Background & aims: Emerging evidence supports ambient fine particulate matter (PM_2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM_2.5 exposure and investigate the underlying mechanism by which PM_2.5 modulates hepatic lipid metabolism. Methods: Both male and female C57BL/6 mice were randomly assigned to ambient PM_2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM_2.5 exposure-induced metabolic disorder. Results: Female mice were more susceptible than their male counterparts to ambient PM_2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM_2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM_2.5-exposed mice as well. In addition, exposure to PM_2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM_2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM_2.5-induced metabolic dysfunction. Conclusions: Ambient PM_2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

Silicosis is characterized by chronic lung inflammation and fibrosis, which are extremely harmful to human health. The pathogenesis of silicosis involves uncontrolled immune processes. Evidence supports that regulatory B cells (Bregs) produce negative regulatory cytokines, such as IL-10, which can negatively regulate immune responses in inflammation and autoimmune diseases. Our previous study found that IL-10-producing B cells (B10) were involved in the development of silica-induced lung inflammation and fibrosis of mice. However, little is known about the role of regulatory B cells in silicosis patients. In this study, we found that serum concentrations of IL-10 were significantly increased in silicosis patients by using protein array screening.We further determined that the frequency of IL-10-producing CD1dhiCD5+regulatory B cells, not IL-10-producing non-B lymphocytes, was significantly higher in silicosis patients compared to subjects under surveillance and healthy workers by flow cytometry. We also found that regulatory T cells (Tregs) and Th2 cytokines (IL-4, IL-5 and IL-13) were significantly increased in silicosis patients. Th1 cytokines (IFN-γ, IL-2 and IL-12) and inflammatory cytokines (IL-1β, IL-6 and TNF-α) were not significantly different between silicosis patients, subjects under surveillance and healthy workers. Our study indicated that IL-10-producing CD1dhiCD5+regulatory B cells might maintain Tregs and regulate Th1/Th2 polarization in silicosis patients, suggesting that IL-10-producing Bregs may play a critical role in modulating immune homeostasis in silicosis patients.

The consumption of disposable materials is booming with the rapid development of urbanization and industrialization, which may inevitably cause the release of toxic and harmful substances during use of them in daily life. This study was to estimate element levels such as Beryllium (Be), Vanadium (V), Zinc (Zn), Manganese (Mn), Cadmium (Cd), Chromium (Cr), Nickel (Ni), Cobalt (Co), Antimony (Sb), Barium (Ba), Lead (Pb), Iron (Fe), Copper (Cu), and Selenium (Se) in leachate and subsequently assess the health risk of exposure to those disposable products such as paper and plastic food containers. We found that a large amount of metals was released from disposable food containers in hot water, and the order of metal concentration is Zn > Ba > Fe > Mn > Ni > Cu > Sb > Cr > Se > Be > Pb > Co > V > Cd. Additionally, the hazard quotient (HQ) of metals in young adults were less than 1, and were decreased in the order of Sb > Fe > Cu > Be > Ni > Cr > Pb > Zn > Se > Cd > Ba > Mn > V > Co. Furthermore, the excess lifetime cancer risk (ELCR) results of Ni and Be indicated that chronic exposure to Ni and Be may have a non-negligible carcinogenic risk. These findings suggest that potential health risk of metals may exist for the individuals to use disposable food containers under high temperature environment.