Atmospheric fine particulate matter (PM2.5) induces pulmonary fibrosis by regulating different cell fates via autophagy.

The presence of respiratory diseases demonstrates a positive correlation with atmospheric fine particulate matter (PM2.5) exposure. The respiratory system is the main target organ affected by PM2.5, and exposure to PM2.5 elevates the likelihood of developing pulmonary fibrosis (PF). In this study, lung epithelial cell (BEAS-2B) and fibroblast (NIH-3T3) were used as in vitro exposure models to explore the mechanisms of PF. PM2.5 exposure caused mitochondrial damage in BEAS-2B cells and increased a fibrotic phenotype in NIH-3T3 cells. Epithelial cells and fibroblasts have different fates after PM2.5 exposure due to their different sensitivities to trigger autophagy. Exposure to PM2.5 inhibits mitophagy in BEAS-2B cells, which hinders the removal of damaged mitochondria and triggers cell death. In this process, the nuclear retention of the mitophagy-related protein Parkin prevents it from being recruited to mitochondria, resulting in mitophagy inhibition. In contrast, fibroblasts exhibit increased levels of autophagy, which may isolate PM2.5 and cause abnormal fibroblast proliferation and migration. Fibrotic phenotypes such as collagen deposition and increased α-actin also appear in fibroblasts. Our results identify PM2.5 as a trigger of PF and delineate the molecular mechanism of autophagy in PM2.5 induced PF, which provides new insights into the pulmonary injury.

Multi-supervised bidirectional fusion network for road-surface condition recognition.

Rapid developments in automatic driving technology have given rise to new experiences for passengers. Safety is a main priority in automatic driving. A strong familiarity with road-surface conditions during the day and night is essential to ensuring driving safety. Existing models used for recognizing road-surface conditions lack the required robustness and generalization abilities. Most studies only validated the performance of these models on daylight images. To address this problem, we propose a novel multi-supervised bidirectional fusion network (MBFN) model to detect weather-induced road-surface conditions on the path of automatic vehicles at both daytime and nighttime. We employed ConvNeXt to extract the basic features, which were further processed using a new bidirectional fusion module to create a fused feature. Then, the basic and fused features were concatenated to generate a refined feature with greater discriminative and generalization abilities. Finally, we designed a multi-supervised loss function to train the MBFN model based on the extracted features. Experiments were conducted using two public datasets. The results clearly demonstrated that the MBFN model could classify diverse road-surface conditions, such as dry, wet, and snowy conditions, with a satisfactory accuracy and outperform state-of-the-art baseline models. Notably, the proposed model has multiple variants that could also achieve competitive performances under different road conditions. The code for the MBFN model is shared at https://zenodo.org/badge/latestdoi/607014079.

2D MoS2 Nanosheets Induce Ferroptosis by Promoting NCOA4-Dependent Ferritinophagy and Inhibiting Ferroportin.

The exposure of MoS2 nanosheets can cause cytotoxicity, which causes health risks and affects its medical applications. However, knowledge of the underlying molecular mechanisms remains limited. This study reports that MoS2 nanosheets induces ferroptosis in vivo and in vitro, which is caused by the nanosheet themselves rather than by the dissolved ions. MoS2 nanosheets induce ferroptosis in epithelial (BEAS-2B) and macrophage (RAW264.7) cells due to nuclear receptor coactivator 4 (NCOA4)-dependent excusive ferritinophagy and the inhibition of ferroportin-1 (FPN). In this process, most of the MoS2 nanosheets enter the cells via macropinocytosis and are localized to the lysosome, contributing to an increase in the lysosomal membrane permeability. At the same time, NCOA4-dependent ferritinophagy is activated, and ferritin is degraded in the lysosome, which generates Fe2+ .Fe2+ leaks into the cytoplasm, leading to ferroptosis. Furthermore, the inhibition of FPN further aggravates the overload of Fe2+ in the cell. It has also been observed that ferroptosis is increased in lung tissue in mouse models exposed to MoS2 nanosheets. This work highlights a novel mechanism by which MoS2 nanosheets induce ferroptosis by promoting NCOA4-dependent ferritinophagy and inhibiting FPN, which could be of importance to elucidate the toxicity and identify the medical applications of 2D nanoparticles.

Polystyrene micro(nano)plastics damage the organelles of RBL-2H3 cells and promote MOAP-1 to induce apoptosis.

The ubiquity of microplastics increases the exposure risks and health threats to humans. In this study, rat basophilic leukemia (RBL-2H3) cells were exposed to polystyrene particles (PS-particles) of 50 nm, 500 nm and 5 µm to investigate organelle damage and the mechanism of cell death. PS-particles induced oxidative stress, which in turn led to mitochondrial and lysosomal damage, arrested the cell cycle in the G0/G1 phase, and finally caused apoptosis. Anti-apoptotic genes (Bcl-2) were down regulated, and pro-apoptotic genes (Bax) and a key gene (caspase-3) in apoptosis were upregulated. The molecular mechanism of apoptosis was further explored via the combination of transcriptome sequencing, RT-qPCR verification and small interfering RNA (siRNA) technology. The modulator of apoptosis-1 (MOAP-1) was significantly upregulated, and apoptosis was abolished by knocking down MOAP-1. This finding clarifies that PS-particles promote MOAP-1 to induce apoptosis. Hence, PS-particles may promote the binding of MOAP-1 and Bax, which ultimately activates caspase-3 and causes apoptosis through the mitochondrial pathway. The 50-nm PS-particles resulted in the most serious mitochondrial damage and apoptosis. Eventually, PS-particles cause oxidative stress, damage organelles and induce apoptosis by promoting MOAP-1. Altogether, our study emphasizes the need to assess the cytotoxicity of micro(nano)plastics and helps to predict the health risks.

Cellular internalization and release of polystyrene microplastics and nanoplastics.

Microplastics and nanoplastics can accumulate in organisms after being ingested, be transported in the food web, and ultimately threaten human health. An understanding of the cellular internalization and release of micro(nano)plastics is important to predict their cytotoxicity. In this study, 50 nm, 500 nm and 5 µm polystyrene particles (PS50, PS500 and PS5000) were exposed to both model cell membranes and rat basophilic leukemia (RBL-2H3) cells. PS50 and PS500 absorb on the model membrane due to hydrophobic interactions and Van der Waals' forces, and may also penetrate the model membrane. PS50 and PS500 are internalized into living cells via both passive membrane penetration and active endocytosis. The passive membrane penetration is due to the partition of polystyrene particles in the water-phospholipid system. The endocytosis of PS50 occurs through the clathrin-mediated pathway, the caveolin-mediated pathway and macropinocytosis, but endocytosis of PS500 is mainly via the macropinocytosis. PS5000 cannot adhere to the cell membrane or be internalized into cells due to its large size and weak Brownian motion. The endocytosed PS50 and PS500 mainly accumulate in the lysosomes. The passively internalized PS50 and PS500 initially distribute in the cytoplasm not in lysosomes, but are transported to lysosomes with energy supply. PS50 and PS500 are excreted from cells via energy-free penetration and energy-dependent lysosomal exocytosis. The masses of the internalized PS50 inside the cells and the excreted PS50 outside the cells were both higher than the masses of PS500, indicating that the smaller particles are more easily enter or leave cells than do their larger counterparts. Our findings will contribute to the risk assessment of micro(nano)plastics and their safe application.