Tao Li

The genetics of schizophrenia and other mental disorders are complex and poorly understood, and made even harder to study because reduced reproduction rates result in negative selection pressure on risk alleles. To date, some copy number variations have been linked to schizophrenia but the studies have been relatively small. Now two independent large-scale genome-wide studies of thousands of patients and controls by two international consortia confirm a previously identified locus but also reveal novel associations. In the first study, a collaboration between SGENE and partners, de novo (spontaneous) copy number variants are reported on chromosomes 1 and 15. In the second study, by the International Schizophrenia Consortium, deletions were also reported on these chromosomes, as was greater overall frequency of copy number variation in the genome. The genetics of schizophrenia and other mental disorders are complex and poorly understood, and made even harder to study due to reduced reproduction resulting in negative selection pressure on risk alleles. Two independent large-scale genome wide studies of thousands of patients and controls by two international consortia confirm a previously identified locus, but also reveal novel associations. In this study, de novo (spontaneous) copy number variants are reported on chromosomes 1 and 15. Reduced fecundity, associated with severe mental disorders1, places negative selection pressure on risk alleles and may explain, in part, why common variants have not been found that confer risk of disorders such as autism2, schizophrenia3 and mental retardation4. Thus, rare variants may account for a larger fraction of the overall genetic risk than previously assumed. In contrast to rare single nucleotide mutations, rare copy number variations (CNVs) can be detected using genome-wide single nucleotide polymorphism arrays. This has led to the identification of CNVs associated with mental retardation4,5 and autism2. In a genome-wide search for CNVs associating with schizophrenia, we used a population-based sample to identify de novo CNVs by analysing 9,878 transmissions from parents to offspring. The 66 de novo CNVs identified were tested for association in a sample of 1,433 schizophrenia cases and 33,250 controls. Three deletions at 1q21.1, 15q11.2 and 15q13.3 showing nominal association with schizophrenia in the first sample (phase I) were followed up in a second sample of 3,285 cases and 7,951 controls (phase II). All three deletions significantly associate with schizophrenia and related psychoses in the combined sample. The identification of these rare, recurrent risk variants, having occurred independently in multiple founders and being subject to negative selection, is important in itself. CNV analysis may also point the way to the identification of additional and more prevalent risk variants in genes and pathways involved in schizophrenia.

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping that is highly concordant with knowledge-based structural classifications3-5. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A-D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309)6 and group F (for example, CR3022)7, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants.

Background The China Mental Health Survey was set up in 2012 to do a nationally representative survey with consistent methodology to investigate the prevalence of mental disorders and service use, and to analyse their social and psychological risk factors or correlates in China. This paper reports the prevalence findings. Methods We did a cross-sectional epidemiological survey of the prevalence of mental disorders (mood disorders, anxiety disorders, alcohol-use and drug-use disorders, schizophrenia and other psychotic disorders, eating disorder, impulse-control disorder, and dementia) in a multistage clustered-area probability sample of adults from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Face-to-face interviews were done with a two-stage design by trained lay interviewers and psychiatrists with the Composite International Diagnostic Interview, the Structured Clinical Interview for DSM-IV Axis I disorders, the Community Screening Instrument for Dementia from the 10/66 dementia diagnostic package, and the Geriatric Mental State Examination. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted to adjust for differential probabilities of selection and differential response as well as to post-stratify the sample to match the population distribution. Findings 32 552 respondents completed the survey between July 22, 2013, and March 5, 2015. The weighted prevalence of any disorder (excluding dementia) was 9·3% (95% CI 5·4–13·3) during the 12 months before the interview and 16·6% (13·0–20·2) during the participants' entire lifetime before the interview. Anxiety disorders were the most common class of disorders both in the 12 months before the interview (weighted prevalence 5·0%, 4·2–5·8) and in lifetime (7·6%, 6·3–8·8). The weighted prevalence of dementia in people aged 65 years or older was 5·6% (3·5–7·6). Interpretation The prevalence of most mental disorders in China in 2013 is higher than in 1982 (point prevalence 1·1% and lifetime prevalence 1·3%), 1993 (point prevalence 1·1% and lifetime prevalence 1·4%), and 2002 (12-month prevalence 7·0% and lifetime prevalence 13·2%), but lower than in 2009 (1-month prevalence 17·5%). The evidence from this survey poses serious challenges related to the high burdens of disease identified, but also offers valuable opportunities for policy makers and health-care professionals to explore and address the factors that affect mental health in China. Funding National Health Commission of Health (Ministry of Health) and Ministry of Science and Technology of China.

Currently, most research on nonnegative matrix factorization (NMF)focus on 2-factor $X=FG^T$ factorization. We provide a systematicanalysis of 3-factor $X=FSG^T$ NMF. While it unconstrained 3-factor NMF is equivalent to it unconstrained 2-factor NMF, itconstrained 3-factor NMF brings new features to it constrained 2-factor NMF. We study the orthogonality constraint because it leadsto rigorous clustering interpretation. We provide new rules for updating $F,S, G$ and prove the convergenceof these algorithms. Experiments on 5 datasets and a real world casestudy are performed to show the capability of bi-orthogonal 3-factorNMF on simultaneously clustering rows and columns of the input datamatrix. We provide a new approach of evaluating the quality ofclustering on words using class aggregate distribution andmulti-peak distribution. We also provide an overview of various NMF extensions andexamine their relationships.

This paper presents a stochastic model for the long-term solution of security-constrained unit commitment (SCUC). The proposed approach could be used by vertically integrated utilities as well as the ISOs in electricity markets. In this model, random disturbances, such as outages of generation units and transmission lines as well as load forecasting inaccuracies, are modeled as scenario trees using the Monte Carlo simulation method. For dual optimization, coupling constraints among scenarios are relaxed and the optimization problem is decomposed into deterministic long-term SCUC subproblems. For each deterministic long-term SCUC, resource constraints represent fuel and emission constraints (in the case of vertically integrated utilities) and energy constraints (in the case of electricity markets). Lagrangian relaxation is used to decompose subproblems with long-term SCUC into tractable short-term MIP-based SCUC subproblems without resource constraints. Accordingly, penalty prices (Lagrangian multipliers) are signals to coordinate the master problem and small-scale subproblems. Computational requirements for solving scenario-based optimization models depend on the number of scenarios in which the objective is to minimize the weighted-average generation cost over the entire scenario tree. In large scale applications, the scenario reduction method is introduced for enhancing a tradeoff between calculation speed and accuracy of long-term SCUC solution. Numerical simulations indicate the effectiveness of the proposed approach for solving the stochastic security-constrained unit commitment

Studies on the 2019 novel coronavirus disease (COVID-19) have generally been limited to the description of the epidemiology and initial clinical characteristics. We investigated the temporal progression in patients with COVID-19.In this retrospective, single-center study, we included confirmed cases of COVID-19 from Jan 20 to Feb 6, 2020 in Shanghai. Final date of follow-up was February 25, 2020.Of the 249 patients enrolled, the median age was 51 years old, and 126 (50.6%) were male. The duration from onset of symptoms to hospitalization was 4(2-7) days in symptomatic patients. Fever was occurred in 235(94.3%) patients. A total of 215 (86.3%) patients had been discharged after 16(12-20) days hospitalization. The estimated median duration of fever in all the patients with fever was 10 days (95 confidential intervals [CIs]: 8-11 days) after onset of symptoms. Patients who were transferred to intensive care units (ICU) had significantly longer duration of fever as compared to those not in ICU (31 days v.s. 9 days after onset of symptoms, respectively, P <0.0001). Radiological aggravation of initial image was observed in 163 (65.7%) patients on day 7 after onset of symptoms. 154(94.5%) of these patients showed radiological improvement on day 14. The median duration to negative reverse-transcriptase PCR tests of upper respiratory tract samples was 11 days (95 CIs: 10-12 days). Viral clearance was more likely to be delayed in patients in ICU than those not in ICU (P <0.0001). In multivariate logistical analysis, age (Odds ratio [OR] = 1.06) and CD4 T cell count (OR = 0.55 per 100 cells/ul increase) were independently associated with ICU admission.The majority of COVID-19 cases are mild. The clinical progression pattern suggests that early control of viral replication and application of host-directed therapy in later stage is essential to improve the prognosis of CVOID-19.

Purpose The efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC. Patients and Methods From June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m 2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m 2 IV day 1, or 25 mg/m 2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival. Results The pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P &lt; .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S ( P = .212). Conclusion This trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

We report the crystal structure of a new nanocluster formulated as Au28(TBBT)20, where TBBT = 4-tert-butylbenzenethiolate. It exhibits a rod-like Au20 kernel consisting of two interpenetrating cuboctahedra. The kernel is protected by four dimeric "staples" (-SR-Au-SR-Au-SR-) and eight bridging thiolates (-SR-). The unit cell of Au28(TBBT)20 single crystals contains a pair of enantiomers. The origin of chirality is primarily rooted in the rotating arrangement of the four dimeric staples as well as the arrangement of the bridging thiolates (quasi-D2 symmetry). The enantiomers were separated by chiral HPLC and characterized by circular dichroism spectroscopy.

A golden opportunity: The total structure of a Au36(SR)24 nanocluster (see figure) reveals an unexpected face-centered-cubic tetrahedral Au28 kernel (magenta). The protecting layer exhibits an intriguing combination of binding modes, consisting of four regular arch-like staples and the unprecedented appearance of twelve bridging thiolates (yellow). This unique protecting network and superatom electronic shell structure confer extreme stability and robustness.

The rod-shaped Au25 nanocluster possesses a low photoluminescence quantum yield (QY=0.1%) and hence is not of practical use in bioimaging and related applications. Herein, we show that substituting silver atoms for gold in the 25-atom matrix can drastically enhance the photoluminescence. The obtained Ag(x)Au(25-x) (x=1-13) nanoclusters exhibit high quantum yield (QY=40.1%), which is in striking contrast with the normally weakly luminescent Ag(x)Au(25-x) species (x=1-12, QY=0.21%). X-ray crystallography further determines the substitution sites of Ag atoms in the Ag(x)Au(25-x) cluster through partial occupancy analysis, which provides further insight into the mechanism of photoluminescence enhancement.

To evaluate the efficacy and safety of hydroxychloroquine (HCQ) in the treatment of patients with moderate coronavirus disease 2019 (COVID-19).We prospectively enrolled 30 treatment-naïve patients with confirmed COVID-19 after informed consent at Shanghai Public Health Clinical Center. The patients were randomized 1：1 to HCQ group and the control group. Patients in HCQ group were given HCQ 400 mg per day for 5 days plus conventional treatments, while those in the control group were given conventional treatment only. The primary endpoint was negative conversion rate of SARS-CoV-2 nucleic acid in respiratory pharyngeal swab on days 7 after randomization. This study has been approved by the Ethics Committee of Shanghai Public Health Clinical Center and registered online (NCT04261517).One patient in HCQ group developed to severe during the treatment. On day 7, nucleic acid of throat swabs was negative in 13 (86.7%) cases in the HCQ group and 14 (93.3%) cases in the control group (P>0.05). The median duration from hospitalization to virus nucleic acid negative conservation was 4 (1,9) days in HCQ group, which is comparable to that in the control group [2 (1,4) days, Z=1.27, P>0.05]. The median time for body temperature normalization in HCQ group was 1 (0,2) day after hospitalization, which was also comparable to that in the control group [1 (0,3) day]. Radiological progression was shown on CT images in 5 cases (33.3%) of the HCQ group and 7 cases (46.7%) of the control group, and all patients showed improvement in follow-up examinations. Four cases (26.7%) of the HCQ group and 3 cases (20%) of the control group had transient diarrhea and abnormal liver function (P>0.05).The prognosis of COVID-19 moderate patients is good. Larger sample size study are needed to investigate the effects of HCQ in the treatment of COVID-19. Subsequent research should determine better endpoint and fully consider the feasibility of experiments such as sample size.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Older adults are vulnerable at the onset of natural disasters and crisis, and this has been especially true during the coronavirus disease 2019 (COVID-19) pandemic.1 With the aggressive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the death toll has risen worldwide. According to an interactive online tool that estimates the potential number of deaths from COVID-19 in a population, by age group, in individual countries and regional groupings worldwide under a range of scenarios, most of those who have died were older adults, most of whom had underlying health problems.

In the Internet age, malware (such as viruses, trojans, ransomware, and bots) has posed serious and evolving security threats to Internet users. To protect legitimate users from these threats, anti-malware software products from different companies, including Comodo, Kaspersky, Kingsoft, and Symantec, provide the major defense against malware. Unfortunately, driven by the economic benefits, the number of new malware samples has explosively increased: anti-malware vendors are now confronted with millions of potential malware samples per year. In order to keep on combating the increase in malware samples, there is an urgent need to develop intelligent methods for effective and efficient malware detection from the real and large daily sample collection. In this article, we first provide a brief overview on malware as well as the anti-malware industry, and present the industrial needs on malware detection. We then survey intelligent malware detection methods. In these methods, the process of detection is usually divided into two stages: feature extraction and classification/clustering . The performance of such intelligent malware detection approaches critically depend on the extracted features and the methods for classification/clustering. We provide a comprehensive investigation on both the feature extraction and the classification/clustering techniques. We also discuss the additional issues and the challenges of malware detection using data mining techniques and finally forecast the trends of malware development.

Gene transcription may be regulated by remote enhancer or insulator regions through chromosome looping. Using a modification of chromosome conformation capture (3C) and fluorescence in situ hybridization, we found that one allele of the insulin-like growth factor 2 ( Igf2 )/ H19 imprinting control region (ICR) on chromosome 7 colocalized with one allele of Wsb1/Nf1 on chromosome 11. Omission of CCCTC-binding factor (CTCF) or deletion of the maternal ICR abrogated this association and altered Wsb1/Nf1 gene expression. These findings demonstrate that CTCF mediates an interchromosomal association, perhaps by directing distant DNA segments to a common transcription factory, and the data provide a model for long-range allele-specific associations between gene regions on different chromosomes that suggest a framework for DNA recombination and RNA trans-splicing.

Direct electrochemical conversion of CO2 to ethanol offers a promising strategy to lower CO2 emissions while storing energy from renewable electricity. However, current electrocatalysts offer only limited selectivity toward ethanol. Here we report a carbon-supported copper (Cu) catalyst, synthesized by an amalgamated Cu–Li method, that achieves a single-product Faradaic efficiency (FE) of 91% at −0.7 V (versus the reversible hydrogen electrode) and onset potential as low as −0.4 V (reversible hydrogen electrode) for electrocatalytic CO2-to-ethanol conversion. The catalyst operated stably over 16 h. The FE of ethanol was highly sensitive to the initial dispersion of Cu atoms and decreased significantly when CuO and large Cu clusters become predominant species. Operando X-ray absorption spectroscopy identified a reversible transformation from atomically dispersed Cu atoms to Cun clusters (n = 3 and 4) on application of electrochemical conditions. First-principles calculations further elucidate the possible catalytic mechanism of CO2 reduction over Cun. Electrocatalytically reducing CO2 to ethanol can provide renewably generated fuel, but catalysts are often poorly selective for this conversion. Here the authors use a Cu catalyst to produce ethanol with high selectivity. Cu dispersion is key to the performance and operando studies indicate that it changes under reaction conditions.

Osteoarthritis (OA) is the most common disabling joint disease throughout the world and its therapeutic effect is still not satisfactory in clinic nowadays. Recent studies showed that the exosomes derived from several types of mesenchymal stem cells (MSCs) could maintain chondrocyte homeostasis and ameliorate the pathological severity of OA in animal models, indicating that MSCs-derived exosomes could be a novel promising strategy for treating OA. In this study, we investigated the role and underlying mechanisms of infrapatellar fat pad (IPFP) MSCs-derived exosomes (MSCIPFP-Exos) on OA in vitro and in vivo. Our data revealed that MSCIPFP could produce amounts of MSCIPFP-Exos, which exhibited the typical morphological features of exosomes. The MSCIPFP-Exos ameliorated the OA severity in vivo and inhibited cell apoptosis, enhanced matrix synthesis and reduced the expression of catabolic factor in vitro. Moreover, MSCIPFP-Exos could significantly enhance autophagy level in chondrocytes partially via mTOR inhibition. Exosomal RNA-seq showed that the level of miR-100-5p that could bind to the 3′-untranslated region (3′UTR) of mTOR was the highest among microRNAs. MSCIPFP-Exos decreased the luciferase activity of mTOR 3′UTR, while inhibition of miR-100-5p could reverse the MSCIPFP-Exos-decreased mTOR signaling pathway. Intra-articular injection of antagomir-miR-100-5p dramatically attenuated MSCIPFP-Exos-mediated protective effect on articular cartilage in vivo. In brief, MSCIPFP-derived exosomes protect articular cartilage from damage and ameliorate gait abnormality in OA mice by maintaining cartilage homeostasis, the mechanism of which may be related to miR100-5p-regulated inhibition of mTOR-autophagy pathway. As it is relatively feasible to obtain human IPFP from OA patients by arthroscopic operation in clinic, MSCIPFP-derived exosomes may be a potential therapy for OA in the future.

Prostate cancer is one of the most common malignant cancers in men. Recent studies have shown that microRNA-21 (miR-21) is overexpressed in various types of cancers including prostate cancer. Studies on glioma, colon cancer cells, hepatocellular cancer cells and breast cancer cells have indicated that miR-21 is involved in tumor growth, invasion and metastasis. However, the roles of miR-21 in prostate cancer are poorly understood. In this study, the effects of miR-21 on prostate cancer cell proliferation, apoptosis, and invasion were examined. In addition, the targets of miR-21 were identified by a reported RISC-coimmunoprecipitation-based biochemical method. Inactivation of miR-21 by antisense oligonucleotides in androgen-independent prostate cancer cell lines DU145 and PC-3 resulted in sensitivity to apoptosis and inhibition of cell motility and invasion, whereas cell proliferation were not affected. We identified myristoylated alanine-rich protein kinase c substrate (MARCKS), which plays key roles in cell motility, as a new target in prostate cancer cells. Our data suggested that miR-21 could promote apoptosis resistance, motility, and invasion in prostate cancer cells and these effects of miR-21 may be partly due to its regulation of PDCD4, TPM1, and MARCKS. Gene therapy using miR-21 inhibition strategy may therefore be useful as a prostate cancer therapy.

Predicting rice (Oryza sativa) productivity under future climates is important for global food security. Ecophysiological crop models in combination with climate model outputs are commonly used in yield prediction, but uncertainties associated with crop models remain largely unquantified. We evaluated 13 rice models against multi-year experimental yield data at four sites with diverse climatic conditions in Asia and examined whether different modeling approaches on major physiological processes attribute to the uncertainties of prediction to field measured yields and to the uncertainties of sensitivity to changes in temperature and CO2 concentration [CO2 ]. We also examined whether a use of an ensemble of crop models can reduce the uncertainties. Individual models did not consistently reproduce both experimental and regional yields well, and uncertainty was larger at the warmest and coolest sites. The variation in yield projections was larger among crop models than variation resulting from 16 global climate model-based scenarios. However, the mean of predictions of all crop models reproduced experimental data, with an uncertainty of less than 10% of measured yields. Using an ensemble of eight models calibrated only for phenology or five models calibrated in detail resulted in the uncertainty equivalent to that of the measured yield in well-controlled agronomic field experiments. Sensitivity analysis indicates the necessity to improve the accuracy in predicting both biomass and harvest index in response to increasing [CO2 ] and temperature.

Content-based music genre classification is a fundamental component of music information retrieval systems and has been gaining importance and enjoying a growing amount of attention with the emergence of digital music on the Internet. Currently little work has been done on automatic music genre classification, and in addition, the reported classification accuracies are relatively low. This paper proposes a new feature extraction method for music genre classification, DWCHs. DWCHs stands for Daubechies Wavelet Coefficient Histograms. DWCHs capture the local and global information of music signals simultaneously by computing histograms on their Daubechies wavelet coefficients. Effectiveness of this new feature and of previously studied features are compared using various machine learning classification algorithms, including Support Vector Machines and Linear Discriminant Analysis. It is demonstrated that the use of DWCHs significantly improves the accuracy of music genre classification.

<h2>Summary</h2> The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed. Notably, the susceptibility of the 501Y.V2 variants to 12 of 17 neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced for these variants. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of spike. The enhanced infectivity in murine ACE2-overexpressing cells suggests the possibility of spillover of the 501Y.V2 variants to mice. Moreover, the neutralization resistance we detected for the 501Y.V2 variants suggests the potential for compromised efficacy of monoclonal antibodies and vaccines.

Many infections and stress signals can rapidly activate the NLRP3 inflammasome to elicit robust inflammatory responses. This activation requires a priming step, which is thought to be mainly for upregulating NLRP3 transcription. However, recent studies report that the NLRP3 inflammasome can be activated independently of transcription, suggesting that the priming process has unknown essential regulatory steps. Here, we report that JNK1-mediated NLRP3 phosphorylation at S194 is a critical priming event and is essential for NLRP3 inflammasome activation. We show that NLRP3 inflammasome activation is disrupted in NLRP3-S194A knockin mice. JNK1-mediated NLRP3 S194 phosphorylation is critical for NLRP3 deubiquitination and facilitates its self-association and the subsequent inflammasome assembly. Importantly, we demonstrate that blocking S194 phosphorylation prevents NLRP3 inflammasome activation in cryopyrin-associated periodic syndromes (CAPS). Thus, our study reveals a key priming molecular event that is a prerequisite for NLRP3 inflammasome activation. Inhibiting NLRP3 phosphorylation could be an effective treatment for NLRP3-related diseases.

The efficiencies of perovskite solar cells (PSCs) are now reaching such consistently high levels that scalable manufacturing at low cost is becoming critical. However, this remains challenging due to the expensive hole-transporting materials usually employed, and difficulties associated with the scalable deposition of other functional layers. By simplifying the device architecture, hole-transport-layer-free PSCs with improved photovoltaic performance are fabricated via a scalable doctor-blading process. Molecular doping of halide perovskite films improved the conductivity of the films and their electronic contact with the conductive substrate, resulting in a reduced series resistance. It facilitates the extraction of photoexcited holes from perovskite directly to the conductive substrate. The bladed hole-transport-layer-free PSCs showed a stabilized power conversion efficiency above 20.0%. This work represents a significant step towards the scalable, cost-effective manufacturing of PSCs with both high performance and simple fabrication processes.

The emergence of Omicron/BA.1 has brought new challenges to fight against SARS-CoV-2. A large number of mutations in the Spike protein suggest that its susceptibility to immune protection elicited by the existing COVID-19 infection and vaccines may be altered. In this study, we constructed the pseudotyped SARS-CoV-2 variant Omicron. The sensitivity of 28 serum samples from COVID-19 convalescent patients infected with SARS-CoV-2 original strain was tested against pseudotyped Omicron as well as the other variants of concern (VOCs, Alpha, Beta, Gamma, Delta) and variants of interest (VOIs, Lambda, Mu). Our results indicated that the mean neutralization ED50 of these sera against Omicron decreased to 66, which is about 8.4-folds compared to the D614G reference strain (ED50 = 556), whereas the neutralization activity of other VOC and VOI pseudotyped viruses decreased only about 1.2-4.5-folds. The finding from our in vitro assay suggest that Omicron variant may lead to more significant escape from immune protection elicited by previous SARS-CoV-2 infection and perhaps even by existing COVID-19 vaccines.

Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural system effects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophrenia before and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments.To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episode schizophrenia before and after treatment with second-generation antipsychotic medication.Case-control study.Huaxi MR Research Center and Mental Health Centre of the West China Hospital.Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echo echo-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-four matched healthy control subjects were studied at baseline for comparison purposes.The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration.After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF.We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs.

Sex differences in schizophrenia are well known, but their genetic basis has not been identified. We performed a genome-wide association scan for schizophrenia in an Ashkenazi Jewish population using DNA pooling. We found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin (RELN) gene (p = 2.9 x 10(-5) in women), with a significant gene-sex effect (p = 1.8 x 10(-4)). We studied rs7341475 in four additional populations, totaling 2,274 cases and 4,401 controls. A significant effect was observed only in women, replicating the initial result (p = 2.1 x 10(-3) in women; p = 4.2 x 10(-3) for gene-sex interaction). Based on all populations the estimated relative risk of women carrying the common genotype is 1.58 (p = 8.8 x 10(-7); p = 1.6 x 10(-5) for gene-sex interaction). The female-specific association between RELN and schizophrenia is one of the few examples of a replicated sex-specific genetic association in any disease.

On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9.We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome.All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment.Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning.National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.

We report the X-ray structure of a cyclohexanethiolate-capped [Au23(SR)16](-) nanocluster (counterion: tetraoctylammonium, TOA(+)). The structure comprises a cuboctahedron-based bipyramidal Au15 kernel, which is protected by two staple-like trimeric Au3(SR)4 motifs, two monomeric Au(SR)2 and four plain bridging SR ligands. Electronic structure analysis reveals nonsuperatomic feature of [Au23(SR)16](-) and confirms the Au15 kernel and surface motifs. The Au15 kernel and trimeric staple motif are unprecedented and offer new insight in understanding the structure evolution of gold nanoclusters.

Sending data to the cloud for analysis was a prominent trend during the past decades, driving cloud computing as a dominant computing paradigm. However, the dramatically increasing number of devices and data traffic in the Internet-of-Things (IoT) era are posing significant burdens on the capacity-limited Internet and uncontrollable service delay. It becomes difficult to meet the delay-sensitive and context-aware service requirements of IoT applications by using cloud computing alone. Facing these challenges, computing paradigms are shifting from the centralized cloud computing to distributed edge computing. Several new computing paradigms, including Transparent Computing, Mobile Edge Computing, Fog Computing, and Cloudlet, have emerged to leverage the distributed resources at network edge to provide timely and context-aware services. By integrating end devices, edge servers, and cloud, they form a hierarchical IoT architecture, i.e., End-Edge-Cloud orchestrated architecture to improve the performance of IoT systems. This article presents a comprehensive survey of these emerging computing paradigms from the perspective of end-edge-cloud orchestration. Specifically, we first introduce and compare the architectures and characteristics of different computing paradigms. Then, a comprehensive survey is presented to discuss state-of-the-art research in terms of computation offloading, caching, security, and privacy. Finally, some potential research directions are envisioned for fostering continuous research efforts.

A stepwise ligand exchange strategy is utilized to prepare a series of isoreticular bio-MOF-100 analogues. Specifically, in situ ligand exchange with progressively longer dicarboxylate linkers is performed on single crystalline starting materials to synthesize products with progressively larger mesoporous cavities. The new members of this series of materials, bio-MOFs 101–103, each exhibit permanent mesoporosity and pore sizes ranging from ∼2.1–2.9 nm and surface areas ranging from 2704 to 4410 m2/g. The pore volume for bio-MOF 101 is 2.83 cc/g. Bio-MOF-102 and 103 have pore volumes of 4.36 and 4.13 cc/g, respectively. Collectively, these data establish this unique family of MOFs as one of the most porous reported to date.

In China, many species of edible wild-grown mushrooms are appreciated as food and also found use in traditional Chinese medicine. In this mini-review, for the first time, is summarized and discussed data available on chemical components of nutritional significance for wild-grown mushrooms collected from China. We aimed to update and discuss the latest data published on ash, fat, carbohydrates, fibre, proteins, essential amino acids and nonessential amino acids, some essential (P, K, Na, Ca, Mg, Fe, Mn, Zn, Cu) and toxic elements (As, Hg, Cd, Pb), vitamins (thiamine, riboflavin, niacin, tocopherol, vitamin D), flavour and taste compounds, antioxidants and also on less studied organic compounds (lectin, adustin, ribonuclease and nicotine) contents of wild-grown mushrooms.

The contribution of cloud computing and mobile computing technologies lead to the newly emerging mobile cloud computing paradigm. Three major approaches have been proposed for mobile cloud applications: 1) extending the access to cloud services to mobile devices; 2) enabling mobile devices to work collaboratively as cloud resource providers; 3) augmenting the execution of mobile applications on portable devices using cloud resources. In this paper, we focus on the third approach in supporting mobile data stream applications. More specifically, we study how to optimize the computation partitioning of a data stream application between mobile and cloud to achieve maximum speed/throughput in processing the streaming data. To the best of our knowledge, it is the first work to study the partitioning problem for mobile data stream applications, where the optimization is placed on achieving high throughput of processing the streaming data rather than minimizing the makespan of executions as in other applications. We first propose a framework to provide runtime support for the dynamic computation partitioning and execution of the application. Different from existing works, the framework not only allows the dynamic partitioning for a single user but also supports the sharing of computation instances among multiple users in the cloud to achieve efficient utilization of the underlying cloud resources. Meanwhile, the framework has better scalability because it is designed on the elastic cloud fabrics. Based on the framework, we design a genetic algorithm for optimal computation partition. Both numerical evaluation and real world experiment have been performed, and the results show that the partitioned application can achieve at least two times better performance in terms of throughput than the application without partitioning.

Clinical studies and mathematical models predict that, to achieve malaria elimination, combination therapies will need to incorporate drugs that block the transmission of Plasmodium falciparum sexual stage parasites to mosquito vectors. Efforts to measure the activity of existing antimalarials on intraerythrocytic sexual stage gametocytes and identify transmission-blocking agents have, until now, been hindered by a lack of quantitative assays. Here, we report an experimental system using P. falciparum lines that stably express gametocyte-specific GFP-luciferase reporters, which enable the assessment of dose- and time-dependent drug action on gametocyte maturation and transmission. These studies reveal activity of the first-line antimalarial dihydroartemisinin and the partner drugs lumefantrine and pyronaridine against early gametocyte stages, along with moderate inhibition of mature gametocyte transmission to Anopheles mosquitoes. The other partner agents monodesethyl-amodiaquine and piperaquine showed activity only against immature gametocytes. Our data also identify methylene blue as a potent inhibitor of gametocyte development across all stages. This thiazine dye almost fully abolishes P. falciparum transmission to mosquitoes at concentrations readily achievable in humans, highlighting the potential of this chemical class to reduce the spread of malaria.

Background In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012–15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. Methods The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age–sex–residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. Findings 28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20–1·72] and 12-month prevalence OR 1·41 [1·12–1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68–3·38] and 12-month OR 2·80 [95% CI 1·88–4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39–2·51] and 12-month OR 1·85 [95% CI 1·40–2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. Interpretation Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. Funding National Health Commission and Ministry of Science and Technology of People's Republic of China. Translation For the Chinese translation of the abstract see Supplementary Materials section.

Highly dispersed palladium chloride catalysts locked in triphenylphosphine-functionalized knitting aryl network polymers (KAPs) are developed and exhibit excellent activity under mild conditions in the Suzuki–Miyaura cross-coupling reactions of aryl chlorides in aqueous media. This work highlights that the microporous polymers not only play the role of support materials, but also protect the Pd species from aggregation and precipitation, hence, positively effect the catalysis activity. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Population stratification is a potential problem for genome-wide association studies (GWAS), confounding results and causing spurious associations. Hence, understanding how allele frequencies vary across geographic regions or among subpopulations is an important prelude to analyzing GWAS data. Using over 350,000 genome-wide autosomal SNPs in over 6000 Han Chinese samples from ten provinces of China, our study revealed a one-dimensional "north-south" population structure and a close correlation between geography and the genetic structure of the Han Chinese. The north-south population structure is consistent with the historical migration pattern of the Han Chinese population. Metropolitan cities in China were, however, more diffused "outliers," probably because of the impact of modern migration of peoples. At a very local scale within the Guangdong province, we observed evidence of population structure among dialect groups, probably on account of endogamy within these dialects. Via simulation, we show that empirical levels of population structure observed across modern China can cause spurious associations in GWAS if not properly handled. In the Han Chinese, geographic matching is a good proxy for genetic matching, particularly in validation and candidate-gene studies in which population stratification cannot be directly accessed and accounted for because of the lack of genome-wide data, with the exception of the metropolitan cities, where geographical location is no longer a good indicator of ancestral origin. Our findings are important for designing GWAS in the Chinese population, an activity that is expected to intensify greatly in the near future.

This paper proposes an integrated model for assessing the impact of interdependency of electricity and natural gas networks on power system security. The integrated model incorporates the natural gas network constraints into the optimal solution of security-constrained unit commitment. The natural gas network is modeled by daily and hourly limits on pipelines, sub-areas, plants, and generating units. The application of fuel diversity (e.g., generating units with fuel switching capability) is presented as an effective peak shaving strategy for natural gas demand which could hedge price volatilities of natural gas and electric power. The proposed model can be used by a vertically integrated utility for the commitment and dispatch of generating units and the allocation of natural gas for the next day utilization. The proposed model can also be used for measuring the security of social services by modeling the interdependency of natural gas and electric power system infrastructures. If the proposed model is used by GENCOs, gas constraints will be submitted to electricity markets as energy constraints. Illustrative examples show the impact of natural gas supply infrastructure on the economic operation of a vertically integrated utility. The examples also discuss the impact of generating units with fuel switching capability on the power system security when the supply of natural gas is limited.

Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity. Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation. Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury. Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome. These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.

Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.

Mercury ion (Hg2+) is able to specifically bind to the thymine–thymine (T–T) base pair in a DNA duplex and single-walled carbon nanotubes (SWNTs) can effectively quench fluorescence of the dye tethered to the DNA, which enables fluorescent detection of Hg2+ in aqueous solution with high selectivity and sensitivity.

Abstract Lithium (Li) metal‐based battery is among the most promising candidates for next‐generation rechargeable high‐energy‐density batteries. Carbon materials are strongly considered as the host of Li metal to relieve the powdery/dendritic Li formation and large volume change during repeated cycles. Herein, we describe the formation of a thin lithiophilic LiC 6 layer between carbon fibers (CFs) and metallic Li in Li/CF composite anode obtained through a one‐step rolling method. An electron deviation from Li to carbon elevates the negativity of carbon atoms after Li intercalation as LiC 6 , which renders stronger binding between carbon framework and Li ions. The Li/CF | Li/CF batteries can operate for more than 90 h with a small polarization voltage of 120 mV at 50% discharge depth. The Li/CF | sulfur pouch cell exhibits a high discharge capacity of 3.25 mAh cm −2 and a large capacity retention rate of 98% after 100 cycles at 0.1 C. It is demonstrated that the as‐obtained Li/CF composite anode with lithiophilic LiC 6 layers can effectively alleviate volume expansion and hinder dendritic and powdery morphology of Li deposits. This work sheds fresh light on the role of interfacial layers between host structure and Li metal in composite anode for long‐lifespan working batteries.

The COVID-19 cases increased very fast in January and February 2020. The mortality among critically ill patients, especially the elder ones, is relatively high. Considering many patients died of severe inflammation response, it is urgent to develop effective therapeutic strategies for these patients. The human umbilical cord mesenchymal stem cells (hUCMSCs) have shown good capabilities to modulate the immune response and repair the injured tissue. Therefore, investigating the potential of hUCMSCs to the treatment of COVID-19 critically ill patients is necessary.A 65-year-old woman felt fatigued and had a fever with body temperature of 38.2C, coughed up white foaming sputum. After 1 day, she had chest tightness with SPO2 of 81%, and blood pressure of 160/91 mm Hg.According to the guideline for the diagnosis and treatment of 2019 novel coronavirus infected pneumonia (Trial 4th Edition), COVID-19 was diagnosed, based on the real-time RT-PCR test of SARS-CoV-2.After regular treatment for 12 days, the inflammation symptom of the patient was still very severe and the potential side effects of corticosteroid were observed. Then, allogenic hUCMSCs were given 3 times (5 × 10 cells each time) with a 3-day interval, together with thymosin α1 and antibiotics daily injection.After these treatments, most of the laboratory indexes and CT images showed remission of the inflammation symptom. The patient was subsequently transferred out of ICU, and the throat swabs test reported negative 4 days later.These results indicated the clinical outcome and good tolerance of allogenic hUCMSCs transfer.

The rapid convergence of legacy industrial infrastructures with intelligent networking and computing technologies (e.g., 5G, software-defined networking, and artificial intelligence), have dramatically increased the attack surface of industrial cyber-physical systems (CPSs). However, withstanding cyber threats to such large-scale, complex, and heterogeneous industrial CPSs has been extremely challenging, due to the insufficiency of high-quality attack examples. In this article, we propose a novel federated deep learning scheme, named DeepFed, to detect cyber threats against industrial CPSs. Specifically, we first design a new deep learning-based intrusion detection model for industrial CPSs, by making use of a convolutional neural network and a gated recurrent unit. Second, we develop a federated learning framework, allowing multiple industrial CPSs to collectively build a comprehensive intrusion detection model in a privacy-preserving way. Further, a Paillier cryptosystem-based secure communication protocol is crafted to preserve the security and privacy of model parameters through the training process. Extensive experiments on a real industrial CPS dataset demonstrate the high effectiveness of the proposed DeepFed scheme in detecting various types of cyber threats to industrial CPSs and the superiorities over state-of-the-art schemes.

Diabetic retinopathy (DR), the leading cause of blindness for working-age adults, is generally intervened by early screening to reduce vision loss. A series of automated deep-learning-based algorithms for DR screening have been proposed and achieved high sensitivity and specificity ( > 90%). However, these deep learning models do not perform well in clinical applications due to the limitations of the existing publicly available fundus image datasets. In order to evaluate these methods in clinical situations, we collected 13,673 fundus images from 9598 patients. These images were divided into six classes by seven graders according to image quality and DR level. Moreover, 757 images with DR were selected to annotate four types of DR-related lesions. Finally, we evaluated state-of-the-art deep learning algorithms on collected images, including image classification, semantic segmentation and object detection. Although we obtain an accuracy of 0.8284 for DR classification, these algorithms perform poorly on lesion segmentation and detection, indicating that lesion segmentation and detection are quite challenging. In summary, we are providing a new dataset named DDR for assessing deep learning models and further exploring the clinical applications, particularly for lesion recognition.

The design of a core-shell metal-organic framework comprising a porous bio-MOF-11/14 mixed core and a less porous bio-MOF-14 shell is reported. The growth of the MOF shell was directly observed and supported by SEM and PXRD. The resulting core-shell material exhibits 30% higher CO2 uptake than bio-MOF-14 and low N2 uptake in comparison to the core. When the core-shell architecture is destroyed by fracturing the crystallites via grinding, the amount of N2 adsorbed doubles but the CO2 adsorption capacity remains the same. Finally, the more water stable bio-MOF-14 shell serves to prevent degradation of the water-sensitive core in aqueous environments, as evidenced by SEM and PXRD.

Non-negative Matrix Factorization (NMF) and Probabilistic Latent Semantic Indexing (PLSI) have been successfully applied to document clustering recently. In this paper, we show that PLSI and NMF (with the I-divergence objective function) optimize the same objective function, although PLSI and NMF are different algorithms as verified by experiments. This provides a theoretical basis for a new hybrid method that runs PLSI and NMF alternatively, each jumping out of the local minima of the other method successively, thus achieving a better final solution. Extensive experiments on five real-life datasets show relations between NMF and PLSI, and indicate that the hybrid method leads to significant improvements over NMF-only or PLSI-only methods. We also show that at first-order approximation, NMF is identical to the χ2-statistic.

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the 'one child policy' and the 'empty-nest elderly' phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of 'exercising more, eating less', while other anti-ageing molecules from molecular gerontologists could help to improve 'healthspan' in the elderly. Machine learning, 'Big Data', and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).

Despite progress in the diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. In this study, we globally assessed long noncoding RNAs (lncRNA) for contributions to HCC using publicly available microarray data, in vitro and in vivo assays. Here, we report that ZFAS1, encoding a lncRNA that is frequently amplified in HCC, is associated with intrahepatic and extrahepatic metastasis and poor prognosis of HCC. ZFAS1 functions as an oncogene in HCC progression by binding miR-150 and abrogating its tumor-suppressive function in this setting. miR-150 repressed HCC cell invasion by inhibiting ZEB1 and the matrix metalloproteinases MMP14 and MMP16. Conversely, ZFAS1 activated ZEB1, MMP14, and MMP16 expression, inhibiting these effects of miR-150. Our results establish a function for ZFAS1 in metastatic progression and suggest its candidacy as a new prognostic biomarker and target for clinical management of HCC.

Photoinduced electron transfer (PET) has been observed for the first time between DNA/Ag fluorescent nanoclusters (NCs) and G-quadruplex/hemin complexes, accompanied by a decrease in the fluorescence of the DNA/Ag NCs. In this PET process, a parallel G-quadruplex and the sensing sequences are blocked by a duplex. The specific combination of targets with the sensing sequence triggers the release of the G-quadruplex and allows it to fold properly and bind hemin to form a stable G-quadruplex/hemin complex. The complex proves favorable for PET because it makes the G-quadruplex bind hemin tightly, which promotes the electron transfer from the DNA/Ag NCs to the hemin FeIII center, thus resulting in a decrease in the fluorescence intensity of the DNA/Ag NCs. This novel PET system enables the specific and versatile detection of target biomolecules such as DNA and ATP with high sensitivity based on the choices of different target sequences.

Membranes with fast and selective ion transport are widely used for water purification and devices for energy conversion and storage including fuel cells, redox flow batteries and electrochemical reactors. However, it remains challenging to design cost-effective, easily processed ion-conductive membranes with well-defined pore architectures. Here, we report a new approach to designing membranes with narrow molecular-sized channels and hydrophilic functionality that enable fast transport of salt ions and high size-exclusion selectivity towards small organic molecules. These membranes, based on polymers of intrinsic microporosity containing Tröger’s base or amidoxime groups, demonstrate that exquisite control over subnanometre pore structure, the introduction of hydrophilic functional groups and thickness control all play important roles in achieving fast ion transport combined with high molecular selectivity. These membranes enable aqueous organic flow batteries with high energy efficiency and high capacity retention, suggesting their utility for a variety of energy-related devices and water purification processes. Ion-selective membranes are widely used for water purification and electrochemical energy devices but designing their pore architectures is challenging. Membranes with narrow channels and hydrophilic functionality are shown to exhibit salt ions transport and selectivity towards small organic molecules.

We have created unique near-infrared (NIR)-emitting nanoscale metal-organic frameworks (nano-MOFs) incorporating a high density of Yb(3+) lanthanide cations and sensitizers derived from phenylene. We establish here that these nano-MOFs can be incorporated into living cells for NIR imaging. Specifically, we introduce bulk and nano-Yb-phenylenevinylenedicarboxylate-3 (nano-Yb-PVDC-3), a unique MOF based on a PVDC sensitizer-ligand and Yb(3+) NIR-emitting lanthanide cations. This material has been structurally characterized, its stability in various media has been assessed, and its luminescent properties have been studied. We demonstrate that it is stable in certain specific biological media, does not photobleach, and has an IC50 of 100 μg/mL, which is sufficient to allow live cell imaging. Confocal microscopy and inductively coupled plasma measurements reveal that nano-Yb-PVDC-3 can be internalized by cells with a cytoplasmic localization. Despite its relatively low quantum yield, nano-Yb-PVDC-3 emits a sufficient number of photons per unit volume to serve as a NIR-emitting reporter for imaging living HeLa and NIH 3T3 cells. NIR microscopy allows for highly efficient discrimination between the nano-MOF emission signal and the cellular autofluorescence arising from biological material. This work represents a demonstration of the possibility of using NIR lanthanide emission for biological imaging applications in living cells with single-photon excitation.

Abstract This article reviews recent progress leading to the generation of optical vortex beams. After introducing the basics of optical vortex beams and their promising applications, we summarized different approaches for optical vortex generation by discrete components and laser cavities. We place particular emphasis on the recent development of vortex generation by the planar phase plates, which are able to engineer a spiral phasefront via dynamic or geometric phase in nanoscale, and highlight the independent operation of these two different phases which leads to a multifunctional optical vortex beam generation and independent spin-orbit interaction. We also introduced the recent progress on vortex lasing, including vortex beam generation from the output of bulk lasers by modification of conventional laser cavities with phase elements and from integrated on-chip microlasers. Similar approaches are also applied to generate fractional vortex beams carrying fractional topological charge. The advanced technology and approaches on design and nanofabrications enable multiple vortex beams generation from a single device via multiplexing, multicasting, and vortex array, open up opportunities for applications on data processing, information encoding/decoding, communication and parallel data processing, and micromanipulations.

Multi-document summarization aims to create a compressed summary while retaining the main characteristics of the original set of documents. Many approaches use statistics and machine learning techniques to extract sentences from documents. In this paper, we propose a new multi-document summarization framework based on sentence-level semantic analysis and symmetric non-negative matrix factorization. We first calculate sentence-sentence similarities using semantic analysis and construct the similarity matrix. Then symmetric matrix factorization, which has been shown to be equivalent to normalized spectral clustering, is used to group sentences into clusters. Finally, the most informative sentences are selected from each group to form the summary. Experimental results on DUC2005 and DUC2006 data sets demonstrate the improvement of our proposed framework over the implemented existing summarization systems. A further study on the factors that benefit the high performance is also conducted.

Low-temperature methane reactions Methane is a potential feedstock for more valuable products. The strong carbon-hydrogen bonds of methane can be activated by heterogeneous catalysts but often at temperatures that make it difficult to control reactions selectively. Liang et al. show that methane, adsorbed on the stoichiometric IrO 2 (110) under ultrahigh-vacuum conditions, reacts with exposed iridium atoms to break the carbon-hydrogen bonds at temperatures as low as 150 K. On heating, the surface fragments react cleanly with surface oxygen to form carbon dioxide, carbon monoxide, and water. Science , this issue p. 299

Nanogap electrodes (namely, a pair of electrodes with a nanometer gap) are fundamental building blocks for the fabrication of nanometer-sized devices and circuits. They are also important tools for the examination of material properties at the nanometer scale, even at the molecular scale. In this review, the techniques for the fabrication of nanogap electrodes, the preparation of assembled devices based on the nanogap electrodes, and the potential application of these nanodevices for analysis of material properties are introduced. The history, the research status, and the prospects of nanogap electrodes are also discussed.

The preparation of nano-sized H[Zn, Al]ZSM-5 zeolite by direct synthesis procedure and its application in the aromatization of methanol were studied. SEM, XRD, and N2 adsorption–desorption data show that H[Zn, Al]ZSM-5 zeolite was composed of aggregates of 250 nm × 50 nm × 25 nm crystals with about 2.1 nm inter-crystal voids. NH3-TPD, pyridine-FTIR, and UV–Vis spectral analyses were also employed to understand the properties of zeolite catalysts prepared by different methods. TGA results confirmed that the nano-structure was resistant to coke in the reaction. BTX yield and catalytic stability were improved in the conversion of methanol over H[Zn, Al]ZSM-5 zeolite. The BTX yield on H[Zn, Al]ZSM-5 was 48% at 437 °C and weight hourly space velocity of 0.8 h−1, slightly decreasing to 32% after 160 h on stream. The ramping rate in the calcinations significantly affected the acidic and catalytic properties of the zeolite. H[Zn, Al]ZSM-5 calcinated at a rate of 1 °C/min showed less Lewis sites, higher BTX yield, and longer lifetime compared to H[Zn, Al]ZSM-5/T calcinated at a rate of 30 °C/min.

Advanced Energy MaterialsVolume 6, Issue 19 1601128 Communication Efficient Semitransparent Perovskite Solar Cells for 23.0%-Efficiency Perovskite/Silicon Four-Terminal Tandem Cells Bo Chen, Bo Chen Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorYang Bai, Yang Bai Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorZhengshan Yu, Zhengshan Yu School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorTao Li, Tao Li Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorXiaopeng Zheng, Xiaopeng Zheng Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorQingfeng Dong, Qingfeng Dong Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorLiang Shen, Liang Shen Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorMathieu Boccard, Mathieu Boccard School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorAlexei Gruverman, Alexei Gruverman Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorZachary Holman, Zachary Holman School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorJinsong Huang, Corresponding Author Jinsong Huang jhuang2@unl.edu Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USAE-mail: jhuang2@unl.eduSearch for more papers by this author Bo Chen, Bo Chen Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorYang Bai, Yang Bai Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorZhengshan Yu, Zhengshan Yu School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorTao Li, Tao Li Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorXiaopeng Zheng, Xiaopeng Zheng Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorQingfeng Dong, Qingfeng Dong Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorLiang Shen, Liang Shen Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorMathieu Boccard, Mathieu Boccard School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorAlexei Gruverman, Alexei Gruverman Department of Physics and Astronomy, University of Nebraska-Lincoln, Lincoln, NE, 68588 USASearch for more papers by this authorZachary Holman, Zachary Holman School of Electrical, Computer, and Energy Engineering, Arizona State University, Tempe, AZ, 85287 USASearch for more papers by this authorJinsong Huang, Corresponding Author Jinsong Huang jhuang2@unl.edu Department of Mechanical and Materials Engineering, University of Nebraska-Lincoln, Lincoln, NE, 68588 USAE-mail: jhuang2@unl.eduSearch for more papers by this author First published: 19 July 2016 https://doi.org/10.1002/aenm.201601128Citations: 199Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Semitransparent perovskite solar cells based on smooth perovskite films and ultrathin Cu (1 nm)/Au (7 nm) metal electrode demonstrate an efficiency of 16.5%. When illuminated through the semitransparent perovskite cell, a near-infrared-enhanced silicon heterojunction solar cell operates with 6.5% efficiency, leading to a total perovskite/silicon four-terminal tandem efficiency of 23.0%. Citing Literature Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Filename Description aenm201601128-sup-0001-S1.pdf5.2 MB Supplementary Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume6, Issue19October 12, 20161601128 RelatedInformation

<h2>Summary</h2><h3>Purpose</h3> Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. <h3>Methods</h3> Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. <h3>Results</h3> 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). <h3>Conclusion</h3> CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as "covert transmitter", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.

There are a few prospective population-based cohort studies evaluating the effects of maternal thyroid dysfunctions on fetal and infant developments, but they are inconsistent.The objective of the study was to investigate the effects of maternal thyroid dysfunction on fetal and infant development.The study was nested within a prospective population-based China-Anhui Birth Defects and Child Development study. A total of 1017 women with singleton pregnancies participated in this study. Maternal serum samples in the first 20 wk of pregnancy were tested for thyroid hormones (TSH and free T(4)). Pregnant women were classified by hormone status into percentile categories based on laboratory assay and were compared accordingly.Outcomes included fetal loss, malformation, birth weight, preterm delivery, fetal stress, neonatal death, and infant development.Clinical hypothyroidism was associated with increased fetal loss, low birth weight, and congenital circulation system malformations; the adjusted odds ratios [95% confidence interval (CI)] were 13.45 (2.54-71.20), 9.05 (1.01-80.90), and 10.44 (1.15-94.62), respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios (95% CI) were 3.65 (1.44-9.26), 3.32 (1.22-9.05), 5.34 (1.09-26.16), and 10.49 (1.01-119.19), respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios (95% CI) were 2.95 (1.08-8.05), 3.55 (1.01-12.83), and 9.12 (1.67-49.70), respectively. Isolated hyperthyroxinemia was associated with spontaneous abortion; the adjusted odds ratio (95% CI) was 6.02 (1.25-28.96). Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio (95% CI) was 12.14 (1.22-120.70).Thyroid dysfunction in the first 20 wk of pregnancy may result in fetal loss and dysplasia and some congenital malformations.

Two states, two applications! An Ag(+)-mediated DNAzyme switch has been designed to detect Ag(+) and cysteine with high sensitivity and selectivity. In the closed state, Ag(+) turns on the switch through the formation of cytosine-Ag(+)-cytosine base pairs, whereas adding cysteine turns off the open switch because it competitively binds to Ag(+). This feature endows the DNAzyme switch with two sensing applications.

Gastric cancer (GC) has one of the highest mortality rates of malignancies globally. Currently, ciRS-7, a novel circular RNA, has emerged as a potential sponge for miR-7. However, few studies on ciRS-7 in GC have been performed. In this study, we investigated the clinical significance and function of ciRS-7 in GC. First, the expression levels of ciRS-7 in 102 primary GC tissues and the matched para-carcinoma tissues were evaluated and the clinical relevance was confirmed in an independent validation cohort (n = 154). Second, the effects of ciRS-7 on miR-7, PTEN, and PI3K were evaluated. Finally, the function of ciRS-7 in GC was analyzed with cell lines and nude mice. The expression of ciRS-7 was significantly upregulated in GC tissues compared with the matched para-carcinoma tissues (P = 0.0023), and the upregulation of ciRS-7 was linked to poor survival in the testing (P = 0.0143) and validation cohort (P = 0.0061). Multivariate survival analysis revealed that ciRS-7 was probably an independent risk factor of overall survival (P < 0.05). Furthermore, overexpression of ciRS-7 blocked the miR-7-induced tumor suppression in MGC-803 and HGC-27 cells and led to a more aggressive oncogenic phenotype, via antagonizing miR-7-mediated PTEN/PI3K/AKT pathway. ciRS-7 may act as a prospective prognostic biological marker and a promising therapeutic target for GC. J. Cell. Biochem. 119: 440-446, 2018. © 2017 Wiley Periodicals, Inc.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors worldwide, and it is always the consequence of chronic hepatitis and liver cirrhosis. The nucleotide-binding domain, leucine-rich family (NLR), pyrin-containing 3 (NLRP3) inflammasome has been shown to orchestrate multiple innate and adaptive immune responses. However, little is known about its role in cancer. This study was performed to investigate the role of the NLRP3 inflammasome in the development and progression of HCC. The expression of NLRP3 inflammasome components was analyzed in HCC tissues and corresponding non-cancerous liver tissues at both the mRNA and protein levels. Our data demonstrate that the expression of all of the NLRP3 inflammasome components was either completely lost or significantly downregulated in human HCC, and that the deficiency correlated significantly with advanced stages and poor pathological differentiation. In addition, our data provide an overview of the expression of NLRP3 inflammasome components in the multi-stage development of HCC and indicate a surprising link between deregulation of the NLRP3 inflammasome molecular platform and HCC progression. In conclusion, this study presents a dynamic expression pattern of NLRP3 inflammasome components in multi-stage hepatocarcinogenesis and demonstrates that deregulated expression of the inflammasome is involved in HCC progression.

The purpose of the present study was to characterize the association between clinical symptoms and anatomical and functional cerebral deficits in a relatively large sample of antipsychotic-naive first-episode schizophrenia patients using optimized voxel-based morphometry and resting state functional connectivity analysis.Participants were 68 antipsychotic-naive first-episode schizophrenia patients and 68 matched healthy comparison subjects. Both patients and healthy comparison subjects were scanned using a volumetric three-dimensional spoiled gradient recall sequence and a gradient-echo echo-planar imaging sequence. Psychopathology of first-episode schizophrenia patients was evaluated using the Positive and Negative Syndrome Scale (PANSS). Optimized voxel-based morphometry was used to characterize gray matter deficits in schizophrenia patients. The clinical significance of regional volume reduction was investigated by examining its association with symptoms in patients with first-episode schizophrenia and with alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.Significantly decreased gray matter volume was observed in schizophrenia patients in the right superior temporal gyrus (Brodmann's area 41), right middle temporal gyrus (Brodmann's area 21), and right anterior cingulate gyrus (Brodmann's area 32). Decreased gray matter volume in these brain regions was related to greater disturbance as shown on PANSS scores for positive symptoms, general psychopathology symptoms, thought disturbance, activation, paranoia, and impulsive aggression as well as total PANSS scores. A positive correlation was observed between PANSS scores for thought disturbance and temporo-putamen connectivity, and negative correlations were found between temporo-precuneus connectivity and total PANSS scores as well as scores for negative symptoms and anergia.The findings revealed volume loss in the right superior temporal gyrus, right middle temporal gyrus, and right anterior cingulate gyrus among antipsychotic-naive first-episode schizophrenia patients. In addition, the functional networks involving the right superior temporal gyrus and middle temporal gyrus were associated with clinical symptom severity. No abnormalities were observed in resting state connectivity with regions of identified gray matter deficits.

Cellular metabolic memory occurs in diabetic microvascular and macrovascular complications, but the underlying mechanisms remain unclear. Here, we investigate the role of sirtuin 1 (SIRT1) and metformin in this phenomenon. In bovine retinal capillary endothelial cells (BRECs) and retinas of diabetic rats, the inflammatory gene, nuclear factor-κB (NF-κB), and the proapoptotic gene, Bax, induced by hyperglycemia, remained elevated after returning to normoglycemia. BRECs with small interfering RNA-mediated SIRT1 knockdown had increased sensitivity to hyperglycemia stress, whereas SIRT1 overexpression or activation by metformin inhibited the increase of mitochondrial reactive oxygen species-mediated glyceraldehyde-3-phosphate dehydrogenase by poly (ADP-ribose) polymerase (PARP) activity through the upregulation of liver kinase B1/AMP-activated protein kinase (LKB1/AMPK), ultimately suppressing NF-κB and Bax expression. Furthermore, we showed that hyperglycemia led to PARP activation, which in turn may have downregulated SIRT1. Of importance, this study also demonstrated that metformin suppressed the "memory" of hyperglycemia stress in the diabetic retinas, which may be involved in the SIRT1/LKB1/AMPK pathway. Our data suggest that SIRT1 is a potential therapeutic target for the treatment of the cellular metabolic memory, and the use of metformin specifically for such therapy may be a new avenue of investigation in the diabetes field.

High-energy-density Li metal batteries suffer from a short lifespan under practical conditions, such as limited lithium, high loading cathode, and lean electrolytes, owing to the absence of appropriate solid electrolyte interphase (SEI). Herein, a sustainable SEI was designed rationally by combining fluorinated co-solvents with sustained-release additives for practical challenges. The intrinsic uniformity of SEI and the constant supplements of building blocks of SEI jointly afford to sustainable SEI. Specific spatial distributions and abundant heterogeneous grain boundaries of LiF, LiNx Oy , and Li2 O effectively regulate uniformity of Li deposition. In a Li metal battery with an ultrathin Li anode (33 μm), a high-loading LiNi0.5 Co0.2 Mn0.3 O2 cathode (4.4 mAh cm-2 ), and lean electrolytes (6.1 g Ah-1 ), 83 % of initial capacity retains after 150 cycles. A pouch cell (3.5 Ah) demonstrated a specific energy of 340 Wh kg-1 for 60 cycles with lean electrolytes (2.3 g Ah-1 ).

Background & Aims Hepatitis B virus (HBV) has developed strategies to evade immune responses. However, the mechanisms involved remain unclear. The NLRP3 inflammasome plays crucial roles in antiviral host defense and its downstream factor IL-1β has been shown to inhibit HBV infection in vivo. This study aims to assess whether HBV can affect the NLRP3 inflammasome signaling pathways and shed light on the underlying mechanisms HBV utilizes to evade host innate immune responses. Methods HBV inhibition of the lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation was evaluated by Western blot, quantitative RT-PCR, flow cytometry and immunofluorescence. Results Kupffer cells expressed significantly more NLRP3 and IL-1β after LPS stimulation; whereas, chronic HBV infection suppressed LPS-induced NLRP3 and pro-IL-1β expression as well as IL-1β maturation. This inhibitory activity is mediated by HBeAg, and is involved in the inhibition of NF-κB signal pathway and reactive oxygen species (ROS) production. The inhibitory effect of HBeAg was confirmed in patients with chronic hepatitis B (CHB) and hepatocellular carcinoma by comparing the levels of IL-1β and NLRP3-related proteins in para-carcinoma tissues from HBeAg-positive or negative patients. Moreover, chronic HBV infection increases the susceptibility of mice to S. typhimurium infection, possibly via inhibiting the NLRP3 inflammasome activation and IL-1β production. Conclusions HBeAg inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing NF-κB pathway and ROS production. This finding provides a novel mechanism for HBV-mediated suppression of innate immune responses, and identifies new therapeutic targets for chronic HBV infection and related diseases. Lay summary HBeAg suppresses LPS-induced NLRP3 inflammasome activation and IL-1β production in two ways, one is to repress NLRP3 and pro-IL-1β expression via inhibiting NF-κB phosphorylation, and the other is to repress caspase-1 activation and IL-1β maturation via inhibiting ROS production. This effect contributes to the HBV persistence and immune tolerance. Hepatitis B virus (HBV) has developed strategies to evade immune responses. However, the mechanisms involved remain unclear. The NLRP3 inflammasome plays crucial roles in antiviral host defense and its downstream factor IL-1β has been shown to inhibit HBV infection in vivo. This study aims to assess whether HBV can affect the NLRP3 inflammasome signaling pathways and shed light on the underlying mechanisms HBV utilizes to evade host innate immune responses. HBV inhibition of the lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation was evaluated by Western blot, quantitative RT-PCR, flow cytometry and immunofluorescence. Kupffer cells expressed significantly more NLRP3 and IL-1β after LPS stimulation; whereas, chronic HBV infection suppressed LPS-induced NLRP3 and pro-IL-1β expression as well as IL-1β maturation. This inhibitory activity is mediated by HBeAg, and is involved in the inhibition of NF-κB signal pathway and reactive oxygen species (ROS) production. The inhibitory effect of HBeAg was confirmed in patients with chronic hepatitis B (CHB) and hepatocellular carcinoma by comparing the levels of IL-1β and NLRP3-related proteins in para-carcinoma tissues from HBeAg-positive or negative patients. Moreover, chronic HBV infection increases the susceptibility of mice to S. typhimurium infection, possibly via inhibiting the NLRP3 inflammasome activation and IL-1β production. HBeAg inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing NF-κB pathway and ROS production. This finding provides a novel mechanism for HBV-mediated suppression of innate immune responses, and identifies new therapeutic targets for chronic HBV infection and related diseases.

<h2>Summary</h2> The presence of DNA in the cytoplasm is normally a sign of microbial infections and is quickly detected by cyclic GMP-AMP synthase (cGAS) to elicit anti-infection immune responses. However, chronic activation of cGAS by self-DNA leads to severe autoimmune diseases for which no effective treatment is available yet. Here we report that acetylation inhibits cGAS activation and that the enforced acetylation of cGAS by aspirin robustly suppresses self-DNA-induced autoimmunity. We find that cGAS acetylation on either Lys384, Lys394, or Lys414 contributes to keeping cGAS inactive. cGAS is deacetylated in response to DNA challenges. Importantly, we show that aspirin can directly acetylate cGAS and efficiently inhibit cGAS-mediated immune responses. Finally, we demonstrate that aspirin can effectively suppress self-DNA-induced autoimmunity in Aicardi-Goutières syndrome (AGS) patient cells and in an AGS mouse model. Thus, our study reveals that acetylation contributes to cGAS activity regulation and provides a potential therapy for treating DNA-mediated autoimmune diseases.

Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.

Lithium (Li) metal with an ultrahigh specific theoretical capacity and the lowest reduction potential is strongly considered as a promising anode for high-energy-density batteries. However, uncontrolled lithium dendrites and infinite volume change during repeated plating/stripping cycles hinder its practical applications immensely. Herein, a house-like Li anode (housed Li) was designed to circumvent the above issues. The house matrix was composed of carbon fiber matrix and affords a stable structure to relieve the volume change. An artificial solid electrolyte layer was formed on composite Li metal, just like the roof of a house, which facilitates uniform Li ions diffusion and serves as a physical barrier against electrolyte corrosion. With the combination of solid electrolyte layer and matrix in the composite Li metal anode, both dendrite growth and volume expansion are remarkably inhibited. The housed Li | LiFePO4 batteries exhibited over 95% capacity retention after 500 cycles at 1.0 C in coin cell and 85% capacity retention after 80 cycles at 0.5 C in pouch cell. The rationally combination of solid electrolyte layer protection and housed framework in one Li metal anode sheds fresh insights on the design principle of a safe and long-lifespan Li metal anode for Li metal batteries.

Air pollution is one of the major challenges faced by the human kind, but cleaning of air is a horrendous task and hugely expensive, because of its large scope and the cost of energy. Up to now, all of the air cleaning systems are generally driven by external power, making it rather expensive and infeasible. Here, we introduce the first self-powered air cleaning system focusing on sulfur dioxide (SO2) and dust removal as driven by the electricity generated by natural wind, with the use of rotating triboelectric nanogenerator (R-TENG). Distinguished from traditional approach of electrostatic precipitation by applying a voltage of thousand volt, our technology takes the advantages of high output voltage of R-TENG, typically in the order of a few hundreds volt. This self-powered air cleaning system not only adsorbs dust particles in air, but also oxidizes SO2 without producing byproducts. Therefore, it could be potential for easing the haze–fog situation, which is one of the most important directions in self-powered electrochemistry.

A novel Zr-MOF based smart adsorbent was fabricated for the simultaneous detection and removal of organophosphorus pesticides in wastewater.

Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. To adequately support their healthcare needs, there is a need to know the prevalence of HCT survivors. We used data on 170,628 recipients of autologous and allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research from 1968 to 2009 to estimate the current and future number of HCT survivors in the United States. Stacked cohort simulation models were used to estimate the number of HCT survivors in the United States in 2009 and to make projections for HCT survivors by the year 2030. There were 108,900 (range, 100,500 to 115,200) HCT survivors in the United States in 2009. This included 67,000 autologous HCT and 41,900 allogeneic HCT survivors. The number of HCT survivors is estimated to increase by 2.5 times by the year 2020 (242,000 survivors) and 5 times by the year 2030 (502,000 survivors). By 2030, the age at transplant will be < 18 years for 14% of all survivors (n = 64,000), 18 to 59 years for 61% survivors (n = 276,000), and 60 years and older for 25% of survivors (n = 113,000). In coming decades, a large number of individuals will be HCT survivors. Transplant center providers, hematologists, oncologists, primary care physicians, and other specialty providers will need to be familiar with the unique and complex health issues faced by this population.

Good interfacial compatibility is the key to realize the full potential of metal-organic framework-based mix matrix membranes for gas separation. Here we report a new approach that uses polyimide brushes covalently grafted on the MOF surface to engineer the MOF-polymer interface. Benefiting from the strong brush-brush interaction, polyimide grafted MOF particles can form a stand-alone membrane at 88 wt % MOF loading without the addition of polymeric matrix. Compared to traditional mixed-matrix membranes, the modified membranes exhibit improved ductility up to 472%, reduced interfacial tearing phenomenon under shear force, decreased matrix chain mobility, and improved plasticization resistance against CO2. Most importantly, with increasing MOF loading, only the modified membranes exhibit simultaneous increase of selectivity and permeability for CO2/N2 and CO2/CH4 separation, following the trend predicted by the modified Maxwell model.

A live-attenuated malaria vaccine, Plasmodium falciparum sporozoite vaccine (PfSPZ Vaccine), confers sterile protection against controlled human malaria infection (CHMI) with Plasmodium falciparum (Pf) parasites homologous to the vaccine strain up to 14 mo after final vaccination. No injectable malaria vaccine has demonstrated long-term protection against CHMI using Pf parasites heterologous to the vaccine strain. Here, we conducted an open-label trial with PfSPZ Vaccine at a dose of 9.0 × 105 PfSPZ administered i.v. three times at 8-wk intervals to 15 malaria-naive adults. After CHMI with homologous Pf parasites 19 wk after final immunization, nine (64%) of 14 (95% CI, 35-87%) vaccinated volunteers remained without parasitemia compared with none of six nonvaccinated controls (P = 0.012). Of the nine nonparasitemic subjects, six underwent repeat CHMI with heterologous Pf7G8 parasites 33 wk after final immunization. Five (83%) of six (95% CI, 36-99%) remained without parasitemia compared with none of six nonvaccinated controls. PfSPZ-specific T-cell and antibody responses were detected in all vaccine recipients. Cytokine production by T cells from vaccinated subjects after in vitro stimulation with homologous (NF54) or heterologous (7G8) PfSPZ were highly correlated. Interestingly, PfSPZ-specific T-cell responses in the blood peaked after the first immunization and were not enhanced by subsequent immunizations. Collectively, these data suggest durable protection against homologous and heterologous Pf parasites can be achieved with PfSPZ Vaccine. Ongoing studies will determine whether protective efficacy can be enhanced by additional alterations in the vaccine dose and number of immunizations.

Summary Arbuscular mycorrhizal ( AM ) symbiosis is known to stimulate plant drought tolerance. However, the molecular basis for the direct involvement of AM fungi ( AMF ) in plant water relations has not been established. Two full‐length aquaporin genes, namely GintAQPF1 and GintAQPF2 , were cloned by rapid amplification of cDNA 5′‐ and 3′‐ends from an AMF, G lomus intraradices . Aquaporin localization, activities and water permeability were examined by heterologous expression in yeast. Gene expression during symbiosis was also analyzed by quantitative real‐time polymerase chain reaction. Gint AQPF 1 was localized to the plasma membrane of yeast, whereas Gint AQPF 2 was localized to both plasma and intracellular membranes. Transformed yeast cells exhibited a significant decrease in cell volume on hyperosmotic shock and faster protoplast bursting on hypo‐osmotic shock. Polyethylene glycol ( PEG ) stimulated, but glycerol inhibited, the aquaporin activities. Furthermore, the expression of the two genes in arbuscule‐enriched cortical cells and extraradical mycelia of maize roots was also enhanced significantly under drought stress. Gint AQPF 1 and Gint AQPF 2 are the first two functional aquaporin genes from AMF reported to date. Our data strongly support potential water transport via AMF to host plants, which leads to a better understanding of the important role of AMF in plant drought tolerance.

We propose an efficient and clean avenue for ammonia synthesis, via electroreduction of nitrate which could be obtained from industrial wastewater, domestic sewage, sodium nitrate ore, and nitrification of bacteria and electrochemical oxidation of nitrogen, which addresses the water pollution issues and simultaneously upgrades the nitrate to high-value ammonia. At a low overpotential of −0.15 V versus RHE, Cu nanosheets achieved an ammonia formation rate of 390.1 μg mg−1 Cu h−1 and a Faradaic efficiency of 99.7%, attributed to suppression of the HER activity and apparent improvement of the rate of rate-determining step on Cu (111). Such an ammonia formation rate is more than two orders of magnitude higher than electrochemical nitrogen reduction reaction to ammonia. This work not only develops a powerful strategy to the rational design of robust and efficient catalysts by crystal facet engineering, but also provides an alternative route for electrochemical ammonia synthesis by reduction of nitrate.

This study aims at identifying the dimensions of experiential quality and investigating the interrelationships among experiential quality, experiential value, experiential satisfaction, theme park image, and revisit intention perceived by theme park visitors. Analysis of data from 424 visitors in Janfusan Fancyworld of Taiwan indicates that the proposed model fits the data well. The results reveal that there are 4 primary dimensions and 11 subdimensions of experiential quality perceived by theme park visitors. In addition, the results indicate that physical environment quality is identified as the most primary dimension of experiential quality perceived by theme park visitors.

A short process for the efficient utilization of transition-metal chlorides in lithium-ion batteries (LIBs) is proposed. A uniformly dispersed tri-component nanocomposite of Ni0.8Co0.1Mn0.1O1.1 microspheres with a porous structure has been prepared from the solution of transition-metal chlorides via spray pyrolysis. When evaluated as anode for LIBs, the Ni0.8Co0.1Mn0.1O1.1 nanocomposite exhibits a reversible capacity of 1180 mAh g−1 after 120 cycles. More strikingly, the nanoparticles-assembled Ni0.8Co0.1Mn0.1O1.1 precursor has its unique advantages in synthesizing well-ordered layered LiNi0.8Co0.1Mn0.1O2, owning to its excellent atomic uniformity, porous structure and Ni3+-rich surface. The as-prepared cathode material shows excellent structural stability. Discharge capacities of 173 mAh g−1 after 100 cycles at 1 C (1 C = 180 mA g-1) between 2.8 and 4.3 V are consistently obtained, corresponding to 95.6% capacity retention. These outstanding electrochemical results are obtained with minimal process optimization, indicating that spray pyrolysis is an efficient, robust synthesis technique for the production of Ni-rich layered cathode from solution of transition-metal chlorides.

Over 50% of patients with heart failure have preserved ejection fraction (HFpEF), rather than reduced ejection fraction. Complexity of its pathophysiology and the lack of animal models hamper the development of effective therapy for HFpEF.This study was designed to investigate the metabolic mechanisms of HFpEF and test therapeutic interventions using a novel animal model.By combining the age, long-term high-fat diet, and desoxycorticosterone pivalate challenge in a mouse model, we were able to recapture the myriad features of HFpEF. In these mice, mitochondrial hyperacetylation exacerbated while increasing ketone body availability rescued the phenotypes. The HFpEF mice exhibited overproduction of IL (interleukin)-1β/IL-18 and tissue fibrosis due to increased assembly of NLPR3 inflammasome on hyperacetylated mitochondria. Increasing β-hydroxybutyrate level attenuated NLPR3 inflammasome formation and antagonized proinflammatory cytokine-triggered mitochondrial dysfunction and fibrosis. Moreover, β-hydroxybutyrate downregulated the acetyl-CoA pool and mitochondrial acetylation, partially via activation of CS (citrate synthase) and inhibition of fatty acid uptake.Therefore, we identify the interplay of mitochondrial hyperacetylation and inflammation as a key driver in HFpEF pathogenesis, which can be ameliorated by promoting β-hydroxybutyrate abundance.

Abstract Soft machines have recently gained prominence due to their inherent softness and the resulting safety and resilience in applications. However, these machines also have disadvantages, as they respond with complex body dynamics when stimulated. These dynamics exhibit a variety of properties, including nonlinearity, memory and potentially infinitely many degrees of freedom, which are often difficult to control. Here, we demonstrate that these seemingly undesirable properties can in fact be assets that can be exploited for real-time computation. Using body dynamics generated from a soft silicone arm, we show that they can be employed to emulate desired nonlinear dynamical systems. First, by using benchmark tasks, we demonstrate that the nonlinearity and memory within the body dynamics can increase the computational performance. Second, we characterize our system’s computational capability by comparing its task performance with a standard machine learning technique and identify its range of validity and limitation. Our results suggest that soft bodies are not only impressive in their deformability and flexibility but can also be potentially used as computational resources on top and for free.

The goal of this study was to evaluate the potential involvement of melatonin in the activation of the nuclear factor erythroid 2-related factor 2 and antioxidant-responsive element (Nrf2-ARE) signaling pathway and the modulation of antioxidant enzyme activity in an experimental model of traumatic brain injury (TBI). In experiment 1, ICR mice were divided into four groups: sham group, TBI group, TBI + vehicle group, and TBI + melatonin group (n = 38 per group). Melatonin (10mg/kg) was administered via an intraperitoneal (ip) injection at 0, 1, 2, 3, and 4h post-TBI. In experiment 2, Nrf2 wild-type (Nrf2(+/+) group) and Nrf2-knockout (Nrf2(-/-) group) mice received a TBI insult followed by melatonin administration (10mg/kg, ip) at the corresponding time points (n = 35 per group). The administration of melatonin after TBI significantly ameliorated the effects of the brain injury, such as oxidative stress, brain edema, and cortical neuronal degeneration. Melatonin markedly promoted the translocation of Nrf2 protein from the cytoplasm to the nucleus; increased the expression of Nrf2-ARE pathway-related downstream factors, including heme oxygenase-1 andquinone oxidoreductase 1; and prevented the decline of antioxidant enzyme activities, including superoxide dismutase and glutathione peroxidase. Furthermore, knockout of Nrf2 partly reversed the neuroprotection of melatonin after TBI. In conclusion, melatonin administration may increase the activity of antioxidant enzymes and attenuate brain injury in a TBI model, potentially via mediation of the Nrf2-ARE pathway.

BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [-35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria. TRIAL REGISTRATION: ClinicalTrials.gov NCT02215707. FUNDING: Support was provided through the US Army Medical Research and Development Command, Military Infectious Diseases Research Program, and the Naval Medical Research Center's Advanced Medical Development Program.

This study aims at identifying the dimensions of experiential quality and examining the interrelationships among experiential quality, perceived value, heritage image, experiential satisfaction, and behavioral intentions for heritage tourists. The dimensions of experiential quality are built on a basis of reflective indicators, and a multidimensional and hierarchical model is used as a framework to synthesize the effects of experiential quality, perceived value, heritage image, and experiential satisfaction on behavioral intentions perceived by heritage tourists. Analysis of data from 427 tourists in the Historic Center of Macau indicates that the proposed model fits the data well. The results reveal that there are four primary dimensions and 10 subdimensions of experiential quality perceived by heritage tourists. In addition, the results indicate that outcome quality is identified as the most primary dimension of experiential quality perceived by heritage tourists.

The use of fundus images for the early screening of eye diseases is of great clinical importance. Due to its powerful performance, deep learning is becoming more and more popular in related applications, such as lesion segmentation, biomarkers segmentation, disease diagnosis and image synthesis. Therefore, it is very necessary to summarize the recent developments in deep learning for fundus images with a review paper. In this review, we introduce 143 application papers with a carefully designed hierarchy. Moreover, 33 publicly available datasets are presented. Summaries and analyses are provided for each task. Finally, limitations common to all tasks are revealed and possible solutions are given. We will also release and regularly update the state-of-the-art results and newly-released datasets at https://github.com/nkicsl/Fundus_Review to adapt to the rapid development of this field.

Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain–binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1–cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA–induced autoinflammatory responses in an Aicardi–Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases. Li and colleagues show that G3BP1, a protein known to regulate the RNA stress response, is critical for DNA sensing and efficient activation of the cytoplasmic DNA sensor cGAS.

MATRICS Consensus Cognitive Battery (MCCB), packaging 10 tests selected from more than 90 nominated tests, is a method developed by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) group to evaluate the efficacy of treatments targeting cognitive impairments in schizophrenia. MCCB had been translated into a number of languages, but only the US and Spain had normative data reported. Inconsistency in translation and cultural differences make direct application of MCCB in China problematic. In this study, we administered the battery to a representative community sample based on Chinese population census in 2005 and obtained normative data. The effects of age, gender, education level, and scale of residence area on test performance were examined. The sample included 656 healthy volunteers from six sites in China. At each site, sample was stratified according to age, gender, and educational level, and scale of the area one was born in, grew up in and currently living in was recorded. We found age, gender, and education had significant effects on the normative data for MCCB in China, which are comparable to those found for the original standardized English version in the U.S. and the Spanish version in Spain. Remarkably, the residence scale effects on neuropsychological performance were significant, which should be taking into account when calculating the standardized T score for each subject. The practice effects were minor and test-retest reliability of MCCB was good, which suggests MCCB as an appropriate measure for clinical and research usage in China.

Abstract Polymeric dielectrics play a key role in the realization of flexible organic electronics, especially for the fabrication of scalable device arrays and integrated circuits. Among a wide variety of polymeric dielectric materials, aromatic polyimides (PIs) are flexible, lightweight, and strongly resistant to high‐temperature processing and corrosive etchants and, therefore, have become promising candidates as gate dielectrics with good feasibility in manufacturing organic electronic devices. More significantly, the characteristics of PIs can be conveniently modulated by the design of their chemical structures. Herein, from the perspective of structure optimization and interface engineering, a brief overview of recent progress in PI‐based dielectrics for organic electronic devices and circuits is provided. Also, an outlook of future research directions and challenges for polyimide dielectric materials is presented.

A novel metalporphyrin-based microporous organic polymer (HUST-1-Co), which exhibits a high CO₂ uptake and efficient chemical conversion of CO₂ under ambient conditions, is reported.

Diabetic Retinopathy (DR) grading is challenging due to the presence of intra-class variations, small lesions and imbalanced data distributions. The key for solving fine-grained DR grading is to find more discriminative features corresponding to subtle visual differences, such as microaneurysms, hemorrhages and soft exudates. However, small lesions are quite difficult to identify using traditional convolutional neural networks (CNNs), and an imbalanced DR data distribution will cause the model to pay too much attention to DR grades with more samples, greatly affecting the final grading performance. In this article, we focus on developing an attention module to address these issues. Specifically, for imbalanced DR data distributions, we propose a novel Category Attention Block (CAB), which explores more discriminative region-wise features for each DR grade and treats each category equally. In order to capture more detailed small lesion information, we also propose the Global Attention Block (GAB), which can exploit detailed and class-agnostic global attention feature maps for fundus images. By aggregating the attention blocks with a backbone network, the CABNet is constructed for DR grading. The attention blocks can be applied to a wide range of backbone networks and trained efficiently in an end-to-end manner. Comprehensive experiments are conducted on three publicly available datasets, showing that CABNet produces significant performance improvements for existing state-of-the-art deep architectures with few additional parameters and achieves the state-of-the-art results for DR grading. Code and models will be available at https://github.com/he2016012996/CABnet.

The transport of water molecules and ions in the nanopores of calcium aluminosilicate hydrate (CASH) influences the durability and sustainability of environmentally friendly cement-based materials with industrial waste substitution. In this study, molecular dynamics was utilized to study aqueous NaCl solution capillary transport through the calcium silicate hydrate (CSH) and calcium aluminosilicate hydrate (CASH) gel pore with pore size of 3.2 nm. The invading depth for the NaCl solution advancing frontier with meniscus shape follows a parabolic relation as a function of time, consistent with the classic Lucas–Washburn equation in capillary adsorption theory. As compared with the solution transport in the CSH pore, both water molecules and ions migrate more slowly in the gel pore of CASH, and sodium ions accumulate in the entrance region of the gel pore. The incorporation of Al atoms in the silicate substrate resists the ingress of ions and water. The Al–Si substitution on the CASH interface enhances the charge negativity of solid oxygen atoms, which polarizes the dipole moment of surface water molecules to a larger extent, strengthens the interfacial hydrogen bond, and elongates the residence time of water near the aluminate substrate. In addition, the silicate–aluminate chains in the CASH substrate provide plenty of oxygen sites to associate with the sodium ions by forming a stable Na–OS bond, immobilizing the cations deeply in the vacancy region of the aluminate–silicate channel. The inner sphere adsorption of Na ions on the CASH surface further contributes to the secondary outer sphere adsorption of the Cl ions by forming the Na–Cl ionic pairs. Hopefully, the transport and adsorption mechanism of the ions and water in the CASH gel can help guide the cementitious material substituted by Al-rich industry waste with sustainability and durability.

To meet the ever-increasing energy demands, advanced electrode materials are strongly requested for the exploration of advanced energy storage and conversion technologies, such as Li-ion batteries, Li-S batteries, Li-/Zn-air batteries, supercapacitors, dye-sensitized solar cells, and other electrocatalysis process (e.g., oxygen reduction/evolution reaction, hydrogen evolution reaction). Transition metal chalcogenides (TMCs, i.e., sulfides and selenides) are forcefully considered as an emerging candidate, owing to their unique physical and chemical properties. Moreover, the integration of TMCs with conductive graphene host has enabled the significant improvement of electrochemical performance of devices. In this review, the recent research progress on TMC/graphene composites for applications in energy storage and conversion devices is summarized. The preparation process of TMC/graphene nanocomposites is also included. In order to promote an in-depth understanding of performance improvement for TMC/graphene materials, the operating principle of various devices and technologies are briefly presented. Finally, the perspectives are given on the design and construction of advanced electrode materials.

User profiling is an important step for solving the problem of personalized news recommendation. Traditional user profiling techniques often construct profiles of users based on static historical data accessed by users. However, due to the frequent updating of news repository, it is possible that a user's fine-grained reading preference would evolve over time while his/her long-term interest remains stable. Therefore, it is imperative to reason on such preference evaluation for user profiling in news recommenders. Besides, in content-based news recommenders, a user's preference tends to be stable due to the mechanism of selecting similar content-wise news articles with respect to the user's profile. To activate users' reading motivations, a successful recommender needs to introduce "somewhat novel" articles to users. In this paper, we initially provide an experimental study on the evolution of user interests in real-world news recommender systems, and then propose a novel recommendation approach, in which the long-term and short-term reading preferences of users are seamlessly integrated when recommending news items. Given a hierarchy of newly-published news articles, news groups that a user might prefer are differentiated using the long-term profile, and then in each selected news group, a list of news items are chosen as the recommended candidates based on the short-term user profile. We further propose to select news items from the user–item affinity graph using absorbing random walk model to increase the diversity of the recommended news list. Extensive empirical experiments on a collection of news data obtained from various popular news websites demonstrate the effectiveness of our method.