TM9SF1 is implicated in promoting the proliferation and invasion of bladder cancer cells.

Zhuo et al looked into the part of transmembrane 9 superfamily member 1 (TM9SF1) in bladder cancer (BC), and evaluated if it can be used as a therapeutic target. They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth, movement, invasion, and cell cycle advancement. Their results show that TM9SF1 can boost the growth, movement, and invasion of BC cells and their access into the G2/M stage of the cell cycle. This research gives a novel direction and concept for targeted therapy of BC.

Simulated Gastric Acid Promotes the Horizontal Transfer of Multidrug Resistance Genes across Bacteria in the Gastrointestinal Tract at Elevated pH Levels.

The assessment of factors that can promote the transmission of antibiotic resistance genes (ARGs) across bacteria in the gastrointestinal tract is in great demand to understand the occurrence of infections related to antibiotic-resistant bacteria (ARB) in humans. However, whether acid-resistant enteric bacteria can promote ARG transmission in gastric fluid under high-pH conditions remains unknown. This study assessed the effects of simulated gastric fluid (SGF) at different pH levels on the RP4 plasmid-mediated conjugative transfer of ARGs. Moreover, transcriptomic analysis, measurement of reactive oxygen species (ROS) levels, assessment of cell membrane permeability, and real-time quantitative assessment of the expression of key genes were performed to identify the underlying mechanisms. The frequency of conjugative transfer was the highest in SGF at pH 4.5. Antidepressant consumption and certain dietary factors further negatively impacted this situation, with 5.66-fold and 4.26-fold increases in the conjugative transfer frequency being noted upon the addition of sertraline and 10% glucose, respectively, compared with that in the control group without any additives. The induction of ROS generation, the activation of cellular antioxidant systems, increases in cell membrane permeability, and the promotion of adhesive pilus formation were factors potentially contributing to the increased transfer frequency. These findings indicate that conjugative transfer could be enhanced under certain circumstances in SGF at elevated pH levels, thereby facilitating ARG transmission in the gastrointestinal tract. IMPORTANCE The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited. In this study, we constructed a conjugative transfer model in the presence of simulated gastric fluid (SGF) and found that SGF could promote the dissemination of ARGs under high-pH conditions. Furthermore, antidepressant consumption and certain dietary factors could negatively impact this situation. Transcriptomic analysis and a reactive oxygen species assay revealed the overproduction of reactive oxygen species as a potential mechanism by which SGF could promote conjugative transfer. This finding can help provide a comprehensive understanding of the bloom of antibiotic-resistant bacteria in the body and create awareness regarding the risk of ARG transmission due to certain diseases or an improper diet and the subsequent decrease in gastric acid levels.

Visual Detection of Vibrio parahaemolyticus using Combined CRISPR/Cas12a and Recombinase Polymerase Amplification.

Objective: To establish an ultra-sensitive, ultra-fast, visible detection method for Vibrio parahaemolyticus (VP) . Methods: We established a new method for detecting the tdh and trh genes of VP using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 12a (CRISPR/Cas12a) combined with recombinase polymerase amplification and visual detection (CRISPR/Cas12a-VD). Results: CRISPR/Cas12a-VD accurately detected target DNA at concentrations as low as 10 -18 M (single molecule detection) within 30 min without cross-reactivity against other bacteria. When detecting pure cultures of VP, the consistency of results reached 100% compared with real-time PCR. The method accurately analysed pure cultures and spiked shrimp samples at concentrations as low as 10 2 CFU/g. Conclusion: The novel CRISPR/Cas12a-VD method for detecting VP performed better than traditional detection methods, such as real-time PCR, and has great potential for preventing the spread of pathogens.

Spatial behavior and source tracking of extracellular antibiotic resistance genes in a chlorinated drinking water distribution system.

Antibiotic resistance genes (ARGs) are receiving increasing concerns due to the antibiotic resistance crisis. Nevertheless, little is known about the spatial behavior and sources of extracellular ARGs (eARGs) in the chlorinated drinking water distribution systems (DWDSs). Here, tap water was continuously collected to reveal the occurrence of both eARGs and intracellular ARGs (iARGs) along a chlorinated DWDS. Afterward, the correlation between eARGs, eDNA-releasing communities, and communities of planktonic bacteria was further analyzed. The eARG concentration decreased significantly, whereas the proportion of vanA and blaNDM-1 increased. Further, the diversity of the eDNA-releasing community increased markedly with increasing distance from the drinking water treatment plant (DWTP). Moreover, the dominant eDNA-releasing bacteria shifted from Acinetobacter, Pseudomonas, and Methylobacterium-Methylorubrum in finished water from the DWTP to Bacteroides, Faecalibacterium, Staphylococcus, and Parabacteroides in the DWDS. In terms of eARG source, thirty genera were significantly correlated with seven types of eARGs that resulted from the lysis of dead planktonic bacteria and detached biofilms. Conversely, the iARGs concentration increased, whereas the biodiversity of the planktonic bacteria community decreased in the sampling points along the DWDSs. Our findings provide critical insights into the spatial behavior and sources of eARGs, highlighting the health risks associated with ARGs in DWDSs.

[Regulative effect of active components of Cistanche deserticola on intestinal dysbacteriosis induced by antibiotics in mice].

Objective: To study the effects of Cistanche deserticola and its active components Cistanche deserticola polysaccharide and Echinacoside on intestinal flora of antibiotic-associated diarrhea (AAD) mice. Methods: Forty-eight Balb/c mice were randomly divided into control (Con) group, AAD Group, inulin (Inu) group, Cistanche deserticola (RCR) group, Cistanche deserticola polysaccharide (RCRDT) group and Echinacoside (Ech) group with 8 mice in each group. The diarrhea model of mice was induced by intragastric administration of lincomycin hydrochloride(3 g/kg) for 7 days, and then treated by intragastric administration of INU(5 g/kg), RCR(5 g/kg), RCRDT(200 mg/kg) and ECH (60 mg/kg),0.2 ml once a day for 7 days, Con group and AAD group were given the same volume of normal saline. By observing general signs of mice, colon HE staining, 16S rDNA high-throughput sequencing analysis, the effects of Cistanche deserticola, Cistanche deserticola polysaccharide and Echinacea glycoside on the imbalance of intestinal flora induced by antibiotics in mice were evaluated. Results: Compared with Con group, AAD group mice lost weight, presented obvious diarrhea symptoms, inflammatory changes in colon tissue and decreased intestinal flora diversity (P＜0.05) indicating the success of the model. Compared with AAD group, the weight and diarrhea of INU, RCR, RCRDT and ECH groups were significantly improved, and the colon pathology of ECH group was restored to normal level. Compared with AAD group, RCR group, RCRDT group and ECH group had significantly decreased intestinal Firmicutes, increased Blautia and Lachnoclostridium, and decreased Clostridium_sensu_stricto_1 (P＜0.05) . In ECH group, the abundance and diversity of intestinal microflora were returned to normal level, and the structure of intestinal microflora was well adjusted, the contents of Bacteroides, Flavonifractor, Agathobacter, Lachnoclostridium and Prevotella-9 were increased (P＜0.01). Conclusion: Both Cistanche deserticola and its active components cistanche deserticola polysaccharide and echinacoside can regulate the intestinal flora imbalance caused by antibiotics and improve the symptoms of AAD, especially echinacoside.