Virulence, antibiotic resistance phenotypes and molecular characterisation of Vibrio furnissii isolates from patients with diarrhoea.

BACKGROUND: Vibrio furnissii is an emerging human pathogen closely related to V. fluvialis that causes acute gastroenteritis. V. furnissii infection has been reported to be rarer than V. fluvialis, but a multi-drug resistance plasmid has recently been discovered in V. furnissii. METHODS: During daily monitoring at a general hospital in Beijing, China, seven V. furnissii strains were collected from patients aged over 14 years who presented with acute diarrhoea between April and October 2018. Genome analysis and comparison were performed for virulence and antimicrobial resistance genes, plasmids and transposon islands, together with phylogenetic analysis. Antimicrobial resistance to 19 antibiotics was investigated using the microbroth dilution method. Virulence phenotypes were investigated based on type VI secretion system (T6SS) expression and using a bacterial killing assay and a haemolysin assay. RESULTS: Phylogenetic analysis based on single-nucleotide polymorphisms revealed a closer relationship between V. furnissii and V. fluvialis than between other Vibrio spp. The seven V. furnissii isolates were in different monophyletic clades in the phylogenetic tree, suggesting that the seven cases of gastroenteritis were independent. High resistance to cefazolin, tetracycline and streptomycin was found in the V. furnissii isolates at respective rates of 100.0%, 57.1% and 42.9%, and intermediate resistance to ampicillin/sulbactam and imipenem was observed at respective rates of 85.7% and 85.7%. Of the tested strains, VFBJ02 was resistant to both imipenem and meropenem, while VFBJ01, VFBJ02, VFBJ05 and VFBJ07 were multi-drug resistant. Transposon islands containing antibiotic resistance genes were found on the multi-drug resistance plasmid in VFBJ05. Such transposon islands also occurred in VFBJ07 but were located on the chromosome. The virulence-related genes T6SS, vfh, hupO, vfp and ilpA were widespread in V. furnissii. The results of the virulence phenotype assays demonstrated that our isolated V. furnissii strains encoded an activated T6SS and grew in large colonies with strong beta-haemolysis on blood agar. CONCLUSION: This study showed that diarrhoea associated with V. furnissii occurred sporadically and was more common than expected in the summer in Beijing, China. The antibiotic resistance of V. furnissii has unique characteristics compared with that of V. fluvialis. Fluoroquinolones and third-generation cephalosporins, such as ceftazidime and doxycycline, were effective at treating V. furnissii infection. Continua laboratory-based surveillance is needed for the prevention and control of V. furnissii infection, especially the dissemination of the antibiotic resistance genes in this pathogen.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline derivative as a fluorescent probe for highly selective detection of Fe3+ ions.

A novel [1, 2, 4]triazolo[5,1-b]quinazoline fluorescent probe (VIi) for Fe3+ was developed, featuring with rapid response (< 5 s) and specific selectivity to Fe3+, low detection limit (1.3 × 10-5 M), as well as the ability to resist interference of chelating agent (e.g. EDTA). VIi-based fluorescent test paper can quickly recognize Fe3+ under irradiation at the wavelength of 365 nm. The fluorescence probe VIi has potential application prospects for the detection of Fe3+ in real circumstance.

Maslinic acid supplementation prevents di(2-ethylhexyl) phthalate-induced apoptosis via PRDX6 in peritubular myoid cells of Chinese forest musk deer.

Chinese forest musk deer (FMD), an endangered species, have exhibited low reproductive rates even in captivity due to stress conditions. Investigation revealed the presence of di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, in the serum and skin of captive FMDs. Feeding FMDs with maslinic acid (MA) has been observed to alleviate the stress response and improve reproductive rates, although the precise molecular mechanisms remain unclear. Therefore, this study aims to investigate the molecular mechanisms underlying the alleviation of DEHP-induced oxidative stress and cell apoptosis in primary peritubular myoid cells (PMCs) through MA intake. Primary PMCs were isolated and exposed to DEHP in vitro. The results demonstrated that DEHP significantly suppressed antioxidant levels and promoted cell apoptosis in primary PMCs. Moreover, interfering with the expression of PRDX6 was found to induce excessive reactive oxygen species (ROS) production and cell apoptosis in primary PMCs. Supplementation with MA significantly upregulated the expression of PRDX6, thereby attenuating DEHP-induced oxidative stress and cell apoptosis in primary PMCs. These findings provide a theoretical foundation for mitigating stress levels and enhancing reproductive capacity of in captive FMDs.

Single-cell RNA sequencing data analysis utilizing multi-type graph neural networks.

Single-cell RNA sequencing (scRNA-seq) is the sequencing technology of a single cell whose expression reflects the overall characteristics of the individual cell, facilitating the research of problems at the cellular level. However, the problems of scRNA-seq such as dimensionality reduction processing of massive data, technical noise in data, and visualization of single-cell type clustering cause great difficulties for analyzing and processing scRNA-seq data. In this paper, we propose a new single-cell data analysis model using denoising autoencoder and multi-type graph neural networks (scDMG), which learns cell-cell topology information and latent representation of scRNA-seq data. scDMG introduces the zero-inflated negative binomial (ZINB) model into a denoising autoencoder (DAE) to perform dimensionality reduction and denoising on the raw data. scDMG integrates multiple-type graph neural networks as the encoder to further train the preprocessed data, which better deals with various types of scRNA-seq datasets, resolves dropout events in scRNA-seq data, and enables preliminary classification of scRNA-seq data. By employing TSNE and PCA algorithms for the trained data and invoking Louvain algorithm, scDMG has better dimensionality reduction and clustering optimization. Compared with other mainstream scRNA-seq clustering algorithms, scDMG outperforms other state-of-the-art methods in various clustering performance metrics and shows better scalability, shorter runtime, and great clustering results.

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials.

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before. Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023. Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h. Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

Metagenomic and Culturomics Analysis of Microbial Communities within Surface Sediments and the Prevalence of Antibiotic Resistance Genes in a Pristine River: The Zaqu River in the Lancang River Source Region, China.

Microbial communities inhabiting sedimentary environments in river source regions serve as pivotal indicators of pristine river ecosystems. While the correlation between antibiotic resistome and pathogenicity with core gut bacteria in humans is well established, there exists a significant knowledge gap concerning the interaction of antibiotic resistance genes (ARGs) and human pathogenic bacteria (HPB) with specific microbes in river source basins, often referred to as "terrestrial gut". Understanding the microbial composition, including bacteria and resident genetic elements such as ARGs, HPB, Mobile Genetic Elements (MGEs), and Virulence Factors (VFs), within natural habitats against the backdrop of global change, is imperative. To address this gap, an enrichment-based culturomics complementary along with metagenomics was conducted in this study to characterize the microbial biobank and provide preliminary ecological insights into profiling the dissemination of ARGs in the Lancang River Source Basin. Based on our findings, in the main stream of the Lancang River Source Basin, 674 strains of bacteria, comprising 540 strains under anaerobic conditions and 124 under aerobic conditions, were successfully isolated. Among these, 98 species were identified as known species, while 4 were potential novel species. Of these 98 species, 30 were HPB relevant to human health. Additionally, bacA and bacitracin emerged as the most abundant ARGs and antibiotics in this river, respectively. Furthermore, the risk assessment of ARGs predominantly indicated the lowest risk rank (Rank Ⅳ) in terms of endangering human health. In summary, enrichment-based culturomics proved effective in isolating rare and unknown bacteria, particularly under anaerobic conditions. The emergence of ARGs showed limited correlation with MGEs, indicating minimal threats to human health within the main stream of the Lancang River Source Basin.

RNA modification-related genes illuminate prognostic signature and mechanism in esophageal squamous cell carcinoma.

Emerging studies have demonstrated the link between RNA modifications and various cancers, while the predictive value and functional mechanisms of RNA modification-related genes (RMGs) in esophageal squamous cell carcinoma (ESCC) remain unclear. Here we established a prognostic signature for ESCC based on five RMGs. The analysis of ESCC clinical samples further verified the prognostic power of the prognostic signature. Moreover, we found that the knockdown of NSUN6 promotes ESCC progression in vitro and in vivo, whereas the overexpression of NSUN6 inhibits the malignant phenotype of ESCC cells. Mechanically, NSUN6 mediated tRNA m5C modifications selectively enhance the translation efficiency of CDH1 mRNA in a codon dependent manner. Rescue assays revealed that E-cadherin is an essential downstream target that mediates NSUN6's function in the regulation of ESCC progression. These findings offer additional insights into the link between ESCC and RMGs, as well as provide potential strategies for ESCC management and therapy.

Centralized industrialization of pork in Europe and America contributes to the global spread of Salmonella enterica.

Salmonella enterica causes severe food-borne infections through contamination of the food supply chain. Its evolution has been associated with human activities, especially animal husbandry. Advances in intensive farming and global transportation have substantially reshaped the pig industry, but their impact on the evolution of associated zoonotic pathogens such as S. enterica remains unresolved. Here we investigated the population fluctuation, accumulation of antimicrobial resistance genes and international serovar Choleraesuis transmission of nine pig-enriched S. enterica populations comprising more than 9,000 genomes. Most changes were found to be attributable to the developments of the modern pig industry. All pig-enriched salmonellae experienced host transfers in pigs and/or population expansions over the past century, with pigs and pork having become the main sources of S. enterica transmissions to other hosts. Overall, our analysis revealed strong associations between the transmission of pig-enriched salmonellae and the global pork trade.