Zhuge Xi

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.

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.

In this study, to screen for candidate markers of temozolomide (TMZ) resistance in glioblastoma, we artificially established TMZ drug-resistant glioblastoma (GBM) cell lines, U251-TMZ and U87-TMZ. In the U251-TMZ and U87-TMZ cell lines, we screened and analyzed differentially expressed proteins using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) differential proteomics. Compared with the U251 and U87 control cell lines, 95 differential proteins were screened in the U251-TMZ and U87-TMZ cell lines, of which 28 proteins were upregulated and 67 proteins were down-regulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the co-upregulated proteins showed that most of the differentially expressed proteins were located in the cytoplasm and were significantly upregulated in the biological processes related to vesicular transport in the intimal system and inflammatory response mediated by myeloid leukocytes. Seven candidates were identified as potential GBM markers of TMZ resistance. Combined with existing research findings, our study supports that UAP1L1 and BCKDK are promising potential markers of TMZ resistance in GBM. This is important for further understanding the molecular mechanisms that drive the development and enhancement of TMZ resistance.