Chinese Center For Disease Control and Prevention

The pathogenesis of type 2 diabetes (T2DM) remained to be fully understood. Meanwhile, exosome have shown its potential to further advance diabetes research as a rich source of biomarkers. This study aims to explore the proteomic profiles of circulating plasma exosomes in individuals with varying glucose statuses and offer potentially new perspective on the pathogenesis of T2DM. Participants with different glucose status were recruited according to the diagnostic criteria of the American diabetes association. Plasma exosomes were collected and went through data independent acquisition mass spectrometry quantitative proteomics analysis. Differential proteins identified through pairwise group comparisons underwent further analysis like protein-protein interaction (PPI) and gene ontology (GO) to reveal their functions and interactions. A total of 75 participants (25 euglycemia; 25 prediabetes; 25 diabetes) were included in this study. Principal coordinates analysis showed that the proteomic patterns of exosomes in groups with prediabetes and diabetes exhibited certain similarities, contrasting with those in euglycemic individuals. From pairwise differential protein comparison, 32 proteins were selected for PPI and functional analysis, of which 7 were deemed significant within the network. GO annotations highlighted a close link between immunity and T2DM. Local STRING clustering, Reactome and KEGG pathway analysis all indicated great significance of complement and coagulation cascades. The proteomic patterns of exosomes in groups with different glucose levels exhibited that even before overt diabetes manifests, the circulating exosome cargo signals immune and coagulatory activation distinct from normal physiology.

The transportation sector powered by fossil fuels is a significant contributor to PM2.5 pollution. Systematic evaluation of traffic-related PM2.5 on acute coronary syndrome (ACS) onset is not yet characterized, and the health benefits of reduced traffic-related PM2.5 and evidence-based mitigation strategies are currently absent. We investigated the association of ACS onset with short-term traffic-related PM2.5 exposure in a nationwide time-stratified case-crossover study, using 627,828 ACS cases extracted from the China Cardiovascular Association. We evaluated the risks of ACS onset associated with traffic-related PM2.5, calculated the attributable onsets, and then conducted cluster analysis using the K-means algorithm to identify priority cities for emission reduction. We found a robust association between traffic-related PM2.5 and ACS onset, i.e., an increased risk of 2.39% (95% CI: 1.79–3.00%) for same-day (lag 0) PM2.5 per 10 μg/m3 increase. The greatest health benefits due to a 1 μg/m3 PM2.5 reduction were achieved by traffic-related PM2.5, reaching 10,267 (95%CI: 4503–16,063) onsets per year. In addition, three obvious categories were clustered, and traffic-polluted cities were highlighted (cluster 2, not belonging to megacities), with high emissions and concentrations of traffic-related PM2.5. Therefore, intensified efforts to mitigate traffic-related PM2.5 emissions should be promoted, and the prioritization of emission reduction strategies in these traffic-polluted cities is imperative for safeguarding public health.

Dietary advanced glycation end products (AGEs) and chronic stress might be involved in psychiatric disorders. It remains unclear whether dietary AGEs and chronic stress work together to trigger anxiety and depression. Firstly, mice were subjected to dietary AGEs (12 weeks) combined with chronic restraint stress (weeks 9-12, with daily restraint in a 50-mL cylindrical plastic tube for 3-4 h), defined as CRA group. Combined exposure aggravated anxiety-like and depression-like behaviors, disrupted gut microbiota homeostasis, induced inflammation, shifted tryptophan (TRP) metabolism towards kynurenine (KYN) pathway, mainly characterized by elevated KYN and 3-hydroxykynurenine (3-HK), and induced ferroptosis in the hippocampus. Secondly, IDO1 inhibitor, 1-methyltryptophan (1-MT), restored the TRP-KYN pathway disturbance post CRA, and inhibited neuronal ferroptosis post CRA. Thirdly, the ferroptosis inhibitor ferrostatin-1 restored CRA-induced neuronal ferroptosis, but had no effect on the TRP-KYN pathway. KYN and 3-HK induced ferroptosis in the mouse hippocampal neuron cell line (HT22), consistent with in vivo experimental results. In conclusion, combined exposure may first disturb gut microbiota homeostasis, followed by intestinal inflammatory responses, subsequently triggering tryptophan towards kynurenine metabolism via the gut-brain axis. These pathological processes led to the abnormal accumulation of neurotoxic metabolites, i.e., KYN and 3-HK, within neurons, which then induced neuronal ferroptosis.