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Background Cardiorespiratory fitness (CRF) is the core element of health-related physical fitness evaluation. High pressure and low oxygen in Tibet (over 3,500 m above sea level) may negatively impact the residents’ CRF. The 20-m shuttle run test (20mSRT) is the most popular field-based assessment and estimate of CRF in children and adolescents worldwide. However, normative CRF data for the children and adolescents residing in China’s plateau region are unavailable, which prevents comparability among those living at high-altitudes around the world. Purpose To measure the CRF of Chinese children and adolescents aged 9–18 years living in Tibet at altitudes exceeding 3,500 m, and to identify correlations between this metric and demographic characteristics (age, sex, and ethnicity). These data were then compared with those generated in the lowland (Shanghai, China) and various global regions. Methods 20mSRT performance (number of completed laps) and predicted peak oxygen consumption (VO2peak) were used as indicators of CRF. We measured the CRF of 1,717 healthy children and adolescents aged 9–18 years living in Tibet. The CRF data from school-age subjects in Shanghai (2,437 boys and 2,396 girls) and worldwide (1,142,026 students from 50 countries/regions in Africa, Asia, Europe, Latin America, North America, and Oceania) were collated from published papers. Results The average CRF of the participants from Tibet was 39.8 mL/kg/min. The male subjects (n = 876; 41.1 ± 4.42 mL/kg/min) had a higher average CRF than their female counterparts (n = 841; 37.8 ± 5.40 mL/kg/min). CRF decreased with age in both sexes at statistical significance (F = 1249.9, p for trend 0.05). The indigenous Tibetans (n = 1289; 40.1 ± 3.71 mL/kg/min) had a significant higher average CRF than those of Han descent (n = 394; 38.9 ± 4.70 mL/kg/min) (p < 0.05). Conclusions Children and adolescents aged 7–18 years residing above 3,500 m in Tibet displayed lower CRF traits compared with their counterparts from the plains area and other high altitude places. CRF varied according to age, sex, and ethnic group. Given the importance of CRF in children and adolescents, effective intervention strategies should be implemented to improve CRF in children and adolescents on the plateau.

Epidermis is the most outer layer of the skin and a physical barrier protecting the internal tissues from mechanical and environmental insults. The basal keratinocytes, which, through proliferation and differentiation, supply diverse cell types for epidermal homeostasis and injury repair. Sustainable culture of murine keratinocyte, however, is a major obstacle. Here we developed murine keratinocyte lines using low-Ca2+(0.06 mM) keratinocyte serum-free medium (KSFM-Ca2+) without feeder cells. Cells derived in this condition could be subcultured for >70 passages. They displayed basal epithelial cell morphology and expressed keratin (Krt) 14, but lacked the epithelial-characteristic intercellular junctions. Moreover, these cells could be adapted to grow in the Defined-KSFM (DKSFM) media containing 0.15 mM Ca2+, and the adapted cells established tight- and adherens-junctions and exhibited increasedKrt1/10expression while retained subculture capacity. Global gene expression studies showed cells derived in KSFM-Ca2+media had enriched stem/proliferation markers and cells adapted in DKSFM media had epithelial progenitor signatures. Correspondingly, KSFM-Ca2+-derived cells exhibited a remarkable capacity of clonal expansion, whereas DKSFM-adapted cells could differentiate to suprabasal epithelial cell types in 3-dimentional (3D) organoids. The generation of stem-like murine keratinocyte lines and the conversion of these cells to epithelial progenitors capable of terminal differentiation provide the critically needed resources for skin research.

Hyperglycemia is generally considered to be an important cause of diabetic retinopathy (DR). The aim of the present study was to investigate the role of miR-5195-3p in high glucose (HG)-induced human retinal pigment epithelial ARPE-19 cell injury. Here, we first found that the expression level of miR-5195-3p was significantly downregulated in HG-stimulated ARPE-19 cells using reverse transcription quantitative PCR. Overexpression of miR-5195-3p attenuated the impaired cell viability, increased apoptosis and pro-inflammatory cytokines secretion in ARPE-19 cells under HG condition using CCK-8 assay, flow cytometry and ELISA assay, respectively. Luciferase reporter assay showed that miR-5195-3p could specifically bind to the 3’UTR of glia maturation factor-β (GMFB). GMFB overexpression reversed, while knockdown enhanced the protective effects of miR-5195-3p overexpression against HG-induced ARPE-19 cell injury. In summary, miR-5195-3p targeting GMFB might be a potential therapeutic target for DR.

We aimed to examine whether the use of aspirin is associated with change in cognitive performance over time, and whether this association is modified by the cognitive stages. This study included a total of 1866 subjects, including 509 subjects with normal cognition (NC), 985 subjects with mild cognitive impairment (MCI), and 372 patients with Alzheimer’s disease (AD). In each group, we further categorized our subjects into two groups based on their aspirin using conditions: Aspirin users and non-aspirin users. Mini-Mental State Examination (MMSE) was the cognitive outcome. Linear mixed models were conducted to examine the longitudinal relationship between the use of aspirin and cognitive performance in each diagnostic group. In the cross-sectional analysis, there were no significant differences in MMSE scores between non-aspirin users and aspirin users in subjects with NC, subjects with MCI or patients with AD. In the longitudinal analysis, we detected an association of the baseline use of aspirin with cognitive decline (MMSE) over time in patients with AD, but not in the NC group or MCI group. Specifically, in AD patients, the use of aspirin at baseline was associated with slower cognitive decline over time. Our data may support an association between the use of aspirin and slower cognitive decline, while this association may be dependent on the clinical stages.

Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the main pathogenic microorganisms causing sexually transmitted infections. In this study, a multiplex thermostable recombinase polymerase amplification-lateral flow detection (RPA-LFD) assay was established, and the reaction conditions such as the ratio of primer concentration, magnesium ion concentration, amplification time and template DNA concentration in the multiplex RPA reaction were optimized. The optimized multiplex RPA-LFD method was used to detect both CT and NG positive control plasmids, and it was found that the LFD could be used to obtain visible results when the plasmid copy number was only 200. The sensitivity of the multiplex RPA-LFD method used for clinical samples was 85.62 (95% CI at 53.66–97.29) for NG detection and 90.90 (95% CI at 57.12–99.52) for CT detection.

Prunus sibirica is an economically important tree species that occurs in arid and semi-arid regions of northern China. For this species, creation of a core collection is critical for future ecological and evolutionary studies, efficient economic utilization, and development and management of the broader collection of its germplasm resources. In this study, we sampled 158 accessions of P. sibirica from Russia and China using 30 pair of simple sequence repeat molecular markers and 30 different schemes to identify candidate core collections. The 30 schemes were based on combinations of two different sampling strategies, three genetic distances, and five different sample sizes of the complete germplasm resource. We determined the optimal core collection from among the 30 results based on maximization of genetic diversity among groups according to Number of observed alleles (Na), Number of effective alleles (Ne), Shannon’s information index (I), Polymorphic information content (PIC), Nei gene diversity (H) and compared to the initial collection of 158 accessions. We found that the optimal core collection resulted from preferred sampling at 25% with Nei & Li genetic distance these ratios of Na, Ne, I, PIC and H to the complete 158 germplasm resources were 73.0%, 113%, 102%, 100% and 103%, respectively, indicating that the core collection comprised a robust representation of genetic diversity in P. sibirica. The proposed core collection will be valuable for future molecular breeding of this species and management of its germplasm resources.

Aiming at conservative Maxwell equations with periodic oscillatory solutions, we adopt exponentially fitted trapezoidal scheme to approximate the temporal and spatial derivatives. The scheme is a multisymplectic scheme. Under periodic boundary condition, the scheme satisfies two discrete energy conservation laws. The scheme also preserves two discrete divergences. To reduce computation cost, we split the original Maxwell equations into three local one-dimension (LOD) Maxwell equations. Then exponentially fitted trapezoidal scheme, applied to the resulted LOD equations, generates LOD multisymplectic scheme. We prove the unconditional stability and convergence of the LOD multisymplectic scheme. Convergence of numerical dispersion relation is also analyzed. At last, we present two numerical examples with periodic oscillatory solutions to confirm the theoretical analysis. Numerical results indicate that the LOD multisymplectic scheme is efficient, stable and conservative in solving conservative Maxwell equations with oscillatory solutions. In addition, to one-dimension Maxwell equations, we apply least square method and LOD multisymplectic scheme to fit the electric permittivity by using exact solution disturbed with small random errors as measured data. Numerical results of parameter inversion fit well with measured data, which shows that least square method combined with LOD multisymplectic scheme is efficient to estimate the model parameter under small random disturbance.

Changes in precipitation patterns greatly impact regional drought/flood risk management and utilization of water resources. The main purpose of this paper was to investigate spatio-temporal variability of precipitation concentration in the transitional zone between Qinling Mountains (QDM), Guanzhong Plain (GZP) and the Loess Plateau (LPNS) in China, using monthly-scale precipitation concentration index (PCI) and daily-scale concentration index (CI) from daily rainfall records. The Mann-Kendall method was employed to illustrate the change in trend of PCI and CI, the Kriging interpolation method was adopted to measure spatial distribution, and the Wavelet transforms were used to explore their spatio-temporal correlation with the Arctic Oscillation (AO) & Western Pacific Subtropical High (WPSH) for revealing the potential attribution of precipitation concentration variation. Also, the regional implication of CI was investigated in the zone to provide local knowledge of the index application. Results showed that annual precipitation demonstrated a north-south increasing layered spatial distribution in the zone, representing a generally decreasing trend. The CI change generally exhibited a more significant decreasing trend than did PCI in LPNS and GZP due to AO slowly increasing over time, with a spatially weak layered or radial north-south decay, and an insignificant increasing trend in QDM impacted by the enhancing WPSH, with an obvious layered or radial spatial distribution. The spatiotemporal pattern of PCI variation represented similar characteristics in attribution with CI, but an inverse spatial distribution due to the phase difference (positive and negative effects) of AO and WPSH influencing seasonal precipitation. Regional analysis of CI showed that the CI value with over 0.62 indicated that approximately 80% of precipitation was contributed by 25% of the rainiest days in this zone. Fortunately, the area with this high CI has been getting smaller, implying a positive trend toward regional flash flood and debris flow control.

Objective Hypertension is more prevalent in African Americans (AA) than other ethnic groups. Genome-wide association studies (GWAS) have identified loci associated with hypertension and other cardio-metabolic traits like type 2 diabetes, coronary artery disease, and body mass index (BMI), however the AA population is underrepresented in these studies. In this study, we examined a large AA cohort for the generalizability of 14 Metabochip array SNPs with previously reported European hypertension associations. Methods To evaluate associations, we analyzed genotype data of 14 SNPs for their associations with a diagnosis of hypertension, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in a case-control study of an AA population (N = 9,534). We also performed an age-stratified analysis (>30, 30≥59 and ≥60 years) following the hypertension definition described by the 8th Joint National Committee (JNC). Associations were adjusted for BMI, age, age2, sex, clinical confounders, and genetic ancestry using multivariable regression models to estimate odds ratios (ORs) and beta-coefficients. Analyses stratified by sex were also conducted. Meta-analyses (including both BioVU and COGENT-BP cohorts) were performed using a random-effects model. Results We found rs880315 to be associated with systolic hypertension (SBP≥140 mmHg) in the entire cohort (OR = 1.14, p = 0.003) and within women only (OR = 1.16, p = 0.012). Variant rs17080093 associated with lower SBP and DBP (β = -2.99, p = 0.0352 and - β = 1.69, p = 0.0184) among younger individuals, particularly in younger women (β = -3.92, p = 0.0025 and β = -1.87, p = 0.0241 for SBP and DBP respectively). SNP rs1530440 associated with higher SBP and DBP measurements (younger individuals β = 4.1, p = 0.039 and β = 2.5, p = 0.043 for SBP and DBP; (younger women β = 4.5, p = 0.025 and β = 2.9, p = 0.028 for SBP and DBP), and hypertension risk in older women (OR = 1.4, p = 0.050). rs16948048 increases hypertension risk in younger individuals (OR = 1.31, p = 0.011). Among mid-age women rs880315 associated with higher risk of hypertension (OR = 1.20, p = 0.027). rs1361831 associated with DBP (β = -1.96, p = 0.02) among individuals older than 60 years. rs3096277 increases hypertension risk among older individuals (OR = 1.26 p = 0.0015), however, this variant also reduces SBP among younger women (β = -2.63, p = 0.0102). Conclusion These findings suggest that European-descent and AA populations share genetic loci that contribute to blood pressure traits and hypertension. However, the OR and beta-coefficient estimates differ, and some are age-dependent. Additional genetic studies of hypertension in AA are warranted to identify new loci associated with hypertension and blood pressure traits in this population.

Plant grafting is a sequential wound healing process. However, whether wounding induces a different jasmonic acid (JA) response within half a day (12 h) after grafting or non-grafting remains unclear. Using the tomato hypocotyl grafting method, we show that grafting alleviates the asymmetrical accumulation of JA and jasmonic acid isoleucine conjugate (JA-Ile) in scion and rootstock caused by wounding, and from 2 h after tomato micrografting, grafting obviously restored the level of JA-Ile in the scion and rootstock. Meanwhile, five JA-related genes, SlLOX11, SlAOS, SlCOI1, SlLAPA and SlJA2L, are detected and show significant changes in transcriptional expression patterns within 12 h of grafting, from asymmetrical to symmetrical, when the expression of 30 JA- and defense-related genes were analyzed. The results indicated that grafting alleviates the asymmetrical JA and defense response between scion and rootstock of the tomato hypocotyl within 12 h as induced by wounding. Moreover, we demonstrate that in the very early hours after grafting, JA-related genes may be involved in a molecular mechanism that changes asymmetrical expression as induced by wounding between scion and rootstock, thereby promoting wound healing and grafting success.

Human adenovirus (HAdV-7) is a highly contagious pathogen that causes severe respiratory illnesses. However, the epidemic patterns and genetic variability of HAdV-7 circulating in mainland China have not been well elucidated. In this study, we used Chinese HAdV sentinel surveillance data obtained from 2012-2015 to investigate the clinical features of 122 HAdV-7-positive cases and performed amplification and sequence determination of three capsid genes (penton base, hexon, and fiber) from 69 isolated viruses covering from seven provinces of China. Additionally, we compared with data from representative sequences of 21 strains covering seven more provinces in China and 32 international HAdV-7 strains obtained from GenBank database to determine the phylogenetic, sequence variations, and molecular evolution of HAdV-7. The results indicated that HAdV-7 infection occurred throughout the year, and a high proportion of severe cases (27 cases, 22.1%) exhibited infantile pneumonia. Moreover, phylogenetic analysis showed that all HAdV-7 strains could be divided into two major evolutionary branches, including subtype 1 and subtype 2, and subtype 3 was also formed according to analysis of the penton base gene. Subtypes 1 and 2 co-circulated in China before 2008, and HAdV-7 strains currently circulating in China belonged to subtype 2, which was also the predominant strain circulating worldwide in recent years. Further sequence variation analysis indicated that three genes of HAdV-7 were relatively stable across time and geographic space, particularly for viruses within subtypes, which shared almost the same variation sites. Owing to continuous outbreaks caused by HAdV-7, resulting in increased illness severity and fatality rates in China, the establishment of a national HAdV surveillance system is urgently needed for the development of effective preventive and infection-control interventions for adenovirus respiratory infections in China.

Based on 0.01°×0.01° grid data of PM2.5 annual concentration and statistical yearbook data for 11 cities in Hebei Province from 2000 to 2015, the temporal and spatial distribution characteristics of PM2.5 in the study area are analysed, the level of intensive land use in the area is evaluated, and decoupling theory and spatial regression are used to discuss the relationship between PM2.5 concentration and intensive land use and the influence of intensive land use variables on PM2.5 in Hebei Province. The results show that 1. In terms of time, the concentration of PM2.5 in Hebei Province showed an overall upward trend from 2000 to 2015, with the highest in winter and the lowest in summer. The daily variations show double peaks at 8:00-10:00 and 21:00-0:00 and a single valley at 16:00-18:00. 2. In terms of space, the concentration of PM2.5 in Hebei Province is high in the southeast and low in the northwest, and the pollution spillover initially decreases and then increases. 3. In the past 16 years, the level of intensive land use in Hebei Province has increased annually, but blind expansion still exists. 4. Decoupling theory and the spatial lag model show that land use intensity, land input level and land use structure are positively correlated with PM2.5 concentration, land output benefit is negatively correlated with PM2.5 concentration, and PM2.5 concentration and land intensive use level have not yet been decoupled; thus, the relationship is not harmonious. This research can provide a scientific basis for reducing air pollution and promoting the development of urban land resources for intensive and sustainable development.

Trichosanthes kirilowii Maxim. (TK) is a dioecious plant in the Cucurbitaceae for which different sexes have separate medicinal uses. In order to study the genes related to sex determination, transcriptome sequencing was performed on flower buds of male and female plants using the high-throughput sequencing technology. A total of 145,975 unigenes and 7110 DEGs were obtained. There were 6776 DEGs annotated to 1234 GO terms and enriched to 18 functional groups, including five biological processes related to sugar metabolism. KEGG pathway analysis indicated genes involved in hormone transduction, hormone synthesis and carbohydrate metabolism. Many DEGs of TK are involved in reproductive organ formation, hormone signal transduction and regulatory networks. Combining the results of GO, KEGG and qRT-PCR, 11 sex determining candidate genes of TK were selected, including MYB80, MYB108, CER1, CBL9, ABCB19, SERK1, HSP81-3, ACS9, SEP3, AUX1 and YUC6. The results provide a foundation for the study of sex differentiation in TK.

BackgroundCell released microvesicles specifically, exosomes, play an important role in mediating immunologic escape, treatment resistance, and disease persistence of Hepatitis C virus (HCV) infection. Reports on the molecular compositions of exosomes released by cells under diverse conditions, especially during viral infections, suggest that their cargo contents are not randomly loaded. However, the precise molecular mechanisms directing the selective cargo sorting and loading inside infectious viral exosomes remains elusive.AimTo decipher the role of Reticulon 3 (RTN3) in the selective molecular cargo sorting and loading inside infectious viral exosomes during HCV infection.MethodsWe used Huh7 cells-JFH1 HCV infection and HCV Full-Length (FL) replicon systems. Additionally, we analyzed human liver and serum exosome samples from healthy and treatment naïve HCV infected individuals. Our experiments made use of molecular biology and immunology techniques.ResultsHCV infection (JFH1-Huh7 or HCV-FL replicon cells) was associated with increased RTN3L&S isoforms expression in cells and cell released exosomes. Accordingly, increased expression of RTN3L&S was observed in liver and serum exosome samples of HCV infected individuals compared to healthy controls. RNA-ChIP analysis revealed that RTN3L&S interacted with dsHCV RNA. Lentiviral CRISPR/Cas9 mediated knockdown (KD) of RTN3 and plasmid overexpression (OE) of wild type, C- and N-terminal deletion mutants of RTN3L&S in HCV- infected Huh7 cells differentially impacted the cellular release of infectious viral exosomes. RTN3L&S KD significantly decreased, while RTN3S OE significantly increased the number of Huh7 cell-released infectious exosomes. The C-terminal domain of RTN3 interacted with and modulated the loading of dsHCV RNA inside infectious exosomes. Antiviral treatment of HCV infected Huh7 cells reduced virus-induced RTN3L&S expression and attenuated the release of infectious exosomes.ConclusionRTN3 constitutes a novel regulator and a potential therapeutic target that mediates the specific loading of infectious viral exosomes.

Objectives To examine patterns of generic escitalopram initiation and substitution among Medicare beneficiaries. Methods This retrospective new user cohort used a 5% random sample of 2013–2015 Medicare administrative claims data. Fee-for-service Medicare beneficiaries continuously enrolled in Parts A, B, and D during a 6-month washout period prior to their initial generic or brand oral escitalopram prescriptions were included (n = 12,351). The primary outcomes were generic escitalopram treatment initiation, and among brand escitalopram initiators, generic substitution within 12 months. Patient demographics, health service utilization, and prescription level factors were measured and assessed. Results Among all escitalopram initiators, about 88.2% Medicare beneficiaries initiated generic escitalopram. Beneficiaries who were younger age, male, residing in non-Northeast regions or urban area, in the Part D plan deductible benefit phase, and filling prescriptions at community/retail pharmacies were more likely to initiate generic treatment. Among brand escitalopram initiators (n = 1,464), about 20.7% switched to generic escitalopram, 31.2% switched to another alternative antidepressant, 25.1% discontinued treatment, and 8.7% were lost to follow up or passed away within 12 months after brand initiation. Factors associated with generic escitalopram substitution included region (Midwest vs. Northeast, adjusted hazard ratio (HR) = 1.46, 95% CI = 1.04–2.05), pre-index hospitalization (HR = 1.31; 95% CI = 1.16–1.48) and lower escitalopram average daily dosage (HR = 0.97; 95% CI = 0.95–0.99). Conclusions In 2013–2015, almost 90% Medicare beneficiaries initiated generic escitalopram treatment. Among brand escitalopram initiators, about 1 in 5 patients switched to generic escitalopram within 1 year, as compared to 1 in 4 or 1 in 3 who discontinued current or switched to alternative treatment, respectively. Medicare beneficiary’s geographic region was independently associated with generic escitalopram initiation and substitution. Findings from this study not only provide up-to-date evidence in generic escitalopram use patterns among Medicare population, but also can guide educational and practice interventions to further increase generic escitalopram use.

This work applies a data-driven coding method for prediction of the COVID-19 spreading profile in any given population that shows an initial phase of epidemic progression. Based on the historical data collected for COVID-19 spreading in 367 cities in China and the set of parameters of the augmented Susceptible-Exposed-Infected-Removed (SEIR) model obtained for each city, a set of profile codes representing a variety of transmission mechanisms and contact topologies is formed. By comparing the data of an early outbreak of a given population with the complete set of historical profiles, the best fit profiles are selected and the corresponding sets of profile codes are used for prediction of the future progression of the epidemic in that population. Application of the method to the data collected for South Korea, Italy and Iran shows that peaks of infection cases are expected to occur before the end of March 2020, and that the percentage of population infected in each city will be less than 0.01%, 0.05% and 0.02%, for South Korea, Italy and Iran, respectively.

Tuber mustard, which is the raw material of Fuling pickle, is a crop with great economic value. However, during growth and development, tuber mustard is frequently attacked by the pathogen Plasmodiophora brassicae and frequently experiences salinity stress. Jasmonic acid (JA) is a hormone related to plant resistance to biotic and abiotic stress. Jasmonate ZIM domain proteins (JAZs) are crucial components of the JA signaling pathway and play important roles in plant responses to biotic and abiotic stress. To date, no information is available about the characteristics of the JAZ family genes in tuber mustard. Here, 38 BjJAZ genes were identified in the whole genome of tuber mustard. The BjJAZ genes are located on 17 of 18 chromosomes in the tuber mustard genome. The gene structures and protein motifs of the BjJAZ genes are conserved between tuber mustard and Arabidopsis. The results of qRT-PCR analysis showed that BjuA030800 was specifically expressed in root, and BjuA007483 was specifically expressed in leaf. In addition, 13 BjJAZ genes were transiently induced by P. brassicae at 12 h, and 7 BjJAZ genes were induced by salt stress from 12 to 24 h. These results provide valuable information for further studies on the role of BjJAZ genes in the regulation of plant growth and development and in the response to biotic and abiotic stress.

Imidacloprid is a neonicotinoid insecticide widely used in the production and cultivation of crops. In recent years, the extensive use of imidacloprid in agricultural production has resulted in large amounts of pesticide residues in agricultural products and the environment. Therefore, it is necessary to establish a rapid, accurate, sensitive and convenient method for detecting imidacloprid pesticide residues to ensure the safety of agricultural products and the environment. To clarify how to use the molecular imprinting method for the electrochemical rapid residue detection of imidacloprid. This paper selected reduced graphene oxide and gold nanoparticles as modifiers modified on screen-printed carbon electrodes (SPCE) chitosan as a functional monomer, and imidacloprid as template molecule to prepare molecularly imprinted polymer, and applied this sensor to the residue detection of imidacloprid. The results showed that the concentration of imidacloprid showed a good linear relationship with the peak response current, and the detection limit of imidacloprid was 0.5 μM, while the sensor had good repeatability and interference resistance. The recoveries of imidacloprid spiked on three samples, mango, cowpea and water, were in the range of 90–110% (relative standard deviation, RSD

In the past, China, like other developing countries in the world, pursued the goal of rapid economic development at the expense of ecology and ignored the issue of environmental protection. But in recent decades, as environmental problems have become increasingly prominent, developing countries have begun to explore ways to coordinate economy and ecological environment. As the largest developing country, China has been actively exploring ecological governance plans, putting forward the concept of green development, setting the goal of building a "beautiful China" and placing the construction of ecological civilization in the ontological status of social systems and national goals. In order to accelerate the green development process of enterprises in developing countries, based on the actual situation in China, this paper constructs a tripartite evolutionary game model of environmental accounting information disclosure with enterprises, investors and media as the research objects, and analyzes the internal mechanism of environmental accounting information disclosure. The model finds that the equilibrium of the three parties is affected by multiple factors. Therefore, this study further uses system dynamics to explore the dynamic process of evolutionary games and the strategic choices among multiple agents, and explore the mechanism of three types of agents to promote environmental accounting information disclosure. The simulation results reveal that government incentives have a greater impact on guiding enterprises and the media to evolve in the direction of legal disclosure and participation in exposure strategies. In addition, the continuous reduction of the cumbersome degree of disclosure procedures and the difficulty of improving environmental performance can fundamentally promote companies to actively choose legal disclosure strategies, which will help improve the quality of environmental accounting information disclosure, boost investor confidence, and enhance government supervision.

Although R&D internationalization plays an important role in enterprises’ globalization, few studies explore the mechanism of R&D internationalization and emerging market companies’ innovation, or the relationship between R&D internationalization, domestic technology alliances and absorptive capacity. How does the R&D internationalization of emerging market enterprises affect the innovation of those enterprises? Under fierce market competition, do absorption capacity and domestic technology alliances have a significant impact on enterprise innovation? From the perspective of the knowledge-based view, this paper studies 185 enterprises undergoing R&D internationalization in China from 2012 to 2017, using high-dimensional Poisson fixed effects model, we use instrumental (HDFE IV) estimation to explain the impact of R&D internationalization on the innovation of the parent company and the mechanism behind it. The study finds that R&D internationalization positively promotes the parent company’s innovation, and domestic technology alliances and absorptive capacity play a partial mediator role in R&D internationalization. In the face of fierce market competition, domestic technical alliances play a significant role in promoting enterprise innovation, while absorptive capacity plays a negative role in promoting enterprise innovation with the moderating effect of market competition.

Aims DPP-4 inhibitors are predicted to exert a protective effect on the progression of coronavirus disease 2019 (COVID-19). We conducted this meta-analysis to investigate this hypothesis. Methods Four databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify studies on DPP-4 and COVID-19. The outcome indicators were the mortality of COVID-19. Funnel plots, Begg’s tests and Egger’s tests were used to assess publication bias. Results Four articles were included with a total of 1933 patients with COVID-19 and type 2 diabetes. The use of DPP-4 inhibitors was negatively associated with the risk of mortality (odds ratio (OR) = 0.58 95% confidence interval (CI), 0.34–0.99). Conclusions DPP-4 inhibitors may improve the mortality of patients with COVID-19 and type 2 diabetes. As few relevant studies are available, more large-scale studies need to be performed.

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

Background Transcatheter aortic valve implantation (TAVI) is an option for treatment for patients with severe aortic stenosis who are at high risk for death with surgical aortic valve replacement (SAVR). It is unknown whether TAVI can be safely introduced to intermediate- and low-risk patients. Objective To compare the efficacy and safety of TAVI and SAVR in patients with intermediate- and low-surgical risk. Data sources Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to April 15, 2019. Study selection We included randomized controlled trials comparing TAVI with SAVR in patients with intermediate- and low-surgical risk. Data extraction Meta-analyses were conducted using random-effects models to calculate risk ratios (RR) with corresponding 95% confidence interval (CI). Two independent reviewers completed citation screening, data abstraction, and risk assessment. Primary outcome was a composite of all-cause mortality or disabling stroke at 12 months. Data synthesis A total of 5 trials randomizing 6390 patients were included. In patients with low risk, TAVI was associated with a significant reduction in the composite of all-cause mortality or disabling stroke compared with SAVR (RR, 0.56; 95%CI, 0.40-0.79; I2 = 0%). This benefit was not replicated in patients with intermediate risk (RR, 0.96; 95% CI, 0.80-1.15; I2 = 0%). Similar results were seen separately in all-cause mortality and disabling stroke when TAVI was compared with SAVR. Conclusion For patients with severe aortic stenosis who were at low risk for death from surgery, TAVI achieved superior clinical outcomes compared to SAVR; however, these benefits were not seen in those with intermediate risk. This information may inform discussions about deciding between SAVR and TAVI for patients with low to intermediate risk separately.

Background Vascular endothelial growth factor (VEGF) is commonly overexpressed in a variety of tumor types including lung cancer. As a key regulator of angiogenesis, it promotes tumor survival, growth, and metastasis through the activation of the downstream protein kinase B (AKT) and extracellular signal-regulated kinase (ERK 1/2) activation. The VEGF promoter contains a 36 bp guanine-rich sequence (VEGFq) which is capable of forming quadruplex (four-stranded) DNA. This sequence has been implicated in the down-regulation of both basal and inducible VEGF expression and represents an ideal target for inhibition of VEGF expression. Results Our experiments demonstrate sequence-specific interaction between a G-rich quadruplex-forming oligonucleotide encoding a portion of the VEGFq sequence and its double stranded target sequence, suggesting that this G-rich oligonucleotide binds specifically to its complementary C-rich sequence in the genomic VEGF promoter by strand invasion. We show that treatment of A549 non-small lung cancer cells (NSCLC) with this oligonucleotide results in decreased VEGF expression and growth inhibition. The VEGFq oligonucleotide inhibits proliferation and invasion by decreasing VEGF mRNA/protein expression and subsequent ERK 1/2 and AKT activation. Furthermore, the VEGFq oligonucleotide is abundantly taken into cells, localized in the cytoplasm/nucleus, inherently stable in serum and intracellularly, and has no effect on non-transformed cells. Suppression of VEGF expression induces cytoplasmic accumulation of autophagic vacuoles and increased expression of LC3B, suggesting that VEGFq may induce autophagic cell death. Conclusion Our data strongly suggest that the G-rich VEGFq oligonucleotide binds specifically to the C-rich strand of the genomic VEGF promoter, via strand invasion, stabilizing the quadruplex structure formed by the genomic G-rich sequence, resulting in transcriptional inhibition. Strand invading oligonucleotides represent a new approach to specifically inhibit VEGF expression that avoids many of the problems which have plagued the therapeutic use of oligonucleotides. This is a novel approach to specific inhibition of gene expression.

Citrus bacterial canker (CBC) caused by Xanthomonas citri subsp. citri (Xcc) is a systemic bacterial disease that affects citrus plantations globally. Biotic stress in plants has been linked to a group of important transcription factors known as Basic Leucine Zippers (BZIPs). In this study, CsBZIP40 was functionally characterized by expression analysis, including induction by Xcc and hormones, subcellular localization, over-expression and RNAi silencing. CsBZIP40 belongs to group D of the CsBZIP family of transcription factors and localizes in the nucleus, potentially serving as a transcriptional regulator. In wild type (WT) plants CsBZIP40 can be induced by plant hormones in addition to infection by Xcc which has given insight into its involvement in CBC. In the present study, over-expression of CsBZIP40 conferred resistance to Xcc while its silencing led to Xcc susceptibility. Both over-expression and RNAi affected salicylic acid (SA) production and expression of the genes involved in the SA synthesis and signaling pathway, in addition to interaction of CsBZIP40 with CsNPR1, as detected by a GST pull-down assay. Taken together, the results of this study confirmed the important role of CsBZIP40 in improving resistance to citrus canker through the SA signaling pathway by the presence of NPR1 to activate PR genes. Our findings are of potential value in the breeding of tolerance to CBC in citrus fruits.

BackgroundHypochondriac symptoms are commonly reported in health science students. With their incomplete medical knowledge, they may compare their own bodily symptoms with disease symptoms during the process of learning, which can lead to mental distress and the need for repeated medical reassurance.ObjectiveTo estimate the prevalence of hypochondriac symptoms in Chinese health science students.MethodsA systematic literature search was conducted on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Data on July 1, 2018. Additionally, the references of the retrieved papers were searched. Cross-sectional studies published in either English or Chinese that reported the prevalence of hypochondriac symptoms in health science students were included. The selection process was executed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, and study quality was assessed with the checklist recommended by the Agency for Healthcare Research and Quality for cross-sectional studies. A random-effects model according to the DerSimonian-Laird method was used to calculate the pooled prevalence.ResultsSeven cross-sectional studies involving 6,217 Chinese health science students were included. The pooled prevalence of hypochondriac symptoms among health science students was 28.0% (95% CI = 19.0%-38.0%). The symptoms were a little more common in females (30.0%, 95% CI = 19.0%-42.0%) than in males (29.0%, 95% CI = 16.0%-42.0%), but the difference was not significant. No significant differences were found between participants grouped by study year. Only three studies explored the coping styles of students with hypochondriasis, and these revealed a high tendency toward help-seeking behaviors.ConclusionOur systematic review and meta-analysis showed a high prevalence of hypochondriac symptoms among health science students, indicating that it is a noteworthy phenomenon. We suggest that counseling and other support services are necessary for health science students.

Diverse fungal endophytes live in plants and are shaped by some abiotic and biotic stresses. Plant disease as particular biotic stress possibly gives an impact on the communities of fungal endophytes. In this study, clubroot disease caused by an obligate biotroph protist, Plasmodiophora brassicae, was considered to analyze its influence on the fungal endophyte community using an internal transcribed spacer (ITS) through high-throughput sequencing and culture-dependent methods. The results show that the diversity of the endophyte community in the healthy roots was much higher than the clubroots. Ascomycota was the dominant group of endophytes (including Phoma, Mortierella, Penicillium, etc.) in the healthy roots while P. brassicae was the dominant taxon in the clubroots. Hierarchical clustering, principal component analysis (PCA) and principal coordinates analysis (PCoA) indicated significant differences between the endophyte communities in the healthy roots and clubroots. Linear discriminant analysis effect size (LefSe) analysis showed that the dominant genera could be regarded as potential biomarkers. The endophyte community in the healthy roots had a more complex network compared with the clubroots. Also, many plant pathogenic Fusarium were isolated from the clubroots by the culture-dependent method. The outcome of this study illustrates that P. brassicae infection may change the fungal endophyte community associated with the roots of tumourous stem mustard and facilitates the entry of soil pathogen into the roots.

Resveratrol, a non-flavonoid polyphenolic compound, is structurally and functionally similar to estrogen and has drawn great attention for its potentially beneficial effects on diabetes. However, it is not known whether it shares the same protective effect against diabetes as estrogen and the underlying mechanisms. The aim of the present study was to investigate the protective effects of phytoestrogen resveratrol and exogenous 17β-estradiol against streptozotocin (STZ)-induced type 1 diabetes. Female mice were ovariectomized (OVX) and chronically injected with different concentrations of resveratrol (0.1, 1 or 10 mg/kg) and 17β-estradiol (0.01, 0.1 or 1 mg/kg) subcutaneously for 4 weeks, and the levels of blood glucose, plasma insulin, plasma antioxidant capacity, the changes of pancreatic islet cells and the expressions of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS-1) and phosphorylation of extracellular signal-regulated kinase (p-ERK) were detected. Resveratrol and 17β-estradiol significantly inhibited the increase of the blood glucose level and the rise of plasma malondialdehyde in STZ-induced diabetic mice, improved the levels of plasma antioxidant capacity and plasma insulin, protected the pancreatic islet cells, and increased the expressions of GLUT4 and IRS-1, but decreased p-ERK expression in skeletal muscle and myocardial tissue. The results suggest that resveratrol or 17β-estradiol shows obvious protection against STZ-induced diabetes in OVX mice, the mechanisms probably involve their ameliorating antioxidant activities and islet function, promoting muscle glucose uptake and inhibiting the expression of p-ERK.

Biochar derived from straw is a potential low-cost adsorbent for metal ions and organic pollutants, but its practical application is still limited by the adsorption capacity. In this study, the correlation between the biochar’s properties and pyrolysis temperature was explored. The adsorption mechanism was studied by monitoring the changes of biochar properties before and after adsorption using BET, SEM, XPS and FT-IR spectroscopy. The adsorption mechanism was revealed following the adsorption kinetics and the changes in biochar’s properties before and after adsorption. The methylene blue (MB) and Pb2+ adsorption removal efficiency reached 95% at the initial concentration of 125 and 500 mg/L, respectively. Physisorption, chemisorption, and pore filling mechanisms determined the adsorption process of MB and Pb2+ on biochar. The Pb2+ adsorption process was highly affected by chemical co-precipitation at higher pyrolysis temperatures. The appearance of tar particles increased the adsorption rate of Pb2+. The biochar obtained at the pyrolysis temperature at 500, 800 and 900°C proved to be applicable for Pb2+ removal. Chemisorption and porosity dominated the MB adsorption, and biochars produced at pyrolysis temperatures of 200, 800 and 900°C are potential materials for MB removal. This study provides optimal pyrolysis conditions for transforming maize straw into valuable, low-cost materials for the removal of different pollutants.

Land subsidence monitoring provides information required when developing land use plans and allows for proactive management of subsidence issues. However, it has been challenging to accurately detect land subsidence areas, especially those under waterbodies. This study evaluated the applicability of integrated use of the optical Landsat-8 OLI and microwave Sentinel-1A TOPSAR imagery to delineate subsidence areas and quantify subsidence rates in a typical coal mining area of North China Plain. An Enhanced Modified Normalized Difference Water Index (E-MNDWI) was combined with Short BAseline Subset-Interferometric Synthetic Aperture Radar (SBAS-InSAR) image to monitor underwater and dry ground subsidence. The results demonstrated that the method could delineate underwater and dry ground subsidence and quantify its rates accurately. The proposed method estimated subsidence area corresponded to 34.8% (16.7 km2) of the study area. The size of underwater subsidence areas was substantial and accounted for 43.7% of the subsidence areas. Seasonal underwater subsidence areas were generally distributed in the vicinity of perennial ones. Dry ground subsidence covered 9.4 km2 of the study area and generally occurred in urban and rural residential areas with the maximum subsidence of up to 80.1 mm/year. This study demonstrates the efficiency and capacity of integrating optical and microwave images to monitor the subsidence progresses, which thus can help develop effective rehabilitation policy and strategy to mitigate the impacts of land subsidence.

The optimal treatment strategy for stage IB2-IIB cervical cancer is controversial. This systematic review with meta-analysis evaluated the efficacy of concomitant chemoradiotherapy (CCRT) and neoadjuvant chemotherapy followed by radical surgery (NACT+S). Studies that evaluated NACT+S versus CCRT for patients with Federation of Gynecology and Obstetrics stage IB2-IIB cervical cancer were searched in MEDLINE, EMBASE, and the Cochrane Library database. Hazard ratios (HRs) with their respective 95% confidence intervals (CIs) were calculated using a random-effects model. Toxicity was also evaluated. Six qualified retrospective studies and one randomized controlled trial (2270 patients) were included in this review. The results suggested that compared with CCRT, NACT+S did not improve overall survival in all patients (HR 0.73, 95% CI 0.52–1.02) or stage IIB patients (HR 0.83, 95% CI 0.61–1.15). NACT+S did not improve disease-free survival (DFS) in stage IIB patients (HR 1.10, 95% CI 0.70–1.71). In the analysis of DFS in all patients, a high degree of heterogeneity was detected (I2 = 84%). Sensitivity analysis that eliminated these heterogeneous data suggested that CCRT could improve DFS over NACT+S (HR 1.47, 95% CI 1.12–1.93). Diarrhea and rectal and bladder complications occurred at a lower rate in the NACT+S group than in the CCRT group. NACT+S had no survival advantage for patients with stage IB2-IIB cervical cancer compared with CCRT but was associated with fewer side effects. Further prospective studies with a larger sample size of treatment protocols for locally advanced cervical cancer are needed.

BackgroundSelf-management is the cornerstone of diabetes care, however, despite the numerous recommendations available for self-management, type-2 diabetes mellitus (T2DM) patients' performance is suboptimal in China. This study aimed to explore the association between self-efficacy and self-management behaviors among Chinese T2DM patients, which might provide evidence to inform effective self-management interventions for these patients.MethodsA cross-sectional survey was conducted using a multi-stage stratified randomized sampling in Shandong Province, China. The Diabetes Empowerment Scale-Short Form (DES-SF) was used to measure patients' self-efficacy to manage diabetes. Latent class analysis (LCA) was used to explore the observed classes of self-management behaviors (dietary control, physical exercise, regular medication and self-monitoring of blood glucose). A two-class solution for self-management behaviors was tested to be the fittest based on LCA; we labelled active and inactive self-management groups. Univariate and multivariate logistic regression analysis were used to examine the associations between self-efficacy and self-management behaviors.ResultsA total of 2166 T2DM patients were included in the analysis. The mean DES-SF score was 31.9 (standard deviation: 5.2). The estimated proportions of T2DM in the active and inactive groups were 54.8% and 45.2%, respectively. The multivariate logistic regression showed that higher DES-SF score was significantly associated with higher possibility of active self-management behaviors (odds ratio = 1.06; 95% confidence interval: 1.04-1.08).ConclusionsSelf-efficacy in managing diabetes is associated with self-management behaviors among Chinese T2DM patients. To improve self-management behaviors, multiple strategies should be conducted to improve patients' self-efficacy.

Peroxisome proliferator activated receptor-alpha (PPARα) and Egl nine homolog 3 (EGLN3) play critical roles in facilitating the adaptation to a hypoxic environment. However, the relationship between EGLN3 and PPARα variants and hypoxic adaptation remains poorly understood in Tibetan chickens. To better understand the effects of genetic variation, we sequenced exons of PPARα and EGLN3 in 138 Lowland chickens (LC) from 7 breeds that were located in Emei, Miyi, Shimian, Wanyuan, Pengxian, and Muchuan in the Sichuan province, and Wenchang in the Hainan province (altitudes for these locations are below 1800 meters). Total 166 Tibetan chickens (TC) from 7 subpopulations that were located in Shigatse, Lhoka, Lhasa, Garze, Aba, Diqing and Yushu in the Tibetan area were also sequenced (altitudes greater than 2700 meters). One single-nucleotide polymorphism (rs316017491, C > T) was identified in EGLN3 and was shared by TC and LC with no significant difference for allele frequencies between them (P > 0.05). Six single-nucleotide polymorphisms (SNP1, A29410G; SNP2, rs13886097; SNP3, T29467C; SNP4, rs735915170; SNP5, rs736599044; and SNP6, rs740077421) including one non-synonymous mutation (SNP2, T > C) were identified in PPARα. This is the first report of SNP1 and SNP3. There was a difference between TC and LC for allele frequencies (P

Non-alcoholic fatty liver disease (NAFLD) is becoming one of the world's most common chronic liver diseases in childhood, yet no therapy is available that has been approved by the food and drug administration (FDA). Previous studies have reported that telomere and telomerase are involved the development and progression of NAFLD. This study was designed to investigate the potential beneficial effects of activated carbon N-acetylcysteine (ACNAC) microcapsules on the development of NAFLD in young rats as well as the underlying mechanism(s) involved. Three-week old male Sprague Dawley rats were given high-fat diet (HFD) with/without ACNAC treatment for 7 consecutive weeks. Liver pathologies were determined by hematoxylin and eosin (H&E) and Oil Red O staining, as well as by changes in biochemical parameters of plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, respectively. Glucose homeostasis was evaluated by the glucose tolerance test and the liver telomere length and activity were measured by real time PCR and telomeric repeat amplification protocol (TRAP). Western blot analysis was performed to determine the expression level of Bcl-2, Bax and Caspase-3. Our results demonstrated that ACNAC supplementation improved liver pathologies of rats that received long-term HFD feeding. ACNAC supplementation prevented HFD-induced telomere shortening and improved telomerase activity. Moreover, in comparison to HFD-fed rats, ACNAC supplementation markedly increased the expression of Bcl-2, but significantly decreased the expression of Bax and Caspase-3 in juvenile rats. Together, these results indicate that ACNAC may be a promising choice for preventing and treating NAFLD among children.

Mycoplasma gallisepticum is a causative agent of chronic respiratory disease in chickens, typically causing great economic losses. Cytoadherence is the critical stage for mycoplasma infection, and the associated proteins are important for mycoplasma pathogenesis. Many glycolytic enzymes are localized on the cell surface and can bind the extracellular matrix of host cells. In this study, the M. gallisepticum pyruvate dehydrogenase E1 alpha subunit (PDHA) and beta subunit (PDHB) were expressed in Escherichia coli, and their enzymatic activities were identified based on 2,6-dichlorophenol indophenol reduction. When recombinant PDHA (rPDHA) and recombinant PDHB (rPDHB) were mixed at a 1:1 molar ratio, they exhibited strong enzymatic activity. Alone, rPDHA and rPDHB exhibited no or weak enzymatic activity. Further experiments indicated that both PDHA and PDHB were surface-exposed immunogenic proteins of M. gallisepticum. Bactericidal assays showed that the mouse anti-rPDHA and anti-rPDHB sera killed 48.0% and 75.1% of mycoplasmas respectively. A combination of rPDHA and rPDHB antisera had a mean bactericidal rate of 65.2%, indicating that rPDHA and rPDHB were protective antigens, and combining the two sera did not interfere with bactericidal activity. Indirect immunofluorescence and surface display assays showed that both PDHA and PDHB adhered to DF-1 chicken embryo fibroblast cells and adherence was significantly inhibited by antisera against PDHA and PDHB. Adherence inhibition of M. gallisepticum to DF-1 chicken embryo fibroblast cells was 30.2% for mouse anti-rPDHA serum, 45.1% for mouse anti-rPDHB serum and 72.5% for a combination of rPDHA and rPDHB antisera, suggesting that rPDHA and rPDHB antisera may have synergistically interfered with M. gallisepticum cytoadherence. Plasminogen (Plg)-binding assays further demonstrated that both PDHA and PDHB were Plg-binding proteins, which may have contributed to bacterial colonization. Our results clarified the enzymatic activity of M. gallisepticum PDHA and PDHB and demonstrated these compounds as Plg-binding proteins involved in cytoadherence.

The present study examined the types of situations that caused Chinese professional and non-professional drivers to become angry and investigated the differences in driving-elicited anger, considering the influences of type A behavior pattern and trait anger between the two groups. The 20-item revised Driving Anger Scale (DAS) was used to assess a sample of 232 drivers (57% professional, 43% non-professional). The non-professional drivers reported significantly higher levels of anger than the professional drivers on the overall Driving Anger Scale (DAS) and the traffic obstructions and discourtesy subscales. In both groups, the preferred driving speeds were positively related to driving anger. Furthermore, drivers with a type A personality exhibited higher overall driving anger scores and higher anger scores in response to traffic obstructions and slow driving than drivers with a type B personality. Trait anger was significantly related to driving anger in both groups. In the non-professional group, type A behavior patterns (TABPs) and time hurry (TH) were positively correlated with anger evoked by slow driving. In the professional group, TABPs, TH and competitive hostility (CH) were positively related to driving anger, and the TABPs exerted an indirect effect on driving anger by mediating the influence of trait anger. Overall, these findings provide a theoretical basis for implementing targeted interventions for driving anger in both professional and non-professional drivers.

Proofreading deficiencies of hepatitis B virus polymerase result in frequent DNA mutations in the hepatitis B virus genome. Here, we performed sequencing analysis of the hepatitis B virus polymerase gene to assess its association with the postoperative survival in 92 patients with HBV-related hepatocellular carcinoma by using the Kaplan-Meier method. The 2525, 2733, 2738, 2768, 2946, 3063, 3066, 3109, 31, 529, 735, 939, 1078, 1137, 1383, 1461, 1485, 1544, and 1613 mutation sites were identified as being associated with HCC outcomes by the log-rank test. After adjusting for clinical characteristics by using the Cox hazard model, site 31 (relative risk, 8.929; 95% confidence interval, 3.433-23.22; P = 0.000) in the spacer domain and sites 529 (relative risk, 5.656; 95% confidence interval, 1.599-19.999; P = 0.007) and 1078 (relative risk, 3.442; 95% confidence interval, 1.070-11.068; P = 0.038) in the reverse transcriptase domain of hepatitis B virus polymerase were identified as independent predictors of postoperative survival in hepatitis B virus related hepatocellular carcinoma. The mutations at the 31 (Ser314Pro), 529 (Asp480Asn), and 1078 (Ser663Ala) sites all resulted in amino acid changes in hepatitis B virus polymerase and were associated with shortened life-span. The 31 and 529 sites were located in the overlapping region for the PreS and S genes but did not induce amino acid substitution in these two regions. Our finding of the correlation between hepatitis B virus DNA polymerase mutations and hepatocellular carcinoma survival will help identify the patients subgroup with poor prognosis, and help the clinicians to refine the therapeutic decision individualized.

Objectives The aim of this study is to clarify the associations between IL-1B31C/T, IL-1B-511C/T, IL-8-251T/A gene polymorphisms and the risk of Helicobacter pylori (H. pylori) infection together with H. pylori-related gastric cancer (GC), peptic ulcer disease (PUD). Methods All eligible literature published up to July 2016 were identified by searching Pubmed, Embase, Web of Science and CNKI. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using a fixed or random effects model. Results 29 case-control studies were eligible, and each of them may focus on more than one gene polymorphism. Ultimately, there were 21 studies (3159 cases and 2816 controls) for IL-1B-31C/T, 16 studies (2486 cases and 1989 controls) for IL-1B-511C/T polymorphisms, 9 studies (1963 cases and 1205 controls) for IL-8-251T/A polymorphisms. Overall, an increased risk of H. pylori infection was found for IL-1B-31C/T polymorphisms in total population [OR = 1.134, 95%CI = 1.008-1.275 for recessive model; OR = 1.145, 95%CI = 1.007-1.301 for TT vs CC model]. While, for IL-1B-511C/T and IL8-251T/A polymorphisms, no evidence indicated that they were associated with the risk of H. pylori infection in all genetic models. Furthermore, we found an increased risk of H. pylori-related GC with IL-1B-511C/T polymorphisms [OR = 1.784, 95%CI = 1.289-2.469 for recessive model; OR = 1.772, 95%CI = 1.210-2.594 for TT vs CC model] and IL8-251A/T polymorphisms [OR = 1.810, 95%CI = 1.229-2.667 for recessive model; OR = 1.717, 95%CI = 1.143-2.580 for TT vs AA model], an increased risk of H. pylori-related PUD with IL8-251T/A polymorphisms [OR = 1.364, 95%CI = 1.010-1.843 for recessive model; OR = 1.427, 95%CI = 1.039-1.959 for AA vs TT model]. Conclusions IL-1B-31C/T gene polymorphisms might increase H. pylori infection risk. IL-1B-511-C/T and IL-8-251T/A gene polymorphisms might act as a risk factor to H. pylori-related diseases including GC or PUD.

Five strains of bacteria, namely, Exiguobacterium sp. ASW-1, Pseudomonas aeruginosa strain ASW-2, Alcaligenes sp. ASW-3, Alcaligenes sp. ASS-1, and Bacillus sp. ASS-2, were isolated from the Zhejiang coast in China. The mixed flora of the five strains performed well with degrading 75.1% crude oil (1%, w/v) in 7 days. The calcium alginate—activated carbon embedding carrier was used to immobilize bacterial consortium. Immobilized cells performed better than free ones in variations of environmental factors containing incubated temperature, initial pH, salinity of the medium and crude oil concentration. The degradation process of crude oil by immobilized bacteria was accelerated compared with that of the free ones. Bacterial consortium showed better performance on biodegradation of normal alkanes than that of PAHs. Improvement of immobilization on the biodegradation efficiency of normal alkanes (31.9%) was apparently high than that of PAHs (1.9%).

Claudins play an important role in regulating the permeability of epithelial and endothelial cells and in the maintenance of cell polarity. We aimed to investigate expression of claudin-11, -23 in different gastric tissues and its relationship with clinicopathologic parameters and prognosis of gastric cancer. We compared their expression levels in the paired cancerous tissues versus those in the adjacent noncancerous tissues by real-time PCR, western blotting and immunohistochemistry. The results showed that the expression of claudin-11, -23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue. We also compared their expression levels of tissues from gastric cancer, superficial gastritis, and atrophic gastritis by immunohistochemistry. The results indicated that the expression of claudin-11 and 23 was significantly higher in superficial gastritis than that in atrophic gastritis and gastric cancer. The expression of claudin-23 was significantly lower in atrophic gastritis than that in gastric cancer, but no obviously difference was observed for claudin-11. As for analysis of clinicopathologic parameters of gastric cancer, logistic multiple regression indicated that claudin-11 was significantly associated with sex, smoking, alcohol, H. pylori infection and Borrmann classification while claudin-23 was significantly associated with vessel cancer embolus. Cox multivariate survival analysis indicated that gastric cancer patients with negative claudin-23 expression had significantly longer overall survival. In conclusion, the expression of claudin-11, -23 was remarkably downregulated in gastric cancer. Abnormal expression of these proteins was significantly correlated with some clinicopathologic parameters. In particular, claudin-23 positive expression was associated with poor prognostic outcomes of gastric cancer patients and may therefore serve as an independent prognosticator of patient survival.

ObjectivesIntestinal barrier dysfunction plays an important role in acute necrotizing pancreatitis (ANP) and intestinal microbiota dysbiosis was involved in intestinal barrier failure. Paneth cells protect intestinal barrier and are associated with intestinal microbiota. Here, we investigated changes in intestinal microbiota and antimicrobial peptides of Paneth cells in ileum during ANP.MethodsRats with ANP were established by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct and sacrificed at 24h and 48h, respectively. Injuries of pancreas and distal ileum were evaluated by histopathological score. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A concentration by ELISA, respectively. 16S rRNA high throughput sequencing on fecal samples was used to investigate the changes in intestinal microbiota in the ANP group at 48h. Lysozyme and α-defensin5 were measured by real-time PCR, western blot and immunofluoresence.ResultsANP rats had more severe histopathological injuries in pancreas and distal ileum, injured intestinal barrier and increased expression of TNFα, IL-1β and IL-17A in plasma and distal ileum compared with those of the sham-operated (SO) group. Principal component analysis (PCA) showed structural segregation between the SO and ANP groups. Operational taxonomic unit (OTU) number and ACE index revealed decreased microbiota diversity in the ANP group. Taxonomic analysis showed dysbiosis of intestinal microbiota structure. At phyla level, Saccharibacteria and Tenericutes decreased significantly. At genus level, Escherichia-Shigella and Phascolarctobacterium increased significantly, while Candidatus_Saccharimonas, Prevotellaceae_UCG-001, Lachnospiraceae_UCG-001, Ruminiclostridium_5 and Ruminococcaceae_UCG-008 decreased significantly. Lysozyme and α-defensin5 mRNA expression levels decreased significantly in ANP group at 48h. Protein expression of lysozyme decreased in ANP groups at 24h and 48h. Meanwhile, the relative abundance of Escherichia-Shigella correlated inversely with the decrease in lysozyme.ConclusionThe disorder in intestinal microbiota and decreases of Paneth cell antimicrobial peptides might participate in the pathogenesis of intestinal barrier dysfunction during ANP.

Slit-lamp images play an essential role for diagnosis of pediatric cataracts. We present a computer vision-based framework for the automatic localization and diagnosis of slit-lamp images by identifying the lens region of interest (ROI) and employing a deep learning convolutional neural network (CNN). First, three grading degrees for slit-lamp images are proposed in conjunction with three leading ophthalmologists. The lens ROI is located in an automated manner in the original image using two successive applications of Candy detection and the Hough transform, which are cropped, resized to a fixed size and used to form pediatric cataract datasets. These datasets are fed into the CNN to extract high-level features and implement automatic classification and grading. To demonstrate the performance and effectiveness of the deep features extracted in the CNN, we investigate the features combined with support vector machine (SVM) and softmax classifier and compare these with the traditional representative methods. The qualitative and quantitative experimental results demonstrate that our proposed method offers exceptional mean accuracy, sensitivity and specificity: classification (97.07%, 97.28%, and 96.83%) and a three-degree grading area (89.02%, 86.63%, and 90.75%), density (92.68%, 91.05%, and 93.94%) and location (89.28%, 82.70%, and 93.08%). Finally, we developed and deployed a potential automatic diagnostic software for ophthalmologists and patients in clinical applications to implement the validated model.

This study aimed to investigate prospective memory (PM) and the association with clinical factors at 1-year follow-up in first-episode schizophrenia (FES). Thirty-two FES patients recruited from a university-affiliated psychiatric hospital in Beijing and 17 healthy community controls (HCs) were included. Time- and event-based PM (TBPM and EBPM) performances were measured with the Chinese version of the Cambridge Prospective Memory Test (C-CAMPROMPT) at baseline and at one-year follow-up. A number of other neurocognitive tests were also administered. Remission was determined at the endpoint according to the PANSS score ≤ 3 for selected items. Repeated measures analysis of variance revealed a significant interaction between time (baseline vs. endpoint) and group (FES vs. HCs) for EBPM (F(1, 44) = 8.8, p = 0.005) and for all neurocognitive components. Paired samples t-tests showed significant improvement in EBPM in FES (13.1±3.7 vs. 10.3±4.8; t = 3.065, p = 0.004), compared to HCs (15.7±3.6 vs. 16.5±2.3; t = -1.248, p = 0.230). A remission rate of 59.4% was found in the FES group. Analysis of covariance revealed that remitters performed significantly better on EBPM (14.9±2.6 vs. 10.4±3.6; F(1, 25) = 12.2, p = 0.002) than non-remitters at study endpoint. The association between EBPM and 12-month clinical improvement in FES suggests that EBPM may be a potential neurocognitive marker for the effectiveness of standard pharmacotherapy. Furthermore, the findings also imply that PM may not be strictly a trait-related endophenotype as indicated in previous studies.

Purpose To compare changes in anterior segment parameters under light and dark (light-to-dark) conditions among eyes with chronic primary angle-closure glaucoma (CPACG), fellow eyes with confirmed or suspect primary angle-closure (PAC or PACS), and age-matched healthy eyes. Methods Consecutive patients with CPACG in one eye and PAC/PACS in the fellow eye, as well as age-matched healthy subjects were recruited. Anterior segment optical coherence tomography measurements were conducted under light and dark conditions, and anterior chamber, lens, and iris parameters compared. Demographic and biometric factors associated with light-to-dark change in iris area were analyzed by linear regression. Results Fifty-seven patients (mean age 59.6±8.9 years) and 30 normal subjects matched for age (60.6±9.3 years) and sex ratio were recruited. In regards to differences under light–to-dark conditions, angle opening distance at 500 μm (AOD500μm) and iris area during light-to-dark transition were smaller in CPACG eyes than fellow PACS/PAC eyes and normal eyes (P

Objective The nasal mucosa is equipped with abundant lymphatic tissues, serving as the first line of defense against invasion by microorganisms. In this study, we characterized the features of the nasal mucosa of Bama minipigs (Sus scrofa domestica) via histological analysis. Methods Five cross sections (I, II, III, IV, and V) were obtained from the distal end of the nasal cavity toward the pharynx (along the cavity axis) and examined. Specifically, CD3+ T cells, immunoglobulin A (IgA)+ cells, and M cells were detected by immunohistochemistry, while dendritic cells (DCs) were detected by immunofluorescence. The distribution of goblet cells was determined by periodic acid-Schiff (PAS) staining. Results The nasal cavity of Bama minipigs can be divided into three parts: the regio vestibularis (I, II), regio respiratoria (III, IV), and regio olfactoria (V). Lymphoid tissue was present at random locations in the nasal cavity. Abundant lymphoid tissue was located in the roof of the nasopharyngeal meatus and was continuous with the lymphoid tissue of the pharynx. The distribution of CD3+ T cells, IgA+ cells, M cells, and DCs increased distally in the nasal cavity. Conclusions The present work comprises a histological study of the nasal cavity of Bama minipigs, and will be beneficial for understanding the mechanisms of immunity in these animals after nasal vaccination.

The principal target organ of duck hepatitis A virus type 1 (DHAV-1) is duckling liver, which is an energy-intensive organ and plays important roles in body's energy metabolism and conversion. As the "power house" of the hepatocytes, mitochondria provide more than 90% of the energy. However, mitochondria are much vulnerable to the oxidative stress for their rich in polyunsaturated fatty acids. Although previous researches have demonstrated that DHAV-1 could induce the oxidative stress in the serum of the infected ducklings, no related study on the mitochondria during the pathological process of DVH has been reported by far. To address this issue, we examined the HE stained tissue pathological slices, detected the hepatic SOD, CAT and GPX activities and MDA contents and analyzed the ATP content, mitochondrial ultrastructure and the mitochondrial SOD, GPX activities and MDA content in the liver tissues. The results showed that the hepatic redox status was significantly disturbed so that causing the mitochondrial dysfunction, ATP depletion and mitochondrial oxidative stress during the process of the DHAV-1 infection, and a prescription formulated with Hypericum japonicum flavone, Radix Rehmanniae Recens polysaccharide and Salvia plebeia flavone (HRS), which had been demonstrated with good anti-oxidative activity in serum, could effectively alleviate the hepatic injury and the oxidative stress in liver tissue induced by DHAV-1 thus alleviating the mitochondrial injury and oxidative stress. In a word, this research discovers the oxidative stress induced mitochondrial dysfunction and oxidative stress during the DVH pathological process and demonstrates HRS exerts good anti-oxidative activity in liver tissue to protect mitochondria against reactive oxygen species (ROS).

International audience; Hfq is a global regulator that is involved in environmental adaptation of bacteria and in pathogenicity. To gain insight into the role of Hfq in Vibrio alginolyticus, an hfq deletion mutant was constructed in V. alginolyticus ZJ-T strain and phenotypically characterized. Deletion of hfq led to an alteration of colony morphology and reduced extracellular polysaccharide production, a general impairment of growth in both rich medium and minimal media with different carbon sources or amino acids, enhanced sensitivity to oxidative stress and to several antibiotics. Furthermore, a differential transcriptomic analysis showed significant changes of transcript abundance for 306 protein coding genes, with 179 genes being up regulated and 127 down-regulated. Several of these changes could be related to the observed phenotypes of the mutant. Transcriptomic data also provided evidence for the induction of the extracytoplasmic stress response in absence of Hfq. Altogether, these findings point to broad regulatory functions for Hfq in V. alginolyticus cells, likely to underlie an important role in pathogenicity.

Objective To collectively evaluate the association of glucose-6-phosphatase catalytic unit 2 (G6PC2) allele variants with elevated fasting glucose (FG) and type 2 diabetes (T2D). Design Meta-analysis. Data sources PubMed, Web of Knowledge and Embase databases. Study selection Full text articles of studies that identified an association of G6PC2 with T2D and elevated FG. Patient involvement There was no T2D patient involvement in the analyses on the association of FG with G6PC2, there were T2D patients and non-diabetes patient involvement in the analyses on the association of T2D with G6PC2. Statistical analysis Random-effects meta-analyses were used to calculate the pool effect sizes. I2 metric and H2 tests were used to calculate the heterogeneity. Begg's funnel plot and Egger's linear regression test were done to assess publication bias. Results Of the 423 studies identified, 21 were eligible and included. Data on three loci (rs560887, rs16856187 and rs573225) were available. The G allele at rs560887 in three ethnicities, the C allele at rs16856187 and the A allele at rs573225 all had a positive association with elevated FG. Per increment of G allele at rs560887 and A allele at rs573225 resulted in a FG 0.070 mmol/l and 0.075 mmol/l higher (s (95% CI) = 0.070 (0.060, 0.079), p = 4.635e-50 and 0.075 (0.065, 0.085), p = 5.856e-48, respectively). With regard to the relationship of rs16856187 and FG, an increase of 0.152 (95% CI: 0.034-0.270; p = 0.011) and 0.317 (95% CI: 0.193-0.442, p = 6.046e-07) was found in the standardized mean difference (SMD) of FG for the AC and CC genotypes, respectively, when compared with the AA reference genotype. However, the G-allele of rs560887 in Caucasians under the additive model and the C-allele of rs16856187 under the allele and dominant models were associated with a decreased risk of T2D (OR (95% CI) = 0.964 (0.947, 0.981), p = 0.570e-4; OR (95% CI) = 0.892 (0.832, 0.956), p = 0.001; and OR (95% CI) = 0.923(0.892, 0.955), p = 5.301e-6, respectively). Conclusions Our meta-analyses demonstrate that all three allele variants of G6PC2 (rs560887, rs16856187 and rs573225) are associated with elevated FG, with two variants (rs560887 in the Caucasians subgroup and rs16856187 under the allele and dominant model) being associated with T2D as well. Further studies utilizing larger sample sizes and different ethnic populations are needed to extend and confirm these findings.

Salvia splendens is a perennial, ornamental herbaceous flower that is widely cultivated as a bedding plant in gardens. The development of novel S. splendens cultivars and investigating the relevant molecular mechanisms are of great significance. In this study, RNA-sequencing and real-time PCR methods were used to analyze the possible molecular mechanism of S. splendens mutant, SX919M. From the wild-type S. splendens 919CK, we firstly selected a natural mutant, SX919M, which displayed multiple branches, clustered spheroids, and radial symmetrical inflorescence with higher numbers of calyces, ovules, stamens, and perianth tubes. Further, the RNA-seq was used to identify the differentially expressed genes (DEGs) in the mutant which included a total of 3568 upregulated and 3290 downregulated unigenes. We further observed that the indole alkaloid biosynthesis pathway showed the highest DEG enrichment, which was supported by a significant increase in the IAA content in mutant SX919M. In addition, we validated three DEGs, namely, CL2200.Contig2_All encoding methyl IAA esterase, CL12462.Contig1_All and CL12462.Contig2_All, which encoded strictosidine synthase, upregulated in mutant SX919M. We selected a novel S. splendens germplasm SX919M with a high ornamental value and determined that the upregulation of IAA biogenesis may be associated with its development.

Acetylcholinesterase (AChE), an important neurotransmitter hydrolase in both invertebrates and vertebrates, is targeted by organophosphorus and carbamate insecticides. In this study, two new AChEs were identified in the pond wolf spider Pardosa pseudoannulata, an important predatory natural enemy of several insect pests. In total, four AChEs were found in P. pseudoannulata (including two AChEs previously identified in our laboratory). The new putative AChEs PpAChE3 and PpAChE4 contain most of the common features of the AChE family, including cysteine residues, choline binding sites, the conserved sequence ‘FGESAG’ and conserved aromatic residues but with a catalytic triad of ‘SDH’ rather than ‘SEH’. Recombinant enzymes expressed in Sf9 cells showed significant differences in biochemical properties compared to other AChEs, such as the optimal pH, substrate specificity, and catalytic efficiency. Among three test substrates, PpAChE1, PpAChE3 and PpAChE4 showed the highest catalytic efficiency (Vmax/KM) for ATC (acetylthiocholine iodide), with PpAChE3 exhibiting a clear preference for ATC based on the VmaxATC/VmaxBTC ratio. In addition, the four PpAChEs were more sensitive to the AChE-specific inhibitor BW284C51, which acts against ATC hydrolysis, than to the BChE-specific inhibitor ISO-OMPA, which acts against BTC hydrolysis, with at least a 8.5-fold difference in IC50 values for each PpAChE. PpAChE3, PpAChE4, and PpAChE1 were more sensitive than PpAChE2 to the tested Carb insecticides, and PpAChE3 was more sensitive than the other three AChEs to the tested OP insecticides. Based on all the results, two new functional AChEs were identified from P. pseudoannulata. The differences in AChE sequence between this spider and insects enrich our knowledge of invertebrate AChE diversity, and our findings will be helpful for understanding the selectivity of insecticides between insects and natural enemy spiders.