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ObjectiveThere is ongoing debate regarding the association between epilepsy and obesity. Thus, the aim of this study was to examine the correlation between epilepsy and obesity.MethodThis study adhered to the PRISMA guidelines for systematic reviews and meta-analyses. On The Prospero website, this study has been successfully registered (CRD42023439530), searching electronic databases from the Cochr-ane Library, PubMed, Web of Sciences and Embase until February 10, 2024.The search keywords included "Epilepsy", "Obesity", "Case-Control Studies", "cohort studies", "Randomized Controlled Trial" and "Cross-Sectional Studies". The medical subject headings(MeSH) of PubMed was utilized to search for relevant subject words and free words, and a comprehensive search strategy was developed. Two reviewers conducted article screening, data extraction and bias risk assessment in strict accordance with the predefined criteria for including and excluding studies. The predefined inclusion criteria were as follows: 1) Inclusion of case-control, cohort, randomized controlled trial, and cross-sectional studies; 2) Segregation of subjects into epileptic patients and healthy controls; 3)Obesity as the outcome measure; 4) Availability of comprehensive data; 5) Publication in English. The exclusion criteria were as follows: 1) Exclusion of animal experiments, reviews, and other types of studies; 2) Absence of a healthy control group; 3) Incomplete data; 4) Unextractable or unconvertible data; 5) Low quality, indicated by an Agency for Healthcare Research and Quality(AHRQ) score of 5 or lower,or a Newcastle-Ottawa Scale (NOS) score less than 3. The subjects included in the study included adults and children, and the diagnostic criteria for obesity were used at different ages. In this study, obesity was defined as having a body mass index(BMI) of 25 kg/m2 or higher in adults and being above the 85th percentile of BMI for age in children. We used obesity as an outcome measure for meta-analysis using RevMan, version 5.3.ResultsA meta-analysis was conducted on a total of 17 clinical studies, which involved 5329 patients with epilepsy and 480837 healthy controls. These studies were selected from a pool of 1497 articles obtained from four electronic databases mentioned earlier. Duplicate studies were removed based on the search strategies employed. No significant heterogeneity was observed in the outcome measure of obesity in epileptic patients compared with healthy controls(p = 0.01,I2 = 49%). Therefore, a fixed effects model was utilized in this study. The findings revealed a significant difference in obesity prevalence between patients with epilepsy and healthy controls(OR = 1.28, 95%CI: 1.20-1.38, pConclusionThe results of this meta-analysis indicate that epilepsy patients are more prone to obesity than healthy people, so we need to pay attention to the problem of post-epilepsy obesity clinically. Currently, there is a scarcity of largescale prospective studies. Additional clinical investigations are warranted to delve deeper into whether obesity is a comorbidity of epilepsy and whether obesity can potentially trigger epilepsy.

BackgroundHypertensive nephropathy (HN) is one of the main causes of end-stage renal disease (ESRD), leading to serious morbidity and mortality in hypertensive patients. However, existing treatment for hypertensive nephropathy are still very limited. It has been demonstrated that aerobic exercise has beneficial effects on the treatment of hypertension. However, the underlying mechanisms of exercise in HN remain unclear.MethodsThe spontaneously hypertensive rats (SHR) were trained for 8 weeks on a treadmill with different exercise prescriptions. We detected the effects of moderate intensity continuous training (MICT) and high intensity interval training (HIIT) on inflammatory response, renal function, and renal fibrosis in SHR. We further investigated the relationship between TLR4 and the NLRC4 inflammasome in vitro HN model.ResultsMICT improved renal fibrosis and renal injury, attenuating the inflammatory response by inhibiting TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. However, these changes were not observed in the HIIT group. Additionally, repression of TLR4/NF-κB pathway by TAK-242 inhibited activation of NLRC4 inflammasome and alleviated the fibrosis in Ang II-induced HK-2 cells.ConclusionMICT ameliorated renal damage, inflammatory response, and renal fibrosis via repressing TLR4/NF-κB pathway and the activation of NLRC4 inflammasome. This study might provide new references for exercise prescriptions of hypertension.

Background and objectivePulmonary fibrosis caused by lung injury is accompanied by varying degrees of inflammation, and diazepam can reduce the levels of inflammatory factors. Therefore, the purpose of this study was to determine whether diazepam can inhibit inflammation and ameliorate pulmonary fibrosis by regulating the let-7a-5p/myeloid differentiation factor 88 (MYD88) axis.MethodsLipopolysaccharide (LPS) was used to induce cell pyroptosis in an animal model of pulmonary fibrosis. After treatment with diazepam, changes in cell proliferation and apoptosis were observed, and the occurrence of inflammation and pulmonary fibrosis in the mice was detected.ResultsThe results showed that LPS can successfully induce cell pyroptosis and inflammatory responses and cause lung fibrosis in mice. Diazepam inhibits the expression of pyroptosis-related factors and inflammatory factors; moreover, it attenuates the occurrence of pulmonary fibrosis in mice. Mechanistically, diazepam can upregulate the expression of let-7a-5p, inhibit the expression of MYD88, and reduce inflammation and inhibit pulmonary fibrosis by regulating the let-7a-5p/MYD88 axis.ConclusionOur findings indicated that diazepam can inhibit LPS-induced pyroptosis and inflammatory responses and alleviate pulmonary fibrosis in mice by regulating the let-7a-5p/MYD88 axis.

More and more evidence shows that abnormal lipid metabolism leads to immune system dysfunction in AMD and promotes the occurrence of AMD by changing the homeostasis of ocular inflammation. However, the molecular mechanism underlying the effect of lipid metabolism on the phenotype and function of macrophages is still unclear, and the mechanism of association between AMD and cancer and COVID-19 has not been reported. The purpose of this study is to explore the interaction between lipid metabolism related genes, ferroptosis related genes and immunity in AMD, find out the key genes that affect the ferroptosis of AMD through lipid metabolism pathway and the molecular mechanism that mediates the action of macrophages, and find out the possible mechanism of lipid metabolism and potential co-therapeutic targets between AMD and cancer and COVID-19, so as to improve treatment decision-making and clinical results. For the first time, we have comprehensively analyzed the fatty acid molecule related genes, ferroptosis related genes and immune microenvironment of AMD patients, and determined that mast cells and M1 macrophages are the main causes of AMD inflammation, and found that SCD is the core gene in AMD that inhibits ferroptosis through lipid metabolism pathway, and verified the difference in the expression of SCD in AMD in a separate external data set. Based on the analysis of the mechanism of action of the SCD gene, we found for the first time that Has-miR-199a-3p/RELA/SCD is the core axis of action of lipid metabolism pathway to inhibit the ferroptosis of AMD. By inhibiting the immune checkpoint, we can enhance the immune cell activity of AMD and lead to the transformation of macrophages from M2 to M1, thereby promoting the inflammation and pathological angiogenesis of AMD. At the same time, we found that ACOX2 and PECR, as genes for fatty acid metabolism, may regulate the expression of SCD during the occurrence and development of COVID-19, thus affecting the occurrence and development of AMD. We found that FASD1 may be a key gene for the joint action of AMD and COVID-19, and SCD regulates the immune infiltration of macrophages in glioma and germ line tumors. In conclusion, our results can provide theoretical basis for the pathogenesis of AMD, help guide the treatment of AMD patients and their potentially related diseases and help to design effective drug targets.

The role of long noncoding RNAs (lncRNAs) has been verified by more and more researches in recent years. However, there are few reports on cellular senescence-associated lncRNAs in lung adenocarcinoma (LUAD). Therefore, to explore the prognostic effect of lncRNAs in LUAD, 279 cellular senescence-related genes, survival information and clinicopathologic parameters were derived from the CellAge database and The Cancer Genome Atlas (TCGA) database. Then, we constructed a novel cellular senescence-associated lncRNAs predictive signature (CS-ALPS) consisting of 6 lncRNAS (AC026355.1, AL365181.2, AF131215.5, C20orf197, GAS6-AS1, GSEC). According to the median of the risk score, 480 samples were divided into high-risk and low-risk groups. Furthermore, the clinicopathological and biological functions, immune characteristics and common drug sensitivity were analyzed between two risk groups. In conclusion, the CS-ALPS can independently forecast the prognosis of LUAD, which reveals the potential molecular mechanism of cellular senescence-associated lncRNAs, and provides appropriate strategies for the clinical treatment of patients with LUAD.

Grey water footprint (GWF) efficiency is a reflection of both water pollution and the economy. The assessment of GWF and its efficiency is conducive to improving water environment quality and achieving sustainable development. This study introduces a comprehensive approach to assessing and analyzing the GWF efficiency. Based on the measurement of the GWF efficiency, the kernel density estimation and the Dagum Gini coefficient method are introduced to investigate the spatial and temporal variation of the GWF efficiency. The Geodetector method is also innovatively used to investigate the internal and external driving forces of GWF efficiency, not only revealing the effects of individual factors, but also probing the interaction between different drivers. For demonstrating this assessment approach, nine provinces in China’s Yellow River Basin from 2005 to 2020 are chosen for the study. The results show that: (1) the GWF efficiency of the basin increases from 23.92 yuan/m3 in 2005 to 164.87 yuan/m3 in 2020, showing a distribution pattern of "low in the western and high in the eastern". Agricultural GWF is the main contributor to the GWF. (2) The temporal variation of the GWF efficiency shows a rising trend, and the kernel density curve has noticeable left trailing and polarization characteristics. The spatial variation of the GWF efficiency fluctuates upwards, accompanied by a rise in the overall Gini coefficient from 0.25 to 0.28. Inter-regional variation of the GWF efficiency is the primary source of spatial variation, with an average contribution of 73.39%. (3) For internal driving forces, economic development is the main driver of the GWF efficiency, and the interaction of any two internal factors enhances the explanatory power. For external driving forces, capital stock reflects the greatest impact. The interaction combinations with the highest q statistics for upstream, midstream and downstream are capital stock and population density, technological innovation and population density, and industrial structure and population density, respectively.

To select elite Robinia pseudoacacia L. germplasm resources for production, 13 phenotypes and three physiological indicators of 214 seedlings from 20 provenances were systematically evaluated and analyzed. The leaf phenotypic and physiological coefficients of variation among the genotypes ranged from 3.741% to 19.599% and from 8.260% to 42.363%, respectively. The Kentucky provenance had the largest coefficient of variation (18.541%). The average differentiation coefficients between and within provenances were 34.161% and 38.756%, respectively. These close percentages showed that R. pseudoacacia presented high genetic variation among and within provenances, which can be useful for assisted migration and breeding programs. Furthermore, based on the results of correlations, principal component analysis and cluster analysis, breeding improvements targeting R. pseudoacacia’s ornamental value, food value, and stress resistance of were performed. Forty and 30 excellent individuals, accounting for 18.692% and 14.019%, respectively, of the total resources. They were ultimately screened, after comprehensively taking into considering leaf phenotypic traits including compound leaf length, leaflet number and leaflet area and physiological characteristics including proline and soluble protein contents. These selected individuals could provide a base material for improved variety conservation and selection.

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.

This paper propose a direct generalization quantile regression estimation method (DGQR estimation) for quantile regression with varying-coefficient models with interval censored data, which is a direct generalization for complete observed data. The consistency and asymptotic normality properties of the estimators are obtained. The proposed method has the advantage that does not require the censoring vectors to be identically distributed. The effectiveness of the method is verified by some simulation studies and a real data example.

Physical distancing has been argued as one of the effective means to combat the spread of COVID-19 before a vaccine or therapeutic drug becomes available. How far people can be spatially separated is partly behavioral but partly constrained by population density. Most models developed to predict the spread of COVID-19 in the U.S. do not include population density explicitly. This study shows that population density is an effective predictor of cumulative infection cases in the U.S. at the county level. Daily cumulative cases by counties are converted into 7-day moving averages. Treating the weekly averages as the dependent variable and the county population density levels as the explanatory variable, both in logarithmic scale, this study assesses how population density has shaped the distributions of infection cases across the U.S. from early March to late May, 2020. Additional variables reflecting the percentages of African Americans, Hispanic-Latina, and older adults in logarithmic scale are also included. Spatial regression models with a spatial error specification are also used to account for the spatial spillover effect. Population density alone accounts for 57% of the variation (R-squared) in the aspatial models and up to 76% in the spatial models. Adding the three population subgroup percentage variables raised the R-squared of the aspatial models to 72% and the spatial model to 84%. The influences of the three population subgroups were substantial, but changed over time, while the contributions of population density have been quite stable after the first several weeks, ascertaining the importance of population density in shaping the spread of infection in individual counties, and in their neighboring counties. Thus, population density and sizes of vulnerable population subgroups should be explicitly included in transmission models that predict the impacts of COVID-19, particularly at the sub-county level.

In genome-wide association studies (GWAS), a wide variety of analysis tools have been designed, leading to various formats of GWAS data. How to convert a dataset in non-PLINK format into PLINK format to use its powerful analysis performance, or to convert a dataset in PLINK format into the format of other analysis tools, is a problem that needs to be faced and solved. To address this issue, we developed a tool called coPLINK, a complementary tool to PLINK, to cooperate with PLINK to implement the conversions of GWAS data formats and to provide some additional functions, such as data files comparison. The tool can implement mutual conversions not only between an existing data format and PLINK PED/BED, but also between a user-defined data format and PLINK PED. The usage and performance of the tool are similar to PLINK. The characteristics of the conversions of existing data formats and user-defined formats make it be a good assistant to PLINK or other tools and, have good potential for GWAS studies or other works.

Acute change in water temperature causes heavy economic losses in the aquaculture industry. The present study investigated the metabolic and molecular effects of acute thermal stress on black rockfish (Sebastes schlegelii). Gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolomics was used to investigate the global metabolic response of black rockfish at a high water temperature (27°C), low water temperature (5°C) and normal water temperature (16°C). Metabolites involved in energy metabolism and basic amino acids were significantly increased upon acute exposure to 27°C (P < 0.05), and no change in metabolite levels occurred in the low water temperature group. However, certain fatty acid levels were elevated after cold stress (P < 0.05), and this effect was not observed in the 27°C group, suggesting that acute high and low temperature exposures caused different physiological responses. Using quantitative real-time PCR, we analyzed the expression of ubiquitin (ub), hypoxia-inducible factor (hif), lactate dehydrogenase (ldh), and acetyl-CoA carboxylase (acac). Higher expression levels of ub, hif, and ldh (P < 0.05) were observed in the high water temperature group, but no changes in these expression levels occurred in the low water temperature group. Our findings provide a potential metabolic profile for black rockfish when exposed to acute temperature stress and provide some insights into host metabolic and molecular responses to thermal stress.

Alpine wetlands are important ecosystems, but an increased availability of soil nutrients may affect their soil nitrous oxide (N2O) fluxes and key enzyme activities. We undertook a 3-year experiment of observing nitrogen (N) and/or phosphorus (P) addition to alpine wetland soils of the Tibetan Plateau, China, with measurements made of soil extracellular enzyme activities and soil N2O fluxes. Our study showed that soil N2O flux was significantly increased by 72% and 102% following N and N+P additions, respectively. N addition significantly increased acid phosphatase (AP) and β-1, 4-N-acetyl-glucosaminidase (NAG) activities by 32% and 26%, respectively. P addition alone exerted a neutral effect on soil AP activities, while increasing NAG activities. We inferred that microbes produce enzymes based on 'resource allocation theory', but that a series of constitutive enzymes or the treatment duration interfere with this response. Our findings suggest that N addition increases N- and P-cycling enzyme activities and soil N2O flux, whereas P addition exerts a neutral effect on P-cycling enzyme activities and N2O flux after 3 years of nutrient applications to an alpine wetland.

Black locust (Robinia pseudoacacia L.) is an easy to raise, fast growing, medium-sized deciduous tree species highly tolerant to harsh eco-conditions, i.e., drought and harsh winters, and it is widely adaptable to sandy, loamy, and marshy soils. The basis for this adaptability remains to be investigated at the transcriptomic level using real-time quantitative PCR (qPCR). Selection of a reliable gene for the normalization of qPCR data is important for obtaining accurate results in gene expression. The goal of this study was to identify an appropriate reference gene from 12 candidate genes for gene expression analysis in black locust exposed to various stressors such as abscisic acid (ABA), NaCl, polyethylene glycol (PEG) and varying temperatures. In GeNorm and NormFinder analyses, ACT (actin) and GAPDH (glyceraldehyde-3-phosphate dehydrogenase) gene expression were the most stable in all conditions except heat stress, but in BestKeeper analysis, GAPDH and helicase gene expression were the most stable under NaCl and heat stress. In contrast, ACT and GAPDH were highest under abscisic acid (ABA), GAPDH and βTUB (beta tubulin) under cold stress, and helicase and EF1α (elongation factor 1 alpha) under PEG stress. We found that the most stable reference gene combination for all conditions was ACT and GAPDH. Additionally, the expression pattern of NAC2 (a transcription factor) and BGL2 in different tissues and under different stress conditions was analyzed relative to ACT and GAPDH and UBQ (ubiquitin) the least stably expressed gene. NAC2 and BGL2 both had highest expression in flowers and pods under ABA stress at 48h. This study provides useful reference genes for future gene expression studies in black locust.

The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism.24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared.During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased.There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics.Institutional Review Board (IRB) ChiCTR-IOC-15007454.

Salinity is one of the most prominent abiotic factors, which greatly influence reproduction, development, growth, physiological and metabolic activities of fishes. Spotted sea bass (Lateolabrax maculatus), as a euryhaline marine teleost, has extraordinary ability to deal with a wide range of salinity changes. However, this species is devoid of genomic resources, and no study has been conducted at the transcriptomic level to determine genes responsible for salinity regulation, which impedes the understanding of the fundamental mechanism conferring tolerance to salinity fluctuations. Liver, as the major metabolic organ, is the key source supplying energy for iono- and osmoregulation in fish, however, little attention has been paid to its salinity-related functions but which should not be ignored. In this study, we perform RNA-Seq analysis to identify genes involved in salinity adaptation and osmoregulation in liver of spotted sea bass, generating from the fishes exposed to low and high salinity water (5 vs 30ppt). After de novo assembly, annotation and differential gene expression analysis, a total of 455 genes were differentially expressed, including 184 up-regulated and 271 down-regulated transcripts in low salinity-acclimated fish group compared with that in high salinity-acclimated group. A number of genes with a potential role in salinity adaptation for spotted sea bass were classified into five functional categories based on the gene ontology (GO) and enrichment analysis, which include genes involved in metabolites and ion transporters, energy metabolism, signal transduction, immune response and structure reorganization. The candidate genes identified in L. maculates liver provide valuable information to explore new pathways related to fish salinity and osmotic regulation. Besides, the transcriptomic sequencing data supplies significant resources for identification of novel genes and further studying biological questions in spotted sea bass.

In the current precision medicine era, more and more samples get genotyped and sequenced. Both researchers and commercial companies expend significant time and resources to reduce the error rate. However, it has been reported that there is a sample mix-up rate of between 0.1% and 1%, not to mention the possibly higher mix-up rate during the down-stream genetic reporting processes. Even on the low end of this estimate, this translates to a significant number of mislabeled samples, especially over the projected one billion people that will be sequenced within the next decade. Here, we first describe a method to identify a small set of Single nucleotide polymorphisms (SNPs) that can uniquely identify a personal genome, which utilizes allele frequencies of five major continental populations reported in the 1000 genomes project and the ExAC Consortium. To make this panel more informative, we added four SNPs that are commonly used to predict ABO blood type, and another two SNPs that are capable of predicting sex. We then implement a web interface (http://qrcme.tech), nicknamed QRC (for QR code based Concordance check), which is capable of extracting the relevant ID SNPs from a raw genetic data, coding its genotype as a quick response (QR) code, and comparing QR codes to report the concordance of underlying genetic datasets. The resulting 80 fingerprinting SNPs represent a significant decrease in complexity and the number of markers used for genetic data labelling and tracking. Our method and web tool is easily accessible to both researchers and the general public who consider the accuracy of complex genetic data as a prerequisite towards precision medicine.

To identify long-term fasting blood glucose trajectories and to assess the association between the trajectories and the risk of arterial stiffness in individuals without diabetes.We enrolled 16,454 non-diabetic participants from Kailuan cohort. Fasting blood glucose concentrations were measured in 2006, 2008, and 2010 survey. Brachial-ankle pulse wave velocities were measured during 2011 to 2016. Multivariate regression model was used to estimate the difference of brachial-ankle pulse wave velocity levels and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of arterial stiffness risk, according to the fasting blood glucose trajectories.We identified five distinct fasting blood glucose trajectories and each of the trajectories was labeled according to its range and change over 2006-2010 survey: elevated-stable pattern (5.0% of participants), elevated-decreasing pattern (6.6%), moderate-increasing pattern (10.9%), moderate-stable pattern (59.3%), and low-stable pattern (18.2%). After adjustment for potential confounders, individuals with elevated-stable pattern had a 42.6 cm/s (95%CI: 24.7 to 60.6 cm/s) higher brachial-ankle pulse wave velocity level and a 37% (OR 1.37, 95%CI: 1.14 to 1.66) higher arterial stiffness risk, and individuals with moderate-increasing pattern had a 19.6 cm/s (95%CI: 6.9 to 32.3 cm/s) higher brachial-ankle pulse wave velocity level and a 17% (OR 1.17, 95%CI: 1.03 to 1.33) higher arterial stiffness risk, related to individuals with moderate-stable pattern. We did not find significant associations of the elevated-decreasing or low-stable patterns with arterial stiffness. Consistently, the cumulative average, variability, and increased rate of fasting blood glucose during 2006-2010 survey were significantly associated with the arterial stiffness risk.Discrete fasting blood glucose trajectories were associated with the arterial stiffness risk in non-diabetic individuals.

ObjectiveTo explore the association between quality of life and social support in elderly osteoporosis patients in a Chinese population.MethodsA total of 214 elderly patients who underwent bone mineral density screening were divided into two groups: elderly patients with primary osteoporosis (case group, n = 112) and normal elderly patients (control group, n = 102). Quality of life and social support were compared between the two groups.ResultsQuality of life and social support were significantly different between the case and control groups. The physical function, role-physical, bodily pain, general health, vitality, social-functioning, role-emotional and mental health scores in case group were significantly lower than those in the control group (P < 0.01). The objective support, subjective support, utilization of support, and total scores in case group were significantly lower than those in the control group (P < 0.01). Quality of life and social support were positively correlated in the case group (r = 0.672, P < 0.01).ConclusionQuality of life and social support in elderly patients with osteoporosis in China were poorer than in elderly patients without osteoporosis and were positively correlated. Our findings indicate that increased efforts to improve the social support and quality of life in elderly osteoporosis patients are urgently needed in China. Further longitudinal studies should be conducted to provide more clinical evidence to determine causative factors for the observed association between risk factors and outcomes.

BackgroundAnti-tuberculosis (anti-TB) drug-induced liver injury (ADLI) is one of the most common adverse effects associated with TB treatment. Cytochrome P450 (CYP) 1A1 and glutathione S-transferase (GST) P1 are important phase I/II metabolizing enzymes involved in drug metabolism and detoxification. Genetic polymorphism and CpG island methylation have been reported as factors influencing the expression of CYP1A1 and GSTP1.ObjectiveThis study aimed to determine the potential relationships of CYP1A1 and GSTP1 polymorphisms and CpG island methylation with ADLI risk.DesignThis was a population-based one-to-one matched case-control study.SettingThe subjects were patients with TB receiving treatment in China from December 2010 to June 2013.PatientsIn total, 127 patients with TB and ADLI (case group) and 127 patients with TB but without liver injury (control group) were included in this study. Subjects were matched in terms of sex, age, and therapeutic regimen.MethodsThe general condition of each patient was assessed using questionnaires. The CYP1A1 MspI and GSTP1 Ile105Val polymorphisms as well as methylation status were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism and the methylation-specific PCR method.ResultsWe found no significant difference in GSTP1 and CYP1A1 genotypes between the two groups, probably because the sample size was not large enough; however, patients with ADLI had significantly higher GSTP1 and CYP1A1 promoter methylation rates than control subjects [odds ratio (OR) = 2.467 and 2.000, respectively]. After adjusting for drinking, which significantly differed between the groups as per univariate analysis, we found that hypermethylation of GSTP1 and CYP1A1 promoters was associated with ADLI (OR = 2.645 and 2.090, respectively).ConclusionHypermethylation of CpG islands of GSTP1 and CYP1A1 promoters may thus play important roles in the development of ADLI and provide evidence of being used as novel markers for ADLI risk prediction.

ObjectiveAcetyl-L-carnitine (ALC), a constructive molecule in fatty acid metabolism, is an agent potentially effective for treating peripheral neuropathic pain (PNP). Its effect, however, remains uncertain. We aimed to access the efficacy and safety of ALC for the treatment of patients with PNP.MethodsWe searched MEDLINE (1996-2014), EMBase (1974-2014), and CENTRAL (May 2014) up to June 27, 2014 for randomized controlled trials (RCTs) comparing ALC with placebo or other active medications in diabetic and non-diabetic PNP patients that reported the change of pain using visual analogue scale (VAS). Mean difference (MD) and 95% confidence interval (CI) were used for pooling continuous data.ResultsFour RCTs comparing ALC with placebo and reporting in three articles (n = 523) were included. Compared with placebo, ALC significantly reduced VAS scores of PNP patients (MD of VAS, 1.20; 95% CI, 0.68-1.72, P ConclusionThe current evidence suggests that ALC has a moderate effect in reducing pain measured on VAS in PNP patients with acceptable safety. Larger trials with longer follow-up, however, are warranted to establish the effects.

Escherichia coli is one of the most common pathogens in nosocomial and community-acquired infections in humans. Fosfomycin is a broad-spectrum antibiotic which inhibits peptidoglycan synthesis responsible for bacterial cell wall formation. Although low, the exact E. coli susceptibility to fosfomycin as well as the mechanisms of resistance in the population from Mainland China are mostly unknown. 1109 non-duplicate clinical E. coli strains isolated from urine, sputum, blood and pus samples in 20 widely dispersed tertiary hospitals from Mainland China were collected from July 2009 to June 2010, followed by determination of minimum inhibitory concentrations of fosfomycin. Detection of the murA, glpT, uhpT, fosA, fosA3 and fosC genes was performed in fosfomycin non-susceptible E. coli strains and conjugation experiments were employed to determine the mobility of fosA3 gene. In this study, 7.8% (86/1109) E. coli strains were fosfomycin non-susceptible. Amino acid substitutions in GlpT and MurA were found in six and four E.coli strains, respectively, while the uhpT gene was absent in eighteen E.coli strains. Twenty-nine isolates carried the transferable plasmid with the fosA3 gene at high frequencies of around 10(-6) to 10(-7) per donor cell in broth mating. The majority of isolates were susceptible to fosfomycin, showing that the drug is still viable in clinical applications. Also, the main mechanism of E. coli resistance in Mainland China was found to be due to the presence of the fosA3 gene.

It is well known that chronic inflammation plays a pivotal role in the development of hepatitis B virus (HBV) related hepatocellular carcinoma (HCC). However, the causes behind aberrant expression of inflammation-related genes occurred in HCC remain unclear.We performed array-based analyses to comprehensively investigate the contributions of DNA methylation and somatic copy number aberration (SCNA) to the aberrant expression of 1,027 inflammation-related genes in 30 HCCs and paired non-tumor tissues. The results were validated in public datasets and an additional sample set of 47 paired HCCs and non-tumor tissues.We identified 252 differentially expressed, 125 aberrantly methylated and 287 copy number changed inflammation-related genes. Despite reasonable statistical power, among them, only 11 genes and 56 genes whose aberrant expression was associated with DNA methylation or SCNA, respectively. DNA methylation and SCNA together contributed to less than 30% aberrant expression of inflammation-related genes.These results suggest that molecular mechanisms other than DNA methylation and SCNA might play major role in the regulation of aberrant expression of inflammation-related gene in HBV-related HCCs.

Central Asia is one of the most significant loess regions on Earth, with an important role in understanding Quaternary climate and environmental change. However, in contrast to the widely investigated loess deposits in the Chinese Loess Plateau, the Central Asian loess-paleosol sequences are still insufficiently known and poorly understood. Through field investigation and review of the previous literature, the authors have investigated the distribution, thickness and age of the Xinjiang loess, and analyzed factors that control these parameters in the Xinjiang in northwest China, Central Asia. The loess sediments cover river terraces, low uplands, the margins of deserts and the slopes of the Tianshan Mountains and Kunlun Mountains and are also present in the Ili Basin. The thickness of the Xinjiang loess deposits varies from several meters to 670 m. The variation trend of the sand fraction (>63 μm) grain-size contour can indicate the local major wind directions, so we conclude that the NW and NE winds are the main wind directions in the North and South Xinjiang, and the westerly wind mainly transport dust into the Ili basin. We consider persistent drying, adequate regional wind energy and well-developed river terraces to be the main factors controlling the distribution, thickness and formation age of the Xinjiang loess. The well-outcropped loess sections have mainly developed since the middle Pleistocene in Xinjiang, reflecting the appearance of the persistent drying and the present air circulation system. However, the oldest loess deposits are as old as the beginning of the Pliocene in the Tarim Basin, which suggests that earlier aridification occurred in the Tarim Basin rather than in the Ili Basin and the Junggar Basin.

The prevalence rate of hypertension increases significantly with the aging society, and hypertension is obviously becoming a major health care concern in China. The aim of the study was to explore the epidemiological characteristics of hypertension in the elderly and to provide a basis for the prevention of hypertension.3-cross sectional studies in 2000, 2004, and 2007, respectively.Beijing, China.A group of 2,832, 1,828, and 2,277 elderly residents aged ≥60 years were included this study in 2000, 2004, and 2007, respectively.None.Statistical sampling techniques included cluster, stratification, and random selection. Trained staff used a comprehensive geriatric assessment questionnaire and a standard survey instrument to complete the assessments. During the person-to-person interviews, the participants' demographic characteristics, living conditions, and health status were collected, and their blood pressure was measured.The prevalence rates (69.2%, 61.9%, and 56.0%) of hypertension and the control rates (22.6%, 16.7%, and 21.5%) lowered annually, while the awareness rates (43.7%, 55.8%, and 57.6%) of the treatment elevated annually in 2000, 2004, and 2007, respectively. There was no increase in the control rates for males (26.2%, 16.7%, and 20.8%), younger participants (28.0%, 18.4%, and 21.0%), and rural residents (19.5%, 9.6%, and 13.4%) in 2000, 2004, and 2007, respectively.Our study findings indicated that the prevalence of hypertension is high in rural elderly participants, while the rates of awareness, treatment, and control were low. This suggests that effective public measures need to be developed to improve the prevention and control of hypertension.

As a subfamily of matrix metalloproteinases (MMPs), gelatinases including MMP-2 and MMP-9 play an important role in remodeling and homeostasis of the extracellular matrix. However, conflicting results have been reported regarding their expression level and activity in the diabetic kidney. This study investigated whether and how MMP-9 expression and activity were changed in glomerular epithelial cells upon albumin overload. In situ zymography, immunostaining and Western blot for renal MMP gelatinolytic activity and MMP-9 protein expression were performed in Zucker lean and Zucker diabetic rats. Confocal microscopy revealed a focal increase in gelatinase activity and MMP-9 protein in the glomeruli of diabetic rats. Increased glomerular MMP-9 staining was mainly observed in hyperplastic parietal epithelial cells (PECs) expressing claudin-1 in the diabetic kidneys. Interestingly, increased parietal MMP-9 was often accompanied by decreased staining for podocyte markers (nephrin and podocalyxin) in the sclerotic area of affected glomeruli in diabetic rats. Additionally, urinary excretion of podocyte marker proteins was significantly increased in association with the levels of MMP-9 and albumin in the urine of diabetic animals. To evaluate the direct effect of albumin on expression and activity of MMP-9, primary cultured rat glomerular PECs were incubated with rat serum albumin (0.25 - 1 mg/ml) for 24 - 48 hrs. MMP-9 mRNA levels were significantly increased following albumin treatment. Meanwhile, albumin administration resulted in a dose-dependent increase in MMP-9 protein and activity in culture supernatants of PECs. Moreover, albumin activated p44/42 mitogen-activated protein kinase (MAPK) in PECs. Inhibition of p44/42 MAPK suppressed albumin-induced MMP-9 secretion from glomerular PECs. Taken together, we have demonstrated that an up-regulation of MMP-9 in activated parietal epithelium is associated with a loss of adjacent podocytes in progressive diabetic nephropathy. Albumin overload may induce MMP-9 expression and secretion by PECs via the activation of p44/42 MAPK pathway.

ObjectivesThe study aimed to investigate the prevalence and epidemiological characteristics of blaNDM-1 (encoding New Delhi metallo-β-lactamase 1) in Enterobacteriaceae and the Acinetobacter calcoaceticus-Acinetobacter baumannii complex (ABC) in China from July 2011 to June 2012.MethodsPCR was used to screen for the presence of blaNDM-1 in all organisms studied. For blaNDM-1-positive strains, 16S rRNA analysis and Analytical Profile Index (API) strips were used to identify the bacterial genus and species. The ABCs were reconfirmed by PCR detection of blaOXA-51-like. Antibiotic susceptibilities of the bacteria were assessed by determining minimum inhibitory concentration (MIC) of them using two-fold agar dilution test, as recommended by the Clinical and Laboratory Standards Institute (CLSI). Molecular typing was performed using pulsed-field gel electrophoresis (PFGE). S1 nuclease-pulsed-field gel electrophoresis (S1-PFGE) and Southern blot hybridization were conducted to ascertain the gene location of blaNDM-1. Conjugation experiments were conducted to determine the transmission of blaNDM-1-positive strains.ResultsAmong 2,170 Enterobacteriaceae and 600 ABCs, seven Enterobacteriaceae strains and two A. calcoaceticus isolates from five different cities carried the blaNDM-1 gene. The seven Enterobacteriaceae strains comprised four Klebsiella pneumoniae, one Enterobacter cloacae, one Enterobacter aerogen and one Citrobacter freundii. All seven were non-susceptible to imipenem, meropenem or ertapenem. Two A. calcoaceticus species were resistant to imipenem and meropenem. Three K. pneumoniae showed the same PFGE profiles. The blaNDM-1 genes of eight strains were localized on plasmids, while one was chromosomal.ConclusionsCompared with previous reports, the numbers and species containing the blaNDM-1 in Enterobacteriaceae have significantly increased in China. Most of them are able to disseminate the gene, which is cause for concern. Consecutive surveillance should be implemented and should also focus on the dissemination of blaNDM-1 among gram-negative clinical isolates.

The Wnt/β-catenin or canonical Wnt signaling pathway plays fundamental roles in early development and in maintaining adult tissue homeostasis. R-spondin 3 (Rspo3) is a secreted protein that has been implicated in activating the Wnt/β-catenin signaling in amphibians and mammals. Here we report that zebrafish Rspo3 plays a negative role in regulating the zygotic Wnt/β-catenin signaling. Zebrafish Rspo3 has a unique domain structure. It contains a third furin-like (FU3) domain. This FU3 is present in other four ray-finned fish species studied but not in elephant shark. In zebrafish, rspo3 mRNA is maternally deposited and has a ubiquitous expression in early embryonic stages. After 12 hpf, its expression becomes tissue-specific. Forced expression of rspo3 promotes dorsoanterior patterning and increases the expression of dorsal and anterior marker genes. Knockdown of rspo3 increases ventral-posterior development and stimulates ventral and posterior marker genes expression. Forced expression of rspo3 abolishes exogenous Wnt3a action and reduces the endogenous Wnt signaling activity. Knockdown of rspo3 results in increased Wnt/β-catenin signaling activity. Further analyses indicate that Rspo3 does not promote maternal Wnt signaling. Human RSPO3 has similar action when tested in zebrafish embryos. These results suggest that Rspo3 regulates dorsoventral and anteroposterior patterning by negatively regulating the zygotic Wnt/β-catenin signaling in zebrafish embryos.

Prostate cancer is the most common non-skin cancer and the second leading cause of cancer related mortality for men in the United States. There is strong empirical and epidemiological evidence supporting a stronger role of genetics in early-onset prostate cancer. We performed a genome-wide association scan for early-onset prostate cancer. Novel aspects of this study include the focus on early-onset disease (defined as men with prostate cancer diagnosed before age 56 years) and use of publically available control genotype data from previous genome-wide association studies. We found genome-wide significant (p

Genotype imputation has become standard practice in modern genetic studies. As sequencing-based reference panels continue to grow, increasingly more markers are being well or better imputed but at the same time, even more markers with relatively low minor allele frequency are being imputed with low imputation quality. Here, we propose new methods that incorporate imputation uncertainty for downstream association analysis, with improved power and/or computational efficiency. We consider two scenarios: I) when posterior probabilities of all potential genotypes are estimated; and II) when only the one-dimensional summary statistic, imputed dosage, is available. For scenario I, we have developed an expectation-maximization likelihood-ratio test for association based on posterior probabilities. When only imputed dosages are available (scenario II), we first sample the genotype probabilities from its posterior distribution given the dosages, and then apply the EM-LRT on the sampled probabilities. Our simulations show that type I error of the proposed EM-LRT methods under both scenarios are protected. Compared with existing methods, EM-LRT-Prob (for scenario I) offers optimal statistical power across a wide spectrum of MAF and imputation quality. EM-LRT-Dose (for scenario II) achieves a similar level of statistical power as EM-LRT-Prob and, outperforms the standard Dosage method, especially for markers with relatively low MAF or imputation quality. Applications to two real data sets, the Cebu Longitudinal Health and Nutrition Survey study and the Women's Health Initiative Study, provide further support to the validity and efficiency of our proposed methods.

While individuals with insomnia consistently complain of cognitive impairment, previous studies on the effect of insomnia on objective measures of cognitive function have obtained ambiguous results. The relationship between daytime sleepiness and cognitive manifestations in insomnia patients is not clear.Thirty-six primary insomnia patients (PIPs) and 26 good sleep controls (GSCs) with age and gender matched manner were included in the study. Participants underwent an overnight polysomnography followed by a multiple sleep latency test (MSLT) and an examination of the attention network test (ANT). ANT reflected three attentional networks including alerting, orienting and executive control. According to whether accompanied with excessive daytime sleepiness (EDS), the insomnia group were subdivided into PIPs with EDS (n = 12, score on MSLT

Heat shock proteins (HSPs) consist of a large group of chaperones whose expression is induced by high temperature, hypoxia, infection and a number of other stresses. Among all the HSPs, Hsp40 is the largest HSP family, which bind to Hsp70 ATPase domain in assisting protein folding. In this study, we identified 57 hsp40s in channel catfish (Ictalurus punctatus) through in silico analysis using RNA-Seq and genome databases. These genes can be classified into three different types, Type I, II and III, based on their structural similarities. Phylogenetic and syntenic analyses provided strong evidence in supporting the orthologies of these HSPs. Meta-analyses of RNA-Seq datasets were conducted to analyze expression profile of Hsp40s following bacterial infection. Twenty seven hsp40s were found to be significantly up- or down-regulated in the liver after infection with E. ictaluri; 19 hsp40s were found to be significantly regulated in the intestine after infection with E. ictaluri; and 19 hsp40s were found to be significantly regulated in the gill following infection with F. columnare. Altogether, a total of 42 Hsp40 genes were regulated under disease situations involving three tissues and two bacterial infections. The significant regulated expression of Hsp40 genes after bacterial infection suggested their involvement in disease defenses in catfish.

PURPOSE: To determine the distributions and relation of central corneal thickness (CCT) and intraocular pressure (IOP) by NT-530P in Chinese juveniles, and the effect of gender, age, height, weight and refractive errors on the CTT and IOP. METHODS: CCT and IOP of 982 eyes in 514 juveniles aged from 7 to 18 years were measured with NT-530P. Multi-linear regression and ANOVA analysis were used to analyze the relation of CCT and IOP, and the effect of gender, age, height, weight, refractive condition on CCT and IOP respectively. RESULTS: The mean CCT and IOP were 554.19±35.46 µm and 15.31±2.57 mmHg. There were significant correlations between the CCT and IOP values. Linear regression analysis revealed a positive correlation between CCT and IOP (r = 0.44, P

BACKGROUND: Allocation of health research funds among diseases has never been evaluated in China. This study aimed to examine the relationship between disease-specific funding levels of National Nature Science Foundation of China (NSFC), the main governmental resource for health research in China, and burden of disease. METHODS: Funding magnitudes for 53 diseases or conditions were obtained from the website of NSFC. Measures of disease burden, mortality, years of life lost (YLLs) and disability-adjusted life years (DALYs), were derived from the Global Burden of Disease Study 2010. The relationship between NSFC funding and disease burden was analyzed with univariate linear regression. For each measure associated with funding, regression-derived estimates were used to calculate the expected funds for each disease. The actual and expected funds were then compared. We also evaluated the impacts of changes of disease burden metrics since 1990, and differences from the world averages on NSFC funding. RESULTS: NSFC health research funding was associated with disease burden measured in mortality (R = 0.33, P = 0.02), YLLs (R = 0.39, P = 0.004), and DALYs (R = 0.40, P = 0.003). But none of the changes of mortality (R = 0.22, P = 0.12), YLLs (R = -0.04, P = 0.79) and DALYs (R = -0.003, P = 0.98) since 1990 was associated with the funding magnitudes. None of the differences of mortality (R = -0.11, P = 0.45), YLLs (R = -0.11, P = 0.43) and DALYs (R = -0.12, P = 0.38) from that of the concurrent world averages were associated with the funding magnitudes. Measured by DALY, stroke and COPD received the least funding compared to expected; while leukemia and diabetes received the most funding compared to expected. CONCLUSION: Although NSFC funding were roughly associated with disease burden as measured in mortality, YLLs and DALYs. Some major diseases such as stroke were underfunded; while others such as leukaemia were overfunded. Change of disease burden during the last 20 years and country-specialized disease burden were not reflected in current allocation of NSFC funds.

Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans.Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P = 8.1 × 10(-8)), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium.Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.

Time-course gene expression datasets, which record continuous biological processes of genes, have recently been used to predict gene function. However, only few positive genes can be obtained from annotation databases, such as gene ontology (GO). To obtain more useful information and effectively predict gene function, gene annotations are clustered together to form a learnable and effective learning system. In this paper, we propose a novel multi-instance hierarchical clustering (MIHC) method to establish a learning system by clustering GO and compare this method with other learning system establishment methods. Multi-label support vector machine classifier and multi-label K-nearest neighbor classifier are used to verify these methods in four yeast time-course gene expression datasets. The MIHC method shows good performance, which serves as a guide to annotators or refines the annotation in detail.

OBJECTIVE:The aim of this study was to confirm the association of RHOB and FAM167A-BLK gene polymorphisms with susceptibility to systemic sclerosis (SSc) in a Chinese Han population. METHODS:A total of 248 SSc patients and 251 healthy controls of Chinese Han ethnicity, which visited the department of dermatology of Peking Union Medical College Hospital, were included in the study. Six selected single nucleotide polymorphisms (SNPs) in the RHOB and FAM167A-BLK regions were selected as markers and were genotyped using a MassARRAY system, which is based on the matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. RESULTS:Three SNPs in the coding regions of the RHOB and FAM167A-BLK genes displayed an association with SSc: (1) rs1062292T, which is a newly discovered SNP in the RHOB gene (P = 0.03, odds ratio [OR] = 1.62, 95% confidence interval (CI) = 1.05-2.50), (2) rs2736340T (P = 0.03, OR = 1.39, 95%CI = 1.03-1.85), and (3) rs13277113A (P = 0.04, OR = 1.34, 95%CI = 1.01-1.76), both in the FAM167A-BLK gene. Our results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to SSc. However, the loci of the SNPs in RHOB region that displayed an association with SSc are quite different from the loci which were identified in studies of Caucasian populations. CONCLUSION:Our results confirm that RHOB and FAM167A-BLK polymorphisms exist in Chinese Han SSc patients. Therefore, variants of the RHOB and FAM167A-BLK genes are promising genetic markers for SSc.

Hyperplasia of synovial fibroblasts, infiltration with inflammatory cytokines, and tissue hypoxia are the major characteristics of rheumatoid arthritis (RA). Interleukin 33 (IL-33) is a newly identified inflammatory cytokine exacerbating the disease severity of RA. Hypoxia-inducible factor-1α (HIF-1α) showed increased expression in RA synovium and could regulate a number of inflammatory cytokine productions. Nevertheless, its correlation with IL-33 remains largely unknown. Here, we showed that elevated levels of IL-33 were demonstrated in RA patient synovial fluids, with upregulated expression of HIF-1α and IL-33 in the synovial fibroblasts. Knocking down HIF-1α compromised IL-33 expression in rheumatoid arthritis synovial fibroblasts (RASF), while enforcing HIF-1α expression in RASF substantially upregulated IL-33 levels. HIF-1α promoted the activation of the signalling pathways controlling IL-33 production, particularly the p38 and ERK pathways. Moreover, we showed for the first time that IL-33 in turn could induce more HIF-1α expression in RASF, thus forming a HIF-1α/IL-33 regulatory circuit that would perpetuate the inflammatory process in RA. Targeting this pathological pathway and HIF-1α may provide new therapeutic strategies for overcoming the persistent and chronic inflammatory disease.

In the Drosophila female germline, spatially and temporally specific translation of mRNAs governs both stem cell maintenance and the differentiation of their progeny. However, the mechanisms that control and coordinate different modes of translational repression within this lineage remain incompletely understood. Here we present data showing that Mei-P26 associates with Bam, Bgcn and Sxl and nanos mRNA during early cyst development, suggesting that this protein helps to repress the translation of nanos mRNA. Together with recently published studies, these data suggest that Mei-P26 mediates both GSC self-renewal and germline differentiation through distinct modes of translational repression depending on the presence of Bam.

Colchicine treatment of G. biloba microsporocytes results in a low mutation rate in the diploid (2n) male gamete. The mutation rate is significantly lower as compared to other tree species and impedes the breeding of new economic varieties. Proteomic analysis was done to identify the proteins that influence the process of 2n gamete formation in G. biloba. The microsporangia of G. biloba were treated with colchicine solution for 48 h and the proteins were analyzed using 2-D gel electrophoresis and compared to protein profiles of untreated microsporangia. A total of 66 proteins showed difference in expression levels. Twenty-seven of these proteins were identified by mass spectrometry. Among the 27 proteins, 14 were found to be up-regulated and the rest 13 were down-regulated. The identified proteins belonged to five different functional classes: ATP generation, transport and carbohydrate metabolism; protein metabolism; ROS scavenging and detoxifying enzymes; cell wall remodeling and metabolism; transcription, cell cycle and signal transduction. The identification of these differentially expressed proteins and their function could help in analysing the mechanism of lower mutation rate of diploid male gamete when the microsporangium of G. biloba was induced by colchicine.

It is known that FGFR2 gene variations confer a risk for breast cancer. FGFR2 and FGF10, the main ligand of FGFR2, are both overexpressed in 5-10% of breast tumors. In our study, we sequenced the most important coding regions of FGFR2 in somatic tumor tissue of 140 sporadic breast cancer patients and performed MLPA analysis to detect copy number variations in FGFR2 and FGF10. We identified one somatic heterozygous missense mutation, p.K660N (c.1980G>C), within the tyrosine kinase domain of FGFR2 in tumor tissue of a sporadic breast cancer patient, which is likely mediated by the FGFR2-IIIb isoform. The presence of wild type and mutated alleles in equal quantities suggests that the mutation has driven clonal amplification of mutant cells. We have analyzed the tyrosine kinase activity of p.K660N and another recently described somatic breast cancer mutation in FGFR2, p.R203C, after expression in HEK293 cells and demonstrated that the intrinsic tyrosine kinase activity of both mutant proteins is strongly increased resulting in elevated phosphorylation and activity of downstream effectors. To our knowledge, this is the first report of functional analysis of somatic breast cancer mutations in FGFR2 providing evidence for the activating nature of FGFR2-mediated signalling in the pathogenesis of breast cancer.

Four methicillin-resistant coagulase-negative staphylococci (MRCoNS), one Staphylococcus haemolyticus and three Staphylococcus cohnii, from infections of humans collected via the Ministry of Health National Antimicrobial Resistance Surveillance Net (Mohnarin) program in China were identified as linezolid-resistant. These four isolates were negative for the 23S rRNA mutations, but positive for the gene cfr. Mutations in the gene for the ribosomal protein L3, which resulted in the amino acid exchanges Gly152Asp and Tyr158Phe, were identified in S. haemolyticus 09D279 and S. cohnii NDM113, respectively. In each isolate, the cfr gene was located on a plasmid of ca. 35.4 kb, as shown by S1 nuclease pulsed-field gel electrophoresis and Southern blotting experiments. This plasmid was indistinguishable from the previously described plasmid pSS-02 by its size, restriction pattern, and a sequenced 14-kb cfr-carrying segment. Plasmid pSS-02 was originally identified in staphylococci isolated from pigs. This is the first time that a cfr-carrying plasmid has been detected in MRCoNS obtained from intensive care patients in China. Based on the similarities to the cfr-carrying plasmid pSS-02 from porcine coagulase-negative staphylococci, a transmission of this cfr-carrying plasmid between staphylococci from pigs and humans appears to be likely.

OBJECTIVES: To evaluate the relationship between Patient Assessment of Chronic Illness Care in community health centers and self-management behaviors and glycemic control and to examine the relationship between Patient Assessment of Chronic Illness Care in community health centers and the utilization of community health centers for monitoring and treating diabetes among the patients with type 2 diabetes. METHODS: A questionnaire including self-management behaviors, glycemic control, Patient Assessment of Chronic Illness Care in community health centers and the most often utilized medical institutions for monitoring and treating diabetes (community health centers vs. hospitals) was administered to 960 patients with type 2 diabetes in Shanghai, China. The relationships between Patient Assessment of Chronic Illness Care and self-management behaviors, self-management behaviors and glycemic control, Patient Assessment of Chronic Illness Care and glycemic control, Patient Assessment of Chronic Illness Care and the most often utilized medical institutions for monitoring and treating diabetes were examined. RESULTS: Wilcoxon rank sum tests showed that the high scores of total Patient Assessment of Chronic Illness Care and five subscales in community health centers were positively related to almost all the proper self-management behaviors and good glycemic control (p

Postnatal permanent childhood hearing impairment (PCHI) is frequent (0.25%-0.99%) and difficult to detect in the early stage, which may impede the speech, language and cognitive development of affected children. Genetic tests of common variants associated with postnatal PCHI in newborns may provide an efficient way to identify those at risk. In this study, we detected a strong association of the p.V37I exclusive genotype of GJB2 with postnatal PCHI in Chinese Hans (P = 1.4×10(-10); OR 62.92, 95% CI 21.27-186.12). This common genotype in Eastern Asians was present in a substantial percentage (20%) of postnatal PCHI subjects, and its prevalence was significantly increased in normal-hearing newborns who failed at least one newborn hearing screen. Our results indicated that the p.V37I exclusive genotype of GJB2 may cause subclinical hearing impairment at birth and increases risk for postnatal PCHI. Genetic testing of GJB2 in East Asian newborns will facilitate prompt detection and intervention of postnatal PCHI.

We describe a novel autosomal dominant hereditary inclusion body myopathy (HIBM) that clinically mimics limb girdle muscular dystrophy in a Chinese family. We performed a detailed clinical assessment of 36 individuals spanning four generations. The age of onset ranged from the 30s to the 50s. Hip girdle, neck flexion and axial muscle weakness were involved at an early stage. This disease progressed slowly, and a shoulder girdle weakness appeared later in the disease course. Muscle biopsies showed necrotic, regenerating, and rimmed vacuolated fibers as well as congophilic inclusions in some of the fibers. Electron micrograph revealed cytoplasmic inclusions of 15-21 nm filaments. A genomewide scan and haplotype analyses were performed using an Illumina Linkage-12 DNA Analysis Kit (average spacing 0.58 cM), which traced the disease to a new locus on chromosome 7q22.1-31.1 with a maximum multi-point LOD score of 3.65. The critical locus for this unique disorder, which is currently referred to as hereditary inclusion body myopathy 4 (HIBM4), spans 8.78 Mb and contains 65 genes. This localization raises the possibility that one of the genes clustered within this region may be involved in this disorder.

REDD1/redd1 is a stress-response gene that is induced under various stressful conditions such as hypoxia, DNA damage, and energy stress. The increased REDD1 inhibits mTOR signaling and cell growth. Here we report an unexpected role of Redd1 in regulating dorsoventral patterning in zebrafish embryos and the underlying mechanisms. Zebrafish redd1 mRNA is maternally deposited. Although it is ubiquitously detected in many adult tissues, its expression is highly tissue-specific and dynamic during early development. Hypoxia and heat shock strongly induce redd1 expression in zebrafish embryos. Knockdown of Redd1 using two independent morpholinos results in dorsalized embryos and this effect can be rescued by injecting redd1 mRNA. Forced expression of Redd1 ventralizes embryos. Co-expression of Redd1 with Wnt3a or a constitutively active form of β-catenin suggests that Redd1 alters dorsoventral patterning by antagonizing the Wnt/β-catenin signaling pathway. These findings have unraveled a novel role of Redd1 in early development by antagonizing Wnt/β-catenin signaling.

Somatic mutations of U2AF1 gene have recently been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In this study, we analyzed the frequency and clinical impact of U2AF1 mutations in a cohort of 452 Chinese patients with myeloid neoplasms. Mutations in U2AF1 were found in 2.5% (7/275) of AML and 6.3% (6/96) of MDS patients, but in none of 81 CML. All mutations were heterozygous missense mutations affecting codon S34 or Q157. There was no significant association of U2AF1 mutation with blood parameters, FAB subtypes, karyotypes and other gene mutations in AML. The overall survival (OS) of AML patients with U2AF1 mutation (median 3 months) was shorter than those without mutation (median 7 months) (P = 0.035). No difference in the OS was observed between MDS patients with and without U2AF1 mutations. Our data show that U2AF1 mutation is a recurrent event at a low frequency in AML and MDS.

NF-E2 related factor-2 (Nrf2) promotes the transcription of many cytoprotective genes and is a major drug target for prevention of cancer and other diseases. Indeed, the cancer-preventive activities of several well-known chemical agents were shown to depend on Nrf2 activation. It is well known that chemopreventive Nrf2 activators stabilize Nrf2 by blocking its ubiquitination, but previous studies have indicated that this process occurs exclusively in the cytoplasm. Kelch-like ECH-associated protein 1 (Keap1) binds to Nrf2 and orchestrates Nrf2 ubiquitination, and it has been a widely-held view that inhibition of Nrf2 ubiquitination by chemopreventive agents results from the dissociation of Nrf2 from its repressor Keap1. Here, we show that while the activation of Nrf2 by prototypical chemical activators, including 5,6-dihydrocyclopenta-1,2-dithiole-3-thione (CPDT) and sulforaphane (SF), results solely from inhibition of its ubiquitination, such inhibition occurs predominantly in the nucleus. Moreover, the Nrf2 activators promote Nrf2 association with Keap1, rather than disassociation, which appears to result from inhibition of Nrf2 phosphorylation at Ser40. Available evidence suggests the Nrf2 activators may block Nrf2 ubiquitination by altering Keap1 conformation via reaction with the thiols of specific Keap1 cysteines. We further show that while the inhibitory effects of CPDT and SF on Nrf2 ubiquitination depend entirely on Keap1, Nrf2 is also degraded by a Keap1-independent mechanism. These findings provide significant new insight about Nrf2 activation and suggest that exogenous chemical activators of Nrf2 enter the nucleus to exert most of their inhibitory impact on Nrf2 ubiquitination and degradation.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P