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Background: The causal association of specific gut microbiota with dementia remains incompletely understood. We aimed to access the causal relationships in which one or more gut microbiota account for dementia. Method: Using data from the MiBioGen and FinnGen consortia, we employed multiple Mendelian randomization (MR) approaches including two-sample MR (TSMR), multivariable MR (MVMR), and Bayesian model averaging MR to comprehensively evaluate the causal associations between 119 genera and dementia, and to prioritize the predominant bacterium. Result: We identified 21 genera that had causal effects on dementia and suggested Barnesiella (OR = 0.827, 95%CI = 0.722–0.948, marginal inclusion probability [MIP] = 0.464; model-averaged causal estimate [MACE] = −0.068) and Allisonella (OR = 0.770, 95%CI = 0.693–0.855, MIP = 0.898, MACE = −0.204) as the predominant genera for AD and all-cause dementia. Conclusions: These findings confirm the causal relationships between specific gut microbiota and dementia, highlighting the necessity of multiple MR approaches in gut microbiota analysis, and provides promising genera as potential novel biomarkers for dementia risk.

The causal association of circulating metabolites with dementia remains uncertain. We assessed the causal association of circulating metabolites with dementia utilizing Mendelian randomization (MR) methods. We performed univariable MR analysis to evaluate the associations of 486 metabolites with dementia, Alzheimer’s disease (AD), and vascular dementia (VaD) risk. For secondary validation, we replicated the analyses using an additional dataset with 123 metabolites. We observed 118 metabolites relevant to the risk of dementia, 59 of which were lipids, supporting the crucial role of lipids in dementia pathogenesis. After Bonferroni adjustment, we identified nine traits of HDL particles as potential causal mediators of dementia. Regarding dementia subtypes, protective effects were observed for epiandrosterone sulfate on AD (OR = 0.60, 95% CI: 0.48–0.75) and glycoproteins on VaD (OR = 0.89, 95% CI: 0.83–0.95). Bayesian model averaging MR (MR-BMA) analysis was further conducted to prioritize the predominant metabolites for dementia risk, which highlighted the mean diameter of HDL particles and the concentration of very large HDL particles as the predominant protective factors against dementia. Moreover, pathway analysis identified 17 significant and 2 shared metabolic pathways. These findings provide support for the identification of promising predictive biomarkers and therapeutic targets for dementia.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05–3.39), 1.62 (1.23–2.12), 2.06 (1.73–2.45), 1.20 (1.16–1.25), and 1.07 (1.05–1.08) per 10 μg/m3 increase in PM2.5, PM2.5–10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33–1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Abstract Aims/Introduction To investigate the efficacy/safety of dulaglutide once‐weekly monotherapy versus glimepiride in Chinese patients with type 2 diabetes. Materials and Methods This was a post‐hoc analysis of a Chinese randomized, double‐blind, non‐inferiority, phase III study. Patients (n = 572) with inadequate glycemic control received dulaglutide 1.5 mg (n = 189) or 0.75 mg (n = 194) once‐weekly or glimepiride (1–3 mg/day; n = 189) for 26 weeks. The primary objective of the study was to investigate the non‐inferiority of dulaglutide 1.5 mg versus glimepiride by the change from baseline to week 26 in glycated hemoglobin (non‐inferiority margin 0.4%). Results Dulaglutide 1.5 mg and 0.75 mg were non‐inferior (P

Many scientists are focusing on the apoptotic-necrotic or the necrotic-apoptotic switch and its mechanism, but little attention has been paid to the viable-apoptotic switch. Most of the techniques and methods used for detecting apoptosis are performed on fixed samples, yielding static information of specific time points. We have studied the viable-apoptotic switch in S-nitrosoglutathione (GSNO)-induced mouse thymocyte apoptosis in real-time by means of a novel technique, intensified charge coupled device (ICCD)-based real-time fluorescence micro-imaging, coupled with Annexin V-FITC labeling for phosphatidylserine (PS) translocation in cell membrane. We have successfully recorded the initiating time points (mostly at 2 h) of the viable-apoptotic switch in GSNO-initiated apoptosis, as well as shown the real-time differences between living and apoptotic thymocytes. These findings suggest that NO is also a switch molecule for the conversion from viable to apoptotic cell. Thymocytes cotreated by N-G-monomethyl-L-arginine acetate salt (L-NMMA) provide further evidence for this suggestion, as well as for the suggestion that L-NMMA prolongs the early stage of thymocyte apoptosis rather than strongly blocks it. [ABSTRACT FROM AUTHOR]