Parental exposure to ambient fine particulate matter (PM2.5) has been associated with some of adverse health outcomes in offspring. The association between parental PM2.5 exposure and the development of metabolic syndrome (MetS) in offspring, and the effects of parental PM2.5 exposure on the susceptibility of offspring mice to PM2.5, has not been evaluated. The C57BL/6 parental mice (male and female mice) were exposed to filtered air (FA) or concentrated PM2.5 (PM) using Shanghai-METAS for a total of 16 weeks. At week 12 during the exposure, we allowed the parental male and female mice to breed offspring mice. The male offspring mice were divided into 4 groups and exposed to PM and FA again. The results showed that whether the parental mice were exposed to PM2.5 or not, the offspring mice exposure to PM2.5 appeared the elevation of blood pressure, insulin resistance, impairment of glucose tolerance, and dyslipidemia when compared to the offspring mice exposure to FA. More importantly, no matter what the offspring mice were exposed to, parental PM exposure overwhelmingly impacted the fasting blood insulin, homeostasis model assessment-insulin resistance, serous low-density lipoprotein cholesterol, and total cholesterol, splenic T helper cell 17 (Th17) and Treg cells, serous interleukin (IL)-17A, IL-6, and IL-10 in offspring mice. The results suggested that the parental exposure to air pollution might induce the development of MetS in offspring and might enhance the susceptibility of offspring to environmental hazards. The effects of parental PM exposure on offspring might be related to the changes of immune microenvironment.

High temperature exposure has been identified as a significant risk factor for respiratory diseases. However, causal evidence is needed to confirm the respiratory effects associated with heat exposure and to elucidate the underlying mechanisms. We conducted a randomized crossover trial among healthy adults in Shanghai, China. Participants received 2 h exposures to moderate-temperature (22 °C) and high-temperature (32 °C) conditions. Spirometry tests, fractional exhaled nitric oxide (FeNO) measurements, and collections of pharyngeal secretion and peripheral blood samples were performed before and after each session. Pharyngeal microbiota was analyzed via 16S rRNA amplicon sequencing. Serum biomarkers, including Clara cell protein (CC16) and Chitinase-3-like protein 1 (YKL-40) were also measured. Heat exposure was associated with decreases of 18.8% (95% CI: 4.7%, 32.8%) in peak expiratory flow, 9.6% (95% CI: 1.9%, 17.3%) in forced expiratory volume in the first second, and 8.8% (95% CI: 3.5%, 14.1%) in the ratio of forced expiratory volume in the first second and forced vital capacity. Corresponding increases were observed in FeNO (13.9%; 95% CI: 3.5%, 24.2%), serum CC16 (20.4%, 95% CI: 1.6%, 39.3%), and serum YKL-40 (17.1%, 95% CI: 3.9%, 30.2%). Additionally, three pathogenic pharyngeal bacteria exhibited a higher relative abundance. In summary, acute heat exposure was associated with reductions in lung function and airway injury. Potential biological mechanisms may involve lung epithelial damage, airway inflammation, and disruption of the airway microbiota.

Multimorbidity of cardiometabolic disease (CMD) and cancer is a growing but understudied global challenge in an aging world. Here, we perform multistate analysis in 429,555 UK Biobank participants to investigate transition patterns, identify multiomics signatures, and construct prediction models from baseline to single and multiple morbidities. During a median follow-up of 15 years, 105,903 participants develop single morbidity and 15,088 develop multimorbidity of CMD and cancer. Participants with multimorbidity have a 13%-33% higher mortality probability than those healthy or with single morbidity. In individuals living with multimorbidity, the development of CMD before cancer presents a higher mortality risk than the reverse order. Distinct and shared multiomics signatures are identified, with proteomics scores outperforming other omics in predicting disease trajectories (ΔC-statistic vs. base model: 0.03–0.14). This study reveals distinct transition patterns in CMD-cancer multimorbidity cluster and develops potentially useful prediction tools for supporting risk management if externally validated.

Objective: This study aimed to identify plasma exosomal microRNAs (miRNAs) associated with weight loss and type 2 diabetes (T2D) remission following low-calorie diet (LCD) intervention. Methods: A 6-month dietary intervention targeting T2D remission was conducted among individuals with T2D. Participants underwent a 3-month intensive weight loss phase consuming LCD (815–835 kcal/day) and a 3-month weight maintenance phase (N = 32). Sixteen participants were randomly selected for characterization of plasma-derived exosomal miRNA profiles at baseline, 3 months, and 6 months using small RNA sequencing. Linear mixed-effects models were used to identify differentially expressed exosomal miRNAs between responders and non-responders. Pathway enrichment analyses were conducted using target mRNAs of differentially expressed miRNAs. Logistic regression models assessed the predictive value of differentially expressed miRNAs for T2D remission. Results: Among the 16 participants, 6 achieved weight loss ≥10% and 12 achieved T2D remission. Eighteen exosomal miRNAs, including miR-92b-3p, miR-495-3p, and miR-452b-5p, were significantly associated with T2D remission and weight loss. Pathway analyses revealed enrichment in PI3K-Akt pathway, FoxO signaling pathway, and insulin receptor binding. The addition of individual miRNAs including miR-15b-3p, miR-26a-5p, and miR-3913-5p to base model improved the area under the curve values by 0.02–0.08 at 3 months and by 0.02–0.06 at 6 months for T2D remission. Conclusions: This study identified exosomal miRNAs associated with T2D remission and weight loss following LCD intervention. Several exosomal miRNAs might serve as valuable predictors of T2D remission in response to LCD intervention.

Background: Exosomal microRNAs (miRNAs) are key regulators of type 2 diabetes (T2D), yet their rapid response to caloric restriction remains undefined. Objective: To characterise plasma exosomal miRNA changes after one week of a low-calorie diet (LCD) in adults with T2D and determine whether these early shifts predict weight and glycaemic outcomes at 12 and 24 weeks. Methods: Sixteen adults with T2D consumed 820–840 kcal day⁻¹ for seven days. Plasma exosomes collected at baseline and day 7 underwent small-RNA sequencing. Differential expression was set at |log₂ fold change| > 1 with P < 0.05 (DESeq2). Target-gene enrichment, correlations with clinical biomarkers, and linear models relating week-1 miRNA changes to body-weight and glycaemic indices at follow-up were performed. Results: Participants lost 3.2 ± 0.9 kg in the first week (P < 0.001). Thirty-two miRNAs were differentially expressed: miR-122-5p, miR-3158-3p and miR-483-5p were down-regulated, whereas miR-126-5p and miR-454-3p were up-regulated. Target genes were enriched in PI3K-Akt, FoxO and endocrine-resistance pathways. Early rises in miR-1268a and miR-6770-3p correlated with interleukin-6 and tumour necrosis factor-α. An increase in miR-494-3p predicted larger HbA1c reductions at 12 weeks (β = −0.47; 95% CI: −0.67 to −0.21) and 24 weeks (β = −0.50; 95% CI: −0.76 to −0.18). Conversely, greater miR-362-5p elevations at week 1 were associated with smaller weight loss. Conclusions: A single week of LCD induces swift, pathway-linked shifts in plasma exosomal miRNAs in T2D. miR-494-3p and miR-362-5p emerge as promising early biomarkers for long-term glycaemic improvement and weight reduction, respectively.