Xi'an Medical University

BackgroundType 2 diabetes mellitus (T2DM) is often accompanied by cognitive dysfunction, though its underlying mechanisms remain unclear. Impaired glymphatic system function may contribute to cognitive impairment. Herein, we aimed to evaluate glymphatic activity in patients with T2DM using diffusion tensor imaging analysis along perivascular spaces (DTI-ALPS) and to explore its mediating role between white matter hyperintensities (Fazekas score) and Montreal Cognitive Assessment (MoCA) scores.MethodsThirty-eight patients with T2DM and 54 age- and sex-matched healthy controls underwent 3.0 T magnetic resonance imaging (MRI) and MoCA testing. The DTI-ALPS index was derived from diffusion tensor imaging data. Clinical variables included demographics, disease duration, metabolic indicators, and the homeostatic model assessment of insulin resistance (HOMA-IR) index. Group differences were analyzed using ANCOVA, correlations were assessed using Pearson analysis, and mediation analysis was used to evaluate the role of the DTI-ALPS index between Fazekas score and MoCA.ResultsThe DTI-ALPS index was significantly lower in patients with T2DM having cognitive impairment compared to both healthy controls and patients with T2DM without cognitive impairment (p < 0.001). MoCA scores positively correlated with the DTI-ALPS index (r = 0.860, p < 0.001), while HOMA-IR showed a negative correlation (r = −0.326, p < 0.05). Longer disease duration and higher Fazekas scores were associated with reduced DTI-ALPS index (p < 0.05). Mediation analysis indicated that the association between Fazekas score and MoCA was significantly and partially accounted for by the DTI-ALPS index in patients with T2DM (effect = −0.344, p < 0.05).ConclusionThe DTI-ALPS index was strongly associated with cognitive performance in patients with T2DM. Mediation analysis suggests that this relationship may reflect a mechanism in which impaired glymphatic function mediates the impact of white matter lesions on cognitive decline.

Heavy metal pollution is increasingly recognized, not merely as a source of static toxicity, but also as a driver of dynamic microbial regulation. At sublethal concentrations, these pollutants function as critical environmental cues that reshape microbial evolutionary trajectories. This review elucidates how low-dose heavy metals bypass acute cellular damage to instead engage bacterial chemical-sensing networks, systematically upregulating virulence factors, biofilm architecture, and the co-selection of antibiotic resistance. By leveraging the Caenorhabditis elegans (C. elegans) infection model (a platform defined by its evolutionarily conserved innate immune architecture), we dissect the tripartite interplay between environmental metal flux, bacterial pathogenic output, and host immunological defense. We synthesize empirical evidence from the C. elegans model to highlight how heavy metals modulate bacterial virulence and host defense mechanisms, thereby providing new insights into the indirect health risks of environmental pollutants and their implications for redefining public health exposure thresholds and infectious disease control in the Anthropocene.

No licensed drugs have been established for the treatment of nonalcoholic steatohepatitis (NASH). Therefore, we aimed to explore the effect of Yes-associated protein (YAP) on NASH to provide a therapeutic target. We constructed a mouse model of NASH, consuming either a methionine-choline deficient (MCD) or Gubra Amylin NASH (GAN) diet. Hepatocyte-specific YAP knockout (YAPΔHep) mice were introduced to investigate the function of hepatocyte YAP in NASH. Furthermore, detailed mechanisms were clarified using AML12 cells. Adeno-associated virus (AAV)-mediated hepatocyte YAP overexpression was used to observe the therapeutic efficacy in mice with NASH. Hepatic YAP protein levels were increased in NASH models. The YAP deletion reduced hepatic steatosis and exacerbated hepatic inflammation and fibrosis. However, YAP overexpression leads to the opposite NASH phenotype. Furthermore, the MCD or GAN diet-fed YAPΔHep mice also exhibited a favorable hepatic steatosis phenotype with exacerbated inflammation and fibrosis in the liver. Conversely, hepatocyte-specific YAP or YAP (5S) overexpression led to an almost complete reversal of hepatic pathologies. Mechanistically, hepatocyte-specific PCSK9 knockdown effectively reversed NASH progression in YAPΔHep mice. Furthermore, the oncostatin M (OSM)-JAK2-STAT3 axis was involved in the YAP-mediated regulation of PCSK9. Notably, AAV8-mediated YAP overexpression in the hepatocyte improved NASH in mice. Our findings demonstrate that hepatocyte YAP mitigates NASH severity by increasing PCSK9 expression via the OSM-JAK2-STAT3 pathway independent of lipid accumulation. Therefore, hepatocyte YAP may be a promising target for the management of NASH.

Patients with chronic kidney disease (CKD) frequently experience constipation, often linked to gut microbiota disruptions. We hypothesized that constipation is not merely a comorbidity but a driver of adverse outcomes through a specific host-microbial metabolic axis. Employing a multi-cohort design for evidence triangulation, we first employed a large U.S. database and mortality data up to 31 December 2019 to investigate the association between constipation and overall mortality in patients with CKD using weighted Cox proportional hazards models. To explore potential microbial and metabolic mechanisms that could underlie such clinical observations, we then used genetic data from the independent FINRISK cohort to investigate causal relationships between specific gut microbiota, their metabolites, and CKD. In the observational cohort, we identified functional constipation as a potent, independent predictor of both all-cause (HR: 1.33; 95% CI: 1.11-1.58) and cardiovascular mortality. This association remained robust across sensitivity analyses and showed a distinct U-shaped dose-response relationship with stool frequency. In the causal inference phase, while the direct causal effect of constipation on CKD was not significant, MR identified a significant causal depletion of the genus Herbidospora driven by constipation. Further analyses revealed that Herbidospora exerts a protective effect against CKD. Crucially, mediation analysis demonstrated that phosphatidylcholine (14:0_18:2) [PC 14:0_18:2] metabolites mediate 12.5% of the protective pathway from Herbidospora to CKD. Constipation is a key and independent predictor of mortality in patients with CKD. We found that constipation leads to a reduction in the number of Herbidospora, thereby disrupting the protective function of the kidney. This is because PC (14:0_18:2) is lacking. This study emphasizes the importance of restoring this microbial metabolic axis as a novel therapeutic strategy for CKD.IMPORTANCEFor millions living with chronic kidney disease (CKD), a common issue such as constipation can be a hidden danger, increasing their mortality risk by over one-third. Our research uncovers why: an unhealthy gut, often indicated by constipation, lacks specific "good"" bacteria essential for producing a protective fat molecule. This natural molecule acts as a key, activating the kidney's own defense and repair systems. This discovery of a "gut-lipid-kidney" connection offers a groundbreaking new strategy: therapies aimed at restoring gut health and supplementing this key protective fat could provide a powerful new way to slow disease progression and improve survival in CKD patients.

Background/Objectives: Short video addiction (SVA) has become a matter of public health concern, impacting the well-being of college students. However, previous studies have largely treated SVA as a homogeneous phenomenon, overlooking the potential heterogeneity in addictive behaviors among individuals and their underlying mechanisms. This study aims to identify distinct SVA subtypes and explore the mediating role of inattention (IA) in the relationship between these subtypes and negative emotions. Methods: The present study recruited a sample of college students through a multicentre online survey conducted from January to August 2025. Latent profile analysis identified distinct SVA categories among college students, and further examination of the mediating role of IA between SVA and negative emotions (anxiety, depression) was undertaken. Results: Latent profile analysis stratified SVA into three cohorts: "Healthy short video use" (8.9%), "Short video dependence" (55.8%), and "Short video addiction" (35.3%). The subtypes differed in levels of IA, anxiety, and depression (p < 0.05), with IA functioning as the link between SVA and negative emotions. It is noteworthy that IA demonstrated a complete mediating effect in the anxiety model, thereby indicating that the adverse impact of SVA on mental health is predominantly mediated by impaired attention function. Conclusions: This study deepens the understanding of students' SVA from a heterogeneity perspective and provides empirical evidence for exploring the potential cognitive mechanisms through which SVA influences mental health. It is suggested that targeting attention function may hold great value in alleviating SVA-related psychological issues.