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Background and purposeStroke may cause extensive after-effects such as motor function impairments and disorder of consciousness (DoC). Detecting these after-effects of stroke and monitoring their changes are challenging jobs currently undertaken via traditional clinical examinations. These behavioural examinations often take a great deal of manpower and time, thus consuming significant resources. Computer-aided examinations of the electroencephalogram (EEG) microstates derived from bedside EEG monitoring may provide an alternative way to assist medical practitioners in a quick assessment of the after-effects of stroke.MethodsIn this study, we designed a framework to extract microstate maps and calculate their statistical parameters to input to classifiers to identify DoC in ischemic stroke patients automatically. As the dataset is imbalanced with the minority of patients being DoC, an ensemble of support vector machines (EOSVM) is designed to solve the problem that classifiers always tend to be the majority classes in the classification on an imbalanced dataset.ResultsThe experimental results show EOSVM get better performance (with accuracy and F1-Score both higher than 89%), improving sensitivity the most, from lower than 60% (SVM and AdaBoost) to higher than 80%. This highlighted the usefulness of the EOSVM-aided DoC detection based on microstates parameters.ConclusionTherefore, the classifier EOSVM classification based on features of EEG microstates is helpful to medical practitioners in DoC detection with saved resources that would otherwise be consumed in traditional clinic checks.

This study, conducted in China in November 2020, was aimed at exploring the variations in growth traits among different provenances and families as well as to select elite materials of Juglans mandshurica. Thus, seeds of 44 families from six J. mandshurica provenances in Heilongjiang and Jilin provinces were sown in the nursery and then transplanted out in the field. At the age of 5 years, seven growth traits were assessed, and a comprehensive analysis was conducted as well as selection of provenance and families. Analysis of variance revealed statistically significant (P < 0.01) differences in seven growth traits among different provenances and families, thereby justifying the pursuit of further breeding endeavors. The genetic coefficient of variation (GCV) for all traits ranged from 5.44% (branch angle) to 21.95% (tree height) whereas the phenotypic coefficient of variation (PCV) ranged from 13.74% (tapering) to 38.50% (branch number per node), indicating considerable variability across the traits. Further, all the studied traits except stem straightness degree, branch angle and branch number per node, showed high heritability (Tree height, ground diameter, mean crown width and tapering, over 0.7±0.073), indicating that the variation in these traits is primarily driven by genetic factors. Correlation analysis revealed a strong positive correlation (r > 0.8) between tree height and ground diameter (r = 0.86), tree height and mean crown width (r = 0.82), and ground diameter and mean crown width (r = 0.83). This suggests that these relationships can be employed for more precise predictions of the growth and morphological characteristics of trees, as well as the selection of superior materials. There was a strong correlation between temperature factors and growth traits. Based on the comprehensive scores in this study, Sanchazi was selected as elite provenance. Using the top-percentile selection criteria, SC1, SC8, DJC15, and DQ18 were selected as elite families. These selected families exhibit genetic gains of over 10% in tree height, ground diameter and mean crown width, signifying their significant potential in forestry for enhancing timber production and reducing production cycles, thereby contributing to sustainable forest management. In this study, the growth traits of J. mandshurica were found to exhibit stable variation, and there were correlations between these traits. The selected elite provenance and families of J. mandshurica showed faster growth, which is advantageous for the subsequent breeding and promotion of improved J. mandshurica varieties.

BackgroundThe relative safety and efficacy of left atrial appendage closure (LAAC) for atrial fibrillation (AF) in patients with chronic kidney disease (CKD) have not been well defined. To evaluate the results in this cohort, we conducted a systematic review and meta-analysis of observational studies.MethodsWe searched the PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to January 2023 for all relevant studies. Our inclusion criteria were met by twelve observational studies that included 61324 patients altogether.ResultsCompared with no CKD group, in-hospital mortality (OR: 2.84, 95% CI: 2.12-3.81, pConclusionsCKD patients who receive LAAC have a greater risk of in-hospital mortality, AKI, pericardial effusion/tamponade, and major bleeding events than those without CKD, especially in patients with ESRD. No significant difference in the risk of stroke was found in the long-term follow-up after LAAC between the two groups, demonstrating a similar efficacy of LAAC to prevent stroke in CKD patients.

[This corrects the article DOI: 10.1371/journal.pone.0095259.].

As one of the severe natural disasters, typhoon hazard brings tremendous tragedy to human beings. The foreland in the southeast of China is one of the most typhoon prone areas in the world. There are amount of damage of civil engineering structures induced by typhoon every year. Especially for the spacious villages, the low-rise buildings are vulnerable to typhoon so that many of them are destroyed regionally. The typhoon vulnerability assessment of civil engineering structures is a classical multiple attribute group decision making (MAGDM) issues. In this paper, the 2-tuple linguistic neutrosophic number grey relational analysis (2TLNN-GRA) method is built based on the grey relational analysis (GRA) and 2-tuple linguistic neutrosophic sets (2TLNSs) with incomplete weight information. For deriving the weight information of the attribute, an optimization model is built on the basis of the GRA, by which the attribute weights can be decided. Then, the optimal alternative is chosen through calculating largest relative relational degree from the 2-tuple linguistic neutrosophic number positive ideal solution (2TLNNPIS) which considers both the largest grey relational coefficient (GRC) from the 2TLNNPIS and the smallest GRC form 2-tuple linguistic neutrosophic number negative ideal solution (2TLNN NIS). Then, combine the traditional fuzzy GRA model with 2TLNNSs information, the 2TLNN-GRA method is established and the computing steps for MAGDM are built. Finally, a numerical example for typhoon vulnerability assessment of civil engineering structures has been given and some comparisons is used to illustrate advantages of 2TLNN-GRA method.

BackgroundSince the outbreak of the respiratory infectious disease caused by the novel coronavirus in 2019, the COVID-19 epidemic has posed a serious threat to the life and safety of the public, and has also seriously affected the normal study and life of college students in China. Although a series of studies have been conducted on college students' knowledge, attitudes and practices of COVID-19, the results vary widely. This study aimed to evaluate the pooled estimated level of knowledge, attitudes, and practices (KAP) about COVID-19 among college students in China.MethodsWe conducted a comprehensive search on Scopus, ProQuest, PubMed, EMbase, Web of Science, the Cochrane Library, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP Database and Wanfang Database up to 13 February 2022. We then assessed the quality of included studies using a checklist developed by the Joanna Briggs Institute (JBI) for cross-sectional studies and analyzed using STATA.15 after two researchers independently extracted relevant data and entered them into Microsoft Excel. Funnel plots and Egger's regression tests were used to check for publication bias, and sensitivity analysis was performed to assess the robustness of the results. A random-effects model was used for the meta-analysis, on the basis of which subgroup analyses were performed by time of investigation (study period) and by gender and major of the subjects.ResultA total of 42 studies including 174,440 subjects were included in this review, and the quality of the included studies was mainly intermediate and advanced. The findings of the meta-analysis showed that the overall levels of Chinese college students' knowledge, positive and negative attitudes, and practice of preventive measures towards COVID-19 were 74% (95%CI: 69%-79%), 84% (95%CI: 80%-88%), 31% (95%CI: 23%-38%) and 82% (95%CI: 77%-86%), respectively. The results of subgroup analysis showed that female and medical college students had higher levels of knowledge and practice on COVID-19.ConclusionThe study findings showed that the overall KAP level of college students in China included in the study was relatively optimistic. Influenced by gender, major and time, there were differences in the KAP level of college students. In order to promote the effective prophylaxis and control of pandemic, we recommend implementing targeted measures to improve the awareness rate of COVID-19-related knowledge among this group and the implementation rate of COVID-19 preventive measures among male and non-medical college students.

This study aims to investigate the association of organizational and patient behaviors (reflecting the internal and external environment of hospital, respectively) with physician well-being. A national cross-sectional survey was conducted in 77 hospitals across seven provinces in China between July 2014 and April 2015. Physician well-being was assessed with job satisfaction, career regret and happiness. Organizational behaviors were assessed with organizational fairness, leadership attention and team interaction; patient behaviors were assessed with patient trust and unreasonable requests from patients. Of a study sample of 3,159 physicians, 1,788 were men (56.6%) and 1,371 were women (43.4%). Overall, positive organizational and patient behaviors reported by physicians were relatively low. Negative organizational behaviors and patient behaviors including lower organizational fairness, lower leadership attention, lower team interaction and lower patient trust were associated with lower job satisfaction and lower life satisfaction, and higher career regret. The association between organizational behaviors and physician well-being exhibited some gender differences, while no clear gender difference was found for the relationship between patient behaviors and physician well-being. Given the importance of physician well-being for the healthcare system, interventions for improving internal and external hospital environments (e.g., organizational fairness, leadership attention, team interaction and patient trust) may benefit physician well-being.

BackgroundSince the successful development of Coronavirus Disease (COVID-19) vaccine, COVID-19 vaccination has been actively advocated all over the world. As the key population for COVID-19 vaccination, the acceptance of Healthcare Workers (HCWs) is not only related to their risk of contracting COVID-19 infection at work, but also affects the decision of the general population on COVID-19 vaccination. Currently, a series of observational studies have been conducted on the acceptance of COVID-19 vaccines among HCWs in China, but there are presently no all-inclusive reviews. Therefore, this paper reviewed to identify a reliable estimate of acceptance rate of COVID-19 vaccine among HCWs in China.MethodsWe conducted a search on PubMed, EMbase, The Cochrane Library, Web of Science, CNKI (Chinese National Knowledge Infrastructure), Wanfang Database, CBM (Chinese Biomedical Literature Database) and VIP database (Chinese Scientific Journal Database) from January 2020 to June 2022. The quality of included articles was estimated using the Newcastle-Ottawa Quality Assessment tool suitable for cross-sectional studies and STATA 16 was used for analysis, A random-effects model was used to calculate acceptance rate for COVID-19 vaccine, as well as subgroup analysis and sensitivity analysis.ResultThis review included 18 studies involving 45,760 subjects, all of which were of medium or high quality. Meta-analysis results represented that, the pooled estimated acceptance rate of COVID-19 vaccine among HCWs in China was 78% (95%CI: 73-83%), and the pooled acceptance rate in 2021 (82%, 95%CI: 78-86%) was significantly higher than that in 2020 (73%, 95%CI: 65%-81%). Subgroup analysis showed different acceptance rates for COVID-19 vaccine among HCWs with different characteristics.ConclusionThe result revealed that HCWs in China generally have a high acceptance rate of COVID-19 vaccines, but the acceptance rate varies with different characteristics of the population. Therefore, corresponding training should be carried out for HCWs with different characteristics, and they should play an exemplary and leading role in COVID-19 vaccination, so as to improve the vaccination rate of the whole population and form an immune barrier at an early date.

OBJECTIVES:To better guide clinicians to choose the appropriate chairside system, we compared and evaluated the morphology of crowns generated by three different biogeneric design modes (biogeneric copy (BC), biogeneric individual (BI), and biogeneric reference (BR)) of the CEREC software. METHODS:Maxillary and mandibular casts were obtained from twelve volunteers and digital impressions were acquired. All ceramic crown preparations of all right maxillary central incisors were prepared and digital impressions were taken. Then, crowns were automatically designed under BC, BI and BR modes separately and their morphologies were evaluated by six doctors. The "optimal fitting alignment" and "3D analysis" functions of the Geomagic Qualify software were carried out between original teeth and auto-generated full crowns. The auto-generated crowns were modified by a technician according to clinical criteria and the adjustment time was recorded. The discrepancies between technician modified crowns and the auto-generated full crowns were evaluated with the same functions in the Geomagic Qualify software. RESULTS:The subjective evaluation results of BC group were significantly better than those of BI and BR group (p < 0.05). Compared with the original teeth and modified crowns, auto-generated crowns in BC group all had the smallest differences, followed by BR and BI group (p < 0.05). BC group needed the shortest adjustment time than BI and BR group (p < 0.05). CONCLUSIONS:Using crowns generated by BC mode is more aesthetic and suitable in clinics use than those generated by BI and BR modes and can reduce clinic adjustment time.

Colored wheat is a valuable resource that is rich in anthocyanins and minerals and thus contributes additional nutritional value to a healthy human diet. However, the effects of nitrogen fertilization on anthocyanin content (AC) and the balance between quality and yield still merit discussion. In this study, blue, purple, and common-colored wheat genotypes were used to investigate three nutrient quality traits, seven processing quality traits, three yield traits and seven grain morphology traits at three nitrogen levels in two years to excavate their possible plasticity under low-nitrogen stress and the tradeoffs among these traits. The highest AC was found in the blue genotypes followed by the purple genotypes. Analysis of variance (ANOVA) showed that AC could be significantly increased by reducing N application, especially in the purple genotypes. Therefore, growing colored wheat with low nitrogen input could allow efficient harvesting of grain with higher AC. However, the other nutrient quality traits and most processing quality traits were observed to decrease under low-nitrogen (LN) stress. Additionally, a correlation analysis indicated that the nutrient quality traits had stable tradeoffs with thousand kernel weight at all N levels because of the significantly negative correlations among them. Therefore, the additive main effect and multiplicative interaction (AMMI) model was used to further identify the most suitable colored genotypes with the best yield potential and also nutrient quality relative characteristics under LN stress. The blue lines Lanmai2999 and purple varieties Zhongkezinuomai 168 were found to be specifically adapted to LN stress with the highest AC values and showed stable performance in the other nutrient quality- and yield-related features. To further investigate the possible mechanism of anthocyanin accumulation in response to reduced N application, the expression of four genes (TaCHS, TaFDR, TaCHI and TaANS) involved in the anthocyanin synthesis pathway was evaluated. All four genes were downregulated under high nitrogen fertilizer application, indicating that anthocyanin synthesis in colored wheat might be inhibited by nitrogen fertilizer. Therefore, this research provided information for optimizing nitrogen fertilizer management in producing colored wheat and also demonstrated that it is efficient and economical to plant colored wheat genotypes in nitrogen-poor areas for use in a healthy human diet, improving the benefits of wheat planting and facilitating nitrogen pollution control.

IntroductionChina has made considerable progress with health system reforms in recent years. Rural China, however, has lagged behind as the diversity of needs of China's 3,000 rural counties were not always well addressed by national top-down reforms. China's Rural Health Reform Project Health XI (HXI) piloted a hybrid process of top down and bottom up implementation of health system reforms which were tailored to rural county level needs and covered a population of more than 21 million. Different studies provide evidence that HXI counties have achieved substantial benefits given the relatively limited investment. The Effectiveness of HXI subsequently raises the question how the hybrid approach may have resulted in effective implementation of interventions. We answer this question to advance understanding of hybrid approaches in general and in the rural Chinese context in particular, where the bottom-up elements might match poorly with the traditional organisational culture and learning style.Materials & methodsWe conducted an in-depth qualitative analysis in three 'best practice' counties, performing document-analyses, observations, semi-structured individual and group interviews. In alignment with the research question, this study is of an explorative nature and follows a sequence of deductive and inductive steps.ResultsHXI struggled initially as counties had difficulties to take initiative and autonomously select and adapt their own reforms. The initial reforms required multiple improvement iterations before achieving the planned results. The effectiveness of these bottom up reform processes has been aided by tight top down supervision and extensive domestic expert involvement. County level leadership is seen as essential to align the top down and bottom up structures and processes. Where successful, HXI has changed mind-sets and counties developed generic health improvement capabilities.ConclusionTailoring innovations to fit local needs formed a severe challenge for the three 'best practice' counties studied. A 'change of mindset' to actively take initiative and assume autonomy was needed to advance. Top down supervision and extensive support of experts was required to overcome the barriers. The studied counties finally achieved sustainable improvements and developed double loop learning capabilities beyond HXI objectives. Taken together, the above findings suggest that the continuum of healthcare reform implementation approaches in which hybrid approaches reside-from bottom up to top down-has two dimensions: a content dimension and a procedural dimension. Enabled by top down procedures, counties were able to bottom up tailor the content of best practice innovations to fit local needs.

BackgroundStudies on adriamycin mice model suggest complement system is activated and together with IgM contributes to the glomerular injury of primary focal segmental glomerulosclerosis (FSGS). We recently reported primary FSGS patients with IgM and C3 deposition showed unfavorable therapeutic responses and worse renal outcomes. Here we examined the plasma and urinary complement profile of patients with primary FSGS, aiming to investigate the complement participation in FSGS pathogenesis.MethodsSeventy patients with biopsy-proven primary FSGS were enrolled. The plasma and urinary levels of C3a, C5a, soluble C5b-9, C4d, C1q, MBL, and Bb were determined by commercial ELISA kits.ResultsThe levels of C3a, C5a and C5b-9 in plasma and urine of FSGS patients were significantly higher than those in normal controls. The plasma and urinary levels of C5b-9 were positively correlated with urinary protein, renal dysfunction and interstitial fibrosis. The plasma C5a levels were positively correlated with the proportion of segmental sclerotic glomeruli. The urinary levels of Bb were elevated, positively correlated with C3a and C5b-9 levels, renal dysfunction, and interstitial fibrosis. The plasma C1q level was significantly decreased, and negatively correlated with urinary protein excretion. Urinary Bb level was a risk factor for no remission (HR = 3.348, 95% CI 1.264-8.870, P = 0.015) and ESRD (HR = 2.323, 95% CI 1.222-4.418, P = 0.010).ConclusionIn conclusion, our results identified the systemic activation of complement in human primary FSGS, possibly via the classical and alternative pathway. The activation of complement system was partly associated with the clinical manifestations, kidney pathological damage, and renal outcomes.

Sex is a hallmark of eukaryotes but its evolution in microbial eukaryotes is poorly elucidated. Recent genomic studies revealed microbial eukaryotes possess a genetic toolkit necessary for sexual reproduction. However, the mechanism of sexual development in a majority of microbial eukaryotes including amoebozoans is poorly characterized. The major hurdle in studying sex in microbial eukaryotes is a lack of observational evidence, primarily due to its cryptic nature. In this study, we used a tractable fusing amoeba, Cochliopodium, to investigate sexual development using stage-specific Differential Gene Expression (DGE) and cytological analyses. Both DGE and cytological results showed that most of the meiosis and sex-related genes are upregulated in Cochliopodium undergoing fusion in laboratory culture. Relative gene ontology (GO) category representations in unfused and fused cells revealed a functional skew of the fused transcriptome toward DNA metabolism, nucleus and ligases that are suggestive of a commitment to sexual development. However, the GO categories of unfused cells were dominated by metabolic pathways and other processes indicative of a vegetative phase. Our study provides strong evidence that the fused cells represent a sexual stage in Cochliopodium. Our findings have further implications in understanding the evolution and mechanism of inheritance involving multiparents in other eukaryotes with a similar reproductive strategy.

ObjectivesWe previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvβ3, a transmembrane integrin receptor involved in intracellular signaling mediated by the tyrosine kinases FAK and Src, we hypothesized that γC alters endothelial barrier function by activating the FAK-Src pathway leading to junction dissociation and RhoA driven cytoskeletal stress-fiber formation.Methods and resultsUsing intravital microscopy of rat mesenteric microvessels, we show increased extravasation of plasma protein (albumin) resulting from γC administration. In addition, capillary fluid filtration coefficient (Kfc) indicated γC-induced elevated lung vascular permeability. Furthermore, γC decreased transendothelial barrier resistance in a time-dependent and dose-related fashion in cultured rat lung microvascular endothelial cells (RLMVECs), accompanied by increased FAK/Src phosphorylation detection by western blot. Experiments with pharmacological inhibition or gene silencing of FAK showed significantly reduced γC-induced albumin and fluid leakage across microvessels, stress-fiber formation, VE-cadherin tyrosine phosphorylation, and improved γC-induced endothelial barrier dysfunction, indicating the involvement of FAK in γC mediated hyperpermeability. Comparable results were found when Src was targeted in a similar manner, however inhibition of FAK prevented Src activation, suggesting that FAK is upstream of Src in γC-mediated hyperpermeability. In addition, γC-induced cytoskeletal stress-fiber formation was attenuated during inhibition or silencing of these tyrosine kinases, concomitantly with RhoA inhibition.ConclusionThe FAK-Src pathway contributes to γC-induced microvascular barrier dysfunction, junction protein phosphorylation and disorganization in a manner that involves RhoA and stress-fiber formation.

Heat stress decreases milk yield and deleteriously alters milk composition. Reduced feed intake partially explains some of the consequences of heat stress, but metabolic changes in the mammary tissue and liver associated with milk synthesis have not been thoroughly evaluated. In the current study, changes of protein abundance in the mammary tissue and liver between heat-stressed cows with ad libitum intake and pair-fed thermal neutral cows were investigated using the iTRAQ proteomic approach. Most of the differentially expressed proteins from mammary tissue and liver between heat-stressed and pair-fed cows were involved in Gene Ontology category of protein metabolic process. Pathway analysis indicated that differentially expressed proteins in the mammary tissue were related to pyruvate, glyoxylate and dicarboxylate metabolism pathways, while those in the liver participated in oxidative phosphorylation and antigen processing and presentation pathways. Several heat shock proteins directly interact with each other and were considered as central "hubs" in the protein interaction network. These findings provide new insights to understand the turnover of protein biosynthesis pathways within hepatic and mammary tissue that likely contribute to changes in milk composition from heat-stressed cows.

[This corrects the article DOI: 10.1371/journal.pone.0120646.].

ObjectivesTo evaluate patients' sense of responsibility to healthcare providers and to determine its predictors using on a national sample in China.MethodsWe conducted a national cross-sectional survey in China with a stratified cluster sample of patients treated in 77 hospitals between July 2014 and April 2015. Patients' sense of responsibility to healthcare providers was measured with four questions assessing patients' perceptions regarding their responsibilities to respect doctors, respect nurses, coordinate with health professionals, and comply with hospital rules. Predictors included patient sociodemographic characteristics and their past hospitalization experience.ResultsSmall proportions of respondents reported that they perceived having no responsibility to respect doctors (8.9%), respect nurses (7.9%), comply with hospital rules (6.7%), or coordinate with health professionals (6.3%). Multivariate regression analyses showed that the strongest predictor of patients' sense of responsibility to healthcare providers was patinets' trust in health professionals, followed by patients' education level. Familiarity with healthcare professionals and past hospitalization frequency were inversely associated with patients' sense of responsibility to healthcare providers.ConclusionsAlthough only a small proportion of the patients reported feeling no or low sense of responsibility to healthcare providers, the lack of respect and collaboration from these patients can negatively affect patient-provider relationships. Healthcare administrators need to communicate clearly with the patients and the public about the role of patients and the limitations of medicine in order to instill a sense of patients' responsibility.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels. In examining 3,080 tumor samples from 8 cancer types in The Cancer Genome Atlas, rDriver predicted 1,389 driver mutations. Compared with existing tools, rDriver identified more low frequency mutations associated with lineage specific functional properties, timing of occurrence and patient survival. Evaluation of rDriver predictions using engineered cell-line models resulted in a positive predictive value of 0.94 in PIK3CA genes. Our study highlights the importance of integrating multi-omic data in predicting cancer driver mutations and provides a statistically rigorous solution for cancer target discovery and development.

Multiple factors introduce uncertainty into projections of species distributions under climate change. The uncertainty introduced by the choice of baseline climate information used to calibrate a species distribution model and to downscale global climate model (GCM) simulations to a finer spatial resolution is a particular concern for mountainous regions, as the spatial resolution of climate observing networks is often insufficient to detect the steep climatic gradients in these areas. Using the maximum entropy (MaxEnt) modeling framework together with occurrence data on 21 understory bamboo species distributed across the mountainous geographic range of the Giant Panda, we examined the differences in projected species distributions obtained from two contrasting sources of baseline climate information, one derived from spatial interpolation of coarse-scale station observations and the other derived from fine-spatial resolution satellite measurements. For each bamboo species, the MaxEnt model was calibrated separately for the two datasets and applied to 17 GCM simulations downscaled using the delta method. Greater differences in the projected spatial distributions of the bamboo species were observed for the models calibrated using the different baseline datasets than between the different downscaled GCM simulations for the same calibration. In terms of the projected future climatically-suitable area by species, quantification using a multi-factor analysis of variance suggested that the sum of the variance explained by the baseline climate dataset used for model calibration and the interaction between the baseline climate data and the GCM simulation via downscaling accounted for, on average, 40% of the total variation among the future projections. Our analyses illustrate that the combined use of gridded datasets developed from station observations and satellite measurements can help estimate the uncertainty introduced by the choice of baseline climate information to the projected changes in species distribution.

Chronic kidney disease (CKD) is a risk factor for all-cause mortality in the United States, but the evidence from China is limited. We investigate whether prognosis of CKD (mortality) differs between the two countries. In particular, we sought to compare the strength of association between CKD stage and all-cause mortality, by country.Mortality-linked data from China National Survey of Chronic Kidney Disease (urban population, n = 25,269) and US NHANES (2005-2010, n = 15,209) for adults >20 years old were analyzed. The Chinese cohort was followed until Dec 31, 2013, while the NHANES cohort until Dec 31, 2011. CKD was defined by eGFR

Inactivating mutations in the control of virulence two-component regulatory system (covRS) often account for the hypervirulent phenotype in severe, invasive group A streptococcal (GAS) infections. As CovR represses production of the anti-phagocytic hyaluronic acid capsule, high level capsule production is generally considered critical to the hypervirulent phenotype induced by CovRS inactivation. There have recently been large outbreaks of GAS strains lacking capsule, but there are currently no data on the virulence of covRS-mutated, acapsular strains in vivo. We investigated the impact of CovRS inactivation in acapsular serotype M4 strains using a wild-type (M4-SC-1) and a naturally-occurring CovS-inactivated strain (M4-LC-1) that contains an 11bp covS insertion. M4-LC-1 was significantly more virulent in a mouse bacteremia model but caused smaller lesions in a subcutaneous mouse model. Over 10% of the genome showed significantly different transcript levels in M4-LC-1 vs. M4-SC-1 strain. Notably, the Mga regulon and multiple cell surface protein-encoding genes were strongly upregulated-a finding not observed for CovS-inactivated, encapsulated M1 or M3 GAS strains. Consistent with the transcriptomic data, transmission electron microscopy revealed markedly altered cell surface morphology of M4-LC-1 compared to M4-SC-1. Insertional inactivation of covS in M4-SC-1 recapitulated the transcriptome and cell surface morphology. Analysis of the cell surface following CovS-inactivation revealed that the upregulated proteins were part of the Mga regulon. Inactivation of mga in M4-LC-1 reduced transcript levels of multiple cell surface proteins and reversed the cell surface alterations consistent with the effect of CovS inactivation on cell surface composition being mediated by Mga. CovRS-inactivating mutations were detected in 20% of current invasive serotype M4 strains in the United States. Thus, we discovered that hypervirulent M4 GAS strains with covRS mutations can arise in an acapsular background and that such hypervirulence is associated with profound alteration of the cell surface.

Human bocaviruses (HBoVs), which were first identified in 2005 and are composed of genotypes 1-4, have been increasingly detected worldwide in pediatric patients with acute gastroenteritis. To investigate if HBoV infection is a risk factor of acute gastroenteritis in children younger than 5 years old, we searched PubMed, Embase (via Ovid), the Chinese Biomedical Literature Database (CBM), and the Cochrane Library for studies assessing the prevalence of HBoVs in individuals from Oct 25, 2005 to Oct 31, 2016. We included studies using PCR-based diagnostics for HBoVs from stool specimens of patients with or without acute gastroenteritis that carried out research for over 1 year on pediatric patients aged younger than 5 years old. The primary outcome was the HBoV prevalence among all cases with acute gastroenteritis. Pooled estimates of the HBoV prevalence were then generated by fitting linear mixed effect meta-regression models. Of the 36 studies included, the pooled HBoV prevalence in 20,591 patients with acute gastroenteritis was 6.90% (95% confidence interval (95% CI): 5.80-8.10%). In the ten studies with a control group, HBoVs were detected in 12.40% of the 3,620 cases with acute gastroenteritis and in 12.22% of the 2,030 control children (odds ratio (OR): 1.44; 95% CI: 0.95-2.19, p = 0.09 between case and control groups). HBoV1 and HBoV2 were detected in 3.49% and 8.59% of acute gastroenteritis cases, respectively, and in 2.22% and 5.09% of control children, respectively (OR: 1.40; 95% CI: 0.61-3.25; p = 0.43 and OR: 1.68; 95% CI: 1.21-2.32; p = 0.002, respectively). Current evidence suggests that the overall HBoV prevalence in children younger than 5 years old is not significantly different between groups with or without acute gastroenteritis. However, when HBoV1 was excluded, the HBoV2 prevalence was significantly different between these two groups, which may imply that HBoV2 is a risk factor of acute gastroenteritis in children younger than 5 years old.

The protective effects of ilexsaponin A on ischemia-reperfusion-induced myocardial injury were investigated. Myocardial ischemia/reperfusion model was established in male Sprague-Dawley rats. Myocardial injury was evaluated by TTC staining and myocardial marker enzyme leakage. The in vitro protective potential of Ilexsaponin A was assessed on hypoxia/reoxygenation cellular model in neonatal rat cardiomyocytes. Cellular viability and apoptosis were evaluated by MTT and TUNEL assay. Caspase-3, cleaved caspase-3, bax, bcl-2, p-Akt and Akt protein expression levels were detected by western-blot. Ilexsaponin A treatment was able to attenuate the myocardial injury in ischemia/reperfusion model by reducing myocardial infarct size and lower the serum levels of LDH, AST and CK-MB. The in vitro study also showed that ilexsaponin A treatment could increase cellular viability and inhibit apoptosis in hypoxia/reoxygenation cardiomyocytes. Proapoptotic proteins including caspase-3, cleaved caspase-3 and bax were significantly reduced and anti-apoptotic protein bcl-2 was significantly increased by ilexsaponin A treatment in hypoxia/reoxygenation cardiomyocytes. Moreover, Ilexsaponin A treatment was able to increase the expression levels of p-Akt in hypoxia/reoxygenation cellular model and myocardial ischemia/reperfusion animal model. Coupled results from both in vivo and in vitro experiments indicate that Ilexsaponin A attenuates ischemia-reperfusion-induced myocardial injury through anti-apoptotic pathway.

The advent of genetically modified (GM) Bt rice creates the possibility of interactions among Bt crops, crop pathogens and non-target herbivores. In particular, information on how pathogen-infected Bt-expressing plants will influence non-target herbivores is necessary to predict the sustainability of GM cropping systems. Laboratory bioassays were conducted to evaluate the potential combined impacts of rice dwarf virus (RDV) and two Bt rice lines, T1C-19 (Cry1C) and T2A-1 (Cry2A), on non-target green rice leafhopper (GRLH), Nephotettix cincticeps (Uhler) (Hemiptera: Cicadellidae). In the first experiment, GRLHs feeding preference tests on Bt rice lines compared to a parental control rice line, MH63, were conducted. As rice plants were uninfected with RDV, GRLHs generally preferred the control MH63 line over the two Bt lines during the initial 8 h, with no significant preference during the following 64 h. As rice plants were infected with RDV, there were no clear preferences between the Bt rice lines and the control MH63 line. In the second experiment, we assessed the combined influence of RDV-infection status and Bt rice lines on GRLH biological parameters. Egg duration, adult weights, and male adult longevity were significantly affected on RDV-infected Bt rice. Other parameters, egg hatching rate, nymph survival and fecundity were not significantly influenced. We infer that interaction effect among two testing Bt rice lines and RDV will not lead to enlarged pest populations, thus demonstrating that growing these two Bt rice lines will poses negligible risk to GRLH in sustainable rice agroecosystems. Long-term field experiments to monitor the population dynamics of GRLHs at large scale need to be carried out to confirm the current results.

Lung cancer is the leading cause of cancer death in the world, and aberrant expression of miRNA is a common feature during the cancer initiation and development. Our previous study showed that levels of miRNA-148a assessed by quantitative real-time polymerase chain reaction (qRT-PCR) were a good prognosis factor for non-small cell lung cancer (NSCLC) patients. In this study, we used high-throughput formalin-fixed and paraffin-embedded (FFPE) lung cancer tissue arrays and in situ hybridization (ISH) to determine the clinical significances of miRNA-148a and aimed to find novel target of miRNA-148a in lung cancer. Our results showed that there were 86 of 159 patients with low miRNA-148a expression and miRNA-148a was significantly down-regulated in primary cancer tissues when compared with their adjacent normal lung tissues. Low expression of miRNA-148a was strongly associated with high tumor grade, lymph node (LN) metastasis and a higher risk of tumor-related death in NSCLC. Lentivirus mediated overexpression of miRNA-148a inhibited migration and invasion of A549 and H1299 lung cancer cells. Furthermore, we validated Wnt1 as a direct target of miRNA-148a. Our data showed that the Wnt1 expression was negatively correlated with the expression of miRNA-148a in both primary cancer tissues and their corresponding adjacent normal lung tissues. In addition, overexpression of miRNA-148a inhibited Wnt1 protein expression in cancer cells. And knocking down of Wnt-1 by siRNA had the similar effect of miRNA-148a overexpression on cell migration and invasion in lung cancer cells. In conclusion, our results suggest that miRNA-148a inhibited cell migration and invasion through targeting Wnt1 and this might provide a new insight into the molecular mechanisms of lung cancer metastasis.

The association between height and lung cancer risk has been investigated by epidemiological studies but the results are inconsistent. This meta-analysis was to evaluate whether the height is associated with lung cancer.We identified relevant articles by searching the MEDLINE and EMBASE databases, and reviewed the reference lists of selected papers. A random effect model was used to calculate summary odds ratios (OR) and relative risk (RR) with 95% confidence intervals (95% CI). Publication bias was estimated using Egger's regression asymmetry test.We included a total 16 studies (15 prospective studies and one case-control study) on adult height and lung cancer risk in the meta-analysis. Overall, per 10-cm height increases were associated with increased risk of lung cancer (RR 1.06; 95% CI 1.03-1.09, I2 = 43.6%).In this meta-analysis, high adult height is related to increased lung cancer risk. Well-designed, large prospective studies are required to obtain a better indication of the relationship.

To provide an empirical examination of patient-provider relationships (PPR) and its association with organizational and individual factors.A national cross-sectional survey was conducted by stratified cluster sampling in 77 hospitals across seven provinces in China between July 2014 and April 2015, involving 3621 doctors, 5561 nurses, and 8022 patients with response rates of 62.93%, 61.16%, and 33.08%, respectively. Self-perceived PPR was the outcome variable. Organizational factors included hospital type (western medicine [WM] and traditional Chinese medicine [TCM] hospital); hospital level (tertiary and secondary hospital); area of specialization (internal medicine and surgery); ratio of doctors (nurses) to ward beds; doctors/nurses' concerns about performance assessment; and patients' perceptions of healthcare cost. Individual factors included consultation, listening to patients and socio-demographic factors.54.6% of doctors, 36.6% of nurses, and 10.2% of patients perceived PPR as poor. Organizational factors independently associated with providers' perception of poor PPR included hospital type (WM vs TCM: OR = 1.25 [95% CI: 1.06-1.47]) and concerns about performance assessment (high vs low levels: OR = 1.40 [95% CI: 1.14-1.72]) for doctors, and concerns about performance assessment (average vs low levels: OR = 0.79 [95% CI: 0.67-0.93]) for nurses. Those associated with patients' perception of poor PPR included hospital type (WM vs TCM: OR = 0.63 [95% CI: 0.53-0.74]) and hospital level (tertiary vs secondary: OR = 0.65 [95% CI: 0.51-0.82]). Doctors and nurses reporting listening to patients "frequently" had better perceptions of PPR (OR = 0.46 [95%CI: 0.38-0.56] and 0.49 [95% CI: 0.41-0.59] for doctors and nurses, respectively), as did their patients (OR = 0.24 [95% CI: 0.18-0.31] and 0.54 [95% CI: 0.35-0.84] for doctors and nurses, respectively).Although our findings require validation in different organizational settings given the likely variability of these associations across systems, our results suggest that implementing moderate levels promoting the level of medical treatment, and broadening doctors/nurses training regarding listening to patients, may benefit to enhance PPR.

Chronic stress induces altered energy metabolism and plays important roles in the etiology of depression, in which the glucocorticoid negative feedback is disrupted due to imbalanced glucocorticoid receptor (GR) functions. The mechanism underlying the dysregulation of GR by chronic stress remains elusive. In this study, we investigated the role of AMP-activated protein kinase (AMPK), the key enzyme regulating cellular energy metabolism, and related signaling pathways in chronic stress-induced GR dysregulation. In cultured rat cortical astrocytes, glucocorticoid treatment decreased the level, which was accompanied by the decreased expression of liver kinase B1 (LKB1) and reduced phosphorylation of AMPK. Glucocorticoid-induced effects were attenuated by glucocorticoid-inducible kinase 1 (SGK1) inhibitor GSK650394, which also inhibited glucocorticoid induced phosphorylation of Forkhead box O3a (FOXO3a). Furthermore, glucocorticoid-induced down-regulation of GR was mimicked by the inhibition of AMPK and abolished by the AMPK activators or the histone deacetylase 5 (HDAC5) inhibitors. In line with the role of AMPK in GR expression, AMPK activator metformin reversed glucocorticoid-induced reduction of AMPK phosphorylation and GR expression as well as behavioral alteration of rats. Taken together, these results suggest that chronic stress activates SGK1 and suppresses the expression of LKB1 via inhibitory phosphorylation of FOXO3a. Downregulated LKB1 contributes to reduced activation of AMPK, leading to the dephosphorylation of HDAC5 and the suppression of transcription of GR.

Lesion mimics (LMs) that exhibit spontaneous disease-like lesions in the absence of pathogen attack might confer enhanced plant disease resistance to a wide range of pathogens. The LM mutant, lm3 was derived from a single naturally mutated individual in the F1 population of a 3-1/Jing411 cross, backcrossed six times with 3-1 as the recurrent parent and subsequently self-pollinated twice. The leaves of young seedlings of the lm3 mutant exhibited small, discrete white lesions under natural field conditions. The lesions first appeared at the leaf tips and subsequently expanded throughout the entire leaf blade to the leaf sheath. The lesions were initiated through light intensity and day length. Histochemical staining revealed that lesion formation might reflect programmed cell death (PCD) and abnormal accumulation of reactive oxygen species (ROS). The chlorophyll content in the mutant was significantly lower than that in wildtype, and the ratio of chlorophyll a/b was increased significantly in the mutant compared with wildtype, indicating that lm3 showed impairment of the biosynthesis or degradation of chlorophyll, and that Chlorophyll b was prone to damage during lesion formation. The lm3 mutant exhibited enhanced resistance to wheat powdery mildew fungus (Blumeria graminis f. sp. tritici; Bgt) infection, which was consistent with the increased expression of seven pathogenesis-related (PR) and two wheat chemically induced (WCI) genes involved in the defense-related reaction. Genetic analysis showed that the mutation was controlled through a single partially dominant gene, which was closely linked to Xbarc203 on chromosome 3BL; this gene was delimited to a 40 Mb region between SSR3B450.37 and SSR3B492.6 using a large derived segregating population and the available Chinese Spring chromosome 3B genome sequence. Taken together, our results provide information regarding the identification of a novel wheat LM gene, which will facilitate the additional fine-mapping and cloning of the gene to understand the mechanism underlying LM initiation and disease resistance in common wheat.

Understanding the interactions between species and their coexistence mechanisms will help explain biodiversity maintenance and enable managers to make sound conservation decisions. Mesocarnivores are abundant and diverse mid-sized carnivores and can have profound impacts on the function, structure and dynamics of ecosystem after the extirpation of apex predators in many ecosystems. The moist temperate forests of Southwest China harbor a diverse community of mesocarnivores in the absence of apex predators. Sympatric species tend to partition limited resources along time, diet and space to facilitate coexistence. We determined the spatial and temporal patterns for five species of mesocarnivores. We used detection histories from a large camera-trap dataset collected from 2004-2015 with an extensive effort of 23,313 camera-days from 495 camera locations. The five mesocarnivore species included masked palm civet Paguma larvata, leopard cat Prionailurus bengalensis, hog badger Arctonyx collaris, yellow-throated marten Martes flavigula, and Siberian weasel Mustela sibirica. Only the masked palm civet and hog badger tended to avoid each other; while for other pairs of species, they occurred independently of each other, or no clear pattern observed. With regard to seasonal activity, yellow-throated marten was most active in winter, opposite the pattern observed for masked palm civet, leopard cat and hog badger. For diel activity, masked palm civet, leopard cat and hog badger were primarily nocturnal and crepuscular; yellow-throated marten was diurnal, and Siberian weasel had no clear pattern for most of the year (March to November), but was nocturnal in the winter (December to February). The seasonal shift of the Siberian weasel may be due to the high diet overlap among species in winter. Our results provided new facts and insights into this unique community of mesocarnivores of southwest China, and will facilitate future studies on the mechanism determining coexistence of animal species within complex system.

PURPOSE:To study the role of long non-coding RNA (lncRNA) MALAT1 in transforming growth factor beta 1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells. METHODS:ARPE-19 cells were cultured and exposed to TGF-β1. The EMT of APRE-19 cells is confirmed by morphological change, as well as the increased expression of alpha-smooth muscle actin (αSMA) and fibronectin, and the down-regulation of E-cadherin and Zona occludin-1(ZO-1) at both mRNA and protein levels. The expression of lncRNA MALAT1 in RPE cells were detected by quantitative real-time PCR. Knockdown of MALAT1 was achieved by transfecting a small interfering RNA (SiRNA). The effect of inhibition of MALAT1 on EMT, migration, proliferation, and TGFβ signalings were observed. MALAT1 expression was also detected in primary RPE cells incubated with proliferative vitreoretinopathy (PVR) vitreous samples. RESULTS:The expression of MALAT1 is significantly increased in RPE cells incubated with TGFβ1. MALAT1 silencing attenuates TGFβ1-induced EMT, migration, and proliferation of RPE cells, at least partially through activating Smad2/3 signaling. MALAT1 is also significantly increased in primary RPE cells incubated with PVR vitreous samples. CONCLUSION:LncRNA MALAT1 is involved in TGFβ1-induced EMT of human RPE cells and provides new understandings for the pathogenesis of PVR.

BACKGROUND AND AIMS:Protein tyrosine phosphatase 1B (PTP1B) is a novel therapeutic target for type-2 diabetes, which negatively regulates the insulin signaling transduction. Bis (2, 3-dibromo-4, 5-dihydroxybenzyl) ether (BDDE), a novel bromophenol isolated from the Red Alga, is a novel PTP1B inhibitor. But the anti-diabetic effects are not clear. In the present study, we evaluated the in vitro and in vivo antidiabetic effects of BDDE. METHODS:The insulin-resistant HepG2 cells were used to evaluate the in vitro antidiabetic effects of BDDE. MTT assay was used to determine the safety concentrations in HepG2 cells. Glucose assay kit was used to check glucose uptake after treated with BDDE. Western blotting assay was used to explore the potent mechanisms. The db/db mice were used to evaluate the in vivo antidiabetic effects of BDDE. Body weight, blood glucose, Glycated hemoglobin (HbA1c), lipid profile, and insulin level were checked at the respective time points. Gastrocnemii were dissected and used to analyze the PTP1B and insulin receptor β (IRβ) expression. RESULTS:BDDE increased the insulin-resisted glucose uptake in HepG2 cells. BDDE also decreased the expression of PTP1B and activated the substrates and downstream signals in insulin signal pathway, such as IRβ, insulin receptor substrate-1/2 (IRS1/2), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB/Akt). In the db/db mice model, BDDE significantly decreased the blood glucose, HbA1c and triglyceride (TG) levels. BDDE also decreased the expression of PTP1B and activated the phosphorylation of IRβ in gastrocnemii. Moreover, BDDE at high doses downregulated the body weight without affecting food and water intake. CONCLUSION:Our results suggest that BDDE as a new PTP1B inhibitor improves glucose metabolism by stimulating the insulin signaling and could be used in the treatment of type-2 diabetes mellitus.

Irisin, a newly discovered myokine, is considered as a promising candidate for the treatment of metabolic disturbances and cardiovascular diseases. In the present study, we used two animal models, apolipoprotein E-deficient mice fed on a high-cholesterol diet and a mouse carotid partial ligation model to test the anti-atherosclerotic effect of irisin. Irisin treatment (0.5 μg/g body weight/day) significantly reduced the severity of aortic atherosclerosis in apolipoprotein E-deficient mice fed on a high-cholesterol diet and suppressed carotid neointima formation in a carotid partial ligation model. It was associated with decreased inflammation and cell apoptosis in aortic tissues. In addition, in a cell culture model, irisin restored ox-LDL-induced human umbilical vein endothelial cell dysfunction by reducing the levels of inflammatory genes via inhibiting the reactive oxygen species (ROS)/ p38 MAPK/ NF-κB signaling pathway activation and inhibiting cell apoptosis via up-regulating Bcl-2 and down-regulating Bax and caspase-3 expression. Our study demonstrated that irisin significantly reduced atherosclerosis in apolipoprotein E-deficient mice via suppressing ox-LDL-induced cell inflammation and apoptosis, which might have a direct therapeutic effect on atherosclerotic diseases.

In the alpine steppe zone on the Central Tibetan Plateau, a large amount of area has been degraded due to natural and artificial factors. N & P fertilization is widely accepted to recover degraded pastures in other regions all over the world. However, it is not clear how alpine steppe communities respond to N & P fertilization, and what is the optimal application rate, in the perspective of forage production. To attempt to explore these questions, in July 2013, two fencing sites were designed in Baingoin County with 12 treatments of different levels of nitrogen (N0: 0; N1: 7.5 g m(-2) yr(-1); N2: 15 g m(-2) yr(-1)) & phosphate (P0: 0; P1: 7.5 gP2O5 m(-2) yr(-1); P2: 15 gP2O5 m(-2) yr(-1); P3: 30 gP2O5 m(-2) yr(-1)). The results indicated N&P addition was capable to ameliorate the quality of the two sites in the Tibetan Plateau steppe. Increasing N application level resulted in significant increment in Gramineae and total biomass in the two sites. P addition significantly improved the quantity of Compositae, total biomass and the biomasss of other species in site II, while it only significantly improved the total biomass in site I. Gramineae was much more sensitive to N-induced changes than P-induced changes, and this indicated N addition was better to ameliorate the quality of plateau steppe than P-induced changes. No strong evidence was found for critical threshold within 15 g N m(-2) yr(-1), and there was decreasing tendency when P addition rate was above 15 g m(-2) yr(-1). N&P has the potential to accelerate soil acidification, which improved the content of available K, likely as a result of nonsignificant correlation between biomass and soil moisture. This work highlights the the tradeoffs that exist in N and P addition in recovering degraded steppe.

Viral infections caused by human bocaviruses 1-4 (HBoV1-4) are more complicated than previously believed. A retrospective, large-scale study was undertaken to explore the prevalence of HBoV1-4 in pediatric patients with various infectious diseases and delineate their phylogenetic characteristics.Clinical samples from four specimen types, including 4,941 respiratory, 2,239 cerebrospinal fluid (CSF), 2,619 serum, and 1,121 fecal specimens, collected from pediatric patients with various infectious diseases were screened for HBoV1-4. A 690-nt fragment in each specimen was then amplified and sequenced for phylogenetic analysis. Clinical characteristics of HBoV-positive patients with different specimen types available were evaluated.Approximately 1.2% of patients were confirmed as HBoV-positive, with the highest positive rate in patients with gastrointestinal infection (2.2%), followed by respiratory (1.65%), central nervous system (0.8%), and hematological infections (0.2%). A single genetic lineage of HBoV1 circulated among children over the 8-year period, while a new cluster of HBoV2, via intra-genotype recombination between HBoV2A and HBoV2B, was prevalent. Some patients had HBoV1-positive respiratory and serum specimens or fecal specimens. Several cases became HBoV1-positive following the appearance of respiratory infection, while several cases were positive for HBoV2 only in CSF and serum specimens, rather than respiratory specimens.A single genetic lineage of HBoV1 is speculated as a viral pathogen of respiratory infection and causes both comorbid infection and acute gastroenteritis. Additionally, a new cluster of HBoV2 is prevalent in China, which may infect the host through sites other than the respiratory tract.

UNLABELLED:A rapid expansion of HFMD with enterovirus 71 infection outbreaks has occurred and caused deaths in recent years in China, but no vaccine or antiviral drug is currently available for EV71 infection. This study aims to provide treatment programs for HFMD patients. We conducted a randomized, double-blind, controlled trial and evaluated clinical efficacy of therapy with rHuIFN-α1b in HFMD patients with EV71 infection. There were statistical differences in outcomes including the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load of the HFMD patients among ultrasonic aerosol inhalation group, intramuscular injection group and control group. rHuIFN-α1b therapy reduced the fever clearance time, healing time of typical skin or oral mucosa lesions, and EV71 viral load in children with HFMD. TRIAL REGISTRATION:Chinese Clinical Trial Registry ChiCTR-TRC-14005153.

BACKGROUND:Ovarian cancer is the most lethal type of malignant tumor in gynecological cancers and is associated with a high percentage of late diagnosis and chemotherapy resistance. Thus, it is urgent to identify a tumor marker or a molecular target that allows early detection and effective treatment. RNA-binding proteins (RBPs) are crucial in various cellular processes at the post-transcriptional level. The eukaryotic translation initiation factor 4 gamma, 1(eIF4G1), an RNA-binding protein, facilitates the recruitment of mRNA to the ribosome, which is a rate-limiting step during the initiation phase of protein synthesis. However, little is known regarding the characteristics of eIF4G1 expression and its clinical significance in ovarian cancer. Therefore, we propose to investigate the expression and clinicopathological significance of eIF4G1 in ovarian cancer patients. METHODS:We performed Real-time PCR in 40 fresh serous ovarian cancer tissues and 27 normal ovarian surface epithelial cell specimens to assess eIF4G1mRNA expression. Immunohistochemistry (IHC) was used to examine the expression of eIF4G1 at the protein level in 134 patients with serous ovarian cancer and 18 normal ovarian tissues. Statistical analysis was conducted to determine the correlation of the eIF4G1 protein levels with the clinicopathological characteristics and prognosis in ovarian cancer. RESULTS:The expression of eIF4G1 was upregulated in serous ovarian cancer tissues at both the mRNA (P = 0.0375) and the protein (P = 0.0007) levels. The eIF4G1 expression was significantly correlated with the clinical tumor stage (P = 0.0004) and omentum metastasis (P = 0.024). Moreover, patients with low eIF4G1 protein expression had a longer overall survival time (P = 0.026). CONCLUSIONS:These data revealed that eIF4G1 is markedly expressed in serous ovarian cancer and that upregulation of the eIF4G1 protein expression is significantly associated with an advanced tumor stage. Besides, the patients with lower expression of eIF4G1 tend to have a longer overall survival time. Thus, eIF4G1 may contribute to the occurrence and metastasis of ovarian cancer and can serve as a potential therapeutic target for the treatment of ovarian cancer.

Renal fibrosis is the common pathological foundation of many chronic kidney diseases (CKDs). The aim of this study was to investigate whether Hydroxysafflor yellow A (HSYA) can preserve renal function by inhibiting the progression of renal fibrosis and the potential mechanisms.Renal fibrosis was induced by unilateral ureteral obstruction (UUO) performed on 7-week-old C57BL/6 mice. HSYA (10, 50 and 100 mg/kg) were intragastrically administered. Sham group and model group were administered with the same volume of vehicle. Serum and kidney samples were collected 14 days after the UUO surgery. Serum biochemical indicators were measured by automatic biochemical analyzer. Histological changes were evaluated by HE and Masson staining. In vitro, the anti-fibrotic effect of HSYA was tested on human recombinant transforming growth factor-β1 (TGF-β1) stimulated HK-2 cells. The protein levels of α-SMA, collagen-I and fibronectin in kidney tissue and HK-2 cells were measured by immunohistochemistry and immunofluorescence. The protein levels of apoptosis-relative and TGF-β1/Smad3 signaling were detected by western blot.HSYA slowed the development of renal fibrosis both in vivo and in vitro. In UUO rats, renal function index suggested that HSYA treatment decreased the level of serum creatinine (Scr) and blood urea nitrogen (BUN) rose by UUO (P

Nutrition risk Screening 2002 (NRS-2002) and Subjective Global Assessment (SGA) are widely used screening tools but have not been compared in a Chinese population. We conducted secondary data analysis of a cross-sectional study which included 332 hospitalized gastrointestinal disease patients, collected by the Gastrointestinal department of Peking Union Medical College Hospital (PUMCH) in 2008. Results of NRS-2002 and SGA screening tools, complications, length of stay (LOS), cost, and death were measured. The agreement between the tools was assessed via Kappa (κ) statistics. The performance of NRS-2002 and SGA in predicting LOS and cost was assessed via linear regression. The complications and death prediction of tools was assessed using receiver operating characteristic (ROC) curves. NRS-2002 and SGA identified nutrition risk at 59.0% and 45.2% respectively. Moderate agreement (κ >0.50) between the two tools was found among all age groups except individuals aged ≤ 20, which only slight agreement was found (κ = 0.087). NRS-2002 (R square 0.130) and SGA (R square 0.140) did not perform differently in LOS prediction. The cost prediction of NRS-2002 (R square 0.198) and SGA (R square 0.190) were not significantly different. There was no difference between NRS-2002 (infectious complications: area under ROC (AUROC) = 0.615, death: AUROC = 0.810) and SGA (infectious complications: AUROC = 0.600, death: AUROC = 0.846) in predicting infectious complication and death, but NRS-2002 (0.738) seemed to perform better than SGA (0.552) in predicting non-infectious complications. The risk of malnutrition among patients was high. NRS-2002 and SGA have similar capacity to predict LOS, cost, infectious complications and death, but NRS-2002 performed better in predicting non-infectious complications.

Ofd1 is a newly identified causative gene for Retinitis pigmentosa (RP), a photoreceptor degenerative disease. This study aimed to examine Ofd1 localization in retina and further to investigate its function in photoreceptor degeneration models. Ofd1 localization in rat retina was examined using immunofluorescence. N-methyl-N-nitrosourea (MNU)-induced rats and Royal College of Surgeons (RCS) rats were used as photoreceptor degeneration models. The expression pattern of Ofd1, other ciliary associated genes and Wnt signaling pathway genes were examined in rat models. Furthermore, pEGFP-Ofd1-CDS and pSUPER-Ofd1-shRNA were constructed to overexpress and knockdown the expression level in 661W and R28 cells. MNU was also used to induce cell death. Cilia formation was observed using immunocytochemistry (ICC). Reactive oxygen species (ROS) were detected using the 2', 7'-Dichlorofluorescin diacetate (DCFH-DA) assay. Apoptosis genes expression was examined using qRT-PCR, Western blotting and fluorescence-activated cell sorting (FACS). Ofd1 localized to outer segments of rat retina photoreceptors. Ofd1 and other ciliary proteins expression levels increased from the 1st and 4th postnatal weeks and decreased until the 6th week in the RCS rats, while their expression consistently decreased from the 1st and 7th day in the MNU rats. Moreover, Wnt signaling pathway proteins expression was significantly up-regulated in both rat models. Knockdown of Ofd1 expression resulted in a smaller population, shorter length of cell cilia, and lower cell viability. Ofd1 overexpression partially attenuated MNU toxic effects by reducing ROS levels and mitigating apoptosis. To the best of our knowledge, this is the first study demonstrating Ofd1 localization and its function in rat retina and in retinal degeneration rat models. Ofd1 plays a role in controlling photoreceptor cilium length and number. Importantly, it demonstrates a neuroprotective function by protecting the photoreceptor from oxidative stress and apoptosis. These data have expanded our understanding of Ofd1 function beyond cilia, and we concluded that ofd1 neuroprotection could be a potential treatment strategy in retina degeneration models.

Breast cancer has various molecular subtypes and displays high heterogeneity. Aberrant DNA methylation is involved in tumor origin, development and progression. Moreover, distinct DNA methylation patterns are associated with specific breast cancer subtypes. We explored DNA methylation patterns in association with gene expression to assess their impact on the prognosis of breast cancer based on Infinium 450K arrays (training set) from The Cancer Genome Atlas (TCGA). The DNA methylation patterns of 12 featured genes that had a high correlation with gene expression were identified through univariate and multivariable Cox proportional hazards models and used to define the methylation risk score (MRS). An improved ability to distinguish the power of the DNA methylation pattern from the 12 featured genes (p = 0.00103) was observed compared with the average methylation levels (p = 0.956) or gene expression (p = 0.909). Furthermore, MRS provided a good prognostic value for breast cancers even when the patients had the same receptor status. We found that ER-, PR- or Her2- samples with high-MRS had the worst 5-year survival rate and overall survival time. An independent test set including 28 patients with death as an outcome was used to test the validity of the MRS of the 12 featured genes; this analysis obtained a prognostic value equivalent to the training set. The predict power was validated through two independent datasets from the GEO database. The DNA methylation pattern is a powerful predictor of breast cancer survival, and can predict outcomes of the same breast cancer molecular subtypes.

Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC) allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP) chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS), and the concomitant investigation of the protective effect of fluoxetine was also evaluated. Identification of plasma metabolic profiles indicated that significant changes in specific metabolites occurred after fluoxetine exposure, including increased phenylalanine, serine, acetyl-L-carnitine, carnitine and decreased creatine, betaine, proline, tryptophan, tyrosine, C16:0 LPC. Some novel biomarkers from this HILIC-UHPLC/MS approach were betaine, proline, tyrosine creatine and serine compared with the results of RP-UHPLC/MS. The complementary nature of this technique is confirmed and is on agreement with previously published studies.

Many HIV serodiscordant couples have a strong desire to have their own biological children. Natural conception may be the only choice in some resource limited settings but data about natural conception is limited. Here, we reported our findings of natural conception in HIV serodiscordant couples. Between January 2008 and June 2014, we retrospectively collected data on 91 HIV serodiscordant couples presenting to Beijing Youan Hospital with childbearing desires. HIV counseling, effective ART on HIV infected partners, pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) in negative female partners and timed intercourse were used to maximally reduce the risk of HIV transmission. Of the 91 HIV serodiscordant couples, 43 were positive in male partners and 48 were positive in female partners. There were 196 unprotected vaginal intercourses, 100 natural conception and 97 newborns. There were no cases of HIV seroconversion in uninfected sexual partners. Natural conception may be an acceptable option in HIV-serodiscordant couples in resource limited settings if HIV-positive individuals have undetectable viremia on HAART, combined with HIV counseling, PrEP, PEP and timed intercourse.

The WRKY transcription factors modulate numerous physiological processes, including plant growth, development and responses to various environmental stresses. Currently, our understanding of the functions of the majority of the WRKY family members and their possible roles in signalling crosstalk is limited. In particular, very few WRKYs have been identified and characterised from an economically important crop, cotton. In this study, we characterised a novel group IIc WRKY gene, GhWRKY68, which is induced by different abiotic stresses and multiple defence-related signalling molecules. The β-glucuronidase activity driven by the GhWRKY68 promoter was enhanced after exposure to drought, salt, abscisic acid (ABA) and H2O2. The overexpression of GhWRKY68 in Nicotiana benthamiana reduced resistance to drought and salt and affected several physiological indices. GhWRKY68 may mediate salt and drought responses by modulating ABA content and enhancing the transcript levels of ABA-responsive genes. GhWRKY68-overexpressing plants exhibited reduced tolerance to oxidative stress after drought and salt stress treatments, which correlated with the accumulation of reactive oxygen species (ROS), reduced enzyme activities, elevated malondialdehyde (MDA) content and altered ROS-related gene expression. These results indicate that GhWRKY68 is a transcription factor that responds to drought and salt stresses by regulating ABA signalling and modulating cellular ROS.

To evaluate the frequency and clinicopathological features of ROS1 and RET rearrangements in N2 node positive stage IIIA (IIIA-N2) non-small cell lung cancer (NSCLC) patients, we retrospectively screened 204 cases with a tissue microarray (TMA) panel by fluorescent in situ hybridization (FISH), and confirmed by direct sequencing and immunohistochemistry (IHC). The relationship between ROS1 or RET rearrangements, clinicopathological features, and prognostic factors were analyzed in resected stage IIIA-N2 NSCLC. Of the 204 cases, 4 cases were confirmed with ROS1 rearrangement, but no RET rearrangement was detected. All 4 ROS1-rearranged cases were adenocarcinomas. The predominant pathological type was acinar pattern in ROS1-rearranged tumors, except for 1 case harboring a mixture acinar and mucous tumor cells. Variants of ROS1 rearrangement were SDC4-ROS1 (E2:E32), SDC4-ROS1 (E4:E32) and SDC4-ROS1 (E4:E34). There was no significant association between ROS1 rearrangement and clinicopathological characteristics. In this cohort, multivariate analysis for overall survival (OS) indicated that squamous cell carcinoma and lobectomy were independent predictors of poor prognosis; R0 surgical resection and non-pleural invasion were independent predictors of good prognosis. In resected stage IIIA-N2 NSCLC patients, ROS1-rearranged cases tended to occur in younger patients with adenocarcinomas. The prognosis of resected stage IIIA-N2 is generally considered poor, but patients with ROS1 rearrangement will benefit from the targeted therapy.

Chemotherapy resistance is the major reason for the failure of ovarian cancer treatment. One mechanism behind chemo-resistance involves the upregulation of multidrug resistance (MDR) genes (ABC transporters) that effectively transport (efflux) drugs out of the tumor cells. As a common symptom in stage III/IV ovarian cancer patients, ascites is associated with cancer progression. However, whether ascites drives multidrug resistance in ovarian cancer cells awaits elucidation. Here, we demonstrate that when cultured with ascites derived from ovarian cancer-bearing mice, a murine ovarian cancer cell line became less sensitive to paclitaxel, a first line chemotherapeutic agent for ovarian cancer patients. Moreover, incubation of murine ovarian cancer cells in vitro with ascites drives efflux function in these cells. Functional studies show ascites-driven efflux is suppressible by specific inhibitors of either of two ABC transporters [Multidrug Related Protein (MRP1); Breast Cancer Related Protein (BCRP)]. To demonstrate relevance of our findings to ovarian cancer patients, we studied relative efflux in human ovarian cancer cells obtained from either patient ascites or from primary tumor. Immortalized cell lines developed from human ascites show increased susceptibility to efflux inhibitors (MRP1, BCRP) compared to a cell line derived from a primary ovarian cancer, suggesting an association between ascites and efflux function in human ovarian cancer. Efflux in ascites-derived human ovarian cancer cells is associated with increased expression of ABC transporters compared to that in primary tumor-derived human ovarian cancer cells. Collectively, our findings identify a novel activity for ascites in promoting ovarian cancer multidrug resistance.

Recent studies found that TIPE2 was involved in cancer development. However, little is known about TIPE2 in lung cancer. Our study aims to clarify the role of TIPE2 in lung carcinogenesis. We examined the expression of TIPE2 in lung squamous cancer (LSC), small cell lung cancer and lung adenocarcinoma (AdC) tissues and found that TIPE2 expression was lost in small cell lung cancer, compared with adjacent non-tumor tissues. Overexpression of TIPE2 significantly inhibited the growth of lung cancer cell H446 in vitro and even suppressed tumor formation in vivo. Flow cytometry analysis found TIPE2 overexpression promoted apoptosis of H446. In TIPE2 over-expression cells, caspase-3, caspase-9, and Bax were significantly up-regulated while Bcl-2 was down-regulated. Moreover, coincident results were shown by immunohistochemistry in tumors from nude mice. TIPE2 inhibited the phosphorylation of Akt, while promoting the phosphorylation of P38, but had no effect on IκBα and ERK pathway. Taken together, TIPE2 promoted lung cancer cell apoptosis through affecting apoptosis-related molecules caspase-3, caspase-9, Bcl-2 and Bax, possibly via regulating P38 and Akt pathways, indicating that TIPE2 might be a novel marker for lung cancer diagnosis and therapy.

Pea (Pisum sativum L.) is an important food legume globally, and is the plant species that J.G. Mendel used to lay the foundation of modern genetics. However, genomics resources of pea are limited comparing to other crop species. Application of marker assisted selection (MAS) in pea breeding has lagged behind many other crops. Development of a large number of novel and reliable SSR (simple sequence repeat) or microsatellite markers will help both basic and applied genomics research of this crop. The Illumina HiSeq 2500 System was used to uncover 8,899 putative SSR containing sequences, and 3,275 non-redundant primers were designed to amplify these SSRs. Among the 1,644 SSRs that were randomly selected for primer validation, 841 yielded reliable amplifications of detectable polymorphisms among 24 genotypes of cultivated pea (Pisum sativum L.) and wild relatives (P. fulvum Sm.) originated from diverse geographical locations. The dataset indicated that the allele number per locus ranged from 2 to 10, and that the polymorphism information content (PIC) ranged from 0.08 to 0.82 with an average of 0.38. These 1,644 novel SSR markers were also tested for polymorphism between genotypes G0003973 and G0005527. Finally, 33 polymorphic SSR markers were anchored on the genetic linkage map of G0003973 × G0005527 F2 population.

An initial step in amyloid-β (Aβ) production includes amyloid precursor protein (APP) cleavage via β-Site amyloid precursor protein cleaving enzyme 1 (BACE1). Increased levels of brain Aβ have been implicated in the pathogenesis of Alzheimer's disease (AD). Thus, β-secretase represents a primary target for inhibitor drug development in AD. In this study, aptamers were obtained from combinatorial oligonucleotide libraries using a technology referred to as systematic evolution of ligands by exponential enrichment (SELEX). A purified human BACE1 extracellular domain was used as a target to conduct an in vitro selection process using SELEX. Two DNA aptamers were capable of binding to BACE1 with high affinity and good specificity, with Kd values in the nanomolar range. We subsequently confirmed that one aptamer, A1, exhibited a distinct inhibitory effect on BACE1 activity in an AD cell model. We detected the effects of M17-APPsw cells that stably expressed Swedish mutant APP after aptamer A1 treatment. Aβ40 and Aβ42 concentrations secreted by M17-APPsw cells decreased intracellularly and in culture media. Furthermore, Western blot analysis indicated that sAPPβ expression significantly decreased in the A1 treated versus control groups. These findings support the preliminary feasibility of an aptamer evolved from a SELEX strategy to function as a potential BACE1 inhibitor. To our knowledge, this is the first study to acquire a DNA aptamer that exhibited binding specificity to BACE1 and inhibited its activity.

A number of studies have explored the time course of Chinese semantic and syntactic processing. However, whether syntactic processing occurs earlier than semantics during Chinese sentence reading is still under debate. To further explore this issue, an event-related potentials (ERPs) experiment was conducted on 21 native Chinese speakers who read individually-presented Chinese simple sentences (NP1+VP+NP2) word-by-word for comprehension and made semantic plausibility judgments. The transitivity of the verbs was manipulated to form three types of stimuli: congruent sentences (CON), sentences with a semantically violated NP2 following a transitive verb (semantic violation, SEM), and sentences with a semantically violated NP2 following an intransitive verb (combined semantic and syntactic violation, SEM+SYN). The ERPs evoked from the target NP2 were analyzed by using the Residue Iteration Decomposition (RIDE) method to reconstruct the ERP waveform blurred by trial-to-trial variability, as well as by using the conventional ERP method based on stimulus-locked averaging. The conventional ERP analysis showed that, compared with the critical words in CON, those in SEM and SEM+SYN elicited an N400-P600 biphasic pattern. The N400 effects in both violation conditions were of similar size and distribution, but the P600 in SEM+SYN was bigger than that in SEM. Compared with the conventional ERP analysis, RIDE analysis revealed a larger N400 effect and an earlier P600 effect (in the time window of 500-800 ms instead of 570-810ms). Overall, the combination of conventional ERP analysis and the RIDE method for compensating for trial-to-trial variability confirmed the non-significant difference between SEM and SEM+SYN in the earlier N400 time window. Converging with previous findings on other Chinese structures, the current study provides further precise evidence that syntactic processing in Chinese does not occur earlier than semantic processing.