This study examines how sitting for a long time affects the prevalence of multiple metabolic diseases early in life, focusing on differences between men and women. Researchers analyzed data from over 21,000 young adults aged 18 to 45, finding that men who sat for more than 6 h a day showed a higher prevalence of metabolic diseases like obesity, high blood pressure, and diabetes. Specifically, sitting 6–8 h daily was associated with a 22

Lithium-ion batteries (LIBs) have become the core driving force for the global clean energy transition, and silicon carbide nanoparticles (SiC NPs) could be used anode material for lithium-ion batteries. With the rapid development of new energy industries, exposure to SiC NPs has increased significantly. However, the detrimental effects of SiC NPs on the heart and the underlying mechanisms remained largely unexplored. In the present study, we established a 5d exposure SiC NPs mice model through intratracheal instillation and mouse cardiomyocyte (HL-1 and primary cardiomyocytes) model. By single-nucleus RNA sequencing (snRNA-seq) analysis, we investigated the adverse reactions of heart and potential molecular mechanisms associated with SiC NPs exposure. Our results showed that short-term exposure of SiC NPs exposure could cause myocardial injury in mice. SiC NPs regulated METTL1 to reduce the m7G modification level and abundance of mt-tRNA-Trp, causing mitochondrial translational dysfunction, thereby inducing cardiomyocyte senescence. Supplementation of METTL1 alleviated SiC NPs-induced cellular senescence in vitro and in vivo. This study elucidated novel insights into the prevention and treatment of myocardial injury, while providing a solid experimental foundation for the development of mitochondrial-targeted therapeutic strategies.

Carbon black nanoparticles (CBNPs) have been identified as a potential contributing factor to idiopathic pulmonary fibrosis (IPF), though the specific mechanisms by which they induce endothelial-mesenchymal transition (EndMT) remain to be fully elucidated. The objective of this study was to ascertain whether CBNPs induce EndMT in pulmonary microvascular endothelial cells via PANoptosis-mediated mitochondrial transfer in alveolar macrophages (AMs). A mouse model of CBNPs inhalation exposure was established to evaluate pulmonary function, collagen deposition, and EndMT biomarkers. Co-culture systems of alveolar macrophages cells (M-HS) and pulmonary microvascular endothelial cells (MPVECs) were employed to investigate the process by which PANoptosis induced mitochondrial transfer. Key mechanisms were validated using Western blot, qPCR, molecular docking, co-immunoprecipitation, and bioinformatics analyses. The results showed that CBNPs exposure significantly impaired pulmonary function, induced collagen deposition, and activated EndMT. Conditioned media from CBNPs-treated M-HS triggered EndMT in MPVECs, mediated by the transfer of damaged mitochondria. Mechanistically, CBNPs suppressed the PINK1/Parkin mitophagy pathway, driving PANoptosis in M-HS and subsequent released of dysfunctional mitochondria. IFI27 was identified as a critical regulator of PANoptosis, directly binding to PINK1 to exacerbate mitochondrial dysfunction. Silencing IFI27 alleviated PANoptosis and mitochondrial transfer, reversing the EndMT phenotype in MPVECs. Collectively, these findings indicated that CBNPs induced EndMT in MPVECs via mitochondrial transfer, with the IFI27-PINK1 axis regulating this transfer process. This mitochondrial transfer represents as a novel therapeutic target for CBNPs-induced IPF. Moreover, modulating the process of mitochondrial transfer with IFI27 as a regulatory factor mitigate nanotoxicity-driven pulmonary fibrotic progression.

Polystyrene nanoplastics (PS-NPs), widespread environmental contaminant, have been increasingly recognized as a potential neurotoxic hazard. Neuroinflammation has been recognized as an important contributor to neurobehavioral dysfunction. However, the neuroinflammatory mechanisms underlying neurobehavioral dysfunction induced by PS-NPs have not been fully elucidated. Here, PS-NPs exposure induced depression-like behaviors in mice, suggesting adverse effects on neurobehavioral function. Using both in vivo and in vitro models, we further investigated the role of glycolytic metabolism in PS-NPs–triggered neuroinflammation. PS-NPs exposure significantly enhanced glycolytic activity, which contributed to the amplification of inflammatory responses in microglia. Mechanistically, PS-NPs upregulated N-acetyltransferase 10 (NAT10) expression, leading to increased N⁴-acetylcytidine (ac⁴C) modification of glycolytic transcripts, including Slc2a1 and Pdk1, thereby promoting glycolysis and sustaining inflammatory activation. Moreover, PS-NPs exposure elevated hypoxia-inducible factor-1α (HIF-1α) levels, which in turn transcriptionally induced NAT10 expression. This study identifies a HIF-1α-NAT10-ac⁴C axis that drives glycolytic reprogramming and amplifies neuroinflammation. Our results provided mechanistic insight into the neurotoxic effects of PS-NPs and identify NAT10-mediated RNA acetylation as a potential regulatory target involved in neurobehavioral dysfunction induced by PS-NPs.

Air pollution represents the greatest global environmental risk to human health, particularly regarding pulmonary fibrosis. Among atmospheric pollutants, airborne fine particulate matter (PM2.5) contributes most significantly to global mortality and disease burden. The epithelial-mesenchymal transition (EMT) constitutes a critical process in PM2.5-induced pulmonary fibrosis, concomitant with iron deposition and disrupted lipid peroxide metabolism. We found that PM2.5-induced ferroptosis contributes to EMT in lung tissue of mice after PM2.5 exposure. An in vitro macrophage-epithelial cell co-culture model demonstrated that exosomes from PM2.5-exposed macrophage induced ferroptosis, thereby driving EMT in epithelial cells. Pharmacological inhibition of the HO-1, which is involved in ferroptosis regulation significantly reversed the EMT alterations. Crucially, miR-218-5p was identified as a potential macrophage-derived exosomal miRNA targeting HO-1 to mediate ferroptosis-driven EMT in epithelial cells. Furthermore, engineered exosomes encapsulating miR-218-5p were constructed and administered via nebulization to alleviate PM2.5-induced pulmonary fibrosis in mice. In summary, this work provides experimental evidence supporting a targeted delivery strategy against PM2.5-induced pulmonary fibrosis.

Ambient fine particulate matter (PM2.5) was recognized as one of the most pressing environmental challenges confronting public health. There was a strong association between PM2.5 and pulmonary vascular diseases, the primary feature of which was pulmonary vascular remodeling. However, the underlying mechanisms by which PM2.5 induces pulmonary vascular remodeling have not been clarified. To address this gap, we established an environmental PM2.5-exposed mouse model and an in vitro cell model. Bioinformatics-based approaches were employed to identify potential regulators associated with pulmonary vascular remodeling, followed by an investigation into their potential roles in regulating pulmonary arterial function. Our results showed that PM2.5 exposure induced elevated pulmonary artery pressure and increased pulmonary artery wall thickness in mice. PM2.5 exposure induced cellular senescence in mouse pulmonary arterial endothelial cells (MPAECs) in vivo and in vitro, and PM2.5 treatment promoted mitochondrial dysfunction in MPAECs. Next, we used bioinformatics methods and experimental validation to identify MSC as potential regulator for mitochondrial dysfunction. And overexpression of MSC alleviated mitochondrial dysfunction-associated senescence (MiDAS) induced by PM2.5. In the mechanism, as a transcription factor, MSC regulated its downstream target gene NDUFB3, thereby facilitating PM2.5-induced MIDAS. This study offered novel insights into the molecular mechanisms underlying PM2.5-induced pulmonary vascular diseases and presented strategies for the precise intervention of pulmonary vascular injury triggered by atmospheric environmental factors.

Fine particulate matter (PM2.5), as a widespread environmental pollutant, is closely associated with cardiovascular diseases. The adverse effects of PM2.5 on the cardiovascular system and the molecular mechanisms driving PM2.5-aggravated atherosclerosis remain incompletely understood. In this study, in vivo and in vitro PM2.5 exposure models were established to explore the relevant pathogenic mechanisms. Male ApoE⁻/⁻ mice were randomly divided into three groups: filtered air(FA) group, unfiltered air(UA) group, and concentrated PM2.5 air(CA) group. For in vitro experiments, mouse aortic vascular smooth muscle cells were exposed to PM2.5 at concentrations of 0, 25, 50, and 100 μg/ml, meanwhile,group control was set up, DRP1 inhibitor Mdivi-1 and ferroptosis inhibitor Fer-1 were used to intervention, and PINK1 knockdown cell model was constructed. Aortic vascular function was evaluated via ultrasonography after exposure. Histopathological changes, collagen deposition, and lipid accumulation in arterial tissues and cells were evaluated via HE staining, Masson staining, Oil Red O, and BODIPY staining, respectively. Immunofluorescence and Western blot were applied to analyze the expression of related proteins in the arterial wall. The results demonstrated that PM2.5 exposure accelerated atherosclerosis progression and VSMC phenotypic switching.PM2.5 exposure upregulated mitochondrial fission proteins and downregulated fusion proteins, with DRP-1 as a critical regulatory molecule. PM2.5 specifically activated PINK1/Parkin-mediated mitophagy rather than the FUNDC1 pathway. PINK1 knockdown markedly attenuated pro-ferroptotic signaling. Mdivi-1 intervention alleviated PM2.5-induced excessive mitophagy, upregulated pro-ferroptotic signaling and phenotypic switching of VSMC. Fer-1 treatment also efficiently inhibited VSMC phenotypic switching.The results of this study demonstrate that DRP1-driven PINK1/Parkin- mediated mitophagy and inducing pro-ferroptotic signaling to promote the phenotypic switching of VSMCs in PM2.5-aggravated atherosclerosis, These findings provide new insights into the pathogenesis of environmental atherosclerosis and potential targets for therapeutic intervention.

Accumulating evidence indicates that maternal exposure to carbon black nanoparticles (CBNPs) during gestation can induce multiple system abnormalities in offspring, whereas its potential mechanism in respiratory disease is still largely unknown. In order to explore the effect of maternal exposure to CBNPs on offspring’s lung and latent pathogenesis, we respectively established in vivo model of pregnant rats exposed to CBNPs and ex vivo model of lung epithelial cells treated with pups’ serum of pregnant rats exposed to CBNPs. After maternal exposure to CBNPs, epithelial-mesenchymal transition (EMT) and fibrosis levels increased as a result of DDRGK1-mediated reticulophagy upregulated in offspring’s lung. DDRGK1 as FAM134B’s cargo bound with FAM134B to mediate reticulophagy. Transcription factor “SP1” positively regulated DDRGK1 gene expression by binding to its promoter. Furthermore, the upregulation of NSUN2 elevated m5C methylation of SP1 mRNA and the protein level of SP1 subsequently increased through Ybx1 recognizing and stabilizing m5C-methylated SP1 mRNA, followed by the increased levels of reticulophagy and fibrosis in lung epithelial cells treated with offspring’s serum of matrix exposed to CBNPs during gestation. In conclusion, NSUN2/Ybx1/m5C-SP1 axis promoted DDRGK1-mediated reticulophagy, which played an important role in EMT-induced fibrosis in offspring’s lung tissue after maternal exposure to CBNPs during gestation.

Volatile organic compounds (VOCs) are widespread indoor gaseous pollutants that are associated with vascular diseases. However, due to methodological limitations, the underlying mechanisms of VOC-induced aortic fibrosis remains unclear. To address this gap, we established a real-world indoor renovation VOC inhalation mouse model and used an innovative ex vivo biosensor assay with endothelial cells to respond to serum derived from VOC exposed mice, exploring the adverse health outcomes of total VOCs on the aorta and its potential mechanisms. The ex vivo biosensor assay confirmed that VOCs triggered phenotypic transformation of aortic smooth muscle cells via epigenetic changes in aortic endothelial cells. Mechanistically, VOCs elevated mitochondrial DNA (mtDNA) methylation by upregulating DNMT1, leading to mtDNA leakage and subsequent activation of the cGAS-STING inflammatory pathway. By integrating real-world indoor VOC exposure with mechanistic cellular analysis, this ex vivo biosensor assay offers a physiologically relevant model to elucidate the systemic vascular toxicity of complex environmental mixtures. Overall, this study revealed the molecular mechanism of indoor VOC-induced aortic fibrosis based on increased mtDNA methylation in aortic endothelial cells, which mediated the phenotypic transformation of aortic smooth muscle cells. mtDNA methylation may serve as a potential target for preventing aortic fibrosis or alleviating symptoms in affected patients. Our study highlights the urgent need for improved VOC monitoring in indoor environments and provides strategies for more precise environmental risk assessments.

Inhalation of silica nanoparticles (SiNPs) triggers progressive pulmonary fibrosis, a pathological process closely associated with macrophage polarization. However, its underlying molecular mechanisms have not been fully elucidated. To elucidate the pathogenic mechanisms, we developed both an mice model of SiNPs-induced pulmonary fibrosis coupled with an indirect co-culture model of RAW264.7 and NIH/3T3 cells. Our findings demonstrated that SiNPs not only promoted macrophage M1 polarization but also led to pulmonary fibrosis. In the indirect co-culture model, M1-polarized RAW264.7 cells induced by SiNPs significantly upregulated collagen I and α-SMA expression in NIH/3T3 cells through enhanced secretion of cytokines IL-6 and TNF-α. Mechanistic investigations uncovered that SiNPs markedly augmented endoplasmic reticulum (ER) stress in RAW264.7 cells, as evidenced by activation of the protein kinase R-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP)/HMG-CoA reductase degradation protein 1 (HRD1) axis. Bioinformatics mining molecular docking and Co-immunoprecipitation (Co-IP) assays demonstrated that HRD1 directly binds STBD1. Pharmacological inhibition of ER stress significantly attenuated M1 polarization in RAW264.7 cells, and subsequent fibrotic markers expression in NIH/3T3 cells via suppression of STBD1-mediated glycophagy activation. Genetic inhibition of glycophagy through STBD1 knockdown effectively reversed both ER stress-driven M1 polarization in RAW264.7 cells and fibrotic markers in NIH/3T3 cells. These findings collectively establish a novel mechanistic paradigm wherein ER stress-mediated glycophagy plays a pivotal role in driving macrophage M1 polarization during SiNPs-induced pulmonary fibrosis.

AIM:This study investigated the factors influencing the mental health of rural doctors in Hebei Province, to provide a basis for improving the mental health of rural doctors and enhancing the level of primary health care. BACKGROUND:The aim of this study was to understand the mental health of rural doctors in Hebei Province, identify the factors that influence it, and propose ways to improve their psychological status and the level of medical service of rural doctors. METHODS:Rural doctors from 11 cities in Hebei Province were randomly selected, and their basic characteristics and mental health status were surveyed via a structured questionnaire and the Symptom Checklist-90 (SCL-90). The differences between the SCL-90 scores of rural doctors in Hebei Province and the Chinese population norm, as well as the proportion of doctors with mental health problems, were compared. Logistic regression was used to analyse the factors that affect the mental health of rural doctors. RESULTS:A total of 2593 valid questionnaires were received. The results of the study revealed several findings: the younger the rural doctors, the greater the incidence of mental health problems (OR = 0.792); female rural doctors were more likely to experience mental health issues than their male counterparts (OR = 0.789); rural doctors with disabilities and chronic diseases faced a significantly greater risk of mental health problems compared to healthy rural doctors (OR = 2.268); rural doctors with longer working hours have a greater incidence of mental health problems; and rural doctors with higher education backgrounds have a higher prevalence of somatization (OR = 1.203). CONCLUSION:Rural doctors who are younger, male, have been in medical service longer, have a chronic illness or disability, and have a high degree of education are at greater risk of developing mental health problems. Attention should be given to the mental health of the rural doctor population to improve primary health care services.

The widespread application of silica nanoparticles (SiNPs) presents potential health risks to humans, particularly leading to severe pulmonary fibrosis. Macrophage polarization is essential in SiNPs-induced pulmonary fibrosis. However, the underlying molecular mechanisms have not been fully elucidated. Recent studies have indicated that lactylation significantly influences macrophage polarization. In this study, we established an inflammatory-stage pulmonary fibrosis mouse model by intratracheal instillation of SiNPs over 28 days, revealing concurrent enhancement of macrophage M1 polarization and histone lactylation. In vitro experiments demonstrated that SiNPs drove RAW264.7 cells polarization to M1 type via H3K18 lactylation (H3K18la), accompanied by elevating IL-6 and TNF-α secretion. These cytokines were shown to upregulate the collagen I and α-SMA expression in NIH3T3 cells. Integrated CUT&Tag and RNA-seq analyses identified direct targeting of NOS2 gene-a key biomarker of macrophage M1 polarization by H3K18la. Notably, SiNPs downregulated SIRT3 expression, which enhanced H3K18la levels through dual mechanisms: delactylase activity and modulation of lactate metabolism. This SIRT3/H3K18la/NOS2 axis establishes a novel pathway driving macrophage M1 polarization in fibrotic microenvironments, positioning SIRT3 as a promising therapeutic target for intervening in SiNPs-induced pulmonary fibrosis.

Carbon black (CB) is a vital constituent of airborne pollutants, comprising diesel exhaust and fine particulate matter (PM2.5 ), as well as a prevalent manufacturing material. CB was known to cause pulmonary dysfunction and fibrosis. However, the detailed molecular mechanisms underlying fibrosis development are poorly understood. In this study, 18 C57BL/6 mice were randomized into two groups and exposed to CB and filtered air (FA) for 28 days, with 6 hr/day and 7 days per week exposure regimen, respectively. The human normal bronchial epithelial cell line (BEAS-2B) was subjected to CB treatment for 24 h in vitro , with CB concentrations in 0, 50, 100, and 200 mu g/mL. Our study indicated that exposure to CB resulted in a reduction in lung function and the development of pulmonary fibrosis in mice. Furthermore, our results showed cytoskeleton rearrangement and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells were happened, after CB exposure. Subsequent studies revealed that elevated expression of THBS2 after CB primarily contributed to the development of pulmonary fibrosis. The research findings from both in vivo and in vitro studies provided evidence that piR-713551 was involved in CB exposure-induced EMT by targeting the THBS2 gene and activating the beta-catenin pathway. Mechanically, piR-713551/PIWIL4 complex activated the THBS2 transcription by recruitment of histone demethyltransferase KDM4A to reduce H3K9me3 modification at the THBS2 gene promoter. Conclusively, our research showed that CB exposure could activate EMT and lead pulmonary fibrosis which was modulated by (c) 2025 The Research Center for Eco-Environmental Sciences, Chinese Academy of

Owing to the widespread use and improper emissions of carbon black nanoparticles (CBNPs), the adverse effects of CBNPs on human health have attracted much attention. In toxicological research, carbon black is frequently utilized as a negative control because of its low toxicity and poor solubility. However, recent studies have indicated that inhalation exposure to CBNPs could be a risk factor for severe and prolonged pulmonary inflammation and fibrosis. At present, the pathogenesis of pulmonary fibrosis induced by CBNPs is still not fully elucidated, but it is known that with small particle size and large surface area, CBNPs are more easily ingested by cells, leading to organelle damage and abnormal interactions between organelles. Damaged organelle and abnormal organelles interactions lead to cell structure and function disorders, which is one of the important factors in the development and occurrence of various diseases, including pulmonary fibrosis. This review offers a comprehensive analysis of organelle structure, function, and interaction mechanisms, while also summarizing the research advancements in organelles and organelle interactions in CBNPs-induced pulmonary fibrosis.

BACKGROUND:While short sleep duration is linked to higher risk of non-alcoholic fatty liver disease (NAFLD), the combined effects of sleep timing and sleep duration on NAFLD are less explored. METHODS:In this cross-sectional study of 39,471 participants from Beijing-Tianjin-Hebei region of China, self-reported sleep information and ultrasonography-diagnosed NAFLD were obtained from Jan 2018 to Jan 2020. Sleep timing was categorized based on sleep midpoint: early-type (before 2:00 AM), intermediate-type (2:00-2:30 AM), and late-type (after 2:30 AM). We used multivariable logistic regression to explore the relationship between sleep timing, duration, and NAFLD. We analyzed sleep midpoint and duration categorically and continuously, and conducted stratification analyses by age, sex, body mass index, hypertension, diabetes, and dyslipidemia. RESULTS:Intermediate-type (OR: 1.15, 95% confidence interval: 1.05-1.26) and late-type sleep timing (OR: 1.08, 1.00-1.16) were associated with higher NAFLD risk compared to early-type. Additionally, longer sleep duration was linked to lower risk (OR: 0.92, 0.90-0.95 per hour increase). Notably, intermediate to late-type sleepers with normal sleep duration (7 to <8 h) exhibited a 20% higher NAFLD risk compared to early-type sleepers with the same duration (OR: 1.20, 1.04-1.39). The increased NAFLD risk associated with intermediate to late sleep timing was particularly evident in men, hypertension, and prediabetes or diabetes participants. CONCLUSIONS:Intermediate to late sleep timing, even with normal sleep duration, is associated with increased NAFLD risk. These findings underscore the importance of considering both sleep timing and sleep duration for NAFLD prevention, especially in men and individuals with cardiometabolic conditions.

Metal exposure has been reported to be associated with metabolic syndrome (MetS), however, the evidence remains inconclusive, particularly in elderly individuals. From May to July 2016, serum levels of 16 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS) in 852 elderly individuals (>= 65 years) residing in Wuhan, China. Biological detection and disease recognition were based on individual surveys conducted during health check-ups. Spearman's rank correlation analysis was performed to identify the correlation among serum metals. The data were Ln-transformed to fit a normal distribution for further analyses. Linear and logistic regression were applied to explore the associations between metals and diseases. Restricted cubic spline (RCS) analysis was utilized to examine dose-response relationships. The Weighted Quantile Sum (WQS) score was applied to determine the empirical weights of each heavy metal in the context of their combined effect on metabolic diseases. The prevalence of MetS, hypertension, diabetes, and hyperlipidemia were 46.36 %, 68.90 %, 24.65 %, and 21.60 %, respectively. Serum metal mixture was positively associated with the prevalence of MetS (OR = 1.92, 95 % CI: 1.30-2.82), hypertension (OR = 1.50, 95 % CI: 1.01-2.23), and diabetes (OR = 2.18, 95 % CI: 1.48-3.22). In single metal models, we found that serum zinc levels were associated with an increased risk of MetS, while rubidium had a protective effect against MetS. Interestingly, different metals had distinct effects on specific diseases in this study: lithium and barium were more likely to influence blood pressure, while selenium had a more significant effect on blood glucose. Lipids were more susceptible to the effects of zinc, selenium, and strontium. Platelet count (PLT) and lymphocyte count (LYM) mediated the association between selenium exposure and hyperlipidemia, while neutrophil count (NEU) mediated the relationship between serum rubidium exposure and MetS. Our findings offer valuable etiological insights into the relationship between serum heavy metals and the prevalence of MetS, suggesting that peripheral blood cells may play a mediating role in this association.

As an environmental pollutant, ambient fine particulate matter (PM2.5) was linked to cardiovascular diseases. The molecular mechanisms underlying PM2.5-induced extrapulmonary disease has not been elucidated clearly. In this study the ambient PM2.5 exposure mice model we established was to explore adverse effects of vessel and potential mechanisms. Long-term PM2.5 exposure caused reduced lung function and vascular stiffness in mice. And chronic PM2.5 induced migration and epithelial-mesenchymal transition (EMT) phenotype in BEAS-2B cells. After PM2.5 treatment, the circRNAs and mRNAs levels of exosomes released by BEAS-2B cells were detected by competing endogenous RNA (ceRNA) array, which contained 1664 differentially expressed circRNAs (DE-circRNAs) and 308 differentially expressed mRNAs (DE-mRNAs). By bioinformatics analysis on host genes of DE-circRNAs, vascular diseases and some pathways related to vascular diseases including focal adhesion, tight junction and adherens junction were enriched. Then, ceRNA network was constructed, and DE-mRNAs in ceRNA network were conducted functional enrichment analysis by Ingenuity Pathway Analysis, which indicated that hsa_circ_0012627, hsa_circ_0053261 and hsa_circ_0052810 were related to vascular endothelial dysfunction. Furthermore, it was verified experimentally that ExoPM2.5 could induce endothelial dysfunction by increased endothelial permeability and decreased relaxation in vitro. In present study, we investigated in-depth knowledge into the molecule events related to PM2.5 toxicity and pathogenesis of vascular diseases.

Air pollution has been recognized as a contributing factor to sleep disorders (SD), which have been correlated with an elevated susceptibility to a variety of human diseases. Nevertheless, research has not definitively established a connection between SD and interior decorative volatile organic compounds (ID-VOCs), a significant indoor air pollutant. In this study, we employed a mouse model exposed to ID-VOCs to explore the impacts of ID-VOCs exposure on sleep patterns and the potential underlying mechanism. Of the 23 key compositions of ID-VOCs identified, aromatic hydrocarbons were found to be the most prevalent. Exposure to ID-VOCs in mice resulted in SD, characterized by prolonged wake fullness and decreased sleep during the light period. ID-VOCs exposure triggered neuroinflammatory responses in the suprachiasmatic nucleus (SCN), with microglia activation leading to the overproduction of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and complement component 1q (C1q), ultimately inducing A1 astrocytes. Consequently, the upregulation of branched chain amino acid transaminase 2 (BCAT2) in A1 astrocytes resulted in elevated extracellular glutamate and disruption of the wake-sleep transition mechanism, which might be the toxicological mechanism of SD caused by ID-VOCs.

Background: Fine particulate matter (PM2.5) is noxious to female reproductive development and facilitates the occurrence of subsequent diseases. Early menopause is initiative factor of female aging. But due to the lack of historical exposure of PM2.5, we could not gain insight into the linkage between ambient PM2.5 exposure and early menopause. Methods: We conducted a community-based retrospective cross-sectional study and pooled 1173 postmenopausal women. The machine learning algorithm of LightGBM was processed to derive the historical concentrations of PM2.5 based on aerography of 1956-2022. The quantile g-computation and binary logistic regression were employed to estimate the mixed and single associations between PM2.5 and early menopause. Results: The visibility topped the most important feature for derivations of historical PM2.5 concentrations. The R-2 of 10-fold cross-validation and predictive capability during processing were all above 0.8. The prevalence of early menopause was 7.3 %. Each 10 mu g/m(3) PM2.5 increased the prevalence of early menopause during prior 2 years exposure (OR: 1.49, 95 %CI: 1.03-2.16) and spring and autumn (OR: 1.28, 95 %CI: 1.07-1.54). After adjusting the reverse effects of temperature, the prior 2 years exposure of PM2.5 remained positively associated with early menopause in the fourth quantile vs the first quantile (OR: 3.36, 95 %CI: 1.53-7.36) in the spring and autumn. The higher BMI (OR: 1.40, 95 %CI: 1.14-1.72), waistline (OR: 1.42, 95 %CI: 1.09-1.85) and unfavourable dietary habits of less meat (OR: 1.72, 95 %CI: 1.11-2.68), more fried food (OR: 2.39, 95 %CI: 1.15-4.99) elevated the prevalence of early menopause. Conclusions: The accurate environmental exposure assessment of historical PM2.5 vigorously promoted the researches on the relationship between PM2.5 and early menopause. It sounds the alarm on female infertility menace associated with particulate matter especially during the turbulent 2 years before menopause.