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Asthma is prevalent in children and cats, and needs means of noninvasive diagnosis. We sought to distinguish noninvasively the differences in 53 cats before and soon after induction of allergic asthma, using NMR spectra of exhaled breath condensate (EBC). Statistical pattern recognition was improved considerably by preprocessing the spectra with probabilistic quotient normalization and glog transformation. Classification of the 106 preprocessed spectra by principal component analysis and partial least squares with discriminant analysis (PLS-DA) appears to be impaired by variances unrelated to eosinophilic asthma. By filtering out confounding variances, orthogonal signal correction (OSC) PLS-DA greatly improved the separation of the healthy and early asthmatic states, attaining 94% specificity and 94% sensitivity in predictions. OSC enhancement of multi-level PLS-DA boosted the specificity of the prediction to 100%. OSC-PLS-DA of the normalized spectra suggest the most promising biomarkers of allergic asthma in cats to include increased acetone, metabolite(s) with overlapped NMR peaks near 5.8 ppm, and a hydroxyphenyl-containing metabolite, as well as decreased phthalate. Acetone is elevated in the EBC of 74% of the cats with early asthma. The noninvasive detection of early experimental asthma, biomarkers in EBC, and metabolic perturbation invite further investigation of the diagnostic potential in humans.

Breast cancer (BRCA) is among the most prevalent cancers and is responsible for numerous patient fatalities. Immunotherapy has emerged as a promising approach to cancer treatment. Recent studies have identified Siglec-15 as a novel immune target that plays a crucial role in tumor immune evasion, suggesting its potential significance in BRCA. We utilized databases such as TCGA to investigate the relevance of SIGLEC15 in BRCA. The expression of the Siglec-15 protein in 74 breast cancer patients was detected using immunohistochemistry, and its association with clinicopathological features and overall survival was evaluated. The co-expression of Siglec-15, CD68, CK, and CD8 in BRCA tissues was identified through multiplex immunofluorescence staining. Our study revealed that SIGLEC15 expression in BRCA was significantly elevated compared to adjacent normal tissues. Kaplan-Meier analysis identified SIGLEC15 as a prognostic protective factor. According to the receiver operating characteristic curve analysis, SIGLEC15 could predict the luminal subtype of BRCA. Enrichment analysis demonstrated that SIGLEC15 involves various biological pathways, including immunity, metabolism, tumors, and infectious diseases. Correlation analysis revealed an association between SIGLEC15 expression and immune infiltration in BRCA. We also confirmed that the Siglec-15 protein is expressed in cancer cells, tumor-infiltrating T cells, and macrophages in BRCA tissues, significantly higher levels than in normal breast tissues. Consequently, SIGLEC15 correlates with tumor immune infiltration, molecular subtypes, and BRCA progression and prognosis. However, further research is required to elucidate the role of SIGLEC15 in breast cancer.

This research paper introduces a novel approach by combining a Backpropagation (BP) neural network with a non-angular and non-radial directional distance function to construct a BPNN-DDF model. This innovative model evaluates, decomposes, and analyzes China's agricultural sector's carbon emission rate across nine key subregions between 2010 and 2021. The key findings of this study are that China's agricultural carbon emission rate is decreasing, primarily due to technological advancements rather than technological efficiency. Subregions with robust economies and stable climates exhibit higher carbon emission efficiency, whereas those with underdeveloped economies, low agricultural technology, and volatile climates show relatively lower efficiency. The Dagum Gini coefficient analysis reveals a widening disparity in carbon emission rates among agricultural subregions, escalating from 0.174 in 2010 to 0.425 in 2021, indicating a growing gap between subregions that demands immediate attention. The kernel density distribution demonstrates an overall upward trend in China's carbon emission efficiency but also highlights an increasing divergence among subregions, particularly between the South China Area, the Huang-Huai-Hai Plain, and other regions. Therefore, this paper posits that strategies focusing on technological progress, sustainable agricultural development, regional development initiatives, and addressing inter-subregional imbalances will be crucial pathways for China's future low-carbon agricultural development.

To improve the accuracy of the Hami melon discrete element model, the parameters of the Hami melon seed discrete element model were calibrated by combining practical experiments and simulation tests. The basic physical parameters of Hami melon seeds were obtained through physical experiments, including triaxial size, 100-grain mass, moisture content, density, Poisson's ratio, Young's modulus, shear modulus, angle of repose, suspension speed and various contact parameters. Taking the repose angle of seed simulation as an index, the parameters of each simulation model were significantly screened by the Plackett-Burman test. The results showed that the recovery coefficient, static friction coefficient and rolling friction coefficient of Hami melon seeds had significant effects on repose angle. Based on the steepest climbing test and quadratic regression orthogonal rotation combination test, it was determined that the significant order of the influence of various contact parameters on the angle of repose was static friction coefficient, collision recovery coefficient, and rolling friction coefficient. The optimal parameter combination was obtained through the mathematical regression model between the angle of repose and various contact parameters, namely, the collision recovery coefficient of Hami melon seeds was 0.518, the static friction coefficient of Hami melon seeds was 0.585 and the rolling friction coefficient of Hami melon seeds was 0.337. Under this condition, three static seed-dropping experiments and dynamic rolling accumulation experiments were carried out. The average simulated angle of repose was 31.93°, and the relative error with the actual value was only 1.71%. The average simulated rolling accumulation angle was 51.98°, and the relative error with the actual value was only 1.92%.

It is important for China to break the "low-end lock" of the manufacturing value chain worldwide by revealing how digital trade promotes and reallocates the export technology complexity of the manufacturing industry. Panel data for 30 provinces in China from 2011 to 2020 were employed to measure the digital trade development and export technology complexity of the manufacturing industry. Benchmark regression, intermediary effect regression, panel threshold and other models were used to test the promotion and reallocation of digital trade on the export technology complexity of the manufacturing industry. The findings are as follows: (1) Digital trade promotes the export technology complexity of the manufacturing industry, with significant regional heterogeneity (eastern, central and western regions), and the most obvious promotion in technology-intensive manufacturing. (2) Technological innovation and human capital play a reallocation role in the process of digital trade, affecting the technological complexity of manufacturing exports, with mediating effects of 14.19% and 8.61%, respectively. (3) Digital trade promotes and reallocates the export technology complexity of the manufacturing industry through industrial structure upgrading, and a nonlinear relationship was found. These results provide empirical support and a decision-making basis for digital trade in promoting the export technology complexity of the manufacturing industry. The development of digital trade should be encouraged; the differential development of digital trade in the eastern, central, and western regions should be boosted; importance should be attached to the intermediary incentive role of technological innovation and human capital; and the upgrading of the industrial structure should be promoted scientifically.

Based on panel data of 108 cities in China's Yangtze River Economic Belt from 2003 to 2019, a multiple mediation model is used in this study to assess the impact and mechanism of financial development on new urbanization. The main conclusions are that financial development can directly promote the improvement of new urbanization and indirectly improve the level of new urbanization by increasing infrastructure investment, optimizing industrial structure, and enhancing human capital. Further, the financial development of middle-upstream cities has a stronger promoting effect on new urbanization. Whereas the financial development of downstream cities mainly promotes the construction of new urbanization through both infrastructure investment and industrial structure optimization, middle-upstream cities rely more solely on infrastructure investment.

BackgroundThe WD40-encoding RNA antisense to p53 (WRAP53) is an antisense gene of TP53 with three transcriptional start sites producing three transcript variants involved in the progression of non-small cell lung cancer. However, the mechanism by which these different transcript variants regulate non-small cell lung cancer cell behaviors is to be elucidated.MethodsTwo non-small cell lung cancer cell lines, A549 cells with wild-type p53 and H1975 with mutated p53, were transfected with WRAP53-1α and WRAP53-1β siRNA. The biological effects were assessed via colony formation, cell viability, apoptosis, cell cycle, wound healing and cell invasion assays, as well as immunoblotting.ResultsKnockdown of WRAP53-1α increased the mRNA and protein levels of p53; suppressed colony formation and proliferation of A549 cells but promoted them in H1975 cells; increased the proportion of cells in the G0/G1 phase in A549 cells but decreased that in H1975 cells; and suppressed migration and invasion in A549 cells but not in H1975 cells. Conversely, knockdown of WRAP53-1β had no effect on p53 expression; promoted the growth of A549 cells but not of H1975 cells; decreased the proportion of cells in the G0/G1 phase in A549 cells but not in H1975 cells; and promoted migration and invasion in A549 cells but not in H1975 cells. Knockdown of both WRAP53-1α and WRAP53-1β promoted apoptosis in A549 cells but not in H1975 cells.ConclusionsWRAP53 transcript variants exerted different functions in non-small cell lung cancer cells and regulated non-small cell lung cancer cell behaviors depending on the p53 expression.

BackgroundAnopheles stephensi Listen (1901) is a major vector of malaria in Asia and has recently been found in some regions of Africa. The An. stepehnsi species complex is suspected to have three sibling species: type, intermediate, and mysorensis, each with its own vector competence to the malaria parasite and ecology. To identify the members of the species complex in our An. stephensi insectary colony, we used the morphological features of eggs and genetic markers such as AnsteObp1 (Anopheles stephensi odorant binding protein 1), mitochondrial oxidases subunit 1 and 2 (COI and COII), and nuclear internal transcribed spacer 2 locus (ITS2).MethodsEggs were collected from individual mosquitoes (n = 50) and counted for the number of ridges under stereomicroscope. Genomic DNA was extracted from female mosquitoes. After the amplification of partial fragments of AnsteObp1, COI, COII and ITS2 genes, the PCR products were purified and sequenced. Phylogenetic analysis was performed after aligning query sequences against the submitted sequences in GenBank using MEGA 7.ResultsThe range of ridges number on each egg float was 12-13 that corresponds to the mysorensis form of An. stephensi. The generated COI, COII and ITS2 sequences showed 100%, 99.46% and 99.29% similarity with the sequences deposited for Chinese, Indian and Iranian strains of An. stephensi, respectively. All the generated AnsteObp1 intron I region sequences matched 100% with the sequences deposited for An. stephensi sibling species C (mysorensis form) from Iran and Afghanistan.ConclusionsThis manuscript precisely describes the morphological and molecular details of the 'var mysorensis' form of An. stephensi that could be exploited in elucidating its classification as well as in differentiation from other biotypes of the same or other anopheline species. Based on our findings, we recommend AnsteObp1 as a robust genetic marker for rapid and accurate discrimination (taxonomic identification) of the An. stephensi species complex, rather than the COI, COII, and ITS2 marker, which could only be utilized for interspecies (Anopheles) differentiation.

BackgroundPediatric osteoarticular infections are commonly caused by Staphylococcus aureus. The contribution of S. aureus genomic variability to pathogenesis of these infections is poorly described.MethodsWe prospectively enrolled 47 children over 3 1/2 years from whom S. aureus was isolated on culture-12 uninfected with skin colonization, 16 with skin abscesses, 19 with osteoarticular infections (four with septic arthritis, three with acute osteomyelitis, six with acute osteomyelitis and septic arthritis and six with chronic osteomyelitis). Isolates underwent whole genome sequencing, with assessment for 254 virulence genes and any mutations as well as creation of a phylogenetic tree. Finally, isolates were compared for their ability to form static biofilms and compared to the genetic analysis.ResultsNo sequence types predominated amongst osteoarticular infections. Only genes involved in evasion of host immune defenses were more frequently carried by isolates from osteoarticular infections than from skin colonization (p = .02). Virulence gene mutations were only noted in 14 genes (three regulating biofilm formation) when comparing isolates from subjects with osteoarticular infections and those with skin colonization. Biofilm results demonstrated large heterogeneity in the isolates' capacity to form static biofilms, with healthy control isolates producing more robust biofilm formation.ConclusionsS. aureus causing osteoarticular infections are genetically heterogeneous, and more frequently harbor genes involved in immune evasion than less invasive isolates. However, virulence gene carriage overall is similar with infrequent mutations, suggesting that pathogenesis of S. aureus osteoarticular infections may be primarily regulated at transcriptional and/or translational levels.

PurposeTo explore the value of radiomics in the identification of lung adenocarcinomas with predominant lepidic growth in pure ground-glass nodules (pGGNs) larger than 10 mm.MethodsWe retrospectively analyzed CT images of 204 patients with large pGGNs (≥ 10 mm) pathologically diagnosed as minimally invasive adenocarcinomas (MIAs), lepidic predominant adenocarcinomas (LPAs), and non-lepidic predominant adenocarcinomas (NLPAs). All pGGNs in the two groups (MIA/LPA and NLPA) were randomly divided into training and test cohorts. Forty-seven patients from another center formed the external validation cohort. Baseline features, including clinical data and CT morphological and quantitative parameters, were collected to establish a baseline model. The radiomics model was built with the optimal radiomics features. The combined model was developed using the rad_score and independent baseline predictors. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. The differential diagnosis performance of the models was compared with three radiologists (with 20+, 10+, and 3 years of experience) in the test cohort.ResultsThe radiomics (training AUC: 0.833; test AUC: 0.804; and external validation AUC: 0.792) and combined (AUC: 0.849, 0.820, and 0.775, respectively) models performed better for discriminating than the baseline model (AUC: 0.756, 0.762, and 0.725, respectively) developed by tumor location and mean CT value of the whole nodule. The DeLong test showed that the AUCs of the combined and radiomics models were significantly increased in the training cohort. The highest AUC value of the radiologists was 0.600.ConclusionThe application of CT radiomics improved the identification performance of lung adenocarcinomas with predominant lepidic growth appearing as pGGNs larger than 10 mm.

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies.

Mercury exists naturally and mainly as a man-made pollutant in the environment, where it exerts adverse effects on local ecosystems and living organisms. It is important to develop an appropriate synthetic biological device that recognizes, detects and removes the bioavailable fraction of environmental mercury. Both single-signal and double-signal output mercury biosensors were assembled using a natural mer operon as a template. Selectivity and sensitivity of whole-cell biosensors based on artificial mer operons were determined. Three whole-cell biosensors were highly stable at very high concentrations of mercuric chloride, and could detect bioavailable Hg(II) in the concentration range of 6.25-200 μM HgCl2. A novel Hg(II) bioadsorption coupled with biosensing artificial mer operon was assembled. This would allow Hg(II)-induced Hg(II) binding protein cell surface display and green fluorescence emission to be achieved simultaneously while retaining the linear relationship between fluorescent signal and Hg(II) exposure concentration. The present study provides an innovative way to simultaneously detect, quantify, and remove bioavailable heavy metal ions using an artificially reconstructed heavy metal resistance operon.

BackgroundThe paradigm shift in hepatitis C virus (HCV) treatment options in the last five years has raised the prospect of eliminating the disease as a global health threat. This will require a step-change in the number being treated with the new direct-acting antivirals (DAAs). Given constrained budgets and competing priorities, policy makers need information on how to scale-up access to HCV treatment. To inform such decisions, we examined the cost effectiveness of screening and treatment interventions in Yunnan, China.Methods and findingsWe simulated the HCV epidemic using a previously published model of HCV transmission and disease progression, calibrated to Yunnan data, and implemented a range of treatment and screening interventions from 2019. We incorporated treatment, diagnosis, and medical costs (expressed in 2019 US Dollars, USD) to estimate the lifetime benefits and costs of interventions. Using this model, we asked: is introducing DAAs cost effective from a healthcare sector perspective; what is the optimal combination of screening interventions; and what is the societal return on investment of intervention? The incremental cost-effectiveness ratio (ICER) of switching to DAAs with a median cost of 7,400 USD (50,000 Chinese Yuan) per course is 500 USD/disability adjusted life year (DALY) averted; at a threshold of 50% of Yunnan gross domestic product (2,600 USD), switching to DAAs is cost effective 94% of the time. At this threshold, the optimal, cost-effective intervention comprises screening people who inject drugs, those in HIV care, men who have sex with men, and ensuring access to DAAs for all those newly diagnosed with HCV. For each USD invested in this intervention, there is an additional 0·80 USD (95% credible interval: 0·17-1·91) returned through reduced costs of disease or increased productivity. Returns on investment are lower (and potentially negative) if a sufficiently long-term horizon, encompassing the full stream of future benefits, is not adopted. The study had two key limitations: costing data were not always specific to Yunnan province but were taken from China-level studies; and modelled interventions may require more operational research to ensure they can be effectively and efficiently rolled-out to the entire province.ConclusionsIntroducing DAAs is cost effective, the optimal package of screening measures is focussed on higher risk groups, and there are likely to be positive returns from investing in such HCV interventions. Our analysis shows that targeted investment in HCV interventions will have net benefits to society; these benefits will only increase as DAA costs fall.

The combination of a fluorescent reporter and enzymatic reporter provides a flexible and versatile way for the study of diverse biological processes, such as the detection of transcription and translation. Thus, there is an urgent need to develop this novel bifunctional reporter system. This study reports the design, construction, and validation of a new dicistronic mCherry-lacZα reporter system by artificial lac operon and pbr operon models in lacZM15-producing E. coli. It allows two reporter genes to be co-transcribed into a dicistronic mRNA strand, followed by coupled expression of mCherry and lacZα. In artificial lac operons, expression of the downstream lacZα was demonstrated to be positively related to expression of the upstream ORF. In artificial pbr operons, compared with the insertion of downstream full-length lacZ, the insertion of downstream lacZα exerted a slight effect on the response from the upstream mCherry. Furthermore, the downstream lacZα reporter showed stronger response to Pb(II) than the downstream full-length lacZ. Importantly, the response sensitivity of downstream lacZα was still higher than that of upstream mCherry in a dual RFP-lacZα reporter construct. The highly efficient expression profile of the reporter lacZα peptide makes it a preferred downstream reporter in polycistronic constructs. This novel bifunctional reporter system offers a robust tool for biological studies.

At present, a large number of studies have reported that hydrogen has antioxidant functions and prevents oxidative stress damage. However, it is not clear whether hydrogen can prolong longevity based on these effects. Therefore, we studied and explored the antiaging potential of exogenous hydrogen and its ability to extend longevity using Caenorhabditis elegans (C. elegans) as an animal model. Our results showed that the lifespans of the N2, sod-3 and sod-5 mutant strains were extended by approximately 22.7%, 9.5%, and 8.7%, respectively, after hydrogen treatment, but hydrogen had no effect on the lifespans of the daf-2 and daf-16 mutant strains. Meanwhile, the level of reactive oxygen species (ROS) in the hydrogen treatment group was significantly lower than that in the control group. At the transcript level, the expression of age-1 and let-363 was obviously decreased, while the expression of ins-18 was increased at the same time point (14 d). Compared with the control group, paraquat (PQ) could reduce the lifespan of the N2 and sod-5 mutant strains. Importantly, the longevity of these mutant strains recovered to normal levels when the animals were treated with exogenous hydrogen. According to these results, the lifespan of C. elegans is closely related to oxidative stress and can be significantly prolonged by reducing oxidative stress damage. Taken together, our data showed that hydrogen is a valuable antioxidant that can significantly reduce the body's ROS levels and extend the lifespan of C. elegans. This study also laid a foundation for the subsequent application of hydrogen in antiaging studies.

BackgroundA recent cluster of pneumonia cases in Wuhan, China, has been caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We propose the protocol described below to perform an individual-patient data (IPD) network meta-analysis (NMA) in order to evaluate the efficacies of different antiviral drugs to treat patients with coronavirus disease 2019 (COVID-19).Materials and methodsWe will search the Medline, EMBASE, Cochrane Library, SinoMed, CNKI and VIP databases from their inceptions through July 2020. There will be no restrictions on language, publication year, or publication type. Randomized clinical trials (RCTs) and prospective cohort studies with antiviral treatments for COVID-19 will be considered. Two reviewers will independently select studies and collect data. Risk-of-bias assessments will be completed using the Cochrane risk-of-bias scale. Primary outcome will be the COVID-19 recovery rate. We will combine aggregated data from IPD with the NMA in a single model, compare the effects of different antiviral drugs on patient-relevant efficacy, and rank the results to decide which is the most effective.Trial registrationPROSPERO registration number: CRD42020167038.

Information in working memory (WM) can guide visual attention towards matched features. While recent work has suggested that cognitive control can act upon WM guidance of visual attention, little is known about how the state of memorized items retaining in WM contribute to its influence over attention. Here, we disentangle the role of inhibition and maintenance on WM-guided attention with a novel delayed match-to-sample dual-task. The results showed that active inhibition facilitated searching by diminishing sensory processing and deterring attentional guidance, indexed by an attenuated P1 amplitude and unaffected N2pc amplitude, respectively. By contrast, active maintenance impaired searching by attentional guidance while sensory processing remained unimpaired, indexed by an enhanced N2pc amplitude and unchanged P1 amplitude, respectively. Furthermore, multivariate pattern analyses could sucessfully decode maintenance and inhibition, suggesting that two states differed in modulating visual attention. We propose that remembered contents may play an anchoring role for attentional guidance, and the state of those contents retaining in WM may directly influence the shifting of attention. The maintenance could guide attention by accessing input information, while the inhibition could deter the shifting of attention by suppressing sensory processing. These findings provide a possible reinterpretation of the influence of WM on attention.

Considering the divergent temperature habitats and morphological traits of four Percidae species: yellow perch (Perca flavescens), Eurasian perch (Perca fluviatilis), pike perch (Sander lucioperca), and ruffe (Gymnocephalus cernua), we stepped into the transcriptome level to discover genes and mechanisms that drive adaptation to different temperature environments and evolution in body shape. Based on 93,566 to 181,246 annotated unigenes of the four species, we identified 1,117 one-to-one orthologous genes and subsequently constructed the phylogenetic trees that are consistent with previous studies. Together with the tree, the ratios of nonsynonymous to synonymous substitutions presented decreased evolutionary rates from the D. rerio branch to the sub-branch clustered by P. flavescens and P. fluviatilis. The specific 93 fast-evolving genes and 57 positively selected genes in P. flavescens, compared with 22 shared fast-evolving genes among P. fluviatilis, G. cernua, and S. lucioperca, showed an intrinsic foundation that ensure its adaptation to the warmer Great Lakes and farther south, especially in functional terms like "Cul4-RING E3 ubiquitin ligase complex." Meanwhile, the specific 78 fast-evolving genes and 41 positively selected genes in S. lucioperca drew a clear picture of how it evolved to a large and elongated body with camera-type eyes and muscle strength so that it could occupy the highest position in the food web. Overall, our results uncover genetic basis that support evolutionary adaptation of temperature and body shape in four Percid species, and could furthermore assist studies on environmental adaptation in fishes.

BackgroundThe Gram-negative bacterium Kerstersia gyiorum, a potential etiological agent of clinical infections, was isolated from several human patients presenting clinical symptoms. Its significance as a possible pathogen has been previously overlooked as no disease has thus far been definitively associated with this bacterium. To better understand how the organism contributes to the infectious disease, we determined the complete genomic sequence of K. gyiorum SWMUKG01, the first clinical isolate from southwest China.ResultsThe genomic data obtained displayed a single circular chromosome of 3, 945, 801 base pairs in length, which contains 3, 441 protein-coding genes, 55 tRNA genes and 9 rRNA genes. Analysis on the full spectrum of protein coding genes for cellular structures, two-component regulatory systems and iron uptake pathways that may be important for the success of the bacterial survival, colonization and establishment in the host conferred new insights into the virulence characteristics of K. gyiorum. Phylogenomic comparisons with Alcaligenaceae species indicated that K. gyiorum SWMUKG01 had a close evolutionary relationships with Alcaligenes aquatilis and Alcaligenes faecalis.ConclusionsThe comprehensive analysis presented in this work determinates for the first time a complete genome sequence of K. gyiorum, which is expected to provide useful information for subsequent studies on pathogenesis of this species.

BackgroundHypertension (HTN) disproportionately affects African Americans (AAs), who respond better to thiazide diuretics than other antihypertensives. Variants of the APOL1 gene found in AAs are associated with a higher rate of kidney disease and play a complex role in cardiovascular disease.MethodsAA subjects from four HTN trials (n = 961) (GERA1, GERA2, PEAR1, and PEAR2) were evaluated for blood pressure (BP) response based on APOL1 genotype after 4-9 weeks of monotherapy with thiazides, beta blockers, or candesartan. APOL1 G1 and G2 variants were determined by direct sequencing or imputation.ResultsBaseline systolic BP (SBP) and diastolic BP (DBP) levels did not differ based on APOL1 genotype. Subjects with 1-2 APOL1 risk alleles had a greater SBP response to candesartan (-12.2 +/- 1.2 vs -7.5 +/- 1.8 mmHg, p = 0.03; GERA2), and a greater decline in albuminuria with candesartan (-8.3 +/- 3.1 vs +3.7 +/- 4.3 mg/day, p = 0.02). APOL1 genotype did not associate with BP response to thiazides or beta blockers. GWAS was performed to determine associations with BP response to candesartan depending on APOL1 genotype. While no SNPs reached genome wide significance, SNP rs10113352, intronic in CSMD1, predicted greater office SBP response to candesartan (p = 3.7 x 10-7) in those with 1-2 risk alleles, while SNP rs286856, intronic in DPP6, predicted greater office SBP response (p = 3.2 x 10-7) in those with 0 risk alleles.ConclusionsHypertensive AAs without overt kidney disease who carry 1 or more APOL1 risk variants have a greater BP and albuminuria reduction in response to candesartan therapy. BP response to thiazides or beta blockers did not differ by APOL1 genotype. Future studies confirming this initial finding in an independent cohort are required.

[This corrects the article DOI: 10.1371/journal.pone.0200374.].

Follicle-stimulating hormone (FSH) has key roles in animal reproduction, including spermatogenesis and ovarian maturation. Many factors influence FSH secretion. However, despite the broad functions of microRNAs (miRNAs) via the regulation of target genes, little is known about their roles in FSH secretion. Our previous results suggested that miR-186-5p targets the 3' UTR of FSHb; therefore, we examined whether miR-186-5p could regulate FSH secretion in rat anterior adenohypophyseal cells. miR-186-5p was transfected into rat anterior pituitary cells. The expression of FSHb and the secretion of FSH were examined by RT-qPCR and ELISA. A miR-186-5p mimic decreased the expression of FSHb compared with expression in the control group and decreased FSH secretion. In contrast, both the mRNA levels and secretion of FSH increased in response to miR-186-5p inhibitors. Our results demonstrate that miR-186-5p regulates FSH secretion by directly targeting the FSHb 3' UTR, providing additional functional evidence for the importance of miRNAs in the regulation of animal reproduction.

Driving behaviors play an important role in accident involvement. Concretely speaking, aberrant driving behaviors would cause more accidents, and oppositely positive driving behaviors would promote to build safety traffic environment. The main goals of this study were to explore the positive driving behavior and its relationship with personality in a Chinese sample. A total of 421 licensed drivers (286 male and 135 female) from Beijing, China completed the Positive Driver Behavior Scale (PDBS), the Driver Behavior Questionnaire (DBQ), the Dula Dangerous Driving Index (DDDI) and the Big Five Inventory (BFI) on a voluntary and anonymous basis. The results showed that the Chinese version of the PDBS has both reliability and validity and that the PDBS was significantly correlated with the BFI. Specifically, the PDBS was negatively correlated with neuroticism (r = -0.38) and positively correlated with extraversion, agreeableness, conscientiousness and openness to experience (the correlation coefficient ranged from 0.36 to 0.55). In contrast with previous research, age was negatively correlated with the PDBS (r = -0.38) in our sample, which may have resulted from less driving experience or a lack of available cognitive resources.

Cathepsin H is a member of the papain superfamily of lysosomal cysteine proteases. It is the only known aminopeptidase in the family and is reported to be involved in cancer and other major diseases. Like many other proteases, it is synthesized as an inactive proenzyme. Although the crystal structure of mature porcine cathepsin H revealed the binding of the mini-chain and provided structural basis for the aminopeptidase activity, detailed structural and functional information on the inhibition and activation of procathepsin H has been elusive. Here we present the crystal structures of human procathepsin H at 2.00 Å and 1.66 Å resolution. These structures allow us to explore in detail the molecular basis for the inhibition of the mature domain by the prodomain. Comparison with cathepsin H structure reveals how mini-chain reorients upon activation. We further demonstrate that procathepsin H is not auto-activated but can be trans-activated by cathepsin L.

Women with advanced maternal age exhibit low anti-Müllerian hormone (AMH) levels and an altered follicular environment, which is associated with poor oocyte quality and embryonic developmental potential. However, the underlying mechanism is poorly understood. The present study aimed to assesswhether aging patients exhibit an activated DNA double-strandbreak (DSB) repair pathway in cumulus cells and thus, an association with poor outcomes after in vitro fertilization-embryo transfer (IVF-ET) treatment. Cumulus cells from young (≤29 y) and aging (≥37 y) human female patients were collected after oocyte retrieval. Our results indicated that aging patients showed a higher rate of γ-H2AX-positive cells than in young patients (24.33±4.55 vs.12.40±2.31, P

Driving style is an important factor in driving psychology, which is useful for effectively evaluating driving behaviors. Exploring driving style in a Chinese sample could help understand the overall situation of Chinese drivers. This study aims to develop a measurement of driving style fit for the Chinese situation and to validate the validity and reliability of this scale. In this study, 296 drivers from China completed the Chinese version of the multidimensional driving style inventory (MDSI), the Big Five Inventory (BFI), and the Driver Behavior Questionnaire (DBQ) as well as several questions about socio-demographic information. After testing the assumed structure by a confirmatory factor analysis, and adjusting the structure, a brief version of Chinese version of MDSI with twelve items categorized into four driving styles, namely, risky style, angry- high-velocity style, careful style and anxious style was revised. The validity and reliability of the scales were acceptable. The results showed that driving styles were closely correlated with self-reported driving behaviors. Specifically, risky style, angry- high-velocity style, and anxious style are all positively associated with dangerous driving behaviors. Meanwhile, careful style was positively associated with positive driving behaviors and negatively correlated with dangerous driving behaviors. Anxious was also found to be negatively associated with fines. For personality, we found a positive relationship between risky, angry- high-velocity, careful and anxious styles and the personality traits that often have negative effects on driving, such as extraversion and neuroticism. Meanwhile, these three styles were negatively correlated with conscientiousness and agreeableness in general. In addition, careful style was positively correlated with conscientiousness and agreeableness. The current study shows convincing evidence for the validity and reliability of the brief MDSI-C and develops a useful tool for identify the driving style of Chinese drivers for future research and relevant departments of road safety.

Pancreatic ductal carcinoma (PDAC) is a common malignant tumor of the digestive system. GATA4 is one of the transcriptional regulatory factors, which regulates the development of endoderm-derived organs, including heart and gut. GATA4 may act as a putative tumor suppressor gene. However, the role of GATA4 in pancreatic carcinogenesis is not yet clarified. This study showed that GATA4 was highly expressed in pancreatic cancer tissues, and its expression level was positively related to the grade of pathological differentiation, suggesting that it may contribute to the progression of pancreatic neoplasia. Ectopic expression of GATA4 gene reduced cell viability and interference of GATA4 expression significantly increased the colony formation ability of pancreatic cancer cells. Furthermore, GATA4 inhibited tumor growth in xenograft mice. Agilent expression microarray profiling analysis indicated that the genes with significant levels of differential expression in GATA4 over-expressing cells were enriched in the cell differentiation process. Analysis of KEGG signaling pathway demonstrated that the regulated genes were partially enriched in MAPK and JAK-STAT signaling pathways. Re-expression of GATA4 up-regulated P53 gene expression. Our data indicate that GATA4 gene might play a role in cell proliferation and differentiation during the progression of pancreatic cancer.

The regulatory role of miRNAs has been explored in ovarian cells, and their effects on gonadal development, apoptosis, ovulation, steroid production and corpus luteum (CL) development have been revealed. In this study, we analyzed the expression of miR-29b at different stages of bovine CL development and predicted the target genes of miR-29b. We confirmed that miR-29b reduces the expression of the oxytocin receptor (OXTR), affects progesterone (PROG) secretion and regulates the function of the CL. RT-PCR showed that the expression of miR-29b was significantly higher in functional CL phases than in the regressed CL phase. Immunohistochemistry showed that OXTR was expressed in both large and small CL cells and was mainly located in the cell membrane and cytoplasm of these cells. We analyzed the expression levels of OXTR and found that transfection with a miR-29b mimic decreased OXTR expression, but transfection with the inhibitor had a limited effect on the expression of the OXTR protein. At the same time, the secretion of PROG was significantly increased in the miR-29b mimic-transfected group. We also analyzed the effect of miR-29b on the apoptosis of CL cells. Finally, we found that miR-29b could promote the proliferation of bovine CL cells. In conclusion, we found that miR-29b reduces the expression of OXTR and can promote PROG secretion and the proliferation of CL cells via OXTR.

ObjectivesTo assess the associations of fresh fruit consumption and total physical activity with all-cause and cardiovascular mortality among Chinese adults who have been diagnosed with cardiovascular disease (CVD) or hypertension.MethodsDuring 2004-08, the China Kadoorie Biobank study recruited 70,047 adults, aged 30-79 years, with physician-diagnosed stroke or transient ischaemic attack, ischemic heart disease, or hypertension. Information on diet and physical activity was collected using an interviewer-administered electronic questionnaire. Cox regression was used to yield hazard ratios (HRs) for the independent and joint associations of fresh fruit consumption and total physical activity with mortality.ResultsAt baseline, 32.9% of participants consumed fresh fruit regularly (i.e. >3 days/week) and the mean total physical activity were 15.8 (SD = 11.8) MET-hr/day. During ~7-years follow-up, 6569 deaths occurred with 3563 from CVD. Compared to participants with 16.53 MET-hr/day) was associated with about 40% lower mortality.ConclusionAmong Chinese adults with pre-existing vascular disease, higher physical activity and fruit consumption were both independently and jointly associated with lower mortality.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6). Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.

To observe risk factors for recurrence after withdrawal from antiepileptic drugs.We assessed 1282 patients with a definite diagnosis of epilepsy.In total, 292 patients between 14 and 80 years of age were grouped according to risk factors for recurrence. Of these individuals, 119 discontinued AED(s) and relapsed. The relapse rate was 34.4 per 100 person-years. We used a Cox regression for multivariate analysis to investigate the influence of the following on seizure recurrence: receiving more than one type of AED (HR = 2.53, 95% CI 1.24-5.16) and more than 6 months prior to initiation of AED treatment (HR 1.47, 95% CI = 1.004-2.15).Although the decision to discontinue AED treatment necessitates an individual evaluation of each patient, our study suggests that there may be a high risk of recurrence in individuals who: were receiving more than one AEDs and had initiated their AED treatment more than 6 months after the initial appearance of epilepsy symptoms.

While improper pedestrian behavior has become an important factor related to road traffic fatalities, especially in developing countries, the effects of personality traits and/or stress on pedestrian behavior have been rarely reported. The current study explored the joint effects of five personality traits (i.e., extraversion, openness, neuroticism, normlessness and altruism) and global perceived stress (measured with the Perceived Stress Scale-10) on pedestrian behavior (measured with the Pedestrian Behavior Scale) in 311 Chinese individuals. Results showed that altruism, neuroticism and openness significantly affected different pedestrian behavior dimensions, while global perceived stress also significantly and positively predicted positive behavior. Moreover, the effect of neuroticism on positive behavior was fully mediated by stress. Some explanations and implications are provided in the discussion section.

Fstl1, a secreted protein of the BMP antagonist class, has been implicated in the regulation of lung development and alveolar maturation. Here we generated a Fstl1-lacZ reporter mouse line as well as a Fstl1 knockout allele. We localized Fstl1 transcript in lung smooth muscle cells and identified Fstl1 as essential regulator of lung smooth muscle formation. Deletion of Fstl1 in mice led to postnatal death as a result of respiratory failure due to multiple defects in lung development. Analysis of the mutant phenotype showed impaired airway smooth muscle (SM) manifested as smaller SM line in trachea and discontinued SM surrounding bronchi, which were associated with decreased transcriptional factors myocardin/serum response factor (SRF) and impaired differentiation of SM cells. Fstl1 knockout mice also displayed abnormal vasculature SM manifested as hyperplasia SM in pulmonary artery. This study indicates a pivotal role for Fstl1 in early stage of lung airway smooth muscle development.

Sheath blight is one of the most devastating wheat diseases worldwide. Breeding resistant cultivars is the most powerful strategy to defeat the disease. Plant resistance on "disease escape" works through modulation of morphological traits and shows sustainable resistance to disease. Plant architectural traits have been reported to play a significant role in disease response. Therefore, exploring the genetic relationship between plant architecture and disease resistance is of importance to the understanding of plant resistance via "disease escape". Using an F9 population of 266 RILs (Recombinant Inbred Lines) derived from the cross of Luke × AQ24788-83, we have generated a linkage map of 631 markers on 21 chromosomes. In this study, we present the QTL identification of fourteen plant architectural characteristics and heading time from two years and analyze their genetic relationships with seven previously published QTLs to sheath blight (QSBs, QSe.cau), including plant height (PH), the space between the flag leaf and penultimate leaf (fdR), heading date (Hd), and other traits. Twelve stable QTLs of the morphological traits were identified with good consistency across five replicates. For the seven previously published QSBs, we found no significant association with plant height. However, some of the QSBs displayed strong associations with plant architectural traits and heading date. Especially, QfdR.cau-1AS, QHd.cau-2BS, QfdR.cau-5DL, and QfdR.cau-6BL were respectively mapped to the same regions as QSe.cau-1AS, QSe.cau-2BS, QSe.cau-5DL, and QSe.cau-6BL. Taken together, we have demonstrated that plant height did not exert a direct influence on the resistance to sheath blight conferred by the seven QSBs and that the plant architecture and heading date did exhibit a tight relationship with the resistance. Therefore, this study provides a novel evidence to help understand sheath blight resistance in wheat. In addition, the linked morphological characteristics and the generated flanking markers will facilitate breeding for resistance to sheath blight in wheat.

We here evaluated the potential anti-colorectal cancer activity by erastin, a voltage-dependent anion channel (VDAC)-binding compound. Our in vitro studies showed that erastin exerted potent cytotoxic effects against multiple human colorectal cancer cell lines, possibly via inducing oxidative stress and caspase-9 dependent cell apoptosis. Further, mitochondrial permeability transition pore (mPTP) opening was observed in erastin-treated cancer cells, which was evidenced by VDAC-1 and cyclophilin-D (Cyp-D) association, mitochondrial depolarization, and cytochrome C release. Caspase inhibitors, the ROS scavenger MnTBAP, and mPTP blockers (sanglifehrin A, cyclosporin A and bongkrekic acid), as well as shRNA-mediated knockdown of VDAC-1, all significantly attenuated erastin-induced cytotoxicity and apoptosis in colorectal cancer cells. On the other hand, over-expression of VDAC-1 augmented erastin-induced ROS production, mPTP opening, and colorectal cancer cell apoptosis. In vivo studies showed that intraperitoneal injection of erastin at well-tolerated doses dramatically inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Together, these results demonstrate that erastin is cytotoxic and pro-apoptotic to colorectal cancer cells. Erastin may be further investigated as a novel anti-colorectal cancer agent.

Embryo implantation is an essential step for the establishment of pregnancy and dynamically regulated by estrogen and progesterone. NDRG4 (N-myc down-regulated gene 4) is a tumor suppressor that participates in cell survival, tumor invasion and angiogenesis. The objective of this study was to preliminarily explore the role of NDRG4 in embryo implantation. By immunohistochemistry (IHC) and quantitive RT-PCR (qRT-PCR), we found that uterine expression of NDRG4 was increased along with puberal development, and its expression in adult females reached the peak at the estrus stage during the estrus cycle. Furthermore, uterine NDRG4 expression was significantly induced by the treatment of estradiol (E2) both in pre-puberty females and ovariectomized adult females. Uterine expression pattern of NDRG4 during the peri-implantation period in mice was determined by IHC, qRT-PCR and Western blot. It was observed that NDRG4 expression was up-regulated during the implantation process, and its expression level at the implantation sites was significantly higher than that at the inter-implantation sites. Meanwhile, an increased expression in NDRG4 was associated with artificial decidualization as well as the activation of delayed implantation. By qRT-PCR and Western blot, we found that the in vitro decidualization of endometrial stromal cells (ESCs) was accompanied by up-regulation of NDRG4 expression, whereas knockdown of its expression in these cells by siRNA inhibited the decidualization process. In addition, Western blot analysis showed that NDRG4 protein expression was decreased in human villus tissues of recurrent miscarriage (RM) patients compared to normal pregnant women. Collectively, these data suggested that uterine NDRG4 expression could be induced by estrogen, and NDRG4 might play an important role during early pregnancy.

INTRODUCTION:Polyamidoamine dendrimer nanoparticles (~ 4 nanometers) are inert polymers that can be linked to biologically active compounds. These dendrimers selectively target and accumulate in inflammatory cells upon systemic administration. Dendrimer-linked compounds enable sustained release of therapeutic compounds directly at the site of damage. The purpose of this study was to determine if dendrimers can be used to target the optic nerve (ON) ischemic lesion in our rodent and nonhuman primate models of nonarteritic anterior ischemic optic neuropathy (NAION), a disease affecting >10,000 individuals in the US annually, and for which there currently is no effective treatment. METHODS:NAION was induced in male Long-Evans rats (rNAION) and in one adult male rhesus monkey (pNAION) using previously described procedures. Dendrimers were covalently linked to near-infrared cyanine-5 fluorescent dye (D-Cy5) and injected both intravitreally and systemically (in the rats) or just systemically (in the monkey) to evaluate D-Cy5 tissue accumulation in the eye and optic nerve following induction of NAION. RESULTS:Following NAION induction, Cy-5 dendrimers selectively accumulated in astrocytes and circulating macrophages. Systemic dendrimer administration provided the best penetration of the ON lesion site when injected shortly after induction. Systemic administration 1 day post-induction in the pNAION model gave localization similar to that seen in the rats. CONCLUSIONS:Dendrimers selectively target the ischemic ON lesion after induction of both rNAION and pNAION. Systemic nanoparticle-linked therapeutics thus may provide a powerful, targeted and safe approach to NAION treatment by providing sustained and focused treatment of the cells directly affected by ischemia.

[This corrects the article DOI: 10.1371/journal.pone.0122726.].

To compare the efficacy and safety of current treatments in diabetic macular edema (DME).PubMed, Embase and CENTRAL were systematically reviewed for randomized controlled trials of current treatments in DME through August 2015. Data on the mean change of best-corrected visual acuity (BCVA) and central macular thickness (CMT) were extracted, and adverse events (AEs) were collected.A total of 21 trials were included in our network meta-analysis. Intravitreal ranibizumab improved BCVA most significantly (OR: +7.01 95%CI (2.56 to 11.39)) in 6 months and intravitreal aflibercept (+8.19 (5.07 to 11.96)) in 12 months. Intravitreal triamcinolone combined with LASER decreased CMT most significantly (-111.34 (-254.61 to 37.93)) in 6 months and intravitreal aflibercept (-110.83 (-190.25 to -35.27)) in 12 months. Compared with the relatively high rate of ocular AEs in the groups with administration of steroids, systematic AEs occurred more frequently in the groups with vascular endothelial growth factor inhibitors involved.Our analysis confirms that intravitreal aflibercept is most favorable with both BCVA improvement and CMT decrease than other current therapies in the management of DME within 12 months. Vascular endothelial growth factor inhibitors for DME should be used with caution due to systematic AEs. Combined intravitreal triamcinolone with LASER has a stronger efficacy in decreasing CMT than the other interventions in the early stage after injection. More high-quality randomized controlled trials will be necessary.

Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function. Moreover, we found that FSTL1 function was blocked by the epithelial polarization, which was reflected by the remarkable apical secretion of FSTL1 and the basolateral BMP signaling. Taken together, this study demonstrates that tightly spatial interaction of FSTL1 and BMP signaling plays an essential role in lung development.

Ischemia-reperfusion injury after central nervous system (CNS) injury presents a major health care challenge with few promising treatments. Recently, it has become possible to reduce edema after CNS injury by antagonizing a sulfonylurea receptor 1 (SUR1) regulated ion channel expressed after injury. SUR1 upregulation after injury is a necessary precondition for the formation of this channel, and has been implicated in white matter injury after clinical spinal cord trauma. Glibenclamide, an SUR1 antagonist, appears to have neuroprotective effect against cerebral stroke in an open-label small clinical trial and great effectiveness in reducing damage after varied experimental CNS injury models. Despite its importance in CNS injuries, SUR1 upregulation appears to play no part in rodent anterior ischemic optic neuropathy (rAION) injury as tested by real-time PCR and immunohistochemical staining of rAION-injured rat optic nerve (ON). Furthermore, the SUR1 antagonist glibenclamide administered immediately after rAION injury provided no protection to proximal ON microvasculature 1 day post-injury but may reduce optic nerve head edema in a manner unrelated to ON SUR1 expression. Our results suggest that there may be fundamental differences between rAION optic nerve ischemia and other CNS white matter injuries where SUR1 appears to play a role.

The behavioral and cognitive characteristics of dangerous drivers differ significantly from those of safe drivers. However, differences in emotional information processing have seldom been investigated. Previous studies have revealed that drivers with higher anger/anxiety trait scores are more likely to be involved in crashes and that individuals with higher anger traits exhibit stronger negativity biases when processing emotions compared with control groups. However, researchers have not explored the relationship between emotional information processing and driving behavior. In this study, we examined the emotional information processing differences between dangerous drivers and safe drivers. Thirty-eight non-professional drivers were divided into two groups according to the penalty points that they had accrued for traffic violations: 15 drivers with 6 or more points were included in the dangerous driver group, and 23 drivers with 3 or fewer points were included in the safe driver group. The emotional Stroop task was used to measure negativity biases, and both behavioral and electroencephalograph data were recorded. The behavioral results revealed stronger negativity biases in the dangerous drivers than in the safe drivers. The bias score was correlated with self-reported dangerous driving behavior. Drivers with strong negativity biases reported having been involved in mores crashes compared with the less-biased drivers. The event-related potentials (ERPs) revealed that the dangerous drivers exhibited reduced P3 components when responding to negative stimuli, suggesting decreased inhibitory control of information that is task-irrelevant but emotionally salient. The influence of negativity bias provides one possible explanation of the effects of individual differences on dangerous driving behavior and traffic crashes.

To investigate the prevalence, location and genetic environments of fosfomycin-resistance (fos) genes in methicillin-resistant Staphylococcus aureus (MRSA) clinical strains, 67 fosfomycin-resistant MRSA strains were isolated from the blood and cerebrospinal fluid samples at a teaching hospital in Shanghai. The presence of fos genes in these clinical strains was detected by PCR and sequencing. The locations of fos genes were determined by Southern blotting and genetic environments were analyzed by primer walking sequencing. Multiple locus sequence typing (MLST) was used to characterize genetic diversity. Conjugation was performed to evaluate the transferability of fos genes. Among 67 fosfomycin-resistant MRSA strains, nine high level fosfomycin resistant strains (≥128 μg/ml) were fosB-positive. Three new subtypes of fosB, designated as fosB4, fosB5, and fosB6, were identified. fosB1, fosB4 or fosB6 genes were located on small plasmids (ca. 2.5 kb) and flanked by an analogous replication gene (rep). Differently, the fosB5 gene was surrounded by a shorter rep gene and two copies of a transposon gene (tnp) that shared high identity with the IS257-like transposon. Four MLST types were found among the nine fosB-positive strains. Transconjugants with the fosB genes were resistant to fosfomycin with MIC 64 or 128 μg/ml. In conclusion, different subtypes and genetic environment of fosB genes indicate that gene heterogeneity for fosfomycin resistance in MRSA isolates.

OBJECTIVE:Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. METHODS:164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. RESULTS:There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P

Anger is an emotion that drivers often feel and express while driving, and it is believed by researchers to be an important cause of dangerous driving behavior. In this study, the relationships between driving trait anger, driving anger expression, and dangerous driving behaviors were analyzed. The Driving Anger Scale (DAS) was used to measure driving trait anger, whereas the Driving Anger Expression (DAX) Inventory was used to measure expressions of driving anger. A sample of 38 drivers completed the DAS, DAX, and a driving simulation session on a simulator where their driving behaviors were recorded. Correlation analysis showed that the higher scores on the DAS were associated with longer durations of speeding in the simulator. The more participants expressed their anger in verbal and physical ways, the more likely they were to crash the virtual vehicle during the simulation. Regression analyses illustrated the same pattern. The findings suggest that, although trait anger is related to speeding, the passive expression of anger is the real factor underling traffic accidents. This study extends findings about the predictive effects of self-report scales of driving behaviors to behaviors recorded on a simulator. Thus, if in traffic safety propaganda, guiding drivers to use positive ways to cope with driving anger is recommended by our findings.

BACKGROUND:Millions of people move from rural areas to urban areas in China to pursue new opportunities while leaving their spouses and children at rural homes. Little is known about the impact of migration-related separation on mental health of these rural migrants in urban China. METHODS:Survey data from a random sample of rural-to-urban migrants (n = 1113, aged 18-45) from Wuhan were analyzed. The Domestic Migration Stress Questionnaire (DMSQ), an instrument with four subconstructs, was used to measure migration-related stress. The relationship between spouse/child separation and stress was assessed using survey estimation methods to account for the multi-level sampling design. RESULTS:16.46% of couples were separated from their spouses (spouse-separation only), 25.81% of parents were separated from their children (child separation only). Among the participants who married and had children, 5.97% were separated from both their spouses and children (double separation). Spouse-separation only and double separation did not scored significantly higher on DMSQ than those with no separation. Compared to parents without child separation, parents with child separation scored significantly higher on DMSQ (mean score = 2.88, 95% CI: [2.81, 2.95] vs. 2.60 [2.53, 2.67], p < .05). Stratified analysis by separation type and by gender indicated that the association was stronger for child-separation only and for female participants. CONCLUSION:Child-separation is an important source of migration-related stress, and the effect is particularly strong for migrant women. Public policies and intervention programs should consider these factors to encourage and facilitate the co-migration of parents with their children to mitigate migration-related stress.

Heavy metal pollution is a major limiting factor that severely affects plant growth worldwide, and the accumulation of heavy metal in the plant may be hazardous to human health. To identify the processes involved in cadmium detoxification, we constructed a cDNA library of tobacco roots acclimated to cadmium (Cd) stress. According to the results of functional screening cDNA library with a yeast Cd-sensitive mutant, ycf1Δ, we obtained a series of candidate genes that were involved in Cd response. Sequence analysis and yeast functional complementation of 24 positive cDNA clones revealed that, in addition to antioxidant genes, genes implicated in abiotic and biotic stress defenses, cellular metabolism, and signal transduction showed Cd detoxification effects in yeast. The real time RT-PCR analyses revealed that some Cd tolerance/ detoxification genes may be able to anticipate in other stresses such as biotic defense and water balance in tobacco. Taken together, our data suggest that plants' acclimation to Cd stress is a highly complex process associated with broad gene functions. Moreover, our results provide insights into the Cd detoxification mechanisms along with the antioxidant system, defense gene induction, and calcium signal pathway.