Jie Zhou

As two representative environmental contaminants, the individual toxic effects of microplastics and triclosan have been extensively studied; however, systematic evidence regarding their combined toxicity in mammals and the underlying mechanisms remains lacking. In this study, mice were orally exposed to triclosan (TCS) or/and polystyrene microplastics (PS), and their toxicity to intestine and liver was evaluated through histopathological examination, biochemical assays, and 16S rRNA sequencing. Results demonstrated that co-exposure to TCS and PS elicited markedly aggravated toxicological effects compared to individual exposures. Histopathological evaluation revealed exacerbated tissue damage, with histological scores substantially higher in co-exposed mice (colon: 7.27; liver: 5.0) than in PS-alone (colon: 6.07; liver: 3.0) or TCS-alone (colon: 3.0; liver: 0.7) groups. Quantitative Integrated Biomarker Response (IBR) analysis confirmed this potential additive or synergistic interaction: co-exposure not only dramatically elevated colonic oxidative stress (R_IB = 12.30 vs. 5.88 in PS and 0.23 in TCS groups) but also exacerbated inflammatory responses (R_IB = 11.69 vs. 3.52 in PS and 0 in TCS). Hepatic assessment demonstrated the most severe compromise in liver function and oxidative homeostasis following co-exposure (R_IB = 16.48), markedly exceeding the effects of individual PS (4.75) or TCS (0.43) exposure. In-depth exploration found that co-exposure to TCS and PS significantly disrupted gut microbiota homeostasis, characterized by enrichment of opportunistic pathogens and depletion of short-chain fatty acid-producing bacteria; these alterations were not only correlated with intestinal barrier impairment but also exacerbated gut–liver axis dysregulation. Together, the findings not only highlight the synergistic toxicity of triclosan and polystyrene microplastics in mice but also identify the gut–liver axis as a mediator of this effect, thereby providing novel evidence for health risk assessment and underscoring a potential concern for human health under co-exposure.

Metformin disinfection byproducts Y and C have emerged as pollutants of concern in drinking water systems and are suspected to possess significant toxicity to mammals. However, effective strategies to mitigate the effects of Y and C exposure in mammals have not been thoroughly formulated. This study aimed to investigate the toxicity and characteristic phenotypes of short-term, high-dose exposure to Y and C in the intestine and liver of mice and to evaluate the protective effects of Dictyophora rubrovolvata extract (DRE) on Y- and C-induced intestinal and liver damage. The results showed that exposure-induced intestinal toxicity manifested mainly as intestinal barrier dysfunction, induction of immune response and oxidative stress, and disruption of intestinal flora homeostasis. Hepatotoxicity was mainly characterized by histopathological changes such as vacuolar degeneration, abnormal liver function, and oxidative stress. Additionally, marked changes in gut microbiota and biochemical indicators were closely related to hepatic and intestinal injuries after exposure. DRE effectively alleviated Y- and C-induced intestinal and liver damage, reshaped the gut microbiota, and maintained gut–liver axis homeostasis. These findings provide new insights into the toxic effects of disinfection byproduct exposure through the gut-liver axis and suggest that functional food extracts may serve to protect against these adverse health outcomes.

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis (M. tb). It is regarded as a major health threat all over the world, mainly because of its high mortality and drug-resistant nature. Toxin-antitoxin (TA) systems are modules ubiquitously found in prokaryotic organisms, and the well-studied MazEF systems (MazE means “what is it?” in Hebrew) are implicated in the formation of “persister cells” in the M. tb pathogen. Here, we report cocrystal structures of M. tb MazF-mt1 and -mt9, two important MazF members responsible for specific mRNA and tRNA cleavages, respectively, in complexes with truncated forms of their cognate antitoxin peptides. These peptides bind to the toxins with comparable affinities to their full-length antitoxins, which would reduce the RNA-cleavage capacities of the toxins in vitro. After structural analysis of the binding modes, we systemically tested the influence of the substitutions of individual residues in the truncated MazE-mt9 peptide on its affinity. This study provides structural insight into the binding modes and the inhibition mechanisms between the MazE/F-mt TA pairs. More importantly, it contributes to the future design of peptide-based antimicrobial agents against TB and potentially relieves the drug-resistance problems by targeting novel M. tb proteins.

Introduction: Community-acquired pneumonia (CAP) is the main acute complication of type 2 diabetes mellitus (T2DM) and the main cause of hospitalization for infectious diseases. Unfortunately, in the treatment of type 2 diabetes mellitus complicated with community-acquired pneumonia (T2DM-CAP), modern medicine is still faced with enormous challenges because of insulin resistance and drug-resistant bacteria. In recent decades, clinical and experimental evidence shows that Chinese herbal medicine (CHM) has a certain beneficial effect on diabetes and pneumonia. Therefore, this trial aims to assess the efficacy and safety of CHM plus western medicines for the treatment of T2DM-CAP. Methods: We propose a double-blind, placebo-controlled, randomized superiority trial. A total of 92 participants with T2DM-CAP will be randomly allocated at a 1:1 ratio to either the experimental group, which will receive modified Ban-Xia-Xie-Xin-Decotion and basic treatment, or the control group, which will receive basic treatment only. The study duration will be 14 days. The primary outcome will be the total clinical effective rate. The secondary outcomes are traditional Chinese medicine symptom score scale, pneumonia severity index, usage time of antibiotic, time required for blood sugar to reach the required level, frequency of hypoglycemia, and chest CT. Liquid chromatograph-mass spectrometry method will be used to explore the blood metabolism profiles of the subjects, to explore the pathogenesis of T2DM-CAP and the mechanism of CHM on T2DM-CAP. Adverse events will also be evaluated. Discussion: This trial will provide evidence of the effectiveness and safety of traditional CHM in treating patients with T2DM-CAP. Trial registration number: ChiCTR2000035204