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Background and objectiveThe measurement of portal venous pressure (PVP) has been extensively studied, primarily through indirect methods. However, the potential of ultrasound-guided percutaneous transhepatic PVP measurement as a direct method has been largely unexplored. This study aimed to investigate the accuracy, safety, and feasibility of this approach.MethodsIn vitro, the experiment aimed to select a needle that could accurately transmit pressure, had a small inner diameter and was suitable for liver puncture, and performed on 20 healthy New Zealand white rabbits. An ultrasound-guided percutaneous transhepatic portal vein puncture was undertaken to measure PVP. Additionally, free hepatic venous pressure (FHVP) and wedged hepatic venous pressure (WHVP) were measured under digital subtraction angiography (DSA). The correlation between the two methods was assessed. Enroll study participants from October 18, 2023 to November 11, 2023 with written informed consent. Five patients were measured the PVP under ultrasound guidance before surgery to determine the feasibility of this measurement method.ResultsThere was no significant difference in the results obtained using 9 different types of needles (P > 0.05). This demonstrated a great repeatability (P < 0.05). The 22G chiba needle with small inner diameter, allowing for accurate pressure transmission and suitable for liver puncture, was utilized for percutaneous transhepatic PVP measurement. There were positive correlations between PVP and HVPG (r = 0.881), PVP and WHVP (r = 0.709), HVPG and WHVP (r = 0.729), IVCP and FHVP (r = 0.572). The PVP was accurately and safely measured in 5 patients with segmental hepatectomy. No complications could be identified during postoperative ultrasound.ConclusionPercutaneous transhepatic portal venous puncture under ultrasound guidance is accurate, safe and feasible to measure portal venous pressure.Clinical trial registration numberThis study has been registered in the Chinese Clinical Trial Registry with registration number ChiCTR2300076751.

ObjectiveTo investigate the effect of aerobic exercise on five dimensions of physical self-worth, exercise capacity, physical condition, physical attractiveness, and physical quality in body self-esteem of Chinese college students.MethodsBy searching PubMed, Web of Science, Cochrane Library, CNIK database, VIP database, WANFANG database platform, we searched for the subject terms or keywords "body self-esteem", "Chinese college students", "Systematic evaluation", "Aerobic exercise", "Exercise intervention", "Meta-Analysis". The search method was a combination of subject terms and keywords and title, and the search period was from database creation to The search was conducted from database creation to May 2022. A total of 3221 articles were searched, and 9 articles were included in the study through repeated screening. Risk of bias was assessed with Cochrane and the quality of studies in the literature was assessed using Grade pro software. The outcome indicators of the included literature were analysed using review manager 5.4 software and StataMP 17.0 software.ResultsNine papers including 1613 subjects were included. results of Meta-analysis showed that aerobic exercise was effective in improving physical self-worth (WMD = 1.46, 95% CI: 1.08-1.83, pConclusionAerobic exercise can effectively improve the body self-esteem of Chinese college students. In exercise, male students pursue is athletic ability and physical fitness, and female students pursue is the sense of physical self-worth and physical attractiveness. Aerobic exercise has a greater increase in body self-esteem for obese or Obese college students. Aerobics and physical dance are the most cost-effective for improving body self-esteem. Medium-intensity relative to low-intensity exercise was effective for body self-esteem intervention. A single exercise session of 90 minutes was more effective than a single 30-minute session in boosting body self-esteem, and the overall intervention duration of 16 weeks was more effective than 10 weeks.

Though the brain was long characterized as an immune-privileged organ, findings in recent years have shown extensive communications between the brain and peripheral immune cells. We now know that alterations in the peripheral immune system can affect the behavioral outputs of the central nervous system, but we do not know which brain cells are affected by the presence of peripheral immune cells. Glial cells including microglia, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells (OPCs) are critical for the development and function of the central nervous system. In a wide range of neurological and psychiatric diseases, the glial cell state is influenced by infiltrating peripheral lymphocytes. However, it remains largely unclear whether the development of the molecular phenotypes of glial cells in the healthy brain is regulated by lymphocytes. To answer this question, we acutely purified each type of glial cell from immunodeficient Rag2-/- mice. Interestingly, we found that the transcriptomes of microglia, astrocytes, and OPCs developed normally in Rag2-/- mice without reliance on lymphocytes. In contrast, there are modest transcriptome differences between the oligodendrocytes from Rag2-/- and control mice. Furthermore, the subcellular localization of the RNA-binding protein Quaking, is altered in oligodendrocytes. These results demonstrate that the molecular attributes of glial cells develop largely without influence from lymphocytes and highlight potential interactions between lymphocytes and oligodendrocytes.

Environmental abiotic stresses limit plant growth, development, and reproduction. This study aims to reveal the response of Brassica napus to salt stress. Here, transcriptomics, metabolomics, and proteomics analysis were performed on 15 Brassica napus leave samples treated with salt at different times. Through functional enrichment analyzing the differentially expressed genes (DEGs), differential metabolites (DMs) and differentially expressed proteins (DEPs), the key factors that dominate Brassica napus response to salt stress were identified. The results showed that the two key hormones responding to salt stress were Abscisic acid (ABA) and jasmonic acid (JA). Salt stress for 24h is an important milestone. Brassica napus adjusted multiple pathways at 24h to avoid over-response to salt stress and cause energy consumption. The increased expression in BnPP2C is tangible evidence. In response to salt stress, JA and ABA work together to reduce the damage caused by salt stress in Brassica napus. The increased expression of all BnJAZs after salt stress highlighted the function of JA that cannot be ignored responding to salt stress. In addition, some metabolites, such as N-acetyl-5-hydroxytryptamine, L-Cysteine and L-(+)-Arginine, play a critical role in maintaining the balance of ROS. Proteins like catalase-3, cysteine desulfurase, HSP90 and P450_97A3 were the most critical differential proteins in response to salt stress. These findings of this study provide data support for Brassica napus breeding.

Vaginal microbiota (VMB) is associated with changes in Human papilloma virus (HPV) status, which consequently influences the risk of cervical cancer. This association was often confounded by personal risk factors. This pilot research aimed to explore the relationship between vaginal microbiota, personal risk factors and their interactions with HPV status conversion to identify the vaginal microbiota that was associated with HPV clearance under heterogeneous personal risk factors. A total of 38 women participated by self-collecting a cervicovaginal mucus (CVM) sample that was sent for metagenomics sequencing. Most of the participants also filled in personal risk factors questionnaire through an eHealth platform and authorized the use of their previous HPV genotyping results stored in this eHealth platform. Based on the two HPV results, the participants were grouped into three cohorts, namely HPV negative, HPV persistent infection, and HPV status conversion. The relative abundance of VMB and personal factors were compared among these three cohorts. A correlation investigation was performed between VMB and the significant personal factors to characterize a robustness of the panel for HPV status change using R programming. At baseline, 12 participants were HPV-negative, and 22 were HPV-positive. Within one year, 18 women remained HPV-positive, 12 were HPV-negative and 4 participants showed HPV clearance. The factors in the eHealth questionnaire were systematically evaluated which identified several factors significantly associated with persistent HPV infection, including age, salary, history of reproductive tract infection, and the total number of sexual partners. Concurrent vaginal microbiome samples suggest that a candidate biomarker panel consisting of Lactobacillus gasseri, Streptococcus agalactiae, and Timona prevotella bacteria, which may be associated with HPV clearance. This pilot study indicates a stable HPV status-related vaginal microbe environment. To establish a robust biomarker panel for clinical use, larger cohorts will be recruited into follow-up studies.

To explore the shape characteristics of ablation lesions created via laser ablation (LA), radiofrequency ablation (RFA) and microwave ablation (MWA) in canine prostates and the clinical significance of these characteristics, six adult male beagles were randomly assigned to the LA, RFA, and MWA groups. These ablations were performed with common parameters applied in clinical practice (LA, 3 W/1200 J; RFA and MWA, 30 W/120 s). One ablation lesion was created in each lobe of the prostate via the ablation technique, resulting in a total of twelve ablation lesions. Transrectal ultrasound (TRUS) was used as guidance during puncture and to monitor changes in the ablation lesions. Finally, the ablation efficacy was assessed using transrectal contrast-enhanced ultrasonography (CEUS), and the transverse diameter (TRD), anteroposterior diameter (APD) and longitudinal diameter (LD) of each ablation lesion were measured. The volume (V) and the ratio (R) value were calculated. R reflects the shape characteristic of the ablation lesion (the R value close to 1.0 indicates a more spherical shape). The R values of the ablation lesions were 0.89 ± 0.02, 0.72 ± 0.01, and 0.65 ± 0.03 for RFA, MWA and LA, respectively, and they were significantly different (P = 0.027). The volumes of the ablation lesions were 2.17 ± 0.10 ml, 1.51 ± 0.20 ml, and 0.79 ± 0.07 ml for MWA, LA and RFA, respectively, and they were also significantly different (P = 0.001). The three abovementioned thermal ablation techniques with common parameters in clinical practice can be used for ablation in the prostate. The shapes and volumes of the ablation lesions of the three techniques were varied: The RFA-created lesions had the lowest volumes and were more spherical in shape, demonstrating that RFA could be used for the treatment of relatively small lesions or tumours adjacent to vital organs. The MWA lesions had the largest size with a spherical shape, which could be advantageous for the ablation of tumours with relatively large sizes. The sizes of the ablation lesions created via LA were between those of RFA and MWA but presented more oval in shape, suggesting that this method is highly appropriate for the ablation of benign prostatic hyperplasia (BPH).

The recognition potential (RP) is an early visually evoked response (~250 ms) whose magnitude is sensitive to object recognizability and related factors. The RP is often measured when objects are embedded in a rapid stream of masking stimuli (the RSS paradigm), especially in reading research. The idea is that RSS provides greater stimulus-dependent variations in RP, compared to the corresponding variations without RSS. However, this idea has never been subject to systematic evaluation. We directly test whether RSS can enhance 2 types of RP stimulus selectivity, by measuring the RP in conditions that only differ in the presence or absence of a masking stream and in the type of stimulus shown. We measure the effect of image inversion on RP for Chinese characters (experiment 1); the effect of orthographical correctness on RP for Chinese characters (experiment 3); and as a control study, the effect of image inversion on the N170 response to faces (experiment 2). To ensure a fair comparison, the earliest negative deflections (RP/N170) measured with and without RSS should at least have similar channel ranges, and topographical distributions of both amplitude and selectivity. Our first set of results clearly supports this. Our main results clearly show an increase in stimulus-selectivity for RSS over non-RSS in both of the RP (Chinese character) experiments, but no such enhancement in the N170 (face) experiment. This provides incentive for investigations into the underlying mechanisms of selectivity enhancement. Our findings may also help to explain contradictory findings between RP/N170 studies that differ only in the use of noise masks, which is sometimes treated as trivial detail in papers that do not reference the RP/RSS literature.

BACKGROUND:HIV testing rates are suboptimal among at-risk men. Crowdsourcing may be a useful tool for designing innovative, community-based HIV testing strategies to increase HIV testing. The purpose of this study was to use a stepped wedge cluster randomized controlled trial (RCT) to evaluate the effect of a crowdsourced HIV intervention on HIV testing uptake among men who have sex with men (MSM) in eight Chinese cities. METHODS AND FINDINGS:An HIV testing intervention was developed through a national image contest, a regional strategy designathon, and local message contests. The final intervention included a multimedia HIV testing campaign, an online HIV testing service, and local testing promotion campaigns tailored for MSM. This intervention was evaluated using a closed cohort stepped wedge cluster RCT in eight Chinese cities (Guangzhou, Shenzhen, Zhuhai, and Jiangmen in Guangdong province; Jinan, Qingdao, Yantai, and Jining in Shandong province) from August 2016 to August 2017. MSM were recruited through Blued, a social networking mobile application for MSM, from July 29 to August 21 of 2016. The primary outcome was self-reported HIV testing in the past 3 months. Secondary outcomes included HIV self-testing, facility-based HIV testing, condom use, and syphilis testing. Generalized linear mixed models (GLMMs) were used to analyze primary and secondary outcomes. We enrolled a total of 1,381 MSM. Most were ≤30 years old (82%), unmarried (86%), and had a college degree or higher (65%). The proportion of individuals receiving an HIV test during the intervention periods within a city was 8.9% (95% confidence interval [CI] 2.2-15.5) greater than during the control periods. In addition, the intention-to-treat analysis showed a higher probability of receiving an HIV test during the intervention periods as compared to the control periods (estimated risk ratio [RR] = 1.43, 95% CI 1.19-1.73). The intervention also increased HIV self-testing (RR = 1.89, 95% CI 1.50-2.38). There was no effect on facility-based HIV testing (RR = 1.00, 95% CI 0.79-1.26), condom use (RR = 1.00, 95% CI 0.86-1.17), or syphilis testing (RR = 0.92, 95% CI 0.70-1.21). A total of 48.6% (593/1,219) of participants reported that they received HIV self-testing. Among men who received two HIV tests, 32 individuals seroconverted during the 1-year study period. Study limitations include the use of self-reported HIV testing data among a subset of men and non-completion of the final survey by 23% of participants. Our study population was a young online group in urban China and the relevance of our findings to other populations will require further investigation. CONCLUSIONS:In this setting, crowdsourcing was effective for developing and strengthening community-based HIV testing services for MSM. Crowdsourced interventions may be an important tool for the scale-up of HIV testing services among MSM in low- and middle-income countries (LMIC). TRIAL REGISTRATION:ClinicalTrials.gov NCT02796963.

INTRODUCTION:Recently, a small but growing literature has depicted the beneficial effects of nocturnal hemodialysis (NHD) over conventional hemodialysis (CHD) in the fields of sleep disorders such as sleep apnea. The impact of various dialysis models on sleep disorders, however, has not been determined. The objective of our meta-analysis is to examine the potential effects of NHD, compared with CHD, on sleep disorders in HD patients. METHODS:Several electronic databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and CNKI were searched, using the search terms "nocturnal" (or "nightly") and "dialysis" (or "hemodialysis" or "renal dialysis") from the earliest available date of indexing to March 2018. Two authors independently extracted data, evaluated the study quality, and conducted random-effects meta-analyses using STATA 12.0. RESULTS:Of 1789 potentially relevant citations, 9 fulfilled eligibility criteria, consisting of 6 single-arm studies (comparing pre- and post-intervention outcomes), 1 observational study, and 2 randomized controlled trials (a total of 286 participants). Regarding objective sleep assessments, conversion from CHD to NHD resulted in a significant reduction in the AHI (Mean difference was -14.90; 95% CI, -20.12 to -9.68), a significant increase of SaO2 (Mean difference was 1.38%; 95% CI, 0.35% to 2.42%), and a significant decrease of TST (Mean difference was -0.31; 95% CI, -0.47 to -0.15). The trends were even stronger in the HD patients with sleep disorders. However, regarding subjective sleep assessments, improved sleep quality was found in the prospective pre-post intervention studies and cohort studies, while no significant improvements were found in the randomized controlled trials. CONCLUSION:Although a significant improvement of sleep apnea was observed by switching from CHD to NHD, it may not yield a net benefit in overall subjective sleep quality.

Arachis hypogaea L. geocarpy is a unique feature different from other legume plants. Flowering and fertilization occur above ground, while the following processes of pod formation and development proceed in the soil. The zygote divides only few times to develop into pre-embryo and then further embryo developmental process stops when the gynoecium is exposed to light condition or normal day/night period. In this study, eight phytochrome genes were identified in two wild peanuts (four in Arachis duranensis and four in Arachis ipaensis). Using RACE and homologous cloning, the full CDS of AhphyA, AhphyA-like, AhphyB and AhphyE were acquired in cultivated peanut. Protein structure analysis showed that the conservative coding domains of phytochromes from a number of other plant species were found in these proteins. The C-terminal of AhphyA, AhphyA-like and AhphyB could interact with phytochrome-interacting factor 3 in vitro. The expression patterns of these genes in various tissues were analyzed by qRT-PCR, and significant differences were observed. Interestingly, the expression levels of AhphyA-like changed significantly during gynophore growth and early pod development. Furthermore, protein accumulation patterns of AhphyA and AhphyB in gynophore were different during early pod development stages in that AhphyA and AhphyB proteins were not detected in S1 and S2 gynophores, while significant accumulation of AhphyA and AhphyB were detected in S3 gynophore. These results provided evidence that phytochromes mediated light signal transduction may play key roles in peanut geocarpy development.

Platelets have been implicated in pulmonary inflammation following exposure to bacterial stimuli. The mechanisms involved in the platelet-mediated host response to respiratory bacterial infection remain incompletely understood. In this study, we demonstrate that platelet-derived chemokine (C-X-C motif) ligand 4 (CXCL4) plays critical roles in a mouse model of acute bacterial pneumonia using Pseudomonas aeruginosa. Platelets are activated during P. aeruginosa infection, and mice depleted of platelets display markedly increased mortality and impaired bacterial clearance. CXCL4 deficiency impairs bacterial clearance and lung epithelial permeability, which correlate with decreased neutrophil recruitment to BALF. Interestingly, CXCL4 deficiency selectively regulates chemokine production, suggesting that CXCL4 has an impact on other chemokine expression. In addition, CXCL4 deficiency reduces platelet-neutrophil interactions in blood following P. aeruginosa infection. Further studies revealed that platelet-derived CXCL4 contributes to the P. aeruginosa-killing of neutrophils. Altogether, these findings demonstrate that CXCL4 is a vital chemokine that plays critical roles in bacterial clearance during P. aeruginosa infection through recruiting neutrophils to the lungs and intracellular bacterial killing.

BACKGROUND:Recent studies showed that increased fresh fruit consumption is significantly associated with lower risks of diabetes, hypertension, and cardiovascular disease (CVD); other studies suggested that albuminuria is associated with diabetes, hypertension, and CVD. Therefore, we hypothesized that lower fresh fruit consumption is associated with higher risk of incident albuminuria among Chinese adults in rural areas, where fresh fruit consumption level is very low and prevalence of albuminuria is high. METHODS:We tested the hypothesis in a village-based cohort study of 3574 participants aged ≥ 30 years from the Handan Eye Study conducted from 2006 to 2013. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS:Overall, 35.4% of the participants never or rarely consumed fresh fruits, and 33.9, 21.6, and 9.1% consumed fresh fruits 1-3 times/month, 1-2 times/week, and ≥ 3 times/week, respectively. During a median follow-up period of 5.6 years, albuminuria developed in 17.6% (n = 629) of the participants. Compared with participants who consumed fresh fruits ≥ 3 times/week, the multivariable adjustment odds ratios (ORs) for incident albuminuria associated with fruit consumption 1-2 times/week, 1-3 times/month, and no or rare consumption were 1.58 (95% confidence intervals (CI), 1.05-2.40), 1.74 (95% CI, 1.17-2.58), and 1.78 (95% CI, 1.20-2.64), respectively. After excluding participants with diabetes, the association remained significant. CONCLUSIONS:Lower fresh fruit consumption was significantly associated with higher risk of incident albuminuria, and fresh fruit consumption frequency could be an essential intervention target to prevent albuminuria in rural China.

BackgroundRecreational drug use has increased considerably among Chinese men who have sex with men (MSM). The phenomenon has the potentially to increase HIV transmission among Chinese MSM. The aims of this study were: 1) to investigate the prevalence of recreational drug use among Chinese MSM, and 2) to explore the correlation between gay smartphone based sex-seeking applications (gay apps), HIV/STIs testing, group sex, commercial sex, sexual roles and poppers use among Chinese MSM.MethodsMSM who were born biologically male, were at least 16 years of age and had engaged in anal sex with a man at least once were recruited through a nation-wide online survey in 2014. Information regarding socio-demographics, risk behaviors, recreational drug use, HIV and other STIs testing history and gay app use were collected. Univariate and multivariate analysis were used to determine factors associated with recreational drug use among Chinese MSM.ResultsAmong 1424 participating MSM, 1100 (77.3%) reported ever using recreational drugs in their lifetime. In the last 12 months, 303 (21.3%) used poppers, 34 (2.4%) used crystal meth and 15 (1.0%) used ecstasy. The mean age of respondents was 25.6±6.8 years, 72.9% identified as gay, 41.3% were students, and 83.8% had never been married. Multiple logistic regression models revealed that compared with non-popper users, popper users were more likely to have been tested for HIV (adjusted OR (aOR) = 1.50, 95% CI: 1.15-1.96) and other STIs (aOR = 1.65, 95% CI: 1.26-2.17). In addition, popper users were more likely to engage in group sex (aOR = 2.63, 95% CI:1.80-3.86), commercial sex (aOR = 1.86, 95% CI:1.13-3.06) and used gay mobile apps to seek sexual partners (aOR = 2.10, 95% CI:1.58-2.80).ConclusionChinese MSM has a high rate of recreational drug use, including poppers. Public health programs serving MSM may consider integrating intervention programs to decrease recreational drug use related harms.

Mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) gene were recently discovered in vast majority of World Health Organization (WHO) grade II/III gliomas. This study is to understand the effects of IDH1 R132H mutation in gliomagenesis and to develop new strategies to treat glioma with IDH1 R132H mutation.Over expression of IDH1 R132H in U87MG cells was done by transfecting cells with IDH1 R132H plasmid. MTT assay, scratch repair assay and western blot were performed to study effects of IDH1 R132H mutation on cell proliferation, migration, regulating AKT-mTOR signaling pathway and cell death respectively. NADP+/NADPH and GSH quantification assays were performed to evaluate effects of IDH1 R132H mutation on the production of antioxidant NADPH and GSH.We found that over expression of IDH1 R132H mutation decreased cell proliferation consistent with previous reports; however, it increased cell migration and enhanced AKT-mTOR signaling pathway activation. Mutations in isocitrate dehydrogenase (IDH) 1 also change the function of the enzymes and cause them to produce 2-hydroxyglutarate and not produce NADPH. We tested the level of NADPH and GSH and demonstrated that IDH1 R132H mutant stable cells had significantly low NADPH and GSH level compared to control or IDH1 wild type stable cells. The reduced antioxidants (NADPH and GSH) sensitized U87MG cells with IDH R132H mutant to 5-FU treatment.Our study highlights the important role of IHD1 R132H mutant in up- regulating AKT-mTOR signaling pathway and enhancing cell migration. Furthermore, we demonstrate that IDH1 R132H mutation affects cellular redox status and sensitizes gliomas cells with IDH1 R132H mutation to 5FU treatment.

Living organisms in space are constantly exposed to radiation, toxic chemicals or reactive oxygen species generated due to increased levels of environmental and psychological stresses. Understanding the impact of spaceflight factors, microgravity in particular, on cellular responses to DNA damage is essential for assessing the radiation risk for astronauts and the mutation rate in microorganisms. In a study conducted on the International Space Station, confluent human fibroblasts in culture were treated with bleomycin for three hours in the true microgravity environment. The degree of DNA damage was quantified by immunofluorescence staining for γ-H2AX, which is manifested in three types of staining patterns. Although similar percentages of these types of patterns were found between flight and ground cells, there was a slight shift in the distribution of foci counts in the flown cells with countable numbers of γ-H2AX foci. Comparison of the cells in confluent and in exponential growth conditions indicated that the proliferation rate between flight and the ground may be responsible for such a shift. We also performed a microarray analysis of gene expressions in response to bleomycin treatment. A qualitative comparison of the responsive pathways between the flown and ground cells showed similar responses with the p53 network being the top upstream regulator. The microarray data was confirmed with a PCR array analysis containing a set of genes involved in DNA damage signaling; with BBC3, CDKN1A, PCNA and PPM1D being significantly upregulated in both flight and ground cells after bleomycin treatment. Our results suggest that whether microgravity affects DNA damage response in space can be dependent on the cell type and cell growth condition.

IntroductionChina is amidst a sexual revolution, with changing sexual practices and behaviors. Sex-seeking mobile phone applications (gay apps) that allow multiple people to meet up quickly may facilitate group sex. This study was therefore undertaken to evaluate group sex among Chinese MSM and to better understand factors associated with group sex.MethodsAn online survey was conducted from September-October 2014, collecting data on socio-demographics, sexual behaviors, use of gay apps and occurrence of group sex among Chinese MSM. Univariate and multivariable logistic regressions were used to compare group sex and non-group sex participants.ResultsOf the 1,424 MSM, the majority were under 30 years old (77.5%), unmarried (83.9%), and were gay apps users (57.9%). Overall, 141 (9.9%) participants engaged in group sex in the last 12 months. Multivariate analyses showed that men living with HIV, engaged in condomless anal intercourse with men, and used gay apps were more likely to engage in group sex, with adjusted ORs of 3.74 (95% CI 1.92-7.28), 2.88 (95% CI 2.00-4.16) and 1.46 (95% CI: 1.00-2.13), respectively. Among gay app users, the likelihood of group sex increases with the number of sex partners and the number of sex acts with partners met through a gay app.ConclusionsChinese MSM who engage in group sex are also more likely to engage in other risky sexual behaviors, and gay app use may facilitate group sex. Further research is needed among MSM who engage in group sex in order to target interventions and surveillance.

Small molecule inhibitors that can simultaneously inhibit multiple oncogenic proteins in essential pathways are promising therapeutic chemicals for hepatocellular carcinoma (HCC). To combine the anticancer effects of combretastatins, chalcones and isatins, we synthesized a novel hybrid molecule 3',4',5'-trimethoxy-5-chloro-isatinylchalcone (3MCIC). 3MCIC inhibited proliferation of cultured HepG2 cells, causing rounding-up of the cells and massive vacuole accumulation in the cytoplasm. Paxillin and focal adhesion plaques were downregulated by 3MCIC. Surprisingly, unlike the microtubule (MT)-targeting agent CA-4 that inhibits tubulin polymerization, 3MCIC stabilized tubulin polymers both in living cells and in cell lysates. 3MCIC treatment reduced cyclin B1, CDK1, p-CDK1/2, and Rb, but increased p53 and p21. Moreover, 3MCIC caused GSK3β degradation by promoting GSK3β-Ser9 phosphorylation. Nevertheless, 3MCIC inhibited the Wnt/β-catenin pathway by downregulating β-catenin, c-Myc, cyclin D1 and E2F1. 3MCIC treatment not only activated the caspase-3-dependent apoptotic pathway, but also caused massive autophagy evidenced by rapid and drastic changes of LC3 and p62. 3MCIC also promoted cleavage and maturation of the lysosomal protease cathepsin D. Using ligand-affinity chromatography (LAC), target proteins captured onto the Sephacryl S1000-C12-3MCIC resins were isolated and analyzed by mass spectrometry (MS). Some of the LAC-MS identified targets, i.e., septin-2, vimentin, pan-cytokeratin, nucleolin, EF1α1/2, EBP1 (PA2G4), cyclin B1 and GSK3β, were further detected by Western blotting. Moreover, both septin-2 and HIF-1α decreased drastically in 3MCIC-treated HepG2 cells. Our data suggest that 3MCIC is a promising anticancer lead compound with novel targeting mechanisms, and also demonstrate the efficiency of LAC-MS based target identification in anticancer drug development.

This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer.

AIM:All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia. METHODS:Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide. RESULTS:Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P

Long non-coding RNAs (lncRNAs) (> 200 bp) play crucial roles in transcriptional regulation during numerous biological processes. However, it is challenging to comprehensively identify lncRNAs, because they are often expressed at low levels and with more cell-type specificity than are protein-coding genes. In the present study, we performed ab initio transcriptome reconstruction using eight purified cell populations from mouse cortex and detected more than 5000 lncRNAs. Predicting the functions of lncRNAs using cell-type specific data revealed their potential functional roles in Central Nervous System (CNS) development. We performed motif searches in ENCODE DNase I digital footprint data and Mouse ENCODE promoters to infer transcription factor (TF) occupancy. By integrating TF binding and cell-type specific transcriptomic data, we constructed a novel framework that is useful for systematically identifying lncRNAs that are potentially essential for brain cell fate determination. Based on this integrative analysis, we identified lncRNAs that are regulated during Oligodendrocyte Precursor Cell (OPC) differentiation from Neural Stem Cells (NSCs) and that are likely to be involved in oligodendrogenesis. The top candidate, lnc-OPC, shows highly specific expression in OPCs and remarkable sequence conservation among placental mammals. Interestingly, lnc-OPC is significantly up-regulated in glial progenitors from experimental autoimmune encephalomyelitis (EAE) mouse models compared to wild-type mice. OLIG2-binding sites in the upstream regulatory region of lnc-OPC were identified by ChIP (chromatin immunoprecipitation)-Sequencing and validated by luciferase assays. Loss-of-function experiments confirmed that lnc-OPC plays a functional role in OPC genesis. Overall, our results substantiated the role of lncRNA in OPC fate determination and provided an unprecedented data source for future functional investigations in CNS cell types. We present our datasets and analysis results via the interactive genome browser at our laboratory website that is freely accessible to the research community. This is the first lncRNA expression database of collective populations of glia, vascular cells, and neurons. We anticipate that these studies will advance the knowledge of this major class of non-coding genes and their potential roles in neurological development and diseases.

Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis), and include the widely used decongestants and appetite suppressants (1S,2S)-pseudoephedrine and (1R,2S)-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO) terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications.

Behavioral interventions (BIs) remained the cornerstone of HIV prevention in resource-limited settings. One of the major concerns for such efforts is the loss-to-follow-up (LTFU) that threatens almost every HIV control program involving high-risk population groups.To evaluate the factors associated with LTFU during BIs and HIV testing among men who have sex with men (MSM), 410 HIV sero-negatives MSM were recruited using respondent driven sampling (RDS) in Nanjing, China during 2008, they were further followed for 18 months. At baseline and each follow-up visits, each participant was counseled about various HIV risk-reductions BIs at a designated sexually transmitted infection (STI) clinic.Among 410 participants recruited at baseline, altogether 221 (53.9%) were LTFU at the 18-month follow-up visit. Overall, 46 participants were found to be positive for syphilis infection at baseline while 13 participants were HIV sero-converted during the follow-up period. Increasing age was less (Adjusted Odds Ratio(aOR) of 0.90, 95% confidence Interval (CI) 0.86-0.94) and official residency of provinces other than Nanjing (AOR of 2.49, 95%CI 1.32-4.71), lower level of education (AOR of 2.01, 95%CI 1.10-3.66) and small social network size (AOR of 1.75, 95%CI 1.09-2.80) were more likely to be associated with higher odds of LTFU.To improve retention in the programs for HIV control, counseling and testing among MSM in Nanjing, focused intensified intervention targeting those who were more likely to be LTFU, especially the young, less educated, unofficial residents of Nanjing who had smaller social network size, might be helpful.

Although alterations of topological organization have previously been reported in the brain functional network of Parkinson's disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD.

The Han Chinese are the largest ethnic group in the world, and their origins, development, and expansion are complex. Many genetic studies have shown that Han Chinese can be divided into two distinct groups: northern Han Chinese and southern Han Chinese. The genetic history of the southern Han Chinese has been well studied. However, the genetic history of the northern Han Chinese is still obscure. In order to gain insight into the genetic history of the northern Han Chinese, 89 human remains were sampled from the Hengbei site which is located in the Central Plain and dates back to a key transitional period during the rise of the Han Chinese (approximately 3,000 years ago). We used 64 authentic mtDNA data obtained in this study, 27 Y chromosome SNP data profiles from previously studied Hengbei samples, and genetic datasets of the current Chinese populations and two ancient northern Chinese populations to analyze the relationship between the ancient people of Hengbei and present-day northern Han Chinese. We used a wide range of population genetic analyses, including principal component analyses, shared mtDNA haplotype analyses, and geographic mapping of maternal genetic distances. The results show that the ancient people of Hengbei bore a strong genetic resemblance to present-day northern Han Chinese and were genetically distinct from other present-day Chinese populations and two ancient populations. These findings suggest that the genetic structure of northern Han Chinese was already shaped 3,000 years ago in the Central Plain area.

To explore the prevalence rates and predictors of somatic symptoms among child and adolescent survivors with probable posttraumatic stress disorder (PTSD) after an earthquake.A total of 3053 students from 21 primary and secondary schools in Baoxing County were administered the Patient Health Questionnaire-13 (PHQ-13), a short version of PHQ-15 without the two items about sexuality and menstruation, the Children's Revised Impact of Event Scale (CRIES), and the self-made Earthquake-Related Experience Questionnaire 3 months after the Lushan earthquake.Among child and adolescent survivors, the prevalence rates of all somatic symptoms were higher in the probable PTSD group compared with the controls. The most frequent somatic symptoms were trouble sleeping (83.2%), feeling tired or having low energy (74.4%), stomach pain (63.2%), dizziness (58.1%), and headache (57.7%) in the probable PTSD group. Older age, having lost family members, having witnessed someone get seriously injured, and having witnessed someone get buried were predictors for somatic symptoms among child and adolescent survivors with probable PTSD.Somatic symptoms among child and adolescent earthquake survivors with probable PTSD in schools were common, and predictors of these somatic symptoms were identified. These findings may help those providing psychological health programs to find the child and adolescent students with probable PTSD who are at high risk of somatic symptoms in schools after an earthquake in China.

Histone lysine (K) residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs) counteract the activity of methyl-transferases and remove methyl group(s) from specific K residues in histones. KDM3A (also known as JHDM2A or JMJD1A) is an H3K9me2/1 demethylase. KDM3A performs diverse functions via the regulation of its associated genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanism by which the activity of KDM3A is regulated is largely unknown. Here, we demonstrated that mitogen- and stress-activated protein kinase 1 (MSK1) specifically phosphorylates KDM3A at Ser264 (p-KDM3A), which is enriched in the regulatory regions of gene loci in the human genome. p-KDM3A directly interacts with and is recruited by the transcription factor Stat1 to activate p-KDM3A target genes under heat shock conditions. The demethylation of H3K9me2 at the Stat1 binding site specifically depends on the co-expression of p-KDM3A in the heat-shocked cells. In contrast to heat shock, IFN-γ treatment does not phosphorylate KDM3A via MSK1, thereby abrogating its downstream effects. To our knowledge, this is the first evidence that a KDM can be modified via phosphorylation to determine its specific binding to target genes in response to thermal stress.

BACKGROUND: Hantaan virus (HTNV) infection causes a severe form of HFRS(hemorrhagic fever with renal syndrome)in Asia. Although HTNV has been isolated for nearly forty years, the pathogenesis of HFRS is still unknown, and little is known regarding the signaling pathway that is activated by the virus. METHODOLOGY/PRINCIPAL FINDINGS: Cardamonin was selected as a NF-κB inhibitor, and indirect immunofluorescence assays were used to detect the effect of cardamonin on HTNV-infected HUVECs. The effect of cardamonin on the HTNV-induced phosphorylation of Akt and DNA-binding activity of NF-κB were determined using Western blot analysis and electrophoretic mobility shift assays (EMSAs), respectively. Then, flow cytometric and quantitative real-time PCR analyses were performed to quantify the expression levels of the adhesion molecules ICAM-1 and VCAM-1, and the concentrations of IL-6, IL-8, and CCL5 in HUVEC supernatants were examined using ELISA. The results showed that cardamonin did not effect the proliferation of HUVECs or the replication of HTNV in HUVECs. Instead, cardamonin inhibited the phosphorylation of Akt and nuclear transduction of NF-κB and further reduced the expression of the adhesion molecules ICAM-1 and VCAM-1 in HTNV-infected HUVECs. Cardamonin also inhibited the secretion of IL-6 and CCL5, but not IL-8. CONCLUSION/SIGNIFICANCE: HTNV replication may not be dependent upon the ability of the virus to activate NF-κB in HUVECs. The Akt/NF-κB pathways may be involved in the pathogenesis of HFRS; therefore, cardamonin may serve as a potential beneficial agent for HFRS therapy.

Vascular hyperpermeability induced by lipopolysaccharide (LPS) is a common pathogenic process in cases of severe trauma and sepsis. Vascular endothelial cadherin (VE-cad) is a key regulatory molecule involved in this process, although the detailed mechanism through which this molecule acts remains unclear. We assessed the role of clathrin-mediated and caveolae-mediated endocytosis of VE-cad in LPS-induced vascular hyperpermeability in the human vascular endothelial cell line CRL-2922 and determined that vascular permeability and VE-cad localization at the plasma membrane were negatively correlated after LPS treatment. Additionally, the loss of VE-cad at the plasma membrane was caused by both clathrin-mediated and caveolae-mediated endocytosis. Clathrin-mediated endocytosis was dominant early after LPS treatment, and caveolae-mediated endocytosis was dominant hours after LPS treatment. The caveolae-mediated endocytosis of VE-cad was activated through the LPS-Toll-like receptor 4 (TLR4)-Src signaling pathway. Structural changes in the actin cytoskeleton, specifically from polymerization to depolymerization, were important reasons for the switching of the VE-cad endocytosis pathway from clathrin-mediated to caveolae-mediated. Our findings suggest that clathrin-mediated and caveolae-mediated endocytosis of VE-cad contribute to LPS-induced vascular hyperpermeability, although they contribute via different mechanism. The predominant means of endocytosis depends on the time since LPS treatment.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and outcomes of critical patients with hemorrhagic fever with renal syndrome (HFRS) complicated by acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: To observe the demographic, epidemiological and clinical characteristics, and to explore the predictive effects for prognosis in laboratory findings, we conducted a detailed retrospective analysis of clinical records for critical patients with HFRS complicated by ARDS, treated at the center for infectious diseases, Tangdu Hospital, between January 2008 and December 2012. RESULTS: A total of 48 critical patients with laboratory confirmed HFRS accompanied by ARDS were enrolled in the study, including 27 survivors and 21 non-survivors, with a fatality rate of 43.75%. Thirty-one individuals (64.6%) contracted HFRS between the months of September and December. The non-survivors tended to have lower incidence of overlapping phase (P = 0.025). There were no obvious differences in the needs for mechanical ventilation (MV) and renal replacement therapy (RRT), except for the need for vasoactive drugs between the survivors and non-survivors (P = 0.001). The non-survivors were found to have higher frequencies of encephalopathy, refractory shock and multiple organ dysfunction syndrome (MODS), lower incidences of acute renal failure (ARF) and secondary hypertension (P

Human infection with avian influenza A H7N9 virus was first identified in March 2013 and represents an ongoing threat to public health. There is a need to optimize serological methods for this new influenza virus. Here, we compared the sensitivity and specificity of the hemagglutinin inhibition (HI), microneutralization (MN), and Western blot (WB) assays for the detection of human antibodies against avian influenza A (H7N9) virus. HI with horse erythrocytes (hRBCs) and a modified MN assay possessed greater sensitivity than turkey erythrocytes and the standard MN assay, respectively. Using these assays, 80% of tested sera from confirmed H7N9 cases developed detectable antibody to H7N9 after 21 days. To balance sensitivity and specificity, we found serum titers of ≥20 (MN) or 160 (HI) samples were most effective in determining seropositive to H7N9 virus. Single serum with HI titers of 20-80 or MN titer of 10 could be validated by each other or WB assay. Unlike serum collected from adult or elderly populations, the antibody response in children with mild disease was low or undetectable. These combinations of assays will be useful in case diagnosis and serologic investigation of human cases.

Nonlinear dependence is general in regulation mechanism of gene regulatory networks (GRNs). It is vital to properly measure or test nonlinear dependence from real data for reconstructing GRNs and understanding the complex regulatory mechanisms within the cellular system. A recently developed measurement called the distance correlation (DC) has been shown powerful and computationally effective in nonlinear dependence for many situations. In this work, we incorporate the DC into inferring GRNs from the gene expression data without any underling distribution assumptions. We propose three DC-based GRNs inference algorithms: CLR-DC, MRNET-DC and REL-DC, and then compare them with the mutual information (MI)-based algorithms by analyzing two simulated data: benchmark GRNs from the DREAM challenge and GRNs generated by SynTReN network generator, and an experimentally determined SOS DNA repair network in Escherichia coli. According to both the receiver operator characteristic (ROC) curve and the precision-recall (PR) curve, our proposed algorithms significantly outperform the MI-based algorithms in GRNs inference.

OBJECTIVE: To explore the neural mechanisms of negative emotion regulation in patients with post-traumatic stress disorder (PTSD). METHODS: Twenty PTSD patients and 20 healthy subjects were recruited. Event-related functional magnetic resonance imaging (fMRI) was used to investigate the modification of emotional responses to negative stimuli. Participants were required to regulate their emotional reactions according to the auditory regulation instructions via headphones, to maintain, enhance or diminish responses to negative stimuli during fMRI scans. RESULTS: The PTSD group showed poorer modification performance than the control group when diminishing responses to negative stimuli. On fMRI, the PTSD group showed decreased activation in the inferior frontal cortex, inferior parietal lobule, insula and putamen, and increased activation in posterior cingulate cortex and amygdala during up-regulation of negative emotion. Similar decreased activation regions were found during down-regulation of negative emotion, but no increased activation was found. CONCLUSION: Trauma exposure might impair the ability to down-regulate negative emotion. The present findings will improve our understanding of the neural mechanisms of emotion regulation underlying PTSD.

Disgust is argued to be an emotion that motivates the avoidance of disease-causing entities in the physical domain and unacceptable behaviors in the social-moral domain. Empirical work from behavioral, physiological and brain imaging studies suggests moral judgments are strongly modulated by disgust feelings. Yet, it remains unclear how they are related in the time course of neural processing. Examining the temporal order of disgust emotion and morality could help to clarify the role of disgust in moral judgments. In the present research, a Go/No-Go paradigm was employed to evoke lateralized readiness potentials (LRPs) to investigate the temporal order of physical disgust and moral information processing. Participants were asked to give a "yes" or "no" response regarding the physical disgust and moral wrongness of a social act. The results showed that the evaluation of moral information was processed prior to that of physical disgust information. This suggests that moral information is available earlier than physical disgust, and provides more data on the biological heterogeneity between disgust and morality in terms of the time course of neural activity. The findings implicate that physical disgust emotion may not be necessary for people to make moral judgments. They also suggest that some of our moral experience may be more fundamental (than physical disgust experience) to our survival and development, as humans spend a considerable amount of time engaging in social interaction.

PURPOSE: The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI). METHODS: The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients' intraocular pressure (IOP) and impairment of visual field (VF) were also studied. RESULTS: 92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ(2)-test, P>0.05). CONCLUSIONS: The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP.

Hantaan virus (HTNV) is a major zoonotic pathogen that causes hemorrhagic fever with renal syndrome (HFRS) in Asia, especially in China. Shaanxi province, which is located in northwest of China, is one of the areas in China most severely afflicted with HFRS epidemics annually. This study aims to establish a quantitative RT-PCR (qRT-PCR) assay to detect HTNV both in cell culture and clinical serum samples. We established a SYBR Green I-based one-step qRT-PCR assay that targets the S segment of the HTNV genome for rapid detection and quantification. The HTNV cRNA standards were constructed by in vitro transcription, and the copy numbers of the HTNV cRNA were quantified. Standard curve was generated by determining the mean cycle threshold (Ct) values versus 10-fold serial dilutions of the HTNV cRNA over a range of 1 × 10(8) to 1 × 10(3) copies/μl. The standard curve had a reaction efficiency of 102.1%, a correlation coefficient (R(2)) of 0.998, and a slope of -3.273. The coefficient of variation (CV) of the intra- and inter-assays ranged from 0.68% to 3.00% and from 0.86% to 3.21%, respectively. The cycle intervals of the qRT-PCR assay between each dilution ranged from 2.9 to 3.8 cycles, and the lowest detection limit of the qRT-PCR assay was 10 copies/μl. The assay exhibited high specificity that was confirmed by melting curve analysis, and no cross reaction with the Seoul virus (SEOV) and other viruses (HBV, HCV and HIV) was observed. HTNV RNA was also detected in the 27 serum samples of clinical HFRS patients using the assay, and the HTNV RNA viral load ranged from 2.06 × 10(1) to 1.95 × 10(5) copies/μl. The SYBR Green I-based one-step qRT-PCR assay is a sensitive, specific, reproducible, and simple method for detecting and quantifying HTNV in cell culture and clinical samples.

BackgroundDuring the 2009 pandemic influenza H1N1 (2009) virus (pH1N1) outbreak, school students were at an increased risk of infection by the pH1N1 virus. However, the estimation of the attack rate showed significant variability.MethodsTwo school outbreaks were investigated in this study. A questionnaire was designed to collect information by interview. Throat samples were collected from all the subjects in this study 6 times and sero samples 3 times to confirm the infection and to determine viral shedding. Data analysis was performed using the software STATA 9.0.FindingsThe attack rate of the pH1N1 outbreak was 58.3% for the primary school, and 52.9% for the middle school. The asymptomatic infection rates of the two schools were 35.8% and 37.6% respectively. Peak virus shedding occurred on the day of ARI symptoms onset, followed by a steady decrease over subsequent days (p = 0.026). No difference was found either in viral shedding or HI titer between the symptomatic and the asymptomatic infectious groups.ConclusionsSchool children were found to be at a high risk of infection by the novel virus. This may be because of a heightened risk of transmission owing to increased mixing at boarding school, or a lack of immunity owing to socio-economic status. We conclude that asymptomatically infectious cases may play an important role in transmission of the pH1N1 virus.

A large number of Fusarium isolates was collected from blighted wheat spikes originating from 175 sampling sites, covering 15 provinces in China. Species and trichothecene chemotype determination by multilocus genotyping (MLGT) indicated that F. graminearum s. str. with the 15-acetyl deoxynivalenol (15ADON) chemotype and F. asiaticum with either the nivalenol (NIV) or the 3-acetyl deoxynivalenol (3ADON) chemotype were the dominant causal agents. Bayesian model-based clustering with allele data obtained with 12 variable number of tandem repeats (VNTR) markers, detected three genetic clusters that also show distinct chemotypes. High levels of population genetic differentiation and low levels of effective number of migrants were observed between these three clusters. Additional genotypic analyses revealed that F. graminearum s. str. and F. asiaticum are sympatric. In addition, composition analysis of these clusters indicated a biased gene flow from 3ADON to NIV producers in F. asiaticum. In phenotypic analyses, F. asiaticum that produce 3ADON revealed significant advantages over F. asiaticum that produce NIV in pathogenicity, growth rate, fecundity, conidial length, trichothecene accumulation and resistance to benzimidazole. These results suggest that natural selection drives the spread of a more vigorous, more toxigenic pathogen population which also shows higher levels of fungicide resistance.

Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinese population. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790-6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475-5.521; OR = 1.638; 95% CI = 1.044-2.571; OR = 1.641; 95% CI = 0.983-2.739, respectively) (p

Sox2 is a key component of the transcription factor network that maintains the pluripotent state of embryonic stem cells (ESCs). Sox2 is regulated by multiple post-translational modifications, including ubiquitination, sumoylation, acetylation and phosphorylation. Here we report that Sox2 is in association with and methylated by coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase that plays a pivotal role in ESCs. We found that CARM1 facilitates Sox2-mediated transactivation and directly methylates Sox2 at arginine 113. This methylation event enhances Sox2 self-association. Furthermore, the physiological retention of Sox2 on chromatin restricts the Sox2 methylation level. Our study reveals the direct regulation of Sox2 by CARM1 that sheds lights on how arginine methylation signals are integrated into the pluripotent transcription factor network.

BACKGROUND: Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. METHODOLOGY/PRINCIPAL FINDINGS: The hemagglutinin (HA) and neuraminidase (NA) matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains) and a highly pathogenic avian influenza A virus (H5N1) were studied using a pseudotyped particle (pp) system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005) could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. CONCLUSIONS/SIGNIFICANCE: Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

Autopsy studies have shown that human highly pathogenic avian influenza virus (H5N1) can infect multiple human organs other than just the lungs, and that possible causes of organ damage are either viral replication and/or dysregulation of cytokines and chemokines. Uncertainty still exists, partly because of the limited number of cases analysed. In this study, a full autopsy including 5 organ systems was conducted on a confirmed H5N1 human fatal case (male, 42 years old) within 18 hours of death. In addition to the respiratory system (lungs, bronchus and trachea), virus was isolated from cerebral cortex, cerebral medullary substance, cerebellum, brain stem, hippocampus ileum, colon, rectum, ureter, aortopulmonary vessel and lymph-node. Real time RT-PCR evidence showed that matrix and hemagglutinin genes were positive in liver and spleen in addition to positive tissues with virus isolation. Immunohistochemistry and in-situ hybridization stains showed accordant evidence of viral infection with real time RT-PCR except bronchus. Quantitative RT-PCR suggested that a high viral load was associated with increased host responses, though the viral load was significantly different in various organs. Cells of the immunologic system could also be a target for virus infection. Overall, the pathogenesis of HPAI H5N1 virus was associated both with virus replication and with immunopathologic lesions. In addition, immune cells cannot be excluded from playing a role in dissemination of the virus in vivo.