Is Short-Course Antibiotic Therapy Suitable for Pseudomonas aeruginosa Bloodstream Infections in Onco-hematology Patients With Febrile Neutropenia? Results of a Multi-institutional Analysis.

BACKGROUND: Several studies have suggested that short-course antibiotic therapy was effective in Pseudomonas aeruginosa (PA) bloodstream infections (BSI) in immunocompetent patients. But similar studies in patients with hematological malignancies were rare. METHODS: This cohort study included onco-hematology patients at 2 hematology centers in China. Inverse probability of treatment weighting was used to balance the confounding factors. Multivariate regression model was used to evaluate the effect of short-course antibiotic therapy on clinical outcomes. RESULTS: In total, 434 patients met eligibility criteria (short-course, 7-11 days, n = 229; prolonged, 12-21 days, n = 205). In the weighted cohort, the univariate and multivariate analysis indicated that short course antibiotic therapy had similar outcomes to the prolonged course. The recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group (P = .979). The recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group (P = .139), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group (P = .957). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital (P < .001). CONCLUSIONS: In the study, short-course therapy was non-inferior to prolonged-course therapy in terms of clinical outcomes. However, due to its biases and limitations, further prospective randomized controlled trials are needed to generalize our findings.

Population structure and selection signal analysis of indigenous sheep from the southern edge of the Taklamakan Desert.

Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (FST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change.

Analysis of full and empty ratio of EV71 virus by using capillary zone electrophoresis.

Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios.

Combining serum microRNAs and machine learning algorithms for diagnosing infectious fever after HSCT.

Infection post-hematopoietic stem cell transplantation (HSCT) is one of the main causes of patient mortality. Fever is the most crucial clinical symptom indicating infection. However, current microbial detection methods are limited. Therefore, timely diagnosis of infectious fever and administration of antimicrobial drugs can effectively reduce patient mortality. In this study, serum samples were collected from 181 patients with HSCT with or without infection, as well as the clinical information. And more than 80 infectious-related microRNAs in the serum were selected according to the bulk RNA-seq result and detected in the 345 time-pointed serum samples by Q-PCR. Unsupervised clustering result indicates a close association between these microRNAs expression and infection occurrence. Compared to the uninfected cohort, more than 10 serum microRNAs were identified as the combined diagnostic markers in one formula constructed by the Random Forest (RF) algorithms, with a diagnostic accuracy more than 0.90. Furthermore, correlations of serum microRNAs to immune cells, inflammatory factors, pathgens, infection tissue, and prognosis were analyzed in the infection cohort. Overall, this study demonstrates that the combination of serum microRNAs detection and machine learning algorithms holds promising potential in diagnosing infectious fever after HSCT.

Synthesis and biological evaluations of 8-biaryl-2,2-dimethylbenzopyranamide derivatives against Alzheimer's disease and ischemic stroke.

Alzheimer's disease, the commonest cause of dementia, is a growing global health concern with huge implications for individuals and society. Stroke has still been a significant challenge in clinics for a long time, which is the second leading cause of death in the world, especially ischemic stroke. Both Alzheimer's disease and stroke are closely related to oxidative stress and HIF-1 signaling pathways in nerve cells. Herein, we describe our structure-based design, synthesis, and biological evaluation of a new class of 8-biaryl-2,2-dimethylbenzopyranamide derivatives as natural product derivatives. Our efforts have resulted in the discovery of highly potent neuroprotective agents, as exemplified by compound D13 as a HIF-1α inhibitor, which significant improvement in the behavior of Alzheimer's disease mice and shows great potential improvement of brain infarct volume in pMCAO model rats, improves the increase of blood-brain barrier permeability after cerebral ischemia in rats, neuroprotective effect, reduce the level of apoptotic cells in rats after cerebral ischemia, better than Edaravone.

Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses. RESULTS: We evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10. CONCLUSIONS: Our results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

Association between social integration and loneliness among the female migrant older adults with children: the mediating effect of social support.

BACKGROUND: The number of migrant older adults with children (MOAC) in China has been increasing in recent years, and most of them are women. This study aimed to explore the mediating effect of social support between social integration and loneliness among the female MOAC in Jinan, China. METHODS: In this study, 418 female MOAC were selected using multi-stage cluster random sampling in Jinan, Shandong Province, China. Loneliness was measured by the eight-item version of the University of California Los Angeles Loneliness Scale (ULS-8), and social support was measured by The Social Support Rating Scale (SSRS). Descriptive analyses, t-tests, ANOVA, and structural equation modeling (SEM) were used to illustrate the relationship between social integration, social support, and loneliness. RESULTS: The average scores of ULS-8 and SSRS were 12.9 ± 4.0 and 39.4 ± 5.9 among female MOAC in this study. Social integration and social support were found to be negatively related to loneliness, and the standardized direct effect was -0.20 [95% CI: -0.343 to -0.068] and -0.39 [95% CI: -0.230 to -0.033], respectively. Social support mediated the relationship between social integration and loneliness, and the indirect effect was -0.16 [95% CI: -0.252 to -0.100]. CONCLUSION: The female MOAC's loneliness was at a relatively lower level in this study. It was found that social integration was negatively associated with loneliness, and social support mediated the relationship between them. Helping female MOAC integrate into the inflow city and improving their social support could be beneficial for alleviating their loneliness.

Association between social capital, mental health, and digital health literacy among the university students in China: a multigroup analysis based on major difference.

BACKGROUND: This study aimed to clarify medical-nonmedical difference on the relationship between social capital, mental health and digital health literacy of university students in China, and furtherly provide evidence-based suggestions on the improvement of the digital health literacy for the university students. METHODS: The snowball sampling method was used to collect data from the university students (including medical students and nonmedical students) through online questionnaires, and finally 1472 university students were included for the data analysis, of whom, 665 (45.18%) were medical students, 807 (54.82%) were nonmedical students; 462 (31.39%) were male, 1010 (68.61%) were female. Mean value of the age was 21.34 ± 2.33 for medical students vs. 20.96 ± 2.16 for nonmedical students. Descriptive analysis, chi-square test analysis, one-way Analysis of Variance (conducted by SPSS) and structural equation modeling (conducted by AMOS) were employed to explore the difference on the relationship between social capital, mental health and digital health literacy between the medical students and nonmedical students. RESULTS: The mean value of the digital health literacy was 36.27 (37.33 for medical students vs. 35.39 for nonmedical students). The SEM analysis showed that there was a statistically positive correlation between social capital and digital health literacy (stronger among the nonmedical students (0.317) than medical students (0.184)). Mental health had a statistically positive impact on the digital health literacy among medical students (0.242), but statistically significant correlation was not observed in nonmedical students (0.017). Social capital was negatively correlated with the mental health for both medical students and NMS (stronger among the nonmedical students (0.366) than medical students (0.255)). And the fitness indices of SEM were same between medical students and nonmedical students (GFI = 0.911, AGFI = 0.859, CFI = 0.922, RMSEA = 0.074). CONCLUSION: The digital health literacy of the university student was relatively high. Both social capital and mental health could exert a positive effect on digital health literacy, while social capital was found to be positively associated with mental health. Statistical difference was found between medical students and nonmedical students on the above correlations. Implications were given on the improvement of the digital health literacy among university students in China.

Genome-wide selection reveals candidate genes associated with multiple teats in Hu sheep.

Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.

Clinical Characteristics, Prognosis Factors and Metagenomic Next-Generation Sequencing Diagnosis of Mucormycosis in patients With Hematologic Diseases.

INTRODUCTION: New diagnostic methods and antifungal strategies may improve prognosis of mucormycosis. We describe the diagnostic value of metagenomic next⁃generation sequencing (mNGS) and identify the prognostic factors of mucormycosis. METHODS: We conducted a retrospective study of hematologic patients suffered from mucormycosis and treated with monotherapy [amphotericin B (AmB) or posaconazole] or combination therapy (AmB and posaconazole). The primary outcome was 84-day all-cause mortality after diagnosis. RESULTS: Ninety-five patients were included, with "proven" (n = 27), "probable" (n = 16) mucormycosis confirmed by traditional diagnostic methods, and "possible" (n = 52) mucormycosis with positive mNGS results. The mortality rate at 84 days was 44.2%. Possible + mNGS patients and probable patients had similar diagnosis processes, overall survival rates (44.2% vs 50.0%, p = 0.685) and overall response rates to effective drugs (44.0% vs 37.5%, p = 0.647). Furthermore, the median diagnostic time was shorter in possible + mNGS patients than proven and probable patients (14 vs 26 days, p < 0.001). Combination therapy was associated with better survival compared to monotherapy at six weeks after treatment (78.8% vs 53.1%, p = 0.0075). Multivariate analysis showed that combination therapy was the protective factor (HR = 0.338, 95% CI: 0.162-0.703, p = 0.004), though diabetes (HR = 3.864, 95% CI: 1.897-7.874, p < 0.001) and hypoxemia (HR = 3.536, 95% CI: 1.874-6.673, p < 0.001) were risk factors for mortality. CONCLUSIONS: Mucormycosis is a life-threatening infection. Early management of diabetes and hypoxemia may improve the prognosis. Exploring effective diagnostic and treatment methods is important, and combination antifungal therapy seems to hold potential benefits.

Acinetobacter spp. bloodstream infection in hematological patients: a 10-year single-center study.

PURPOSE: This study investigated the clinical and antimicrobial characteristics of Acinetobacter spp. bloodstream infection (BSI) in hematological patients. Risk factors for 30-day mortality and carbapenem-resistant Acinetobacter spp. (CRA) BSI acquisition were also identified. METHODS: We reviewed forty hematological patients with Acinetobacter spp. BSI in a large Chinese blood disease hospital between 2013 and 2022. The remaining CRA isolates were subjected to whole-genome sequencing. RESULTS: The 30-day mortality rate was high at 35%. Hematological patients with Acinetobacter spp. BSI often presented with severe conditions and co-infections at multiple sites. All strains were colistin-susceptible and 40.0% were CR. Multivariate analysis identified several risk factors associated with CRA BSI acquisition, including previous exposure to carbapenems within 30 days and CRA colonization. Very severe aplastic anaemia, tetracycline-resistant Acinetobacter spp. BSI, and unresolved neutropenia after infection were closely associated with 30-day mortality. Non-survivors often presented with higher median PCT and CRP levels and severe complications, such as intracranial infection, cardiac dysfunction, respiratory failure, and severe sepsis or septic shock. Our study also identified inappropriate empirical antibiotic therapy as an independent predictor of 30-day mortality (OR: 11.234, 95% CI: 1.261-20.086, P = 0.030). This study was the first to report A. oleivorans as a human pathogen, and to identify its unique oxacillinase, OXA-325. CONCLUSION: An environment-originated non-pathogenic species can become pathogenic when the body's immunity is compromised. Our results also highlighted the importance of improving neutropenia after infection, treating severe organ dysfunction, and administering appropriate empirical antibiotic therapy to reduce mortality in this patient population.

Visual detection of fowl adenovirus serotype 4 via a portable CRISPR/Cas13a-based lateral flow assay.

The widespread occurrence of fowl adenovirus serotype 4 (FAdV-4)-induced hepatitis-hydropericardium syndrome (HHS) has led to significant economic losses for the poultry industry. A sensitive, accurate, and practical FAdV-4 diagnostic approach is urgently required to limit the incidence of the disease. In the present study, a practical method for detecting FAdV-4 was developed using the CRISPR/Cas13a system and recombinase-aided amplification. The approach was based on 37°C isothermal detection with visible results being achieved. The detection limit of the target gene with this approach was only 101 copies/µl, making it very sensitive and specific. Clinical samples fared well when tested with the Cas13a detection method. For identifying FAdV-4, this novel detection approach was found to be sensitive, specific, and effective.RESEARCH HIGHLIGHTS First study using the CRISPR/Cas13a-based lateral flow detection assay for FAdV-4 detection.The results can be observed by the naked eye.The developed assay could provide an alternative tool for detection of FAdV-4 with minimal equipment.

Bloodstream infections due to Carbapenem-Resistant Enterobacteriaceae in hematological patients: assessment of risk factors for mortality and treatment options.

PURPOSE: Bloodstream infection (BSI) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) are associated with poor outcomes in hematological patients. The aim of this study was to identify risk factors for mortality and evaluate the value of epidemiological feature of carbapenemases in guiding antimicrobial treatment options. METHODS: Hematological patients with monomicrobial CRE BSI between January 2012 and April 2021 were included. The primary outcome was all-cause mortality 30 days after BSI onset. RESULTS: A total of 94 patients were documented in the study period. Escherichia coli was the most common Enterobacteriaceae, followed by Klebsiella pneumoniae. 66 CRE strains were tested for carbapenemase genes, and 81.8% (54/66) were positive, including NDM (36/54), KPC (16/54), IMP (1/54). Besides, one E. coli isolate was found to express both NDM and OXA-48-like genes. Overall, 28 patients received an antimicrobial treatment containing ceftazidime-avibactam (CAZ-AVI), of which 21 cases were combined with aztreonam. The remaining 66 patients were treated with other active antibiotics (OAAs). The 30-day mortality rate was 28.7% (27/94) for all patients, and was only 7.1% ((2/28) for patients treated with CAZ-AVI. In multivariate analysis, the presence of septic shock at BSI onset (OR 10.526, 95% CI 1.376-76.923) and pulmonary infection (OR 6.289, 95% CI 1.351-29.412) were independently risk factors for 30-day mortality. Comparing different antimicrobial regimens, CAZ-AVI showed a significant survive benefit than OAAs (OR 0.068, 95% CI 0.007-0.651). CONCLUSION: CAZ-AVI-containing regimen is superior to OAAs for CRE BSI. As the predominance of blaNDM in our center, we recommend the combination with aztreonam when choose CAZ-AVI.

Effect of screw speed, temperature and moisture on physicochemical properties of corn gluten meal extrudate.

BACKGROUND: Corn gluten meal (CGM) is the main by-product of corn starch with rich protein and dietary fiber. The extrusion of CGM with a twin-screw extruder aimed to expand the novel utilization of this plant-protein resource. The impacts of screw speed, extrusion temperature, and material moisture on physicochemical properties of the extrudates were assessed. RESULTS: The microstructure depicted a favorable fiber-like structure formed under screw speed 120-150 rpm, extrusion temperature 140-150 °C, and material moisture 40-45%. Expansion ratio, rehydration ratio, water solubility index, hardness, and chewiness increased until screw speed reached 120 rpm. With accelerating extrusion temperature, these indicators showed an overall increasing trend. As for material moisture, expansion ratio, hardness, and chewiness showed a decreasing trend. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) showed that disulfide bonds were necessary for protein crosslinking during extrusion. CONCLUSION: It can be concluded that CGM is extrudable, whose textural and physicochemical properties vary as functions of the extruding parameters, providing diversity for its potential applications. © 2023 Society of Chemical Industry.

Genome-wide detection of genetic structure and runs of homozygosity analysis in Anhui indigenous and Western commercial pig breeds using PorcineSNP80k data.

BACKGROUND: Runs of homozygosity (ROH) are continuous homozygous regions typically located in the DNA sequence of diploid organisms. Identifications of ROH that lead to reduced performance can provide valuable insight into the genetic architecture of complex traits. Here, we systematically investigated the population genetic structure of five Anhui indigenous pig breeds (AHIPs), and compared them to those of five Western commercial pig breeds (WECPs). Furthermore, we examined the occurrence and distribution of ROHs in the five AHIPs and estimated the inbreeding coefficients based on the ROHs (FROH) and homozygosity (FHOM). Finally, we identified genomic regions with high frequencies of ROHs and annotated candidate genes contained therein. RESULTS: The WECPs and AHIPs were clearly differentiated into two separate clades consistent with their geographical origins, as revealed by the population structure and principal component analysis. We identified 13,530 ROHs across all individuals, of which 4,555 and 8,975 ROHs were unique to AHIPs and WECPs, respectively. Most ROHs identified in our study were short (< 10 Mb) or medium (10-20 Mb) in length. WECPs had significantly higher numbers of short ROHs, and AHIPs generally had longer ROHs. FROH values were significantly lower in AHIPs than in WECPs, indicating that breed improvement and conservation programmes were successful in AHIPs. On average, FROH and FHOM values were highly correlated (0.952-0.991) in AHIPs and WECPs. A total of 27 regions had a high frequency of ROHs and contained 17 key candidate genes associated with economically important traits in pigs. Among these, nine candidate genes (CCNT2, EGR2, MYL3, CDH13, PROX1, FLVCR1, SETD2, FGF18, and FGF20) found in WECPs were related to muscular and skeletal development, whereas eight candidate genes (CSN1S1, SULT1E1, TJP1, ZNF366, LIPC, MCEE, STAP1, and DUSP) found in AHIPs were associated with health, reproduction, and fatness traits. CONCLUSION: Our findings provide a useful reference for the selection and assortative mating of pig breeds, laying the groundwork for future research on the population genetic structures of AHIPs, ultimately helping protect these local varieties.

The effects of oral health and social support on health-related quality of life of migrant older with children in Weifang, China.

BACKGROUND: With the accelerated urbanization and aging population in China, more and more migrant older with children (MOC) moved to new cities. Previous studies mainly explored the acculturation of MOC, yet few focused on the health conditions of this vulnerable group. This study aimed to investigate the effects of oral health and social support on health-related quality of life (HRQOL) of MOC in Weifang, China. METHOD: This study was a cross-sectional study and participants were selected by multi-stage cluster random sampling in Weifang, China. The HRQOL was assessed via the 12-item Short-Form Health Survey (SF-12) which included the mental component summary (MCS) and the physical component summary (PCS). The oral health was evaluated by the Geriatric Oral Health Assessment Index (GOHAI). The social support was administered using the Social Support Rating Scale (SSRS). Descriptive analysis was used to describe participants' sociodemographic variables, oral health and social support. Univariate analysis and binary logistic regression analysis was used to investigate the association between the social support, oral health and HRQOL. RESULTS AND DISCUSSION: It was found that 25.0% of MOC were defined as MCS poor and PCS poor, respectively. Those participants with average and low monthly household income compared to those around them, average and poor oral health, and low levels of social support were more likely to have poor PCS. Those with temporary residence permits, fair and poor oral health, and medium and low levels of social support were more likely to report poor MCS. CONCLUSION: Results indicated that better social support and oral health led to higher HRQOL of MOC. Implications for the government, communities and families of MOC were given to improve their HRQOL.

Inhibitory Effects of Nobiletin on Voltage-Gated Na+ Channel in Rat Ventricular Myocytes Based on Electrophysiological Analysis and Molecular Docking Method.

Nobiletin (NOB) has attracted much attention owing to its outstanding bioactivities. This study aimed to investigate its anti-arrhythmic effect through electrophysiological and molecular docking studies. We assessed the anti-arrhythmic effects of NOB using aconitine-induced ventricular arrhythmia in a rat model and the electrophysiological effects of NOB on rat cardiomyocytes utilizing whole-cell patch-clamp techniques. Moreover, we investigated the binding characters of NOB with rNav1.5, rNav1.5/QQQ, and hNaV1.5 via docking analysis, comparing them with amiodarone and aconitine. NOB pretreatment delayed susceptibility to ventricular premature and ventricular tachycardia and decreased the incidence of fatal ventricular fibrillation. Whole-cell patch-clamp assays demonstrated that the peak current density of the voltage-gated Na+ channel current was reversibly reduced by NOB in a concentration-dependent manner. The steady-state activation and recovery curves were shifted in the positive direction along the voltage axis, and the steady-state inactivation curve was shifted in the negative direction along the voltage axis, as shown by gating kinetics. The molecular docking study showed NOB formed a π-π stacking interaction with rNav1.5 and rNav1.5/QQQ upon Phe-1762, which is the homolog to Phe-1760 in hNaV1.5 and plays an important role in antiarrhythmic action This study reveals that NOB may act as a class I sodium channel anti-arrhythmia agent.

The mediating effect of social support on the association between socioeconomic status and self-reported oral health status among the migrant elderly following children in Weifang, China: a cross-sectional study.

BACKGROUND: Driven by population aging and the rapid urbanization in China, many migrant elderly following children (MEFC) moved to big cities to care for their grandchildren. The purpose of this study is to clarify the mediating effect of social support on the relationship between socioeconomic status (SES) and self-reported oral health status among the MEFC in Weifang, China. METHODS: Multistage cluster random sampling was used to select the participants and finally 613 MEFC were included in the survey. The Social Support Rating Scale (SSRS) and the Chinese version of the Geriatric Oral Health Assessment Index (GOHAI) scale were used for data collection. Descriptive analysis, Rao-Scott test, t-test and structural equation modeling (SEM) were conducted in this study. RESULTS: Mean score of GOHAI of the MEFC was 54.95 ± 6.47. The SES of MEFC exerted positive direct effect both on social support (standardized coefficient = 0.15) and self-reported oral health status (standardized coefficient = 0.22); social support exerted positive direct effect on self-reported oral health status (standardized coefficient = 0.17). Social support partially mediated the association between SES and self-reported oral health status [95% confidence interval (CI) 0.003-0.064, P < 0.05], and the mediating effect of social support accounted for 12.0% of the total effect. CONCLUSIONS: Higher GOHAI score of MEFC indicated their better self-reported oral health status. MEFCs' SES could exert positive effect both on social support and self-reported oral health status, while the mediating effect of social support between SES and self-reported oral health status of MEFC was established.

Differential nitric oxide induced by Mycobacterium bovis and BCG leading to dendritic cells apoptosis in a caspase dependent manner.

Dendritic cells (DCs) are critical for both innate and adaptive immunity. Meanwhile, nitric oxide (NO) is a member of reactive nitrogen species (RNS) generally considered to play a key role in the bactericidal process in innate immunity against Mycobacterium tuberculosis complex infection. The present study therefore investigated the mechanism of NO production in murine DCs induced by Mycobacterium bovis (M.bovis) and its attenuated strain Bacillus Calmette-Guérin (BCG) infection. The expression of genes Slc7A1, Slc7A2, iNOS, and ArgI essential to NO synthesis was up-regulated in M.bovis/BCG infected DCs. IFN-γ addition further increased, while the iNOS inhibitor L-NMMA significantly inhibited their expression. Accordingly, the end products of arginine metabolism, NO and urea, were found to be significantly increased. In addition, BCG induced significantly higher levels of apoptosis in DCs compared to M.bovis shown by higher levels of DNA fragmentation using flow cytometry and release of mitochondrial Cytochrome C, and up-regulation of the genes caspase-3, caspase-8, caspase-9 and dffa critical to apoptosis by qRT-PCR detection and western blot analysis. Furthermore, IFN-γ increased, but L-NMMA decreased apoptosis of M.bovis/BCG infected DCs. In addition, mycobacterial intracellular survival was significantly reduced by IFN-γ treatment in BCG infected DCs, while slightly increased by L-NMMA treatment. Taken altogether, our data show that NO synthesis was differentially increased and associated with apoptosis in M.bovis/BCG infected DCs. These findings may significantly contribute to elucidate the pathogenesis of M.bovis.

TRIM25 upregulation by Mycobacterium tuberculosis infection promotes intracellular survival of M.tb in RAW264.7 cells.

Tripartite motif 25 (TRIM25) is a TRIM family member which is involved in innate immunity. However, its role in the modulation of host defense against Mycobacterium tuberculosis (M.tb) infection has not been investigated. Therefore, this study aimed to demonstrate the significance of TRIM25 in the regulation of macrophage responses to M.tb infection. TRIM25 was found to be significantly overexpressed (3.476-fold) in peripheral blood mononuclear cells (PBMCs) of 67 patients with pulmonary tuberculosis compared with 48 healthy controls. TRIM25 expression was enhanced following M.tb infection of RAW264.7 cells, a macrophage cell line. Overexpression of TRIM25 in M.tb-infected RAW264.7 cells led to a significant increase in phosphorylated p38 levels; however, the production of IL-6, IL-1ß, and TNF-α were significantly reduced. Finally, M.tb intracellular survival increased by 90% at 12 h post-infection (PI) (p < 0.01). To validate the previous results, TRIM25 levels in M.tb-infected RAW264.7 macrophages were down-regulated using small interfering RNA (siRNA). Therefore, it was concluded that TRIM25 promotes intracellular survival of M.tb in RAW264.7 cells, likely by enhancing p38 pathways and thereby inhibiting the production of proinflammatory cytokines. These results contribute to the further understanding of the host defense against M.tb infection.