Emerging research has highlighted the significant role of the gut microbiota in atherosclerosis (AS), with microbiota‐targeted interventions offering promising therapeutic potential. A central component of this process is gut‐derived metabolites, which play a crucial role in mediating the distal functioning of the microbiota. In this study, a comprehensive microbiome‐metabolite analysis using fecal and serum samples from patients with atherosclerotic cardiovascular disease and volunteers with risk factors for coronary heart disease and culture histology is performed, and identified the core strain Bacteroides ovatus ( B. ovatus ). Fecal microbiota transplantation experiments further demonstrated that the gut microbiota significantly influences AS progression, with B. ovatus alone exerting effects comparable to volunteer feces from volunteers. Notably, B. ovatus alleviated AS primarily by restoring the intestinal barrier and enhancing bile acid metabolism, particularly through the production of indole‐3‐acetic acid (IAA), a tryptophan‐derived metabolite. IAA inhibited the TLR4/MyD88/NF‐κB pathway in M1 macrophages, promoted M2 macrophage polarisation, and restored the M1/M2 polarisation balance, ultimately reducing aortic inflammation. These findings clarify the mechanistic interplay between the gut microbiota and AS, providing the first evidence that B. ovatus , a second‐generation probiotic, can improve bile acid metabolism and reduce inflammation, offering a theoretical foundation for future AS therapeutic applications involving this strain.

The O‑linked β‑N‑acetylglucosamine (O‑GlcNAc) modification and autophagy are associated with diabetic myocardial injury, however, the molecular mechanisms between the two processes remain to be fully elucidated. The purpose of the present study was to elucidate the molecular regulation of autophagy by O‑GlcNAc‑modified synaptosomal‑associated protein 29 (SNAP29) in diabetic myocardial injury. A rat model of type I diabetes was established via intraperitoneal injection of streptozotocin (STZ; 55 mg/kg). Significant increases in the O‑GlcNAc modification and accumulation of the autophagy markers microtubule‑associated protein 1 light chain 3α II/I and P62, which suggest that autophagic flux is inhibited, were observed in rats 8 weeks following STZ induction. Subsequently, the selective O‑GlcNAcase inhibitor, thiamet G, increased the level of O‑GlcNAc modification, which further disrupted autophagic flux; deteriorated cardiac diastolic function, as indicated by an increased left ventricular filling peak velocity/atrial contraction flow peak velocity ratio shown by echocardiography; and exacerbated myocardial abnormalities, as characterized by cardiomyocyte disorganization and fat and interstitial fibrosis accumulation. By contrast, 6‑diazo‑5‑oxo‑L‑norleucine, an inhibitor of glucosamine fructose‑6‑phosphate aminotransferase isomerizing 1, acted as an O‑GlcNAc antagonist and reduced the level of O‑GlcNAc modification, which maintained autophagic flux and improved cardiac diastolic function. In vitro, high glucose (25 mM) was used to stimulate primary neonatal rat cardiomyocytes (NRCMs). Consistent with the myocardium of diabetic rats, it was also shown in the NRCMs that O‑GlcNAc modification of SNAP29 negatively regulated autophagic flux. The application of the short hairpin RNA interference lysosome‑associated membrane protein (LAMP2) and the autophagy inhibitor 3‑methyladenine demonstrated that high glucose inhibited autophagy‑mediated degradation rather than affected the initial stage of autophagy. Finally, co‑immunoprecipitation was used to determine the role of the O‑GlcNAc‑modified substrate protein SNAP29, which acted as an SNAP29‑syntaxin‑17 (STX17)‑vesicle‑associated membrane protein 8 (VAMP8) complex during disease progression. The present study is the first, to the best of our knowledge, to demonstrate that SNAP29 is an O‑GlcNAc substrate and that an increase in O‑GlcNAc‑modified SNAP29 inhibits SNAP29‑STX17‑VAMP8 complex formation, thereby inhibiting the degradation of autophagy and exacerbating myocardial injury in type I diabetic rats.

Objectives: Prolonged mechanical ventilation (PMV) is a common complication following cardiac surgery linked to unfavorable patient prognosis and increased mortality. This study aimed to search for the factors associated with the occurrence of PMV after valve surgery and to develop a risk prediction model. Methods: The patient cohort was divided into two groups based on the presence or absence of PMV post-surgery. Comprehensive preoperative and intraoperative clinical data were collected. Univariate and multivariate logistic regression analyses were employed to identify risk factors contributing to the incidence of PMV. Based on the logistic regression results, a clinical nomogram was developed. Results: The study included 550 patients who underwent valve surgery, among whom 62 (11.27%) developed PMV. Multivariate logistic regression analysis revealed that age (odds ratio [OR] = 1.082, 95% confidence interval [CI] = 1.042–1.125; P < 0.000), current smokers (OR = 1.953, 95% CI = 1.007–3.787; P = 0.047), left atrial internal diameter index (OR = 1.04, 95% CI = 1.002–1.081; P = 0.041), red blood cell count (OR = 0.49, 95% CI = 0.275–0.876; P = 0.016), and aortic clamping time (OR = 1.031, 95% CI = 1.005–1.057; P < 0.017) independently influenced the occurrence of PMV. A nomogram was constructed based on these factors. In addition, a receiver operating characteristic (ROC) curve was plotted, with an area under the curve (AUC) of 0.782 and an accuracy of 0.884. Conclusion: Age, current smokers, left atrial diameter index, red blood cell count, and aortic clamping time are independent risk factors for PMV in patients undergoing valve surgery. Furthermore, the nomogram based on these factors demonstrates the potential for predicting the risk of PMV in patients following valve surgery.