Yan Zhang

Background: Rabies is a nearly 100% fatal zoonosis, and a rabies virus-neutralizing antibody (RVNA) titre of ≥0.5 IU/mL is the recognized correlate of protection, making post-vaccination serological monitoring essential. However, the gold-standard methods (RFFIT and FAVN) are time-consuming, require live virus, and are unsuitable for large-scale surveillance, while current ELISA kits often show poor concordance with neutralization tests. Methods: In this study, we established a chemiluminescence immunoassay (CLIA) employing magnetic beads coated with recombinant RABV glycoprotein (short-chain) and an acridinium ester-labeled rabbit anti-dog IgG. Results: The assay exhibited a detection limit of 0.24 IU/mL. Its performance was validated with 250 canine anti-RABV serum samples against the FAVN. The CLIA and FAVN results were strongly correlated (r = 0.9636, p < 0.0001), with a Deming slope of 0.96 (95% confidence interval: 0.92–1.00). The assay achieved a diagnostic sensitivity of 94.4% and a specificity of 97.1%. It demonstrated high accuracy (relative bias within ±10%), good repeatability (intra- and inter-assay coefficients of variation < 8%), and acceptable specificity, showing no cross-reactivity with canine parvovirus, canine distemper virus, or canine parainfluenza virus antibodies. Conclusions: This CLIA kit eliminates the need for live virus, yields quantitative results within 30 min, and offers simple operation and high-throughput capacity, making it a reliable and practical tool for rabies immune monitoring and scientific prevention and control.

Background: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon associated with dysregulated mucosal immunity and gut microbiota imbalance. Safe and effective long-term treatment options remain limited. In this study, we isolated Taraxacum-derived extracellular nanovesicles (TENVs) and evaluated their effects in a dextran sulfate sodium (DSS)-induced colitis model. Methods: Colitis was induced in mice with 3% DSS. The therapeutic effects of TENVs were evaluated using histopathology, inflammatory cytokine profiling, intestinal barrier assessment, and immunofluorescence (IF) analysis. Potential mechanisms were investigated by RNA-seq, Western blotting, 16S rDNA sequencing, and fecal microbiota transplantation (FMT). Results: TENVs showed typical nanovesicular morphology and remained stable in simulated gastric and intestinal fluids. Oral treatment with TENVs markedly attenuated DSS-induced colitis. Mice showed improved clinical indices, less histological damage, and better-preserved epithelial barrier integrity, together with reduced macrophage activation, colonic MPO and IL-17A expression, and circulating pro-inflammatory cytokines. Transcriptomic profiling and immunoblotting revealed changes consistent with attenuation of IL-17/MAPK-associated inflammatory signaling. TENVs also reshaped the gut microbiota. FMT from donors receiving TENVs alleviated colitis in recipient mice. Conclusion: TENVs act on multiple pathological processes in DSS-induced colitis. Their combined effects on mucosal inflammation, epithelial barrier integrity, IL-17/MAPK-associated inflammatory signaling, and the gut microbiota may jointly contribute to the observed protection.

Chronic alcohol consumption is known to compromise the intestinal barrier and disrupt gut homeostasis, contributing to increased vulnerability to various diseases; however, the precise mechanisms remain poorly understood. Emerging evidence suggests that alcohol-induced alterations in host metabolism and gut microbiota composition play a critical role in driving intestinal barrier dysfunction. In this study, we employed a mouse model of chronic alcohol gavage to investigate these interactions. Untargeted metabolomics analysis revealed significant perturbations in isoflavone metabolism caused by chronic alcohol exposure. These metabolic disturbances were accompanied by notable shifts in gut microbiota composition, including an enrichment of Colidextribacter and Ruminococcus . Transcriptomic analysis further identified 286 upregulated and 367 downregulated genes in the alcohol group, and demonstrated that these microbial changes were strongly associated with the downregulation of the Ccr2 gene in intestinal cells, implicating this pathway in intestinal barrier dysfunction. Taken together, these findings suggest that alcohol-induced disruptions in isoflavone metabolism contribute to gut microbiota imbalances, which were associated with suppressed Ccr2 expression and impaired intestinal barrier integrity, although causal relationships and the specific cell types involved remain to be determined, providing new insights into the mechanisms underlying alcohol-related gut pathology.

Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.

Although heart failure (HF) has become one of the most fatal diseases in the whole world, there are fewer drugs for its treatment. Therefore, we focused on the protective effect of Dl-3-n-butylphthalide (NBP) on myocardial injury and oxidative stress in heart failure mice and further investigated the relationship with the Nrf2/HO-1/Ca²⁺-SERCA2a axis. Methods. C57BL/6J mice were divided into the sham group (Sham), heart Failure model group (HF), HF+NBP group (HN), HN+Nrf2 inhibitor (HNM), HN+Calmodulin-dependent protein kinase II (CaMKII) antagonist, KN93 (HNK). The HF mice model was prepared using abdominal aorta ligation. Mices heart function was accessed by echocardiography. Hematoxylin-eosin staining and MASSON staining were used to identify myocardial injury; the cell apoptosis was determined by the TUNEL staining assay. The expression of oxidative stress-related proteins was detected by the ELISA assay. The reactive oxygen species and Nrf2 expression in heart tissue were observed with the immunofluorescence assay. SERCA2a, calmodulin, endoplasmic reticulum stress regulatory proteins, and Nrf2/HO-1 in mice heart tissues were measured using Western blotting. Results. Moreover, NBP could significantly promote heart failure mices heart function, relieve the injury and inhibit cell apoptosis. Meanwhile, it could reduce ERS injury of heart failure mice through increasing SERCA2a level and reducing Ca²⁺ influx. NBP was demonstrated to minimize CaMKII phosphorylation level and decrease cAMP-response element-binding protein phosphorylation level, suggesting NBP could also activate the Nrf2/HO-1 signaling pathway. Conclusions. We demonstrated that NPBs treatment promotes the cardiomyocytes ERS and alleviates myocardial injury in heart failure mice, related to stimulating the Nrf2/HO-1 signaling pathway, regulating Ca²⁺-SERCA2a, and reducing Ca²⁺ influx.

Postoperative cognitive dysfunction (POCD) is a severe complication of cardiopulmonary bypass (CPB) and has common characteristics such as acute cognitive dysfunction, impaired memory, and inattention. Mesenchymal stem cells (MSCs) are multipotent cells that have therapeutic potentials mainly through paracrine action via secreting growth factors and cytokines. Exosomes are one of the important paracrine factors and have been reported as potential cell-free therapy for the treatment of autoimmune and central nervous system disorders. In this study, we examined exosomes derived from antler MSCs (AMSCs) of POCD rats after CPB and evaluated their potential regulatory mechanisms. AMSC-derived exosomes reduced neurological damage and brain damage and prevent apoptosis in CPB rats. Furthermore, AMSC-derived exosomes were found to reduce hippocampal neuronal apoptosis and the expression of TLR2, TLR4, MyD88, and NF-κB in CPB rats. However, the above effects of AMSC-derived exosomes on CPB rats were abolished partially by toll-like receptor 2/4 (TLR2/TLR4) agonist (LPS-EB). In conclusion, AMSC-derived exosomes can improve cognitive function in CPB rats through inhibiting the TLR2/TLR4 signaling pathway.