Triphenyl phosphate-induced macrophages dysfunction by activation TLR4-mediated ERK/NF-κB pathway.

Triphenyl phosphate (TPHP) is one of the most widely used organic phosphorus flame retardants and is ubiquitous in the environment. Studies have been reported that TPHP may lead to obesity, neurotoxicity and reproductive toxicity, but its impact on the immune system is almost blank. The present study was aimed to investigate the potential immunotoxicity of TPHP on macrophages and its underlying mechanism. The results demonstrated for the first time that TPHP (12.5, 25, and 50 µM)-induced F4/80+ CD11c+ phenotype of RAW 264.7 macrophages, accompanied by increased mRNA levels of inflammatory mediators, antigen-presenting genes (Cd80, Cd86, and H2-Aa), and significantly enhanced the phagocytosis of macrophage. Meanwhile, TPHP increased the expression of Toll-like receptor 4 (TLR4), and its co-receptor CD14, leading to significant activation of the downstream ERK/NF-κB pathway. However, co-exposure of cells to TAK-242, a TLR4 inhibitor, suppressed TPHP-induced F4/80+ CD11c+ phenotype, and down-regulated inflammatory mediators and antigen-presentation related genes, via blocked the TLR4/ERK/NF-κB pathway. Taken together, our results suggested that TPHP could induce macrophage dysfunction through activating TLR4-mediated ERK/NF-κB signaling pathway, and it may be the potential reason for health-threatening consequences.

Effects of sleep duration and sleep quality in early pregnancy and their interaction on gestational diabetes mellitus.

PURPOSE: To examine the association of sleep duration and quality in early pregnancy with gestational diabetes mellitus (GDM), and explore their interaction effect on GDM. METHODS: Participants from 2 hospitals were enrolled in this case-control study between April 2018 and November 2020. Sleep duration and quality were measured using the Pittsburg Sleep Quality Index (PSQI). RESULTS: A total of 1300 participants (396 GDM and 904 controls) were included. After adjusting for potential confounders, higher global PSQI scores or poor sleep quality were associated with GDM with odds ratios of 1.13 (95% CI 1.07, 1.19, p < 0.001) and 1.75 (95% CI 1.29, 2.38, p < 0.001), respectively; sleep duration < 7 h, 9-9.9 h and ≥ 10 h were all associated with increased GDM with odds ratios of 4.28 (95% CI 2.51, 7.31, p < 0.001), 1.69 (95% CI 1.20, 2.39, p = 0.003), and 4.42 (95% CI 3.01, 6.50, p < 0.001), respectively. In the stratified analysis based on sleep duration, the effect of poor sleep quality on GDM in the < 7 h group (OR 5.47, 95% CI 2.57, 11.64, p < 0.001) was much stronger than that in the 7-8.9 h group (OR 1.24, 95% CI 0.81, 1.91, p = 0.327), and the p value of the interaction was 0.011. CONCLUSIONS: Poor sleep quality and short or long sleep duration in early pregnancy were all associated with GDM, and an interaction effect between short sleep duration and poor sleep quality on GDM was noted.

Analysis of Biodistribution and in vivo Toxicity of Varying Sized Polystyrene Micro and Nanoplastics in Mice.

Introduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly. Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 µL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated. Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies. Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.