As a global problem, fine particulate matter (PM _2.5 ) really needs local fixes. Considering the increasing epidemiological relevance to anxiety and depression but inconsistent toxicological results, the most important question is to clarify whether and how PM _2.5 causally contributes to these mental disorders and which components are the most dangerous for crucial mitigation in a particular place. In the present study, we chronically subjected male mice to a real-world PM _2.5 exposure system throughout the winter heating period in a coal combustion area and revealed that PM _2.5 caused anxiety and depression-like behaviors in adults such as restricted activity, diminished exploratory interest, enhanced repetitive stereotypy, and elevated acquired immobility, through behavioral tests including open field, elevated plus maze, marble-burying, and forced swimming tests. Importantly, we found that dopamine signaling was perturbed using mRNA transcriptional profile and bioinformatics analysis, with Drd1 as a potential target. Subsequently, we developed the Drd1 expression-directed multifraction isolating and nontarget identifying framework and identified a total of 209 compounds in PM _2.5 organic extracts capable of reducing Drd1 expression. Furthermore, by applying hierarchical characteristic fragment analysis and molecular docking and dynamics simulation, we clarified that phenyl-containing compounds competitively bound to DRD1 and interfered with dopamine signaling, thereby contributing to mental disorders. Taken together, this work provides experimental evidence for researchers and clinicians to identify hazardous factors in PM _2.5 and prevent adverse health outcomes and for local governments and municipalities to control source emissions for diminishing specific disease burdens.

Ambient particulate matter (PM_2.5) is a potential risk factor for metabolic damage to the liver. Epidemiological studies suggest that elevated PM_2.5 concentrations cause changes in hepatic metabolism, but there is a lack of laboratory evidence. Here, we aimed to evaluate the effects of PM_2.5 exposure on liver metabolism in C57BL/6j female mice (10 months old) and to explore the mechanisms underlying metabolic alterations and differential gene expressions by combining metabolomics and transcriptomics analyses. The metabolomics results showed that PM_2.5 exposure notably affected the metabolism of amino acids and organic acids and caused hepatic lipid and bile acid accumulation. The transcriptomic analyses revealed that PM_2.5 exposure led to a series of metabolic pathway abnormalities, including steroid biosynthesis, steroid hormone biosynthesis, primary bile acid biosynthesis, etc. Among them, the changes in the bile acid pathway might be one of the causes of liver damage in mice. In conclusion, this study clarified the changes in liver metabolism in mice caused by PM_2.5 exposure through combined transcriptomic and metabolomic analyses, revealed that abnormal bile acid metabolism is the key regulatory mechanism leading to metabolic-associated fatty liver disease (MAFLD) in mice, and provided laboratory evidence for further clarifying the effects of PM_2.5 on body metabolism.

Particulate matter of size ≤ 2.5 μm (PM_2.5) is a critical environmental threat that considerably contributes to the global disease burden. However, accompanied by the rapid research progress in this field, the existing research on developmental toxicity is still constrained by limited data sources, varying quality, and insufficient in-depth mechanistic analysis. This review includes the currently available epidemiological and laboratory evidence and comprehensively characterizes the adverse effects of PM_2.5 on developing individuals in different regions and various pollution sources. In addition, this review explores the effect of PM_2.5 exposure to individuals of different ethnicities, genders, and socioeconomic levels on adverse birth outcomes and cardiopulmonary and neurological development. Furthermore, the molecular mechanisms involved in the adverse health effects of PM_2.5 primarily encompass transcriptional and translational regulation, oxidative stress, inflammatory response, and epigenetic modulation. The primary findings and novel perspectives regarding the association between public health and PM_2.5 were examined, highlighting the need for future studies to explore its sources, composition, and sex-specific effects. Additionally, further research is required to delve deeper into the more intricate underlying mechanisms to effectively prevent or mitigate the harmful effects of air pollution on human health.

The developmental toxicity and human health risks of triazole fungicides (TFs) have attracted worldwide attention due to the ability to enter the human body in a variety of ways. Nevertheless, the specific mechanism by which TFs exert remains incompletely understood. Given that retinoic acid (RA) signaling pathway are closely related to development, this study aimed to screen and identify developmentally disabled chemicals in commonly used TFs and to reveal the potential effects of TFs on developmental retardation through the RA signaling pathway in mouse embryonic stem cells (mESCs). Specifically, six typical TFs (myclobutanil, tebuconazole, hexaconazole, propiconazole, difenoconazole, and flusilazole) were exposed through the construction of an embryoid bodies (EBs)-based in vitro global differentiation models. Our results clarified that various TFs disturbed lineage commitment during early embryonic development. Crucially, the activation of RA signaling pathway, which alters the expression of key genes and interferes the transport and metabolism of retinol, may be responsible for this effect. Furthermore, molecular docking, molecular dynamics simulations, and experiments using a retinoic acid receptor alpha inhibitor provide evidence supporting the potential modulatory role of the retinoic acid signaling pathway in developmental injury. The current study offers new insights into the TFs involved in the RA signaling pathway that interfere with the differentiation process of mESCs, which is crucial for understanding the impact of TFs on pregnancy and early development.