Yue Shi

Prolonged occupational exposure to oil mist particulate matter (OMPM) poses health risks, yet its neurotoxic effects and underlying mechanisms remain poorly understood. Here, OMPM generated from turbine oil commonly used in occupational labor environments was used to expose rats. The rats were divided into the control and OMPM groups. Following 42 days of exposure, a multidimensional assessment was performed using untargeted metabolomics, phosphoproteomics, behavioral testing, hematoxylin–eosin (HE) staining, transmission electron microscopy (TEM), colorimetric assays, enzyme-linked immunosorbent assay, and Western blotting (WB) to evaluate metabolic alterations, protein phosphorylation, and tissue integrity in the striatum. Integrated omics analyses revealed that differentially phosphorylated proteins and metabolites were remarkably enriched in dopaminergic synapse, Parkinson’s disease, and amphetamine addiction pathways (FDR < 0.05), with a regulatory axis involving L-tyrosine, tyrosine hydroxylase (TH), and dopamine (DA) identified. OMPM-exposed rats exhibited depression- and anxiety-like behaviors, alongside striatal pathological and ultrastructural damage. Biochemical analyses showed elevated malondialdehyde and reactive oxygen species levels; reduced superoxide dismutase, glutathione, and glutathione peroxidase activities and total antioxidant capacity; increased glutathione disulfide and inducible nitric oxide synthase expression; and decreased DA and L-tyrosine levels. Additionally, proinflammatory mediators (IL-1β, IL-6, TNF-α, MCP-1, and PGD₂) were significantly upregulated in the striatum. WB analysis further confirmed significant reductions in the relative phosphorylation levels of key regulators in dopaminergic and calcium signaling pathways, including CALM3, CaMK2b, GSK-3β, PRKCG, and TH. Collectively, these findings reveal critical molecular and biochemical alterations in the rat striatum following OMPM exposure and provide a mechanistic basis for understanding depression-like behaviors associated with prolonged OMPM exposure in occupational workers.

Polystyrene nanoplastics (PS-NPs) can cross the placenta and blood–brain barrier to accumulate in the fetal brain following inhalation or ingestion, raising concerns about PS-NPs-induced developmental neurotoxicity (DNT). However, current evidence regarding the mechanisms underlying PS-NPs-elicited DNT remains critically scarce. Given the inherent limitations of two-dimensional cell culture techniques, we employed a whole-brain organoid (WBO) model, which more faithfully recapitulates the dynamic changes and substantial alterations during the early development of the human nervous system, to investigate the PS-NPs-induced DNT. Developing WBOs were exposed to 50-nm PS-NPs at concentrations of 50 and 100 μg/mL. Additionally, we established an early developmental exposure model in neonatal rat for robust validation. The results revealed aberrant formation of the tissue architecture of neural epithelial buds in PS-NPs-exposed WBOs, accompanied by significant inflammatory responses and oxidative stress. Marked DNA damage and substantial activation of the TLR9/MyD88 pathway were observed in WBOs and in the cerebral cortex of neonatal rat, leading to significant upregulation of the excitotoxicity marker c-Fos and the excitatory synaptic marker NMDAR. In vitro assays revealed that melatonin treatment could efficiently counteract PS-NPs-mediated neuronal impairment, with both the reduced cell viability and excessive DNA damage induced by PS-NPs being restored to levels close to those of the control group. In conclusion, by establishing WBOs and early developmental exposure models in neonatal rat, we found that PS-NPs can induce DNA double-strand breaks, and activation of the TLR9 pathway mediates PS-NPs-induced excitotoxicity.

Copper oxide nanoparticles (CuO-NPs) induce neurological diseases, including neurobehavioral defects and neurodegenerative diseases. Direct evidence indicates that CuO-NPs induce inflammation in the central nervous system and cause severe neurotoxicity. However, the mechanism of CuO-NP-induced damage to the nervous system has rarely been studied, and the toxicity of different CuO-NP particle sizes and their copper ion (Cu²⁺) precipitation in microglia (BV2 cells) is worth exploring. Therefore, this study investigated CuO-NPs with different particle sizes (small particle size: S-CuO-NPs; large particle size: L-CuO-NPs), Cu²⁺ with equal molar mass (replaced by CuCl₂ [Equ group]), and Cu²⁺ precipitated in a cell culture solution with CuO-NPs (replaced by CuCl₂ [Pre group]), and examined the mechanism of action of each on BV2 microglia after co-culture for 12 h and 24 h. The activity of BV2 cells decreased, the morphology was damaged, and the apoptosis rate increased in all the exposed groups. Toxicity increased time- and dose-dependently, and was highest in the Equ group, followed by the S-CuO-NPs, L-CuO-NPs, and Pre groups, respectively. Subsequently, we investigated the mechanism of S-CuO-NP-induced cell injury, and revealed that S-CuO-NPs induced oxidative stress and inflammatory response and increased the membrane permeability of BV2 cells. Moreover, S-CuO-NPs reduced the ratio of p-CSF-1R/CSF-1R, p-PLCγ2/PLCγ2, p-extracellular signal-regulated kinase (ERK)/ERK, p-Nrf2/Nrf2, and Bcl-2/Bax protein expression in microglia, and elevated cleaved caspase-3 expression. The CSF-1R/PLCγ2/ERK/Nrf2 apoptotic pathway was activated. The downregulation of CX3CR1, CSF-1R, brain-derived neurotrophic factor (BDNF), and IGF-1 protein expression indicates impairment of the repair and protection functions of microglia in the nervous system. In summary, our results reveal that CuO-NPs promote an increase in inflammatory molecules in BV2 microglia through oxidative stress, activate the CSF-1R/PLCγ2/ERK/Nrf2 pathway, cause apoptosis, and ultimately result in neurofunctional damage to microglia.

Rapid social and industrial development has resulted in an increasing demand for fossil fuel energy, which increases particulate matter (PM) pollution. In this study, we employed a simple one-step electrospinning technique to fabricate polysulfone (PSF) fiber membranes for PM filtration. A 0.3 g/mL polymer solution with an N,N-dimethylformamide:tetrahydrofuran volume ratio of 3:1 yielded uniform and bead-free PSF fibers with a diameter of approximately 1.17 μm. The PSF fiber membrane exhibited excellent hydrophobicity and mechanical properties, including a tensile strength of 1.14 MPa and an elongation at break of 116.6%. Finally, the PM filtration performance of the PSF fiber membrane was evaluated. The filtration efficiencies of the membrane for PM_2.5 and PM_1.0 were approximately 99.6% and 99.2%, respectively. The pressure drops were 65.0 and 65.2 Pa, which were significantly lower than those of commercial air filters. Using this technique, PSF fiber membrane filters can be easily fabricated over a large area, which is promising for numerous air filtration systems.

Oil-mist particulate matter (OMPM) refers to oily particles with a small aerodynamic equivalent diameter in ambient air. Since the pathogenesis of pulmonary fibrosis (PF) has not been fully elucidated, this study aims to explore the potential molecular mechanisms of the adverse effects of exposure to OMPM at different concentrations in vivo and in vitro on PF. In this study, rats and cell lines were treated with different concentrations of OMPM in vivo and in vitro. Sirius Red staining analysis shows that OMPM exposure could cause pulmonary lesions and fibrosis symptoms. The expression of TGF-β1, α-SMA, and collagen I was increased in the lung tissue of rats. The activities of MMP2 and TIMP1 were unbalanced, and increased N-Cadherin and decreased E-Cadherin upon OMPM exposure in a dose-dependent manner. In addition, OMPM exposure could activate the TGF-β1/Smad3 and TGF-β1/MAPK p38 signaling pathways, and the differentiation of human lung fibroblast HFL-1 cells. Therefore, OMPM exposure could induce PF by targeting the lung epithelium and fibroblasts, and activating the TGF-β1/Smad3 and TGF-β1/MAPK p38 signaling pathways.