residency, and non-citizens with 5 years or less of U.S. residency reduced their probability of being uninsured by 5.81, 9.13, and 8.23%, respectively, in the first 3 years of the ACA. Improvements in other measures of access and utilization were also observed.

The objective of this study was to establish the optimum protocol for the isolation and culture of porcine muscle satellite cells. Mononuclear muscle satellite cells are a kind of adult stem cell, which is located between the basal lamina and sarcolemma of muscle fibers and is the primary source of myogenic precursor cells in postnatal muscle. Muscle satellite cells are a useful model to investigate the mechanisms of muscle growth and development. Although the isolation and culture protocols of muscle satellite cells in some species (e.g. mouse) have been established successfully, the culture system for porcine muscle satellite cells is very limited. In this study, we optimized the isolation procedure of porcine muscle satellite cells and elaborated the isolation and culture process in detail. Furthermore, we characterized the porcine muscle satellite cells using the immunofluorecence. Our study provides a reference for the isolation of porcine muscle satellite cells and will be useful for studying the molecular mechanisms in these cells.

It is well known that cyan-emitting phosphors play a very important role in full-spectrum white LEDs. A large number of cyan-emitting phosphors have been reported in the past few years, however, most of them can only be effectively excited by near-ultraviolet light. There are very few cyan-emitting phosphors that can be intensively excited by blue light (440 and 470 nm). Here, a novel blue-light excitable cyan-emitting phosphor BaLu1.95Ce0.05Al2Ga2SiO12 with excellent performance is reported. The cyan phosphor has a cubic structure in space group Ia3¯d with a = 1.205379(3) nm, which can be easily obtained through a solid-state reaction pathway. The emission peak of the cyan phosphor is located at 500 nm and its internal quantum efficiency is as high as 90.01% when excited at 455 nm at 25 °C. The cyan phosphor exhibits superior resistance against thermal quenching of luminescence, and its intensity at 125 °C is as strong as 92.14% of the intensity at room temperature. Meanwhile, it also shows an outstanding resistance against water, where its luminescence intensity is hardly changed after being immersed in pure water for 528 h. The white LED lamp prepared by employing the obtained BaLu1.95Ce0.05Al2Ga2SiO12 as cyan phosphor displays remarkable optical properties with CCT = 4441 K, Ra = 93.7, CRI = 90.4 and CIE 1931 (x, y) as (x = 0.3648, y = 0.3752). The experimental results demonstrate that BaLu1.95Ce0.05Al2Ga2SiO12 is a promising cyan-emitting phosphor with great application potential in full-spectrum white LEDs.

Our previous studies demonstrated that dietary daidzein improves egg production in ducks during the late period of the laying cycle. The present study was aimed to investigate the effect of daidzein in laying hens, with more focus on eggshell quality. The expression of ER-alpha, GH-R, and IGF-IR mRNA in shell glands was determined to identify the target genes of daidzein action and to reveal the relationship between shell quality and profiles of gene expression in shell glands of laying hens. 1000 ISA hens, at 445 days of age, were allotted at random to two groups and given the basal diet with or without 10 mg of daidzein per kg diet for 9 weeks. Daidzein supplement significantly increased the egg laying rate and the feed conversion ratio. The eggshell thickness increased, while the percentage of cracked eggs decreased in daidzein-treated hens. Serum E2 and phosphate concentrations were not altered, but the level of serum Ca2+ and the tibia bone mineral density were significantly increased in the daidzein-treated group compared with their control counterparts. In parallel with the significant increase of oviduct weight, significant down-regulation of GH-R and IGF-IR mRNA and a trend of decrease in ERalpha mRNA expression in shell glands were observed in daidzein-treated hens. The results indicate that dietary daidzein improves egg laying performance and eggshell quality during the late (postpeak) laying stage of hens, which is associated with modulations in gene expression in the shell gland.

Developmental iodine deficiency results in inadequate thyroid hormone (TH), which damages the hippocampus. Here, we explored the roles of hippocampal doublecortin and neural cell adhesion molecule (NCAM)-180 in developmental iodine deficiency and hypothyroidism.Two developmental rat models were established with either an iodine-deficient diet, or propylthiouracil (PTU)-adulterated water (5 ppm or 15 ppm) to impair thyroid function, in pregnant rats from gestational day 6 until postnatal day (PN) 28. Silver-stained neurons and protein levels of doublecortin and NCAM-180 in several hippocampal subregions were assessed on PN14, PN21, PN28, and PN42.The results show that nerve fibers in iodine-deficient and 15 ppm PTU-treated rats were injured on PN28 and PN42. Downregulation of doublecortin and upregulation of NCAM-180 were observed in iodine-deficient and 15 ppm PTU-treated rats from PN14 on. These alterations were irreversible by the restoration of serum TH concentrations on PN42.Developmental iodine deficiency and hypothyroidism impair the expression of doublecortin and NCAM-180, leading to nerve fiber malfunction and thus impairments in hippocampal development.

Nosema bombycis is a destructive, obligate intracellular parasite of the Bombyx mori. In this study, a single-chain variable fragment (scFv) dependent technology is developed for the purpose of inhibiting parasite proliferation in insect cells. The scFv-G4, which we prepared from a mouse G4 monoclonal antibody, can target the N. bombycis spore wall protein 12 (NbSWP12). Indirect immunofluorescence assays showed that NbSWP12 located mainly on the outside of the N. bombycis cytoskeleton, although some of it co-localized with β-tubulin in the meront-stage of parasites. When meront division began, NbSWP12 became concentrated at both ends of each meront. Western blotting showed that scFv-G4 could express in Sf9-III cells and recognized native NbSWP12. The transgenic Sf9-III cell line showed better resistance than the controls when challenged with N. bombycis, indicating that NbSWP12 is a promising target in this parasite and this scFv dependent strategy could be a solution for construction of N. bombycis-resistant Bombyx mori.

The blunt snout bream (Megalobrama amblycephala) is an important freshwater aquaculture species, but it is sensitive to hypoxia. No transcriptome data related to growth and hypoxia response are available for this species. In this study, we performed de novo transcriptome sequencing for the liver and gills of the fast-growth family and slow-growth family derived from ‘Pujiang No.1’ F10 blunt snout bream that were under hypoxic stress and normoxia, respectively. The fish were divided into the following 4 groups: fast-growth family under hypoxic stress, FH; slow-growth family under hypoxic stress, SH; fast-growth family under normoxia, FN; and slow-growth family under normoxia, SN. A total of 185 million high-quality reads were obtained from the normalized cDNA of the pooled samples, which were assembled into 465,582 contigs and 237,172 transcripts. A total of 31,338 transcripts from the same locus (unigenes) were annotated and assigned to 104 functional groups, and 23,103 unigenes were classified into seven main categories, including 45 secondary KEGG pathways. A total of 22,255 (71%) known putative unigenes were found to be shared across the genomes of five model fish species and mammals, and a substantial number (9.4%) of potentially novel genes were identified. When 6,639 unigenes were used in the analysis of differential expression (DE) genes, the number of putative DE genes related to growth pathways in FH, SH, SN and FN was 159, 118, 92 and 65 in both the liver and gills, respectively, and the number of DE genes related to hypoxic response was 57, 33, 23 and 21 in FH, FN, SH and SN, respectively. Our results suggest that growth performance of the fast-growth family should be due to complex mutual gene regulatory mechanisms of these putative DE genes between growth and hypoxia.

Our previous studies demonstrated that dietary supplementation of daidzein improves egg production in duck breeders during late periods of the laying cycle. The present study was aimed to clarify whether the growth of ducklings hatched from eggs laid by daidzein-treated hens would be affected, and to elucidate the mechanisms underlying potential trans-generational effects, by determining changes of hormone levels and mRNA expression of relevant genes. Daidzein was added to the basal diet of 415-day-old duck breeders at the level of 5 mg/kg. During 9 weeks of daidzein treatment, laying rate increased by 7.70%, average egg mass tended to increase, whereas yolk/albumen ratio decreased significantly. These changes were accompanied by significantly elevated plasma T4 and E2 levels, enhanced gonadotropin releasing hormone (GnRH) mRNA, but diminished estrogen receptor (ER)-β mRNA expression in hypothalamus of daidzein-treated hens. Ducklings hatched from daidzein-treated eggs were significantly smaller at hatching, but they caught up with their control counterparts by 4 weeks of age. Serum levels of T4, pituitary GH, hepatic GH receptor (GHR) and type-1 IGF receptor (IGF-1R) mRNA expression were all suppressed markedly in the daidzein-treated group at hatching, but this suppression proved to be temporary, as at 4 weeks of age, expression levels of all investigated genes were restored. However, it is noteworthy that at 4 weeks of age an obvious down-regulation of hypothalamic GnRH mRNA expression was detected in ducklings maternally exposed to daidzein. Our results provide evidence that maternal exposure to daidzein affects post-hatch growth in the duck with accompanying changes in the secretion of metabolic hormones and expression of growth-related genes. Although the negative effect of maternal daidzein on embryonic growth could be eliminated 4 weeks after hatching, the long-term effect of maternal daidzein on reproductive function is not to be ignored and awaits further investigation.

Abstract Background The biologically active form of transforming growth factor-β1 (TGF-β1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-β1 (L-TGF-β1) to active TGF-β1. To clarify the role of CD36 in the development of silica-induced lung fibrosis, a rat silicosis model was used to observe both the inhibition of L-TGF-β1 activation and the antifibrotic effect obtained by lentiviral vector silencing of CD36 expression. Methods The rat silicosis model was induced by intratracheal injection of 10 mg silica per rat and CD36 expression was silenced by administration of a lentiviral vector (Lv-shCD36). The inhibition of L-TGF-β1 activation was examined using a CCL-64 mink lung epithelial growth inhibition assay, while determination of hydroxyproline content along with pathological and immunohistochemical examinations were used for observation of the inhibition of silica-induced lung fibrosis. Results The lentiviral vector (Lv-shCD36) silenced expression of CD36 in alveolar macrophages (AMs) obtained from bronchoalveolar lavage fluid (BALF) and the activation of L-TGF-β1 in the BALF was inhibited by Lv-shCD36. The hydroxyproline content of silica+Lv-shCD36 treated groups was significantly lower than in other experimental groups. The degree of fibrosis in the silica+Lv-shCD36-treated groups was less than observed in other experimental groups. The expression of collagen I and III in the silica+Lv-shCD36-treated group was significantly lower than in the other experimental groups. Conclusion These results indicate that silencing expression of CD36 can result in the inhibition of L-TGF-β1 activation in a rat silicosis model, thus further preventing the development of silica-induced lung fibrosis.

Purpose.: To examine Chinese neonatal infants with both cycloplegic and noncycloplegic retinoscopy and to compare the distribution of refractive errors for the two techniques. Methods.: Cycloplegic retinoscopy was performed by two experienced pediatric ophthalmologists on 81 neonatal infants randomly selected from a group of 185 neonates who had undergone noncycloplegic retinoscopy. All infants were between 1 day and 6 days of age and were born without incident at full term. Results.: The mean cycloplegic spherical equivalent (CSE) was highly hyperopic (+3.55 diopters [D] ± 2.39 D). The mean noncycloplegic spherical equivalent (nCSE) was +0.58 D ± 2.32 D. The high reliability of the refractive measurements was demonstrated by high correlations between examiners (CSE: OD, r = 0.96; OS, r = 0.97; nCSE: OD, r = 0.94; OS, r = 0.93 OS) and between eyes (CSE: examiner 1, r = 0.94; examiner 2, r = 0.95; nCSE: examiner 1, r = 0.95; examiner 2, r = 0.97). The correlation between CSE and nCSE was much lower (examiner 1: OD, r = 0.76; OS, r = 0.73; examiner 2: OD, r = 0.72; OS, r = 0.70). Prevalence of astigmatism was very low (1.6% ≥ 1.0 D). Conclusions.: The level of hyperopia was very high in these infants, and the offsetting tonic accommodation demonstrated by the difference between CSE and nCSE was much higher than in any previous report. Low amounts of infantile hyperopia and high astigmatism are associated with future myopia in the West. The Chinese neonates in this study had high amounts of hyperopia and little astigmatism, yet they are at high risk to become myopic.

EsDmrt-like is a novel testis-specific Dmrt gene identified from the Chinese mitten crab Eriocheir sinensis. To explore its biological functions, we performed RNA interference (RNAi) by injection of long double-stranded RNA (dsRNA) targeting the coding region of the EsDmrt-like gene. At 24 h post-injection with EsDmrt-like-dsRNA, the relative expression level of EsDmrt-like mRNA significantly decreased by 80% (P < 0.01) compared to negative control of PBS group, while no RNAi effect was detected using a dsRNA of the green fluorescent protein (GFP), indicating target sequence specificity of this interference effect. Although the EsDMRT-like protein could be obviously detected in the PBS group, its expression in the EsDmrt-like-dsRNA group disappeared in four of the five tested individuals. Taken together, the expressions of EsDmrt-like mRNA and its protein were successfully inhibited by RNAi. After extending RNAi treatment for one month, the crab testicular development exhibited inhibitory effects. The average testis size was reduced and the gonadosomatic index (GSI) was significantly decreased by 75% compared with the controls. The histological and immunohistochemical analysis showed that the spermatogenesis was blocked, with rare spermatozoa in the seminiferous tubules, and the immunohistochemical signal in the spermatogonia and spermatocytes became extremely weak in the EsDmrt-like-dsRNA group. These data demonstrated a critical role for EsDmrt-like in testicular development and spermatogenesis in E. sinensis, and in vivo repetitive injection of EsDmrt-like-dsRNA could work efficiently to inhibit male testicular development. The Chinese mitten crab Eriocheir sinensis is one of the most important aquaculture species and has high commercial value as a food source. EsDmrt-like is a novel testis-specific Dmrt gene identified from the E. sinensis. We performed RNAi by repetitive injection of long double-stranded RNA (dsRNA) targeting the coding region of the EsDmrt-like gene, and certified that EsDmrt-like plays a critical role during spermatogenesis and testicular development.

Summary The interactions of digestive enzymes (pepsin, pancreatin) and milk proteins (β‐casein, β‐lactoglobulin (β‐Lg)) with (−)‐epigallocatechin gallate ( EGCG ), (−)‐epigallocatechin ( EGC ) and (−)‐epicatechin ( EC ) at gastric and intestinal pH were investigated by fluorescence spectroscopy. The results indicated that in the gastric environment, all three tea catechins showed binding affinities in descending order of strength with β‐casein first, followed by β‐Lg and then pepsin. The highest affinity was observed for EGCG –β‐casein, with a binding constant ( K A ) of 2.502(±0.201) × 10 5 m −1 . In the intestinal environment, the binding strengths of the proteins with EGCG and EGC were in the order β‐Lg &gt; pancreatin &gt; β‐casein; for binding with EC , the strength order was β‐casein &gt; β‐Lg &gt; pancreatin. The combination EGCG –β‐Lg had the strongest binding affinity, with a K A of 14.300(±0.997) × 10 5 m −1 . Thermodynamic analysis revealed that tea catechins complexed with milk proteins and digestive enzymes via different hydrophilic and hydrophobic interactions depending on the different digestion environments and types of catechins, proteins and enzymes.

BackgroundThe aim of this study was to investigate the prevalence of myopia in key (university‐oriented) and non‐key elementary schools in China using a traditional and a new criterion for myopia diagnosis in an epidemiological study.MethodsThis school‐based, cross‐sectional study examined students from four key schools and seven non‐key schools. Non‐cycloplegic autorefraction and visual acuity (VA) were performed on each student. Myopia was defined as a spherical equivalent (SE) refractive error not better than −1.00 D. A questionnaire was also administered.ResultsOf the 13,220 students examined, 6,546 (49.5 per cent) had myopia using the criterion of SE not better than −1.00-D. However, 2,246 (34.3 per cent) of these myopes had VA ≥ 0 logMAR in both eyes, indicating they were not functioning as myopes. Thus, a second myopia criterion was adopted: SE refractive error not better than −1.00 D + uncorrected VA ≥ 0 logMAR in at least one eye. By this definition, only 32.5 per cent of the overall sample had myopia. Students in key schools had a higher prevalence of myopia than those in non‐key schools (53.8 per cent versus 44.7 per cent) by the initial criterion. By the new criterion, the prevalence of myopia was 41.2 per cent versus 22.7 per cent. Myopia was equal in grade 1 of both school types, but accelerated faster in key schools, where there was a much higher prevalence of myopia by fourth grade, and continued up to 79.2 per cent prevalence by sixth grade based on SE refractive error not better than −1.00 D.ConclusionStudents in more competitive university‐oriented elementary schools developed myopia much faster than those in regular schools, although they started with the same level of myopia. Since one‐third of the 'myopes' had VA ≥ 0 logMAR in both eyes, they would not be prescribed a correction, or be clinically treated as myopes. A new criterion of SE refractive error not better than −1.00 D + uncorrected VA ≥ 0 logMAR in at least one eye was tested. This criterion is more clinically appropriate and could be used in future epidemiological studies.

The present meta-analysis evaluated the role of drug-coated balloon (DCB) angioplasty for in-stent restenosis (ISR) in femoropopliteal artery disease.Cochrane Library, Embase, and PubMed were searched without language restrictions from inception to May 10, 2020. The endpoints included target lesion revascularization (TLR), recurrent ISR, clinical improvement, ankle-brachial index (ABI), and death. There were 5 randomized controlled trials with 425 patients (218 with DCB angioplasty and 207 with plain old balloon angioplasty [POBA]) were included in the meta-analysis.Compared with POBA, DCB angioplasty was associated with lower risk of TLR (odds ratio [OR], 0.21; 95% confidence interval [CI]: 0.09-0.49, P < .001 at 6 months and OR, 0.15; 95% CI, 0.08-0.30; P < .001 at 12 months) and recurrent ISR (OR, 0.22; 95% CI, 0.13-0.38; P < .001 at 6 months and OR, 0.31; 95% CI, 0.16-0.61; P < .001 at 12 months), and superior clinical improvement (OR, 1.98; 95% CI, 1.07-3.65; P = .03 at 6 months and OR, 2.84; 95% CI: 1.50-5.35; P = .001 at 12 months). There were no significant differences between groups in ABI and death. Subgroup analysis for patients with DCB angioplasty showed similar rates of TLR, recurrent ISR, clinical improvement, and death between the short lesion (<15 cm) and long lesion group (≥15 cm) (P > .05).The current meta-analysis suggests that DCB angioplasty is an improvement over POBA for femoropopliteal ISR. Future studies about the effect of lesion length on DCB performance are still needed.

Generative adversarial networks (GANs) and their variants as an effective method for generating visually appealing images have shown great potential in different medical imaging applications during past decades. However, some issues remain insufficiently investigated: many models still suffer from model collapse, vanishing gradients, and convergence failure. Considering the fact that medical images differ from typical RGB images in terms of complexity and dimensionality, we propose an adaptive generative adversarial network, namely MedGAN, to mitigate these issues. Specifically, we first use Wasserstein loss as a convergence metric to measure the convergence degree of the generator and the discriminator. Then, we adaptively train MedGAN based on this metric. Finally, we generate medical images based on MedGAN and use them to build few-shot medical data learning models for disease classification and lesion localization. On demodicosis, blister, molluscum, and parakeratosis datasets, our experimental results verify the advantages of MedGAN in model convergence, training speed, and visual quality of generated samples. We believe this approach can be generalized to other medical applications and contribute to radiologists' efforts for disease diagnosis. The source code can be downloaded at https://github.com/geyao-c/MedGAN.

The role of thyroid hormone (TH) and its receptors (TRs) in the regulation of body growth and muscle accretion is well established in mammals and birds, whereas the involvement of THs and TRs in fish growth, especially during the muscle accretion period of juvenile-adult transition, is unknown. This study describes the cloning of the partial cDNA sequences of TRalpha and TRbeta in large yellow croaker, Pseudosciaena crocea (Richardson) and the patterns of TRalpha and TRbeta mRNA expression in liver and muscle of 1- and 2-year-old large yellow croaker, associated with changes in body mass and muscle characteristics. Two TRalpha isoforms (TRalpha1, TRalpha2) and TRbeta were identified in large yellow croaker. The deduced amino acid sequences showed high homology to the TRs of human and other teleosts. Hepatic TRbeta mRNA expression was markedly lower in 2-year-old large yellow croaker compared with the 1-year-old, while no significant age difference was observed for hepatic TRalpha mRNA expression. Muscle expression of TRalpha mRNA was significantly higher in 2-year-old large yellow croaker, whereas TRbeta exhibited no significant age difference. Meanwhile, serum concentration of T(4) was significantly decreased in 2-year-old large yellow croaker, but no change was observed for T(3). The body mass, fork length and body height of 2-year-old large yellow croaker were 4.7, 1.6 and 1.7 times greater, respectively compared with that of 1-year-old. Average diameters of skeletal muscle in 2-year-old large yellow croaker were remarkably larger than that in 1-year-old with no significant difference in muscle crude fat content. The down-regulation of hepatic TRbeta expression was associated with the decrease in general growth rate and the increase in muscle expression of TRalpha was accompanied with muscle accretion and myofiber hypertrophy, implicating the different roles of TRs in the regulation of growth in large yellow croaker.

This study describes the breed-specific coping characteristics of pigs in response to transport stress. The dynamic changes of behavior, the activities of creatine kinase (CK) and lactate dehydrogenase (LDH), as well as the plasma concentrations of stress and metabolic hormones in Erhualian (EHL) and Pietrain (PIE) pigs during 2 h transport were investigated. The majority of the behavior of EHL pigs consisted of oral/nasal/facial (ONF) and fit behaviors during the initial observations (first 15 min after start), and these behaviors were replaced by increased time sitting and lying in later observations (middle and last 15 min of transport). In contrast, PIE pigs showed high levels of ONF behaviors in initial observation, followed by high frequency and duration of standing during the middle and the last observation period. PIE pigs demonstrated significantly higher plasma CK (P < 0.01) and LDH activities (P < 0.05). There were significant effects of time and time × breed interaction (P < 0.05) on CK activities (P < 0.01) in both breeds. Plasma ACTH levels did not differ between breeds, yet a significant effect of time (P < 0.05) was shown during transport. EHL pigs exhibited consistently higher basal and stimulated plasma cortisol levels (P < 0.05). There were significant time effects on metabolic hormones (insulin, T3 and T4) (P < 0.01), whereas no significant breed effect for these hormones were found. These results indicate that different coping strategies apply in EHL pigs, as reflected by different behavioral, endocrine and biochemical responses during transport as compared with PIE pigs.

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism on long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and hypothyroidism.

Background The objective of this study was to examine differences in availability and use of telehealth services among Medicare enrollees according to Alzheimer’s disease and related dementias (ADRD) status and enrollment in Medicare Advantage (MA) versus Traditional Medicare (TM) during the period surrounding the COVID-19 pandemic. Methods This was a retrospective cross-sectional analysis of data from community-dwelling MA and TM enrollees with and without ADRD from the Medicare Current Beneficiary Survey (MCBS) Fall 2020 and Winter 2021 COVID-19 Supplement Public Use Files. We examined self-reported availability of telehealth service before and during the COVID-19 pandemic and use of telehealth services during COVID-19. We analyzed marginal effects under multivariable logistic regression. Results There were 13,700 beneficiaries with full-year enrollment in MA (6,046) or TM (7,724), 518 with ADRD and 13,252 without ADRD. Telehealth availability during COVID-19 was positively associated with having a higher income (2.81 pp. [percentage points]; 95% CI: 0.57, 5.06), having internet access (7.81 pp.; 95% CI: 4.96, 10.66), and owning telehealth-related technology (3.86; 95% CI: 1.36, 6.37); it was negatively associated with being of Black Non-Hispanic ethnicity (−8.51 pp.; 95% CI: −12.31, −4.71) and living in a non-metro area (−8.94 pp.; 95% CI: −13.29, −4.59). Telehealth availability before COVID-19 was positively associated with being of Black Non-Hispanic ethnicity (9.34 pp.; 95% CI: 3.74, 14.94) and with enrollment in MA (4.72 pp.; 95% CI: 1.63, 7.82); it was negatively associated having dual-eligibility (−5.59 pp.; 95% CI: −9.91, −1.26). Telehealth use was positively associated with being of Black Non-Hispanic ethnicity (6.47 pp.; 95% CI: 2.92, 10.01); it was negatively associated with falling into the age group of 75+ years (−4.98 pp.; 95% CI: −7.27, −2.69) and with being female (−4.98 pp.; 95% CI: −7.27, −2.69). Conclusion Telehealth services were available to and used by Medicare enrollees with ADRD to a similar extent compared to their non-ADRD counterparts. Telehealth services were available to MA enrollees to a greater extent before COVID-19 but not during COVID-19, and this group did not use telehealth services more than TM enrollees during COVID-19.

Abstract Conditionally replicative adenovirus (CRAD) represents a promising approach for cancer therapy. Several CRADs controlled by the human telomerase reverse transcriptase promoter have been developed. However, because of their replicative capacity, the importance of cancer specificity for CRADs needs to be further emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500-mE, which has its E1a and E1b gene controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively. It also carries a mouse endostatin expression cassette controlled by the cytomegalovirus promoter. These properties allow for increased cancer cell targeting specificity and decreased adverse side effects. We showed that CNHK500-mE preferentially replicated in cancer cells. Compared with a replication-defective vector carrying the same endostatin expression cassette, CNHK500-mE–mediated transgene expression level was markedly increased via viral replication within cancer cells. In the nasopharyngeal tumor xenograft model, CNHK500-mE injection resulted in antitumor efficacy at day 7 after therapy. Three weeks later, it led to significant inhibition of xenograft tumor growth due to the combined effects of viral oncolytic therapy and antiangiogenesis gene therapy. Pathologic examination showed that most cancer cells were positive for adenoviral capsid protein and for apoptotic terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling in the CNHK500-mE–treated tumor tissues, and the microvessels in these tumor tissues were diminished in quantity and abnormal in morphology. These results suggest that, as a potential cancer therapeutic agent, the CNHK500-mE is endowed with higher specificity to cancer cells and low cytotoxicity to normal cells. (Mol Cancer Res 2008;6(4):568–75)

Bleomycin showed toxicity to lung and was recognized to induce a well model of lung fibrosis. Activated alveolar macrophages released increased amounts of transforming growth factor-beta1(TGF-beta1) in response to bleomycin-induced lung injury. Thrombospondin-1(TSP-1) was involved in the activation of latent TGF-beta1(L-TGF-beta1) through the association of the TSP-1/L-TGF-beta1 complex with the cell receptor of TSP-1, CD36. The antagonistic effects of the synthetic peptides were studied by the administration of TSP-1 (447-452) synthetic peptides to the mouse model. The hydroxyproline contents of the TSP-1-treated groups were significantly lower than those of other experimental groups. Inflammation, fibrotic degree and distribution of collagen fibers in the interstitial and alveolar in the TSP-1-treated groups were less than those of the other experimental groups. The expressions of collagen I and III in TSP-1-treated groups were significantly lower than in the other experimental groups. TSP-1 synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the model, resulting in the decreased severity of bleomycin-induced lung injury.

Aberrant activation of the Hedgehog (Hh) signaling pathway has been reported in various cancer types including hepatocellular carcinoma (HCC). As a key effector of this signaling, Gli2 plays a crucial role in carcinogenesis, including the activation of genes encoding apoptosis inhibitors and cell-cycle regulators. In this study, we examined the role of Gli2 proliferation and survival of HCC cells. First, the expression levels of Hh pathway components were detected in a subset of HCC cell lines. To establish the role of Gli2 in maintaining the tumorigenic properties of HCC cells, we developed small hairpin RNA (shRNA) targeting Gli2 and transfected it into SMMC-7721 cell, which was selected with high level of Hh signaling expression. Next, effects of Gli2 gene silencing, on cell proliferation and on the expression of cell cycle-related proteins were evaluated, then, whether down-regulation of Gli2 renders HCC cell susceptible to TRAIL was examined in vitro. Knockdown of Gli2 inhibited cell proliferation and induced G1 phase arrest of cell cycle in SMMC-7721 cell through down-regulation of cyclin D1, cyclinE2, and up-regulation of p21-WAF1. Also, Gli2 gene siliencing sensitized SMMC-7721 cell to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by reducing the expression of the long and short isoform of c-FLIP and Bcl-2, and then augmented the activation of initiator caspases-8/-9 and effector caspases-3, which induces PARP cleavage. In conclusion, our data suggest that Gli2 plays a predominant role in the proliferation and apoptosis resistance of HCC cells, and that knockdown of Gli2 may be a novel anticancer strategy for the treatment of HCC.

Abstract Objectives To investigate longitudinal changes in astigmatism in Chinese clinical school-age children and to explore the effect of astigmatism on refraction development. Methods The medical records of patients with long-term follow-up data from 2006 to 2018 were retrospectively reviewed. Patients who were 6–10 years old at initial visit and 16 years old at last assessment were selected for analysis. The enrolled patients had a cylinder refraction of 0.75 or greater. Astigmatism was analyzed in clinical notation and vector notation (J0, J45). The related factors of changes in astigmatism and spherical equivalent per year and the interaction between the two were analyzed. Results A total of 3101 patients (median age 9 years at initial visit) were followed up for an average of 7 years (IQR, 6–8 years). Astigmatism increased with age in low astigmats (&lt; 1.50 D, 0.025 D/y) and decreased with age in high astigmats (≥ 3.00 D, -0.048 D/y). The oblique astigmatism (J45, 0.005D/y) increased and with-the-rule (WTR) astigmatism (J0, -0.008D/y) decreased. Higher myopia of the SE at the initial visit was associated with a greater increase in astigmatism magnitude(p &lt; 0.001). A higher magnitude of initial astigmatism was associated with less progression in spherical equivalent(p &lt; 0.001). Conclusion In Chinese clinical school-age children, the longitudinal development of astigmatism from 6–10 to 16 years of age varied with baseline astigmatism. The presence of myopia at baseline was a risk factor for astigmatism progression. However, high astigmatism seems to prevent the progression of myopia.

Objective: To explore the predictive effect of atypical right bundle branch blocks (ARBBB) on in-hospital sudden cardiac death (SCD) and cardiac rupture (CR) and long-term prognosis in patients with first-episode acute myocardial infarction (AMI) who undergoing percutaneous coronary intervention using a drug-eluting stent (DES-PCI).Methods: In total, 13,886 patients with first-episode AMI who underwent DES-PCI at three centers from January 2017 to January 2022 were enrolled in this retrospective prospective study. The patients were divided into four groups: ARBBB (n = 348), typical right BBB (TRBBB, n = 374), left BBB (LBBB, n = 366), and non-BBB (NBBB, n = 12,798). ARBBB was defined as a notch appearing on the ascending segment of the R-wave in lead V1 or the R-wave of lead V1 being a separate upright style. The primary endpoint events were in-hospital SCD and CR, the secondary endpoint events were 1-year major adverse cardiovascular and cerebrovascular events (MACCEs).Results: During a mean observation period of 12.6 ± 6.7 days in hospital, 334 patients (2.4%) occurred SCD, of which 98 (0.7%) were due to CR. The incidences of in-hospital SCD and CR in the ARBBB group were significantly higher than those in the other three groups (ARBBB vs. LBBB vs. TRBBB vs. NBBB: SCD, 10.6% vs 5.7% vs 4.3% vs 2.0%, p = 0.001. CR, 5.7% vs 2.7% vs 1.3% vs 0.5%, p < 0.001). ARBBB was an independent predictor of in-hospital SCD and CR in patients with first-episode AMI who underwent DES-PCI, furthermore, ARBBB had a stronger predictive ability for CR than for SCD (CR, 3.221 (1.866-7.997) vs SCD, 2.423 (1.709-4.696), p < 0.001). ARBBB could also independently predicte the 1-year MACCEs (HR=2.963, 95% CI: 1.711-5.631, p < 0.001).Conclusion: ARBBB can independently predict the occurrence of in-hospital SCD and CR and 1-year MACCEs in patients with first-episode AMI undergoing DES-PCI.Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Declaration of Interest: The authors declare no potential conflict of interest.Ethical Approval: his study was conducted per the principles of the Declaration of Helsinki and was approved by the Ethics Committees of the Second Affiliated Hospital of Zhejiang University's Medical College and Sheng Jing Hospital affiliated with China Medical University (Ethical approval number: 2023PS661K, approved institution name: Shengjing Hospital of China Medical University, approved date: March 24, 2023).

High product purity, preserving natural IgG architecture, and excellent production efficiency are highly desirable in bispecific antibody manufacturing. We have reported a platform called Bispecific Antibody by Protein Trans-Splicing (BAPTS) to synthesize BsAbs with natural human IgG structure and no chain mispairing. In the method, two antibody fragments carrying different target-specificities are separately expressed in mammalian cells and subsequently fused to form BsAbs by utilizing the trans-splicing property of the split intein Npu DnaE. The hinge region of antibody, a region with less functional impact, is selected for conjugating the two fragments. The method involves the following steps: (i) constructing five plasmids coding antibody components; (ii) separately expressing and purifying two antibody fragments A and B. Fragment A contains one Fab, “Knobs-into-Holes” mutations in the CH3 domain and NPU DnaEC. Fragment B contains another Fab and NPU DnaEN; (iii) mixing of fragments A and B under permissive reducing conditions in vitro to enable trans-splicing reaction; (iv) removing the reductant to allow re-oxidation of disulfide bonds; (v) isolating BsAb product from unreacted precursors by affinity chromatography. The method allows correct assembly of two heavy and two light chains to form bispecific IgG antibodies in natural structure with no synthetic linkers. No chain mispairing was observed in the product by UPLC-MASS. In addition, the observed kinetics and low reaction activation energy confirmed that the trans-splicing is thermodynamically favored reaction. The BAPTS technology is feasible for industrial applications.

Abstract Cadmium (Cd) is phytotoxic and detoxified primarily via phytochelatin (PC) complexation in Arabidopsis . Here, we explore Cd toxicity responses and defence mechanisms beyond the PC pathway using forward genetics approach. We isolated an Arabidopsis thaliana Cd‐hypersensitive mutant, Cd‐induced short root 1 ( cdsr1 ) in the PC synthase mutant ( cad1‐3 ) background. Using genomic resequencing and complementation, we identified PP2A‐4C as the causal gene for the mutant phenotype, which encodes a catalytic subunit of protein phosphatase 2A (PP2A). Root and shoot growth of cdsr1 cad1‐3 and cdsr1 were more sensitive to Cd than their respective wild‐type cad1‐3 and Col‐0. A mutant of the PP2A scaffolding subunit 1A was also more sensitive to Cd. PP2A‐4C was localized in the cytoplasm and nucleus and PP2A‐4C expression was downregulated by Cd in cad1‐3 . PP2A enzyme activity was decreased in cdsr1 and cdsr1 cad1‐3 under Cd stress. The expression of 1‐aminocyclopropane‐1‐carboxylic acid synthase genes ACS2 and ACS6 was upregulated by Cd more in cad1‐3 and cdsr1 cad1‐3 than in Col‐0 and the double mutant had a higher ACS activity. cdsr1 cad1‐3 and cdsr1 overproduced ethylene under Cd stress. The results suggest that PP2A containing 1A and 4C subunits alleviates Cd‐induced growth inhibition by modulating ethylene production.

Silicosis is caused by exposure to crystalline silica (CS). We have previously shown that blocking 4-1BB signaling attenuated CS-induced inflammation and pulmonary fibrosis. However, the cells that express 4-1BB, which plays a vital role in promoting fibrosis, are still unknown. In this study, we demonstrated that the expression of 4-1BB is elevated in alveolar macrophages (AMs) in the lungs of CS-injured mice. CS exposure also markedly enhanced the expression of 4-1BB in macrophage-like, MH-S cells. In these cells, activation of the 4-1BB signaling with an agonist antibody led to up-regulated secretion of pro-fibrotic mediators. Consistently, blocking 4-1BB downstream signaling or genetic deleted 4-1BB alleviated pro-fibrotic responses in vitro, while treatment with a 4-1BB fusion protein promoted pro-fibrotic responses. In vivo experiments showed that blocking 4-1BB signaling decreased the expressions of pro-fibrotic mediators and fibrosis. These data suggest that 4-1BB signaling plays an important role in promoting AMs-mediated pro-fibrotic responses and pulmonary fibrosis. Our findings may provide a potential molecular target to reduce CS-induced fibrotic responses in occupational lung disease.

Utilization of cost-effective essential preventive health services increased after the implementation of the Affordable Care Act's (ACA) provision that non-grandfathered private insurers provide cost-effective preventive services without cost sharing in 2010. Little is known, however, whether this change is also observed among Asians in the US. We examined patterns of preventive services utilization among Asian subgroups relative to non-Latino whites (whites) after the implementation of the ACA's preventive services provisions. Using 2013-2016 Medical Expenditure Panel Survey data, we examined utilization trends in preventive services among Asian Indians, Chinese, Filipinos, and other Asians relative to whites. We also ran logistic regression models to estimate the likelihood of having received each of the seven essential preventive services (routine checkups, flu vaccinations, cholesterol screenings, blood pressure checkups, Papanicolaou "pap" tests, mammograms, and colorectal cancer screenings). Compared to whites, Asians had higher rates of utilization of routine checkups, cholesterol screenings, and flu vaccinations, but they had lower utilization rates of blood pressure checkups, pap tests, and mammograms. The patterns of preventive services utilization differed across the Asian subgroups. All Asian subgroups, except for Filipinos, were less likely to have pap tests or mammograms than whites. Moreover, we observed a decreasing trend in having pap tests, mammograms, or colorectal cancer screenings among all Asian subgroups between 2013 and 2016. Our findings suggest that there are low cancer screening rates across Asian subgroups. This indicates the need for programs tailored to specific Asian subgroups to improve cancer screening.

System-level care coordination strategies can be the most effective to promote continuity of care among people with Alzheimer's disease; however, the evidence is lacking. The objective of this study is to determine whether accountable care organizations are associated with lower rates of potentially preventable hospitalizations for people with Alzheimer's disease and whether hospital accountable care organization affiliation is associated with reduced racial and ethnic disparities in preventable hospitalizations among patients with Alzheimer's disease.This study employed a cross-sectional study design and used 2015 Healthcare Cost and Utilization Project inpatient claims data from 11 states and the 2015 American Hospital Association Annual Survey. Logistic regression and the Blinder-Oaxaca decomposition method were used.African American patients with Alzheimer's disease were less likely to be hospitalized at accountable care organization‒affiliated hospitals than White patients. Among patients with Alzheimer's disease who were hospitalized, hospital accountable care organization affiliation was associated with lower odds of potentially preventable hospitalizations (OR=0.86, p=0.02; OR=0.66, p<0.001 with propensity score matching) after controlling for patient characteristics, hospital characteristics, and state indicators. Hospital accountable care organization affiliation explained 3.01% (p<0.01) of the disparity in potentially preventable hospitalizations between White and African American patients but could not explain disparities between White and Latinx patients.Evidence suggests that accountable care organizations may be able to improve care coordination for people with Alzheimer's disease and to reduce disparities between Whites and African Americans. Further research is needed to determine whether this benefit can be attributed to accountable care organization formation or whether providers that participate in accountable care organizations tend to provide higher-quality care.

Murine serum inducible kinase (mSnk) was recently cloned and characterized as an early-growth response gene involved in cell proliferation. Here we report the isolation and characterization of its human homologue, named hSnk. Sequence comparison shows that hSnk is highly conserved and its deduced protein sequence shares a significant amino acid identity with mSnk and rSnk proteins, as well as with other polo family kinase gene products. A survey ofhSnk expression reveals that while a wide variety of human tissues express a low to moderate level of hSnk transcripts, fetal tissues, testis, and spleen express the most abundant hSnk transcripts. In addition, serum stimulation rapidly induces hSnk expression in fibroblast cells, reaching the peak level of induction within one hour post treatment. Considering that Plk and Prk, two other known human polo-family kinases, control cell cycle checkpoint and cell cycle progression, our current observations suggest that hSnk may also play an important role in cells undergoing rapid cell division or having a high mitotic index.

DBA/2J mouse has been used as a model for spontaneous secondary glaucoma. Here, we investigated changes in expression of NMDA receptor (NMDAR) subunits and Cdk5/p35/NMDAR signaling in retinas of DBA/2J mice using Western blot technique. The protein levels of NR1 and NR2A subunits in retinas of DBA/2J mice at all ages (6-12 months) were not different from those in age-matched C57BL/6 mice. In contrast, the protein levels of NR2B subunits, in addition to age-dependent change, significantly increased with elevated intraocular pressure (IOP) in DBA/2J mice at 6 and 9 months as compared with age-matched controls. Moreover, expression of Cdk5, p35 and ratio of p-NR2A(S1232)/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway. However, the changes in these proteins were in the same levels in both strain mice, except a significant increase of p35 proteins at 6 months in DBA/2J mice. Meanwhile, the protein levels of Brn-3a, a retinal ganglion cell (RGC) maker, remarkably decreased at 9-12 months in DBA/2J mice, which was in parallel with the changes of NR2B expression. Our results suggest that elevated IOP-induced increase in expression of NR2B subunits of NMDARs may be involved in RGC degeneration of DBA/2J mice.

Hepatocellular carcinoma (HCC) is a highly chemoresistant cancer with no effective systemic therapy. Despite of surgical or locoregional therapies, prognosis remains poor because of high tumor recurrence or progression, and currently, there are no well-established effective adjuvant therapies. Glypican-3 (GPC-3) is specifically overexpressed in hepatoma and perhaps is a valuable molecular target for HCC therapy. In this present study, the effect of silencing GPC-3 gene transcription on human HepG2 cell proliferation was investigated by constructing GPC-3 short hairpin RNA (shRNA) plasmid. After HepG2 cells were transfected with the most efficient shRNA, GPC-3 mRNA expression (90.4 %) was inhibited significantly and estimated by fluorescence quantitative reverse transcriptase-polymerase chain reaction, and the result was accordance with downregulation at the protein level. The percentage of the cell proliferation was down to 28.9 % in the shRNA group and 19.9 % in the shRNA plus sorafenib group. The cell cycles were arrested in the G1 phase (65.6 %) and the apoptosis rate was increasing (66.75 %) in the shRNA1 group with significant alteration compared with that in the negative-shRNA group. Specific shRNA might intervene effectively GPC-3 activation and inhibit tumor cell proliferation, suggesting that GPC-3 gene should be a potential molecular target for HCC therapy.

Intramuscular adipose is conducive to good pork quality, whereas subcutaneous adipose is considered as waste in pig production. So uncovering the regulation differences between these two adiposes is helpful to tissue-specific control of fat deposition. In this study, we found the sensitivity to glucocorticoids (GCs) was lower in intramuscular adipocytes (IMA) compared with subcutaneous adipocytes (SA). Comparison of glucocorticoid receptor (GR) revealed that IMA had lower GR level which contributed to its reduced GCs sensitivity. Higher methylation levels of GR promotor 1-C and 1-H were detected in IMA compared with SA. GR expression decrease was also found in adipocytes when treated with muscle conditioned medium (MCM) in vitro, which resulted in significant inhibition of adipocytes proliferation and differentiation. Since abundant myostatin (MSTN) was detected in MCM by ELISA assay, we further investigated the effect of this myokine on adipocytes. MSTN treatment suppressed adipocytes GR expression, cell proliferation and differentiation, which mimicked the effects of MCM. The methylation levels of GR promotor 1-C and 1-H were also elevated after MSTN treatment. Our study reveals the role of GR in muscle fiber inhibition on intramuscular adipocytes, and identifies myostatin as a muscle-derived modulator for adipose GR level.

To evaluate the longitudinal impact on health-related quality of life (HRQOL) during amblyopia treatment for school-aged children from children's perspective.School-aged children prescribed amblyopia treatment for the first time were recruited into the current study. Using a questionnaire, subjects' HRQOL was assessed before patching treatment, and at 8 weeks and 16 weeks after the commencement of patching treatment. Evaluation of visual function and psychosocial aspect was included in the questionnaire. Visual acuity and demographic data of the subjects were recorded.Forty-four children, aged 7-12 years, with anisometropic amblyopia were included in the study. Visual acuity in the amblyopic eye improved 1.90 (0.41-3.74) and 3.98 (2.22-5.11) lines at follow-up weeks 8 and 16, respectively. Both the total score and subscales of the questionnaire were reduced at the first follow-up and recovered at the second follow-up. Scores at week 16 were higher than those before treatment in the psychosocial aspect (p = 0.003), and lower in the visual function aspect (p < 0.001), without significant difference in total score (p = 0.207). Visual acuity in the amblyopic eye and psychosocial expectations for treatment were the most important factors that influenced HRQOL during treatment.From the children's perspective, the impacts on visual function and psychosocial aspect were significant in the first two months of treatment, and could be adapted during therapy for school-aged children. More attention should be paid to negative effects of treatment on daily life and study at the stage of amblyopia treatment for school-aged children. Meanwhile, necessary precautions should be taken to help reduce the impacts.

Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and homeostasis. The failure of IL-2 biosynthesis may play a critical role in tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA (shRNA) on regulating acute rejection in rat liver transplantation. To this end, we successfully designed and selected an effective interference plasmid, pIL-2B. The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the no transfection group. Lewis to BN orthotopic liver transplant model was used to explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with pIL-2-shRNA survived longer (median survival time of 16 d range 7–21 d) than those with empty vector (11; range 5–13) or saline (9; range 5–13) (P < 0.05), and was inferior to those with CsA (24; range 13–36, P < 0.05). The IL-2-shRNA attenuated acute rejection with decreased apoptosis of hepatocytes and reduced cytokine production of IL-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation. Interleukin-2 (IL-2) plays a central role in T-cell activation, expansion, and homeostasis. The failure of IL-2 biosynthesis may play a critical role in tolerance induction. We tested the effect of IL-2 blockade by short hairpin RNA (shRNA) on regulating acute rejection in rat liver transplantation. To this end, we successfully designed and selected an effective interference plasmid, pIL-2B. The IL-2 mRNA expression level in the pIL-2B group was one-fifth of that in the no transfection group. Lewis to BN orthotopic liver transplant model was used to explore the effect of knockdown IL-2 by shRNA in vivo. Recipients treated with pIL-2-shRNA survived longer (median survival time of 16 d range 7–21 d) than those with empty vector (11; range 5–13) or saline (9; range 5–13) (P < 0.05), and was inferior to those with CsA (24; range 13–36, P < 0.05). The IL-2-shRNA attenuated acute rejection with decreased apoptosis of hepatocytes and reduced cytokine production of IL-2, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the graft. Our results suggest that IL-2 targeting using RNA interference approach may be of potential interest in organ transplantation.

Insulin-like growth factor binding-protein 5 (igfbp5), the most conserved member of the IGFBP family in vertebrates, plays a critical role in controlling cell survival, growth, differentiation, and apoptosis. Here, we characterized the expression patterns of igfbp5a and igfbp5b in grass carp (Ctenopharyngodon idella), which are retained in many fish species, likely from the teleost-specific whole-genome duplication. Both igfbp5a and igfbp5b encode 268- and 263-aa peptides, respectively, which share a sequence identity of 71%. Their mRNAs are not detected in zygotes. At 14 hpf, grass carp igfbp5b mRNA was detected in the somites, while igfbp5a mRNA has some possible signal around the eye and head region. At 24 hpf, both igfbp5a and igfbp5b mRNA appear to be limited to the presomitic mesoderm. At 36 hpf, igfbp5a mRNA was only detected in the midbrain, while igfbp5b mRNA was detected in both the midbrain and notochord. Overall, both mRNAs were expressed in most adult tissues. igfbp5a and igfbp5b were significantly upregulated in the muscle and liver after injection of 10 μg per kilogram body weight of zebrafish growth hormone (zGH), while their hepatic expression was downregulated by 50 μg zGH. During fasting, both igfbp5a and igfbp5b mRNAs were significantly downregulated in the muscle but upregulated in the liver. Collectively, the results suggest that the two igfbp5 genes play important but different roles in the regulation of growth and development in grass carp.

Objective To explore the difference of cumulative incidence rate of coal workers’ pneumoconiosis (CWP) among four large state-owned coal enterprises in northern China, we created an index system for evaluating the quality of comprehensive measures against CWP and applied the system to evaluate and compare the measures of the four coal enterprises. Methods A two-round Delphi investigation was conducted to identify the indicators in the index system. The weight values of the indicators were calculated with analytic hierarchy process methods. Measures of CWP, mine annals, records and other information in each coal mine of the four enterprises were collected. The evaluation scores, which ranged from 0 to 100, were calculated and compared with. Results A three-grade index system with 3 first-grade indicators, 9 second-grade indicators and 44 tertiary-grade indicators was established. The expert authority coefficient ( C r ) was 0.75 and the Kendall’s coefficient of concordance (Kendall’s W ) was 0.15 (χ 2 =193.30, P&lt;0.001). The weight value of ‘Geological conditions’ was 0.43, equal to ‘Dust control engineering technology’, and that of ‘Occupational health management’ was 0.14. The medians and quartiles of the evaluation scores of comprehensive measures against CWP of the four enterprises were 58.38 (54.60~63.02), 64.63 (60.83~67.06), 72.99 (68.92~77.67) and 75.07 (70.73~79.20), respectively. Conclusions The index system could be effectively used for evaluation and comparison of the comprehensive measures against CWP among different enterprises. The geological conditions and dust control engineering technology played an important role in preventing and controlling CWP.

The production of anti-Her2 chimeric antigen receptor (CAR) T cells needs to be optimized to make it a reliable therapy.Three types of lentiviral vectors expressing anti-Her2 CAR together with packaging plasmids were co-transfected into 293 T-17 cells. The vector with the best packaging efficiency was selected, and the packaging cell culture system and packaging plasmid system were optimized. Centrifugation speed was optimized for the concentration of lentivirus stock. The various purification methods used included membrane filtration, centrifugation with a sucrose cushion and the novelly-designed instantaneous high-speed centrifugation. The recombinant lentiviruses were transduced into human peripheral T cells with an optimized multiplicity of infection (MOI). CAR expression levels by three vectors and the efficacy of CAR-T cells were compared.When co-transfected, packaging cells in suspension were better than the commonly used adherent culture condition, with the packaging system psPAX2/pMD2.G being better than pCMV-dR8.91/pVSV-G. The optimal centrifugation speed for concentration was 20 000 g, rather than the generally used ultra-speed. Importantly, adding instantaneous centrifugation for purification significantly increased human peripheral T cell viability (from 13.25% to 62.80%), which is a technical breakthrough for CAR-T cell preparation. The best MOI value for transducing human peripheral T cells was 40. pLVX-EF1a-CAR-IRES-ZsGreen1 expressed the highest level of CAR in human peripheral T cells and the cytotoxicity of CAR-T cells reached 63.56%.We optimized the preparation of recombinant lentivirus that can express third-generation anti-Her2 CAR in T cells, which should lay the foundation for improving the efficacy of CAR-T cells with respect to killing target cells.

Hypothyroxinemia induced by maternal mild iodine deficiency causes neurological deficits and impairments of brain function in offspring. Hypothyroxinemia is prevalent in developing and developed countries alike. However, the mechanism underlying these deficits remains less well known. Given that the myelin plays an important role in learning and memory function, we hypothesize that hippocampal myelinated growth may be impaired in rat offspring exposed to hypothyroxinemia induced by maternal mild iodine deficiency. To test this hypothesis, the female Wistar rats were used and four experimental groups were prepared: (1) control; (2) maternal mild iodine deficiency diet inducing hypothyroxinemia; (3) hypothyroidism induced by maternal severe iodine deficiency diet; (4) hypothyroidism induced by maternal methimazole water. The rats were fed the diet from 3 months before pregnancy to the end of lactation. Our results showed that the physiological changes occuring in the hippocampal myelin were altered in the mild iodine deficiency group as indicated by the results of immunofluorescence of myelin basic proteins on postnatal day 14 and postnatal day 21. Moreover, hypothyroxinemia reduced the expressions of oligodendrocyte lineage transcription factor 2 and myelin-related proteins in the treatments on postnatal day 14 and postnatal day 21. Our data suggested that hypothyroxinemia induced by maternal mild iodine deficiency may impair myelinated growth of the offspring.

Connective tissue growth factor (CTGF) is a peptide involved in tissue growth and development, and can be regulated by hypoxia stress. This study aimed to isolate and characterize duplicate Ctgf genes in blunt snout bream Megalobrama amblycephala, and determine their expression patterns and response to hypoxia. The blunt snout bream Ctgfa and Ctgfb were found to be highly divergent, sharing a relatively low sequence identity of 57%. During embryogenesis, Ctgfa mRNA expression levels were low, gradually decreased from zygotes to 12h post-fertilization (hpf), markedly increased from 16 hpf, and then stabilized from 32 to 40 hpf. Ctgfb expression levels were constant but low from zygotes to 20 hpf, then gradually increased from 24 to 40 hpf. Ctgfa mRNA was expressed in the adaxial cells of the somites, floor plate, and tailbud at 24 hpf, and in the notochord and ethmoid plate at 36 hpf, whereas Ctgfb mRNA was weakly expressed in the adaxial cells and floor plate at 24 hpf, and in the notochord at 36 hpf. In adult fish, Ctgfa mRNA was strongly expressed in the kidney, brain, intestine, muscles, and skin, while Ctgfb mRNA was detected in all examined tissues. During hypoxic treatment, the mRNA levels of both Ctgfa and -b were significantly upregulated in the gill and liver, whereas Ctgfa mRNAs in the brain and kidney and Ctgfb mRNAs in the kidney significantly decreased. These results provide new insights into the functional conservation and divergence of Ctgf genes and reveal their responses to hypoxia.

Introduction Smoking cessation is the most effective therapeutic intervention for chronic obstructive pulmonary disease (COPD) patients. However, the proportion of smokers with COPD who have received physician advice to quit smoking is unknown. The purpose of this study is to assess the prevalence of receipt of smoking-cessation advice among adults with COPD and explore factors predicting advice receipt. Methods This study employed nationally representative data from the Medical Expenditure Panel Survey (MEPS), collected in 2008–2011 on adults aged ≥20 years. Logistic regression models were conducted to estimate the likelihood of receiving provider advice. Data were analyzed in 2014. Results Four percent (95% CI=3.8%, 4.2%) of adults reported being diagnosed with COPD. Among them, 38.5% (95% CI=36.1%, 40.8%) were current smokers. Among those who had seen a physician in the past year, 85.6% (95% CI=83.1%, 88.0%) were advised to quit smoking. Logistic regression revealed negative associations between receipt of smoking-cessation advice and having fewer healthcare visits (AOR=0.41, 95% CI=0.23, 0.72); being uninsured (AOR=0.43, 95% CI=0.22, 0.83); having no usual source of care (AOR=0.39, 95% CI=0.19, 0.80); and having no comorbid chronic diseases (AOR=0.50, 95% CI=0.29, 0.85). Conclusions Having no usual source of care and no health insurance are major barriers to receiving smoking-cessation advice among patients with COPD. The Patient Protection and Affordable Care Act has the potential to increase advice receipt in this high-risk population by expanding health insurance coverage and increasing the number of people with a usual source of care.

Canine distemper virus (CDV) is a highly contagious pathogen transmissible to a broad range of terrestrial and aquatic carnivores. Despite the availability of attenuated vaccines against CDV, the virus remains responsible for outbreaks of canine distemper (CD) with significant morbidity and mortality in domesticated and wild carnivores worldwide. CDV uses the signaling lymphocytic activation molecule (SLAM, or CD150) and nectin-4 (PVRL4) as entry receptors, well-known tumor-associated markers for several lymphadenomas and adenocarcinomas, which are also responsible for the lysis of tumor cells and apparent tumor regression. Thus, CDV vaccine strains have emerged as a promising platform of oncolytic viruses for use in animal cancer therapy. Recent advances have revealed that use of the CDV reverse genetic system (RGS) has helped increase the understanding of viral pathogenesis and explore the development of recombinant CDV vaccines. In addition, genetic engineering of CDV based on RGS approaches also has the potential of enhancing oncolytic activity and selectively targeting tumors. Here, we reviewed the host tropism and pathogenesis of CDV, and current development of recombinant CDV-based vaccines as well as their use as oncolytic viruses against cancers.

Background: An oncolytic measles virus encoding interleukin 12 (IL-12) to treat colon cancer in vivo and ex vivo to investigate its effect on the viability and apoptosis of colon cancer cells in this study. Materials and Methods: A rat model was established to evaluate the immunostimulatory capabilities and therapeutic efficacy of vectors encoding an IL-12 fusion protein (MeVac FmIL-12 vectors). TUNEL staining, Western blot, and enzyme-linked immunosorbent assay were performed to examine the impacts of MeVac FmIL-12 on the expression of inflammatory cytokines. Cell transfection was carried out to validate the anti-tumor role of MeVac FmIL-12 in vitro. Flow cytometry and MTT assay were performed to assess the effects of MeVac FmIL-12 on cell apoptosis and viability. Result: High concentrations (10–1000 ng/mL) of murine IL-12 fusion protein (FmIL-12) decreased the production of interferon γ (IFN-γ) in a concentration-dependent manner and reflected FmIL-12-induced overstimulation. Rats treated with MeVac vectors encoding FmIL-12 showed a significantly increased level of FmIL-12 overtime and a concentration-dependent (0.01–10 ng/mL) increase in IFN-γ production. MeVac FmIL-12 also increased the expression of inflammatory cytokines (IFN-γ, tumor necrosis factor α, and IL-6) both in vivo and in vitro. MeVac FmIL-12 promoted cell apoptosis and reduced cell viability, which helped to trigger a systemic anti-tumor immune response, both in vivo and in vitro. Conclusion: In this study, we suggested that MeVac FmIL-12 enhanced the therapeutic efficacy of tumor treatment by improving anti-tumor immunity.

AIM: To analyse the association of sleep quality with myopia under different genetic risk (GR) levels. METHODS: A cross-sectional survey of students aged 9-14y in Wenzhou, China, was conducted. Refraction without cycloplegia and ocular parameters were measured. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). Seventeen single nucleotide polymorphisms (SNPs) were replicated by association analysis and used to compute the GR score (GRS). Possible confounders were assessed by a questionnaire that collected information about the children and their parents. Generalized linear models were used to analyse the sleep quality, the GR, and their interaction effects on the risk of myopia. RESULTS: Out of 1354 children included in this study, 353 (26.07%) had sleep disturbances. The GRS ranged from 4.49 to 12.89 with a mean of 7.74±1.23, and the participants were divided into a low GR group, a moderate GR group and a high GR group according to the GRS quartile. In the generalized linear model, the children with sleep disturbances and high GR had a higher risk of myopia than those without sleep disturbances and with low GR (OR=1.59, 95%CI: 1.12-2.25; OR=1.88, 95%CI: 1.23-2.88, respectively). Compared to those with low GR and SDs, children with high GR with or without SDs had a higher risk of myopia (OR=4.88, 95%CI: 2.03-11.71; OR=1.70, 95%CI: 1.06-2.72, respectively). CONCLUSION: The prevalence of sleep disturbances in elementary school students in Wenzhou was 26.07%. There is a significant interaction between sleep disturbances and a high GR of myopia, suggesting that a high GR of myopia may increase children's sensitivity to sleep disturbances. This study indicates that children with a high GR of myopia need to achieve adequate sleep duration and excellent sleep quality.

Abstract A set of rare earth electrolysis equipment monitoring systems based on OPC unified architecture is proposed given the complex environment of the rare earth electrolysis workshop, the difficulty of data acquisition, and the interconnection between equipment. The monitoring client of rare earth electrolysis equipment based on OPC UA communication protocol is designed and developed with C # language. The connection between the OPC UA server and the monitoring system is realized, and the data acquisition and real-time monitoring of the running state of the electrolysis equipment are completed. The primary goal of the rare earth electrolysis field equipment is to acquire and monitor rare earth electrolysis process current, voltage, and other internal state data in real-time.

The antineoplastic antibiotic, bleomycin, is known to induce a well-recognized model of lung fibrosis. Active transforming growth factor-β1 (TGF-β1) plays a key role in lung fibrosis induced by bleomycin, TSP-1 (thrombospondin-1) being critical to the activation of L (latent)-TGF-β1 by virtue of an association of the TSP-1/L-TGF-β1 complex with CD36, involving the sequence CSVTCG of the TSP-1 functional fragment. To observe the inhibitory effects of TSP-1 functional fragments, critical for CD36 binding, on the activation of L-TGF-β1, we isolated alveolar macrophages from Wistar rat lungs 7 days after bleomycin administration (5 mg/kg body weight) and cultured the cells with or without TSP-1 functional or control fragments. We observed a cell surface association of TGF-β1 with CD36 by immunofluorescence and quantified the active and total TGF-β1 by ELISA. The co-localization of CD36 with TGF-β1, shown by a yellow fluorescence deriving from a mixture of the green and red of the two components, for the TSP-1 functional fragment groups was clearly less than that of the TSP-1 control fragment groups. The quantities and the percentages of active TGF-β1 in the TSP-1 functional fragment groups were lower than those in the TSP-1 control fragment groups (P<0.05 or P<0.01). These findings suggest that TSP-1 functional fragments could inhibit the activation of L-TGF-β1 secreted by activated alveolar macrophages through blocking the binding of TSP-1 to CD36.

Silicosis is a kind of pneumoconiosis caused by inhalation of silica dust, which is characterized by lung fibrosis. The biologically active form of transforming growth factor-β1 (TGF-β1) plays a key role in the development of lung fibrosis. CD36 is involved in the transformation of latent TGF-β1 (L-TGF-β1) to active TGF-β1. The antagonistic effect of the synthetic peptide was analyzed by the administration of CD36 (93-110) synthetic peptide to the silicosis model of mice. The hydroxyproline content of the silica + CD36 (93-110) synthetic peptide group was significantly lower than that of the other experimental groups [silica and silica + CD36 (208-225) synthetic peptide groups] (p &lt; .05). Inflammation, fibrotic degree and distribution of collagen fibers in silicotic nodules of the silica + CD36 (93-110) synthetic peptide group were less than those of the other experimental groups. The expressions of collagen I and III of the silica + CD36 (93-110) synthetic peptide group were significantly lower than those of the other experimental groups (p &lt; .05). CD36 (93-110) synthetic peptide reduced the tissue fibrotic pathologies and collagen accumulation in the silicosis model of mice, resulting in the decreased severity of silica-induced lung fibrosis.

Our previous study showed that the patients with more metabolic risk factors had higher risk of high ankle–brachial index (ABI), but the relationship between high ABI and the risk of severe cardiovascular and cerebrovascular diseases is still under debate. This study aims to evaluate this association in the general population. 1486 subjects of South China were recruited in the study. 61 subjects were defined as high ABI group (ABI≥1.3) and 65 subjects were randomly selected as normal ABI group (0.9<ABI<1.3). Biochemical parameters, clinical characteristics and 10-year hard coronary heart disease (HCHD) Framingham Risk Score (FRS) were compared between two groups. The results showed that the 10-year HCHD FRS of high ABI group was significantly higher than normal ABI group (7.87±6.11 vs. 3.98±2.90%, P<0.001). There was a positive correlation between ABI value and HCHD FRS in overweight participants (R = 0.576, P<0.01). The prevalence of ischemic stroke was higher in high ABI group than normal ABI group (21.3% vs. 6.2%, P<0.05), and it was higher in participants with HCHD FRS≥6% than those with HCHD FRS<6% (19.1% vs. 6.9%, P<0.05). Moreover, the prevalence of ischemic stroke was higher in participants with high ABI and HCHD FRS≥6% than those with normal ABI and HCHD FRS<6% (26.7% vs. 4.1%, P<0.05). BMI, hypertension, hsCRP and smoking were proved to be the independent factors and effective predictors for high ABI (P<0.05). In conclusion, high ABI combined with high HCHD FRS should be a potential predictor of ischemic stroke in the general population of South China.

To explore characteristics of the development of coal workers' pneumoconiosis (CWP) at present and trend in the future, we investigated 16,154 coal miners exposed to dust for at least 1yr in the Tiefa Colliery in China. Occupational categories were divided into tunneling, mining, combining and helping. Four cohorts (before 1958, 1958-, 1968-, and after 1978) were created according to years of first exposure. Life-Table Method was used to calculate cumulative incidence rates of CWP adjusted by duration of dust exposure and predict the number of the new CWP patients. Results indicated that cumulative incidence rates of CWP in four cohorts were 26.65%, 18.94%, 1.15%, and 0.06%, respectively (Χ2=493.57, p<0.0001). The 55-yr cumulative rate of CWP of tunneling miners (25.90%) or that of combining miners (14.53%) was statistically higher than that of mining miners (7.26%) or that of helping miners (0.89%). The number of new CWP patients predicted in future was approximately 77. New CWP patients predicted would mainly occur among coal miners with first dust exposure in 1958-1967 and those working at tunneling. Most of them could be diagnosed in the age group from 45 to 75 and in the period of the next 20 yr from 2008 to 2028.

To investigate the effects of skeletal muscle characteristics on meat tenderness, meat quality of a total of 100 Sutai pigs was evaluated in the present study. Myofibre composition in longissimus dorsi (LD) was investigated by determining the ratios of mRNA abundance of four myosin heavy chain (MyHC) isoforms (MyHC I, IIa, IIx and IIb) to detect the influence of myofibre type on meat tenderness. The expression of candidate genes was analysed to elucidate their possible relationship with meat tenderness. The results showed that under the same tenderization condition in the same breed of pigs, meat tenderness demonstrated the largest amount of variation compared with other meat traits. The proportion of MyHC I fibres was significantly higher in the lowest shear force group, whereas the proportions of MyHC IIa, IIb, IIx fibres did not differ significantly between the two extreme meat tenderness groups. The mRNA expression of myostatin, myogenin, myoD and growth hormone receptor (GHR) genes also did not significantly differ between the two tenderness groups. However, the mRNA expression of calpain 3 and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) changed with the shear force, showing a negative correlation with the shear force (r=−0.38 and −0.65, respectively, P<0.05). Our results showed that the increased percentage of myofibre type I and high expression of calpain 3 and PGC-1α are positively related to meat tenderness. The results provide useful data for meat tenderness selection in pig breeding.

Abstract Consciously and unconsciously perceived rewards are thought to modulate essential cognitive processes in different ways. However, little is known about whether and how they modulate higher-order social cognitive processes. The present ERP study aimed to investigate the effect of consciously and unconsciously perceived rewards on the temporal course of self-face processing. After a monetary reward (high or low) was presented either supraliminally or subliminally, participants gain this reward by rapidly and correctly judging whether the mouth shape of a probe face and a target face (self, friend, and stranger) were same. Results showed a significant three-way interaction between reward value, reward presentation type, and face type observed at the P3 component. For the supraliminal presentations, self-faces elicited larger P3 after high compared to low reward cues; however, friend-faces elicited smaller P3 and stranger-faces elicited equivalent P3 under this condition. For the subliminal presentations, self-faces still elicited larger P3 for high reward cues, whereas there were no significant P3 differences for friend-faces or stranger-faces. Together, these results suggest that consciously processed rewards have distinct advantages over unconsciously processed rewards in facilitating self-face processing by flexibly and effectively integrating reward value with self-relevance.

The current study was carried out to assess the potential functions of exogenous glucose (Glu) on plant growth, nitrogen metabolism, and antioxidant defense system in cucumber seedings under salt stress. Our results revealed that the cucumber seedlings exposed to salinity for 7 d exhibited a significant reduction of plant height, and fresh and dry weight. The salt-induced growth inhibition was effectively alleviated by foliar application of 100 mmol L −1 Glu. Exogenous Glu supplementation strikingly reduced the malondialdehyde content and controlled overaccumulation of superoxide anion ([Formula: see text]) generation rate in the salt-stressed cucumber leaves. In addition, Glu significantly increased the antioxidant enzymes activities such as super oxidase dismutase, peroxidase, catalase and ascorbate peroxidase, and regulated gene expressions of encoding these enzymes, which decreased oxidative damage induced by salt stress. The [Formula: see text] content significantly decreased, but the [Formula: see text] level significantly increased due to salt treatment. However, Glu significantly increased the activities of nitrate reductase and nitrite reductase in salt-stressed cucumber leaves, which coincided with modulating the gene expressions of key enzymes of nitrogen metabolism, and thus, promoted the conversion of ammonium nitrogen to amino acids and proteins. These results suggest that exogenous Glu could alleviate salt-induced growth inhibition through regulating antioxidant capacity and nitrogen metabolism, which is associated with an improvement of cucumber growth and salt tolerance.

Exercise is widely known to lower intraocular pressure and increase ocular blood flow, which may be beneficial for glaucoma management. However, there are few studies that have reported on the relationship between exercise and glaucoma progression. The aim of our study was to investigate the exercise habits of those with primary open angle glaucoma (POAG) and its association with the progression of visual field (VF) loss.Daily physical activity (PA) was monitored by an accelerometer (ActiGraph wGT3x-BT) which patients wore for more than 10 h of being awake on their right wrists for 1 week.Seventy-one non-progressive and 27 progressive patients were enrolled in the study. 24-h moderate to vigorous physical activity (MVPA) exercise showed that POAG patients had similar variation trends consisting of 3 wave peaks and 2 wave hollows. Minutes spent in MVPA was 19.89 ± 15.81 and 21.62 ± 15.10 during 07:00-09:00 h (p = 0.204), 15.40 ± 14.49 and 15.67 ± 12.43 during 15:00-17:00 h (p = 0.822) and 17.26 ± 21.11 and 11.42 ± 11.58 during 18:00-20:00 h (p = 0.001) in the non-progressive and progressive group, respectively. Univariate analysis indicated that 10 min of MVPA (18:00-20:00 h) [odds ratio, OR (95% CI) = 0.82 (0.73, 0.92)], average mean arterial pressure [OR (95% CI) = 0.96 (0.94, 0.98)], age [OR (95% CI) = 1.06 (1.03, 1.08)], male [OR (95% CI) = 0.67 (0.48, 0.96)], spherical equivalent [OR (95% CI) = 1.14 (1.07, 1.22)] and IOP-lowering medications [OR (95% CI) = 1.54 (1.16, 2.05)] were significantly correlated with having progressive VF damage. Multivariable analysis showed that 10 min of MVPA (18:00-20:00 h) [OR (95% CI) = 0.85 (0.75, 0.97)] was associated with progressive VF loss even after adjusting for other risk factors.Evening exercise may lower the odds of VF progression, suggesting that exercise habits possibly play an important role in glaucoma progression.

To construct a tumor-selective replication-competent adenovirus (RCAd), SG300, using a modified promoter of human telomerase reverse transcriptase (hTERT).The antitumor efficacy of SG300 in hepatocellular carcinoma was assessed in vitro and in vivo. In vitro cell viability by MTT assay was used to assess the tumor-selective oncolysis and safety features of SG300, and in vivo antitumor activity of SG300 was assessed in established hepatocellular carcinoma models in nude mice.SG300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI), but could not affect growth of normal cells even at a high MOI. Both in Hep3B and SMMC-7721 xenograft models of hepatocellular carcinoma, SG300 had an obvious antitumor effect, resulting in a decrease in tumor volume. Its selective oncolysis to tumor cells and safety to normal cells was also superior to that of ONYX-015. Pathological examination of tumor specimens showed that SG300 replicated selectively in cancer cells and resulted in apoptosis and necrosis of cancer cells.hTERT promoter-regulated replicative adenovirus SG300 has a better cancer-selective replication-competent ability, and can specifically kill a wide range of cancer cells with positive telomerase activity, and thus has better potential for targeting therapy of hepatocellular carcinoma.

Iodine is an essential component for thyroid hormone synthesis. Epidemiological investigations have demonstrated that maternal mild iodine deficiency (ID)-induced hypothyroxinemia can affect intellectual and behavioral function in offspring. There is no definitive evidence demonstrating the effects of maternal iodine supplementation on neurobehavioral function in regional areas with mild ID. Thus, we aimed to clarify the effects of maternal mild ID and iodine supplementation on motor coordination in offspring and illuminate the underlying molecular mechanisms. Animal models of maternal mild ID and iodine supplementation were generated by providing Wistar rats an iodine-deficient diet and deionized water supplemented with potassium iodide during pregnancy and lactation. We found that mild ID-induced hypothyroxinemia led to a shorter latent time before falling down from the rotarod, a longer time to traverse the balance beam and poorer wire grip of the forelimbs, which imply motor coordination dysfunction. However, these impairments in the offspring were improved by iodine supplementation during pregnancy and lactation. We further observed that the ultrastructure and dendritic tree morphology of cerebellar Purkinje cells were altered in mild ID-induced hypothyroxinemia but that these changes could be reversed by iodine supplementation. Maternal mild ID and iodine supplementation also affected expression of the mGluR1 signaling pathway in offspring. Together, iodine supplementation during pregnancy and lactation can improve motor coordination in offspring by modulating the mGluR1 signaling pathway in mild ID-induced hypothyroxinemia rats.

A large number of studies have shown that mature adipocytes are able to dedifferentiate in vitro into progeny cells, which possess proliferative capacity and mutilineage potential. Our present study confirms that mature adipocytes derived from Angus cattle also dedifferentiate into proliferative-competent progeny cells. However, this report is unlike any published for all other breeds of cattle we have worked with or that we have seen in published reports, in which mature adipocytes retain and distribute lipids into daughter cells symmetrically or asymmetrically. In the present work, we noted that Angus-derived mature adipocytes extruded a majority of their cellular lipid droplets prior to cell division. In this manner, these cells are processing lipid in a manner observed in mature adipocytes isolated from swine tissue. These results suggest that regulation of the mechanism(s) underlying lipid processing might be different between and within animal breeds. Lipid processing in beef-derived adipocytes during dedifferentiation may serve as a unique animal model for studying lipid metabolism during reverse adipogenesis.

ICOSL, a newly identified member of the B7 superfamily, plays a major role in immune responses. In this study, a functional anti-human ICOSL monoclonal antibody (MAb) 3B3 was obtained and characterized by means of flow cytometry, Western blot, and competition assay. This MAb could specifically recognize a distinct epitope of the ICOSL molecule. As a functional antibody, MAb 3B3 could inhibit the proliferation of T lymphocytes stimulated by ICOSL-L929 transfectants. Furthermore, it could enhance IgG production of PWM-driven B cells. The results indicate that the ICOS-ICOSL signal is critically involved in specific humoral immunity.

Hepatocellular carcinoma (HCC) is a common and biologically aggressive malignancy linked to cirrhotic and pre-cirrhotic changes in the liver. We analyzed degrees of fibrosis in affected patients as indices of survival, to establish an effective prognostic nomogram.Eligible patients with HCC and hepatic fibrosis, of varying degrees, were selected from the Surveillance, Epidemiology, and End Results (SEER) database for propensity score matching (PSM). The prognostic value of data was determined using Kaplan-Meier and Cox proportional hazards model. A nomogram based on variables derived from multivariate analyses was established and subjected to internal validation. Its predictive accuracy was tested by concordance index (C-index) and calibration plots.In this propensity score-matched cohort, advanced fibrosis/cirrhosis (vs. none-to-moderate fibrosis) correlated with poorer survival [hazard ratio (HR): 1.131, 95% confidence interval (CI): 1.032-1.240; P=0.009]. Multivariate analysis identified the following as independent risk factors for HCC: age >63 years, higher fibrosis score, American Joint Cancer Committee (AJCC) stages T3-4, distant metastasis (M1), tumor size >1 cm, major vascular invasion, and elevated alpha-fetoprotein (AFP) level. A nomogram that integrated these factors offered a superior prognostic prediction for HCC patients (C-index: 0.749, 95% CI: 0.7485-0.7495) relative to conventional tumor staging the AJCC tumor-node-metastasis (TNM) staging system (0.730). In calibration plots, optimal agreement between nomogram-predicted and observed survival was evident.Increased fibrosis was an independent risk factor for survival of HCC patients. A prognostic nomogram integrating fibrosis score and other independent risk factors offered more accurate depictions in this regard.

Fgfr1 is a fibroblast growth factor receptor involved in regulating cell growth, proliferation, differentiation and migration. Here, we report the isolation and characterization of duplicated fgfr1 genes in blunt snout bream (Megalobrama amblycephala). Blunt snout bream fgfr1a and -1b cDNAs were found to share a relatively high sequence identity of 82%. During embryogenesis, both fgfr1a and -1b mRNAs were highly detected at zygotes but gradually decreased and then constantly expressed after 16hpf, besides a strong expression for the fgfr1b mRNA at 12hpf. Whole-mount in situ hybridization demonstrated that fgfr1a mRNA was transcribed at the eyes, mid-hindbrain boundary (MHB), brain, posterior somites and tailbud at 16hpf, while the fgfr1b mRNA was only detected at the eyes and posterior somites at the same period. At 28hpf embryos, both fgfr1a and -1b mRNAs were expressed in the eyes, brain, pharyngeal arches and tailbud, and in the eyes, brain, pharyngeal arches and notochord at 55hpf. In adult fish, fgfr1a mRNA was strongly expressed in the gill, gonad, brain and midgut, but examined relatively low in the skin and kidney. In contrast, the fgfr1b mRNA was highly detected in the brain and liver and quite low in the skin, gill and kidney. During starvation, both fgfr1a and -1b mRNAs were significantly up-regulated in the intestine and liver, but down-regulated in the brain. Moreover, duplicated fgfr1 mRNAs were differentially inhibited in tissues with exogenous recombinant hGH. Our results suggest that two fgfr1 genes play important roles in regulating growth and development in blunt snout bream.

To study the morphological features of the lungs obtained from autopsies of severe acute respiratory syndrome (SARS) patients.Bilateral lungs from 7 patients died from SARS were carefully studied grossly and microscopically. All tissues from these cases were routinely processed and carefully studied.All lungs from these cases were extremely expanded and became solid. Microscopically, the edema and fibrin exudates in the alveoli was the most common findings, especially in the early phase of the disease. The hyaline membrane was almost always present in the lungs of these cases. The organization of intra-alveolar fibrin exudates along with the interstitial fibrosis led to obliteration of alveoli and consolidation of lungs. The desquamation and hyperplasia of alveolar lining cells was also apparent. Foci of haemorrhage and lobular pneumonia, even diffuse fungal infection were frequently seen in these specimens. Micro-thrombus were easily found in these lungs.The lung of SARS from autopsy is characterized by edema, intra-alveolar fibrin exudates, hyaline membrane formation, organization of intra-alveolar exudates and fibrosis, which lead to the obliteration of alveoli and consolidation of lungs.

To investigate the mechanism by which developmental iodine deficiency and hypothyroidism affect long-term synaptic plasticity, we chose to study the activity of protein kinase C (PKC) and the expression of growth-associated protein-43 (GAP-43) in pup hippocampus following developmental hypothyroidism. Two developmental hypothyroid rat models were created with iodine-deficient diet (IDD) and water containing methimazole. Compared to the control group, in developmental hypothyroid rats: (i) HFS induced less in vivo LTP and more long-term depression (LTD) in area CA1 on postnatal day (PN) 60 (P < 0.0 5); (ii) in IDD pups, HFS-induced LTP showed much smaller population spike amplitude (P < 0.01) and slope of field-excitatory postsynaptic potential (P < 0.01); (iii) PKC activity, on PN30, was much higher on cell membrane and lower in cytosol (P < 0.05) without change of total PKC level (P > 0.05); and (iv) GAP-43 expression was significantly lower (P < 0.01) on both PN30 and PN60. Developmental iodine deficiency and hypothyroidism affect PKC translocation, decrease GAP-43 expression, and impair long-term synaptic plasticity in the rat hippocampus.

β-lactoglobulin (BLG), a dominant allergen in goat milk, is difficult to remove by traditional biochemical methods. Its elimination from goat milk by genetic modification therefore poses a major challenge for modern goat breeders. A shRNA targeting BLG mRNA with high interference efficiency was identified, with which lentiviral vectors were used for mediating stable shRNA interference in goat-fetal fibroblast cells. Apart from high efficiency in the knockdown of BLG expression in these cells, lentivector-mediated RNAi manifested stable integration into the goat genome itself. Consequently, an in vitro model for goat BLG-content control was compiled, and a goat-cell line for accompanying transgenetic goat production created.

The main object of the present study was to explore the effect on thyroidal proteins following mild iodine deficiency (ID)-induced maternal hypothyroxinemia during pregnancy and lactation. In the present study, we established a maternal hypothyroxinemia model in female Wistar rats by using a mild ID diet. Maternal thyroid iodine content and thyroid weight were measured. Expressions of thyroid-associated proteins were analyzed. The results showed that the mild ID diet increased thyroid weight, decreased thyroid iodine content and increased expressions of thyroid transcription factor 1, paired box gene 8 and Na+/I− symporter on gestational day (GD) 19 and postpartum days (PN) 21 in the maternal thyroid. Moreover, the up-regulated expressions of type 1 iodothyronine deiodinase (DIO1) and type 2 iodothyronine deiodinase (DIO2) were detected in the mild ID group on GD19 and PN21. Taken together, our data indicates that during pregnancy and lactation, a maternal mild ID could induce hypothyroxinemia and increase the thyroidal DIO1 and DIO2 levels.

During the process of modern industrialization and urbanization, it has become one of the major daily activities that people drive private cars to fulfill their travel demands. The trajectory data generated during the usage of private cars plays as the intuitive embodiment of people's travel behavior. In particular, the stay behavior, i.e., people need to stay and take time carrying out their own activities when they drive to a specific location, contains crucial information for understanding users' travel behavior and mobility motivations. In this paper, via leveraging the private car trajectory data, we strive to propose a novel approach to percept and predict stay of interests, called SOI. The goal is to predict the stay interest of a private car user will stay to a given location, this is important information for vehicle services such as travel semantic analysis and smart recommendation service. Specifically, we first propose a stay behavior perception method to detect stay behavior from large-scale private car trajectory dataset. Then, we design a spatiotemporal factor extraction method considering the spatial aggregation, time period and spatiotemporal similarity correlation of stay behaviors, which can reduce the sparsity and non-stationary problems of stay behavior data. Furthermore, we propose a prediction method based gradient boosting decision trees to estimate the future stay interest of private car users' stay behavior. We conduct extensive experiments based on the real-life private car trajectory dataset. For the stay interest prediction of stay behavior, achieve prediction precision of 0.89 and recall of 0.85. To the best of authors' knowledge, this is the first work in literature that exploits private car trajectory data and discovers the stay behavior of private car users and hence provides new perspective for understanding people's travel behavior.

Follistatin-like 1 (Fstl1) peptides play important roles in inhibiting myoblast proliferation and differentiation. Here, we characterized and examined the expression patterns of fstl1a and -b in grass carp (Ctenopharyngodon idellus). These genes encode 314 aa and 310 aa peptides, respectively, sharing a sequence identity of 83%. Except for the existence of the follistatin-N-terminal (FOLN) and Kazal-type 2 serine protease inhibitor (Kazal 2) domains, grass carp Fstl1a and -b do not share amino acid sequence similarity with Fst1 and -b. Both fstl1a and -b mRNAs were widely expressed in adult tissues. During embryogenesis, grass carp fstl1a and -b mRNA was detected in the presomitic mesoderm and somites at 12h post fertilization (hpf). At 24hpf, fstl1a mRNA was expressed in the hindbrain, somites, notochord and tailbud, while fstl1b mRNA was only detected in the tailbud. At 36hpf, fstl1a mRNA was detected in the hindbrain and notochord, and fstl1b was also expressed in the notochord. Furthermore, fstl1a and -b were downregulated in brain and liver tissue following injection with 10 or 50μg hGH, while fstl1b was significantly up-regulated in muscle tissue after 10μg hGH treatment. Both fstl1a and -b were significantly up-regulated at 2, 4 or 6days of nutrient restriction, and fstl1a was still highly expressed in the liver and muscle after 3days of refeeding, as was fstl1b in the brain and muscle. The expression of these genes returned to near control levels following 6days of refeeding. Our findings suggest that the two fstls play important but divergent roles in embryonic development and tissue growth regulation in grass carp.

ABSTRACT Iodine deficiency (ID) during early pregnancy had an adverse effect on children's psychomotor and motor function. It is worth noting that maternal marginal ID tends to be a common public health problem. Whether marginal ID potentially had adverse effects on the development of cerebellum and the underlying mechanisms remain unclear. Therefore, our aim was to study the effects of marginal ID on the dendritic growth in filial cerebellar Purkinje cells (PCs) and the underlying mechanism. In the present study, we established Wistar rat models by feeding dam rats with a diet deficient in iodine and deionized water supplemented with potassium iodide. We examined the total dendritic length using immunofluorescence, and Western blot analysis was conducted to investigate the activity of nuclear factor‐κB (NF‐κB) signaling and microtubule‐associated protein 1B (MAP1B). Our results showed that marginal ID reduced the total dendritic length of cerebellar PCs, slightly down‐regulated the activity of NF‐κB signaling and decreased MAP1B in cerebellar PCs on postnatal day (PN) 7, PN14, and PN21. Our study may support the hypothesis that decreased T 4 induced by marginal ID limits PCs dendritic growth, which may involve in the disturbance of NF‐κB signaling and MAP1B on the cerebellum. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1241–1251, 2017.

Abstract Background It was found that delayed activation wave often appeared in terminal QRS wave in non‐ST‐elevated myocardial infarction (NSTEMI) with culprit vessel in left circumflex artery (LCX), yet little is known about the similarities among non‐“N”‐wave non‐ST‐elevated myocardial infarction (N‐NSTEMI) and ST‐elevated myocardial infarction (STEMI). Hypothesis In AMI patients with the culprit vessel in LCX, “N” wave NSTEMI has a risk equivalent to STEMI. Methods All 874 patients admitted to Shenjing Hospital of China Medical University between January 1, 2013 and December 30, 2017 were included and whose coronary angiography (CAG) indicated the culprit vessel in LCX. Patients were divided into three groups: ST‐elevated myocardial infarction group (STEMI group, n = 322), “N” wave non‐ST‐elevated myocardial infarction group (N‐NSTEMI group, n = 232) and non‐“N”‐wave NSTEMI group (non N‐NSTEMI group, n = 320). The basic data and the incidence of MACE during hospitalization and 12 months were analyzed. Results In STEMI and N‐NSTEMI groups, AST, CK, CK‐MB, TnI, and stenosis severity were significantly higher than non N‐NSTEMI ( P &lt; .05). The lesions in the N‐NSTEMI and STEMI groups were more often located proximal LCX before giving rise to OM1 of LCX ( P &lt; .05), however, the non N‐NSTEMI group was often located distal LCX after giving rise to OM1 and the OM1 ( P &lt; .05). The incidence rates of all MACEs, all‐cause death, ST, TVR, and rUAP were similar in N‐NSTEMI and STEMI groups, which were greater than non N‐NSTEMI ( P &lt; .05). Both N‐NSTEMI and STEMI are independent risk factors for MACE ( P &lt; .05). Conclusion The basic data and the incidence of major adverse cardiac event were similar in N‐NSTEMI and STEMI patients, N‐NSTEMI has a risk equivalent to acute STEMI.

The abscopal effect on the tumors is a distant antitumor activity induced by local treatments. The study was to observe the induction of abscopal effect by the combination of H101 oncolytic virotherapy with local heating.Five patients with histologically confirmed, surgically unresectable metastatic malignant tumors (2 nasopharyngeal carcinomas, 1 pulmonary carcinoma, 1 parosteal sarcoma and 1 bladder carcinoma) that had definitely failed to the conventional chemotherapy and radiotherapy or refused these therapies were enrolled in this experimental therapy. All patients were treated with local intra tumor injection of H101 (5x10(11) - 15x10(11) VP) combined with 60-min heating at 42 degrees C.Two patients were cured with complete regressions of both injected and non-injected tumors and have survived for a long period up to date. Three patients responded to the novel therapy variously and eventually died from the disease, who survived 29, 15 and 13 months, respectively.The abscopal antitumor effect could be induced by the combination of H101 local intratumoral injection with heating.

At present, the detection of drainage pipe defects adopts manual frame-by-frame naked eye discrimination, which has low detection efficiency and high cost, so a two-path multi-receptive convolutional neural network is designed, which also takes into account a certain small volume on the basis of obtaining the highest classification index. The experimental results show that the volume accuracy of the designed model is 92.3%, the recall rate is 91.1%, the F1 score is 91.7%, the model volume is 30.7M, the parameter quantity is 8.97M, and the calculation amount is 2.25G. Compared with other networks, this model is more suitable for automatic identification of drainage pipes.

We have demonstrated that the depth of unbalanced interocular suppression can be quantified by balancing the interocular luminance differences required when both eyes are viewing simultaneously. In this study, we aimed to investigate the applicability of this method in children with intermittent exotropia (IXT), offering a quantitative assessment of interocular suppression in individuals with binocular imbalance. Additionally, we evaluated its association with the clinical characteristics of IXT.Interocular suppression in IXT was quantitatively measured using a polarizer and neutral-density (ND) filters. The density of the ND filter was adjusted incrementally from 0.3ND to 3ND, with a step size of 0.3ND (a total of 10 levels). Our prospective study involved 46 patients with IXT (mean age: 10.12 ± 4.89 years; mean ± SD) and 24 normal observers (mean age: 7.88 ± 1.83 years).The suppression test exhibited good test-retest reliability, supported by statistical analysis. We observed more pronounced interocular suppression in individuals with IXT compared to controls. Notably, the magnitude of suppression during distant and near viewing significantly differed in IXT (1.55 ± 0.93 vs. 0.57 ± 0.64; Z = 4.764, p < 0.001). Furthermore, we identified a positive correlation between interocular suppression and data obtained from the Worth-4-Dot test. Additionally, interocular suppression showed a significant association with distance control scores.Our novel test offers a convenient and reliable means to quantify interocular suppression in patients with IXT. The quantitative assessment of interocular suppression provides a sensitive tool to evaluate the clinical characteristics of IXT.

Abstract Objectives: To investigate longitudinal changes in astigmatism in school-age children and to explore the effect of astigmatism on refraction development. Methods: The medical records of patients with long-term follow-up data from 2006 to 2018 were retrospectively reviewed. Patients who were 6-10 years old at initial visit and 16 years old at last assessment were selected for analysis. The enrolled patients had a cylinder refraction of 0.75 or greater. Astigmatism was analyzed in clinical notation and vector notation(J0, J45). The related factors of changes in astigmatism and sphericalequivalent per year and the interaction between the two were analyzed. Results: A total of 3101 patients(median age 9 years at initial visit) were followed up for an average of 7 years(IQR, 6–8 years). The mean cylinder refraction at initial examination was 2.11±1.18Dand decreased to 2.08±1.18Dat 16 years old, which was statistically(p=0.034) but not clinically significant. The Oblique astigmatism(J45, 0.005D/y) increased and with-the-rule astigmatism(J0, -0.008D/y) decreased. A lower magnitude of astigmatism and more myopia of the SE at the initial visit were associated with a greater increase in astigmatism magnitude(p&lt;0.001). A higher magnitude of initial astigmatism was associated with less progression in spherical equivalent(p&lt;0.001). Conclusion: In southern Chinese children, the mean cylinder power decreased slightly from 6-10 to 16 years of age, accompanied by a progression of the oblique axis and a reduction of with-the-rule axis. The presence of myopia at baseline was a risk factor for astigmatism progression. However, high astigmatism seems to prevent reductions in the spherical equivalent.

Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming industry. Nosema bombycis is a typical microsporidium that infects multiple lepidopteran insects via fecal-oral and transovarial transmission (TOT); however, the underlying TOT processes and mechanisms remain unknown. Here, we characterized the TOT process and identified key factors enabling N . bombycis to invade the ovariole and oocyte of silkworm Bombyx mori . We found that the parasites commenced with TOT at the early pupal stage when ovarioles penetrated the ovary wall and were exposed to the hemolymph. Subsequently, the parasites in hemolymph and hemolymph cells firstly infiltrated the ovariole sheath, from where they invaded the oocyte via two routes: (I) infecting follicular cells, thereby penetrating oocytes after proliferation, and (II) infecting nurse cells, thus entering oocytes following replication. In follicle and nurse cells, the parasites restructured and built large vacuoles to deliver themselves into the oocyte. In the whole process, the parasites were coated with B . mori vitellogenin (BmVg) on their surfaces. To investigate the BmVg effects on TOT, we suppressed its expression and found a dramatic decrease of pathogen load in both ovarioles and eggs, suggesting that BmVg plays a crucial role in the TOT. Thereby, we identified the BmVg domains and parasite spore wall proteins (SWPs) mediating the interaction, and demonstrated that the von Willebrand domain (VWD) interacted with SWP12, SWP26 and SWP30, and the unknown function domain (DUF1943) bound with the SWP30. When disrupting these interactions, we found significant reductions of the pathogen load in both ovarioles and eggs, suggesting that the interplays between BmVg and SWPs were vital for the TOT. In conclusion, our study has elucidated key aspects about the microsporidian TOT and revealed the key factors for understanding the molecular mechanisms underlying this transmission.

In the editorial work, abbreviations of English names are often encountered as symbols of measurement units, which are not in line with editorial norms. This study investigated the implementation of standardization in Chinese medical journals by taking “part per billion (ppb)” as an example, analyzed the reasons for its difficulty in implementation, and provided corresponding countermeasures, in order to provide reasonable suggestions for promoting the implementation of national standardization. During the editorial work, it was found that “ppb” was mostly used as a symbol of measurement units for fractional exhaled nitric oxide (FeNO) in exhaled breath. Therefore, “FeNO” and “fractional exhaled nitric oxide” were used as keywords to retrieve relevant literature on China National Knowledge Infrastructure (CNKI, https://www.cnki.net/) from January 2021 to July 2023. A total of 116 articles were retrieved, 8 of which were removed as reviews, or meta-analyses, and other articles without symbols of measurement units. A total of 108 articles were retrieved. Among the 108 articles, only 2 (1.85%) complied with editorial norms, 78 (72.22%) still used “ppb” as a symbol of measurement units, and 28 (25.93%) had different errors. Medical sci-technology journals have a long way to go in implementing the standardization of measurement unit symbols. It requires international and domestic standards and guidelines to be revised from top to bottom, further cooperation and adjustment from instrument manufacturers, and gradual adaptation of clinicians to new standards and norms, in order to fulfill their respective responsibilities in promoting the national standardization process.

This study presents the results of an investigation of respiratory symptoms, pulmonary function and chest X-ray examinations, and analysis of antibodies to fungi of 197 tussah silk-processing workers and 40 control workers. An industrial hygiene survey and environmental mycological studies were also conducted. The dust concentrations in tussah silk processing workshops were less than 5.1 mg/m(3) on average, with a maximum of 7.8 mg/m(3) below the national health limit of 10 mg/m(3). Most dusts in all tussah silk processing workshops contained less than 1.2% silica. Numbers of isolated fungi in tussah silk processing workshops [755-6,544 cfu/m(3) (colony forming unit/m(3)), were significantly higher than those in control environments (63-472 cfu/m(3)). The prevalences of respiratory symptoms in tussah silk processing workers were higher than those in control workers. The prevalences of respiratory symptoms in exposed male non-smoking workers were 44.4% with chronic cough, and 38.9% with chronic phlegm respectively, which were significantly higher than those (12.5%, 12.5% respectively) in male non-smoking control workers (p<0.05). The prevalences in exposed male smoking workers were 42.9% with dyspnea, and 38.1% with chest tightness respectively, which were significantly higher than those (16.7%, 8.3% respectively) in male smoking control workers (p<0.01). The prevalences of respiratory symptoms in exposed female workers were 25.3% with chronic cough, 38.0% with chronic phlegm, 31.0% with dyspnea, and 29.1% with chest tightness respectively, which were significantly higher than those (10.0%, 10.0%, 10.0%, 5.0% respectively) in female control workers (p<0.01). Fifteen exposed workers often suffered from fever. Five X-rays were abnormal and four cases had nodular or patchy shadows. The prevalences of pulmonary function abnormalities in the exposed female group were significantly higher than those in control groups (p<0.01). The OD(450 nm) values for antibodies to fungi in tussah silk processing workers were significantly higher than those of control workers (p<0.05). The positive rates of anti-fungal antibodies in tussah silk-processing workers were also significantly higher than those of control workers (p<0.01). The results suggested that fungi might be one of the main allergens in respiratory diseases in the tussah silk processing workers.

Aims: Iodine is critical for synthesis of thyroid hormones (TH). And iodine deficiency (ID) is one of the most significant reasons of mental retardation and motor memory impairment, although the potential mechanisms are still under investigation. Presently, mild ID and marginal ID are largely ignored problems for women of child bearing age. Mild ID is a subtle form of TH deficiency, which shows low levels of free thyroxine (FT4) and relatively normal free triiodothyronine (FT3) or thyroid stimulation hormone (TSH). And marginal ID is a milder form of ID with decreased total T4 (TT4) but relatively normal FT3, FT4, and TSH. Therefore, we investigated the effects of maternal different degrees of ID on the development of pinceau in cerebellar purkinje cells (PCs) and studied the expression of pinceau related protein, which is crucial for the development and maturation of pinceau. Methods and Results: Three developmental iodine deficient rat models were created by feeding dam rats with an iodine-deficient diet and deionized water supplemented with potassiumiodide. Our study showed that different degrees of ID inhibited cerebellar pinceau synapse development and maturation on postnatal day (PN) 14 and PN21. What’s more, mild and severe ID reduced the expression of AnkG, β4-spectrin, neurofascin186 and NrCAM on PN7, PN14, and PN21. However, marginal ID rarely altered expression of these proteins in the offspring. Conclusion: These results suggested that maternal mild and severe ID impaired the development and maturation of cerebellar pinceau, which may be attributed to the decrease of AnkG, β4-spectrin, neurofascin 186 and NrCAM. And the alteration of development and maturation in cerebellar pinceau in the offspring were also observed following maternal marginal ID, which is slighter than that of mild ID.

During early pregnancy, iodine deficiency (ID) is linked to adverse effects on child motor and psychomotor function. Maternal marginal ID has become a common public health problem. It is unclear whether marginal ID influences the development of the cerebellum or its underlying mechanisms. Thus, the purpose of this study was to determine the effects of marginal ID on the development of cerebellar Bergmann glial cells (BGs) and investigate the activation of the Notch signaling pathway, which is crucial for the development and morphology of BGs. We treated Wistar rats with an ID diet (iodine content 60 ± 1.5 ng/g) supplemented with deionized water containing different concentrations of potassium iodide (KI) (183, 117, and 0 μg/L for the control, marginal ID, and severe ID groups, respectively) during pregnancy and lactation. We explored the morphology of the BGs by Golgi-Cox staining and immunofluorescence and investigated the Notch signaling pathway using western blot. Our results showed that the marginal ID and severe ID groups had decreased cerebellar BG fiber lengths (P < 0.05 and 0.01, respectively) and numbers (P < 0.01 for both) on postnatal day (PN) 7, PN14, and PN21 compared to the control group. Moreover, the data showed that severe ID significantly reduced Dll1, Notch1, RBP-Jκ, and BLBP protein levels at all three time points. Marginal ID slightly reduced the expression of Notch1 on PN7 (P < 0.05) and PN21 (P < 0.01), RBP-Jκ on PN14 (P < 0.01) and PN21 (P < 0.05), and BLBP on PN7 (P < 0.05). There was no significant difference in Dll1 protein levels between the marginal ID and control groups at any time point. Our study suggests that marginal ID leads to mild damage to BG morphogenesis in the cerebellum. The abnormal regulation of the Notch signaling pathway may be involved in the damage to BGs.

In the new era of value-based payment models and pay for performance, hospitals are in search of the silver bullet strategy or bundle of strategies capable of improving their performance on quality measures.To determine whether there is an association between adoption of hospital-based care coordination strategies and Centers for Medicare and Medicaid Services overall hospital quality (star) ratings and readmission rates.We used survey data from the American Hospital Association (AHA) and categorized respondents by the number of care coordination strategies that they reported having widely implemented. We used multiple logistic regression models to examine the association between the number of strategies and hospital overall rating performance and disease-specific 30-day excess readmission ratios, while controlling for hospital and county characteristics and state-fixed effects.A total of 710 general acute care noncritical access hospitals that received star ratings and responded to the 2015 AHA Care Systems and Payment Survey.Centers for Medicare and Medicaid Services overall hospital ratings, 30-day excess readmission ratios.As compared with hospitals with 0-2 strategies, hospitals with 3 to 4 strategies (P=0.007), 5-7 strategies (P=0.002), or 8-12 strategies (P=0.002) had approximately 2.5× the odds of receiving a top rating (4 or 5 stars). Care coordination strategies were positively associated with lower 30-day readmission ratios for patients with chronic medical conditions, but not for surgical patients. Medication reconciliation, visit summaries, outreach after discharge, discharge care plans, and disease management programs were each individually associated with top ratings.Care coordination strategies are associated with high overall hospital ratings.