Effects of nanoplastic exposure during pregnancy and lactation on neurodevelopment of rat offspring.

Microplastics have emerged as a prominent global environmental contaminant, and they have been found in both human placenta and breast milk. However, the potential effects and mechanisms of maternal exposure to microplastics at various gestational stages on offspring neurodevelopment remain poorly understood. This investigation delves into the potential neurodevelopmental ramifications of maternal exposure to polystyrene nanoplastics (PS-NPs) during distinct phases of pregnancy and lactation. Targeted metabolomics shows that co-exposure during both pregnancy and lactation primarily engendered alterations in monoamine neurotransmitters within the cortex and amino acid neurotransmitters within the hippocampus. After prenatal exposure to PS-NPs, fetal rats showed appreciably diminished cortical thickness and heightened cortical cell proliferation. However, this exposure did not affect the neurodifferentiation of radial glial cells and intermediate progenitor cells. In addition, offspring are accompanied by disordered neocortical migration, typified by escalated superficial layer neurons proliferation and reduced deep layer neurons populations. Moreover, the hippocampal synapses showed significantly widened synaptic clefts and diminished postsynaptic density. Consequently, PS-NPs culminated in deficits in anxiolytic-like behaviors and spatial memory in adolescent offspring, aligning with concurrent neurotransmitter and synaptic alterations. In conclusion, this study elucidates the sensitive windows of early-life nanoplastic exposure and the consequential impact on offspring neurodevelopment.

Selective bioaccumulation of polystyrene nanoplastics in fetal rat brain and damage to myelin development.

Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.

Bombyx mori voltage-dependent anion-selective channel induces programmed cell death to defend against Bombyx mori nucleopolyhedrovirus infection.

BACKGROUND: Voltage-dependent anion-selective channels (VDACs) serve as pore proteins within the mitochondrial membrane, aiding in the regulation of cell life and cell death. Although the occurrence of cell death is crucial for defense against virus infection, the function played by VDAC in Bombyx mori, in response to the influence of Bombyx mori nucleopolyhedrovirus (BmNPV), remains unclear. RESULTS: BmVDAC was found to be relatively highly expressed both during embryonic development, and in the Malpighian tubule and midgut. Additionally, the expression levels of BmVDAC were found to be different among silkworm strains with varying levels of resistance to BmNPV, strongly suggesting a connection between BmVDAC and virus infection. To gain further insight into the function of BmVDAC in BmNPV, we employed RNA interference (RNAi) to silence and overexpress it by pIZT/V5-His-mCherry. The results revealed that BmVDAC is instrumental in developing the resistance of host cells to BmNPV infection in BmN cell-line cells, which was further validated as likely to be associated with initiating programmed cell death (PCD). Furthermore, we evaluated the function of BmVDAC in another insect, Spodoptera exigua. Knockdown of the BmVDAC homolog in S. exigua, SeVDAC, made the larvae more sensitive to BmNPV. CONCLUSION: We have substantiated the pivotal role of BmVDAC in conferring resistance against BmNPV infection, primarily associated with the initiation of PCD. The findings of this study shine new light on the molecular mechanisms governing the silkworm's response to BmNPV infection, thereby supporting innovative approaches for pest biocontrol. © 2024 Society of Chemical Industry.

Studying the role of Bombyx mori molybdenum cofactor sulfurase in Bombyx mori nucleopolyhedrovirus infection.

Molybdenum cofactor sulfurase (MoCoS) is a key gene involved in the uric acid metabolic pathway that activates xanthine dehydrogenase to synthesise uric acid. Uric acid is harmful to mammals but plays crucial roles in insects, one of which is the immune responses. However, the function of Bombyx mori MoCoS in response to BmNPV remains unclear. In this study, BmMoCoS was found to be relatively highly expressed in embryonic development, gonads and the Malpighian tubules. In addition, the expression levels of BmMoCoS were significantly upregulated in three silkworm strains with different levels of resistance after virus infection, suggesting a close link between them. Furthermore, RNAi and overexpression studies showed that BmMoCoS was involved in resistance to BmNPV infection, and its antivirus effects were found to be related to the regulation of uric acid metabolism, which was uncovered by inosine- and febuxostat-coupled RNAi and overexpression. Finally, the BmMoCoS-mediated uric acid pathway was preliminarily confirmed to be a potential target to protect silkworms from BmNPV infection. Overall, this study provides new evidence for elucidating the molecular mechanism of silkworms in response to BmNPV infection and new strategies for the prevention of viral infections in sericulture.

Oil mistparticulate matter exposure induces hyperlipidemia-related inflammation via microbiota/ SCFAs/GPR43 axis inhibition and TLR4/NF-κB activation.

Metabolites produced by the human gut microbiota play an important role in fighting and intervening in inflammatory diseases. It remains unknown whether immune homeostasis is influenced by increasing concentrations of air pollutants such as oil mist particulate matters (OMPM). Herein, we report that OMPM exposure induces a hyperlipidemia-related phenotype through microbiota dysregulation-mediated downregulation of the anti-inflammatory short-chain fatty acid (SCFA)-GPR43 axis and activation of the inflammatory pathway. A rat model showed that exposure to OMPM promoted visceral and serum lipid accumulation and inflammatory cytokine upregulation. Furthermore, our research indicated a reduction in both the "healthy" microbiome and the production of SCFAs in the intestinal contents following exposure to OMPM. The SCFA receptor GPR43 was downregulated in both the ileum and white adipose tissues (WATs). The OMPM treatment mechanism was as follows: the gut barrier was compromised, leading to increased levels of lipopolysaccharide (LPS). This increase activated the Toll-like receptor 4 Nuclear Factor-κB (TLR4-NF-κB) signaling pathway in WATs, consequently fueling hyperlipidemia-related inflammation through a positive-feedback circuit. Our findings thus imply that OMPM pollution leads to hyperlipemia-related inflammation through impairing the microbiota-SCFAs-GPR43 pathway and activating the LSP-induced TLR4-NF-κB cascade; our findings also suggest that OMPM pollution is a potential threat to humanmicrobiota dysregulation and the occurrence of inflammatory diseases.

One-Step Fast Fabrication of Electrospun Fiber Membranes for Efficient Particulate Matter Removal.

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 PM2.5 and PM1.0 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.

PM2.5 triggers autophagic degradation of Caveolin-1 via endoplasmic reticulum stress (ERS) to enhance the TGF-ß1/Smad3 axis promoting pulmonary fibrosis.

Air pollution is highly associated with respiratory diseases. However, the influence and mechanism of particulate matter with aerodynamic equal to or less than 2.5 µm (PM2.5) in lung homeostasis remain unclear. Herein, we demonstrated the induction of pulmonary fibrosis (PF) by PM2.5 exposure. The animal model showed that PM2.5 exposure could activate the oxidative stress and inflammation response, promoting epithelial-mesenchymal transition and accumulation of collagen, high expression of pro-fibrotic factors, and pathological characteristics of fibrosis. The proteomic analysis indicated that PM2.5 exposure decreased the expression of caveolin-1 (Cav-1), and many differential proteins were enriched in the TGF-ß1/Smad, endoplasmic reticulum stress (ERS) and autophagy pathways. Combining in vivo and in vitro experiments, it was found that PM2.5 exposure could reduce Cav-1 protein levels and activate TGF-ß1/Smad3 signaling pathways through ERS and autophagy pathways, thereby inducing cell apoptosis and promoting pulmonary fibrosis. However, inhibiting ERS could alleviate the occurrence of autophagy, and blocking the autophagy system could increase the level of Cav-1 protein and inhibit TGF- ß 1/Smad3 signaling pathway to improve pulmonary fibrosis. Therefore, we demonstrated that the exposure of PM2.5 could enhance the ERS induced-autophagy-mediated Cav-1 degradation, thus activating the TGF-ß1/Smad3 axis to promote pneumonocytes apoptosis and overproduction of extracellular matrix (ECM), finally aggravating PF. Moreover, our findings revealed that intermittent exposure to high doses of PM2.5 was more toxic than continuous exposure to low dose.

Correction: Jia et al. Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice. Toxics 2023, 11, 127.

In the original publication [...].

Transcriptomic analysis of the fat body of resistant and susceptible silkworm strains, Bombyx mori (Lepidoptera), after oral treatment with fenpropathrin.

The widespread use of pyrethroid pesticides has brought serious economic losses in sericulture, but there is still no viable solution. The key to solving the problem is to improve silkworm resistance to pesticides, which depends on understanding the resistance mechanism of silkworms to pesticides. This study aimed to use transcriptomes to understand the underlying mechanism of silkworm resistance to fenpropathrin, which will provide a theoretical molecular reference for breeding pesticide-resistant silkworm varieties. In this study, the fat bodies of two strains with differential resistance after 12 h of fenpropathrin feeding were analyzed using RNA-Seq. After feeding fenpropathrin, 760 differentially expressed genes (DEGs) were obtained in the p50(r) strain and 671 DEGs in the 8y strain. The DEGs involved in resistance to fenpropathrin were further identified by comparing the two strains, including 207 upregulated DEGs in p50(r) and 175 downregulated DEGs in 8y. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these fenpropathrin-related DEGs are mainly enriched in the metabolism and transporter pathways. Moreover, 28 DEGs involved in the metabolic pathway and 18 in the transporter pathway were identified. Furthermore, organic cation transporter protein 6 (BmOCT6), a transporter pathway member, was crucial in enhancing the tolerance of BmN cells to fenpropathrin. Finally, the knockdown of the expression of the homologs of BmOCT6 in Glyphodes pyloalis (G. pyloalis) significantly decreased the resistant level of larvae to fenpropathrin. The findings showed that the metabolism and transporter pathways are associated with resistance to fenpropathrin in silkworm, and OCT6 is an effective and potential target not only for silkworm breeding but also for pest biocontrol.

Distribution of Micro-Nano PS, DEHP, and/or MEHP in Mice and Nerve Cell Models In Vitro after Exposure to Micro-Nano PS and DEHP.

Polystyrene (PS) and di-(2-ethylhexyl) phthalate (DEHP) exist widely in the environment. However, their distribution in organisms remains unclear. We used three sizes (50 nm, 500 nm, and 5 µm) of PS and DEHP to study the distribution and accumulation of PS, DEHP, and mono(2-ethylhexyl) phthalate (MEHP) in mice and nerve cell models (HT22 and BV2 cells) and their potential toxicity. Results showed that PS entered the blood of mice, and the distribution of different particle sizes in different tissues was different. After the combined exposure to PS and DEHP, PS carried DEHP, which significantly increased the DEHP content and MEHP content and the highest content of MEHP was in the brain. With the decrease in PS particle size, the contents of PS, DEHP, and MEHP in the body increased. The levels of inflammatory factors were increased in the serum of the PS or/and DEHP group. In addition, 50 nm polystyrene can carry MEHP into nerve cells. These results suggest for the first time that PS and DEHP combined exposure can induce systemic inflammation, and the brain is an important target organ of PS and DEHP combined exposure. This study may serve as a reference for further evaluation of the neurotoxicity induced by combined exposure to PS and DEHP.

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori.

The white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine-fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.

Isopeptide Bond Bundling Superhelix for Designing Antivirals against Enveloped Viruses with Class I Fusion Proteins: A Review.

Viral infection has become one of the worst human lethal diseases. In recent years, major gains have been made in the research of peptide-based antiviral agents on account of the mechanism of viral membrane fusion, among which the peptide Enfuvirtide has been listed for the treatment of AIDS. This paper reviewed a new way to design peptide-based antiviral agents by "bundling" superhelix with isopeptide bonds to construct the active advanced structure. It can solve the problem that peptide precursor compounds derived from the natural sequence of viral envelope protein tend to aggregate and precipitate under physiological conditions and low activity and endow the peptide agents with the feature of thermal stability, protease stability and in vitro metabolic stability. This approach is also providing a new way of thinking for the research and development of broad-spectrum peptide-based antiviral agents.

Exposure to Polypropylene Microplastics via Oral Ingestion Induces Colonic Apoptosis and Intestinal Barrier Damage through Oxidative Stress and Inflammation in Mice.

Extensive environmental pollution by microplastics has increased the risk of human exposure to plastics. However, the biosafety of polypropylene microplastics (PP-MPs), especially of PP particles < 10 µm, in mammals has not been studied. Thus, here, we explored the mechanism of action and effect of exposure to small and large PP-MPs, via oral ingestion, on the mouse intestinal tract. Male C57BL/6 mice were administered PP suspensions (8 and 70 µm; 0.1, 1.0, and 10 mg/mL) for 28 days. PP-MP treatment resulted in inflammatory pathological damage, ultrastructural changes in intestinal epithelial cells, imbalance of the redox system, and inflammatory reactions in the colon. Additionally, we observed damage to the tight junctions of the colon and decreased intestinal mucus secretion and ion transporter expression. Further, the apoptotic rate of colonic cells significantly increased after PP-MP treatment. The expression of pro-inflammatory and pro-apoptosis proteins significantly increased in colon tissue, while the expression of anti-inflammatory and anti-apoptosis proteins significantly decreased. In summary, this study demonstrates that PP-MPs induce colonic apoptosis and intestinal barrier damage through oxidative stress and activation of the TLR4/NF-κB inflammatory signal pathway in mice, which provides new insights into the toxicity of MPs in mammals.

Effects of Different Concentrations of Oil Mist Particulate Matter on Pulmonary Fibrosis In Vivo and In Vitro.

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-ß1, 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-ß1/Smad3 and TGF-ß1/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-ß1/Smad3 and TGF-ß1/MAPK p38 signaling pathways.

Different exposure modes of PM2.5 induces bronchial asthma and fibrosis in male rats through macrophage activation and immune imbalance induced by TIPE2 methylation.

Exposure to PM2.5 can aggravate the occurrence and development of bronchial asthma and fibrosis. Here, we investigated the differences in bronchial injury caused by different exposure modes of PM2.5 (high concentration intermittent exposure and low concentration continuous exposure), and the mechanism of macrophage activation and respiratory immune imbalance induced by PM2.5, leading to bronchial asthma and airway fibrosis using animal and cell models. A "PM2.5 real-time online concentrated animal whole-body exposure system" was used to conduct PM2.5 respiratory exposure of Wistar rats for 12 weeks, which can enhance oxidative stress in rat bronchus, activate epithelial cells and macrophages, release chemokines, recruit inflammatory cells, release inflammatory factors and extracellular matrix, promote bronchial mucus hypersecretion, inhibit the expression of epithelial cytoskeletal proteins, destroy airway barrier, and induce asthma. Furthermore, PM2.5 induced M2 polarization in lung bronchial macrophages through JAK/STAT and PI3K/Akt signaling pathways, and compared with low concentration continuous exposure, high concentration intermittent exposure of PM2.5 could regulate significantly higher expression of TIPE2 protein through promoter methylation of TIPE2 DNA, thereby activating PI3K/Akt signaling pathway and more effectively inducing M2 polarization of macrophages. Additionally, activated macrophages release IL-23, and activated epithelial cells and macrophages released TGF-ß1, which promoted the differentiation of Th17 cells, triggered the Th17 dominant immune response, and activated the TGF-ß1/Smad2 signaling pathway, finally causing bronchial fibrosis. Moreover, when the total amount of PM2.5 exposure was equal, high concentration-intermittent exposure was more serious than low concentration-continuous exposure. In vitro experiments, the co-culture models of PM2.5 with BEAS-2B, WL-38 and rat primary alveolar macrophages further confirmed that PM2.5 could induce the macrophage activation through oxidative stress and TIPE2 DNA methylation, and activate the TGF-ß1/Smad2 signaling pathway, leading to the occurrence of bronchial fibrosis.

PM2.5 exposure at different concentrations and modes induces reproductive toxicity in male rats mediated by oxidative and endoplasmic reticulum stress.

The molecular mechanisms of PM2.5 exposure in the male reproductive system, have scarcely been studied. Here, we demonstrate the possible relationship and molecular mechanisms between endoplasmic reticulum stress (ERS), oxidative stress, and reproductive toxicity caused by PM2.5. A "PM2.5 real-time online concentrated animal whole-body exposure system" was employed to expose male Wistar rats to PM2.5 for 12 weeks, which could induce sperm quality decline, apoptosis, inflammation, oxidative stress, ERS, and histopathological damage in the testis. In vitro study on cultured primary testicular spermatogonia and Leydig cells confirmed that treatment with PM2.5 (0-320 µg/mL) for 24 h decreased cell survival rate, increased reactive oxygen species, lactate dehydrogenase and 8-hydroxydeoxyguanosine levels, induced DNA damage, ERS and apoptosis, and inhibit the secretion and synthesis of testosterone in Leydig cells. These results clarified that ERS pathways triggered by oxidative stress could significantly induce CHOP and caspase-12 activation, which are significantly associated with cell apoptosis. However, oxidative stress and ERS inhibitors significantly inhibited the occurrence of these injuries. In conclusion, PM2.5 triggers the ERS pathway and induces DNA damage in rat testicular cells through oxidative stress, ultimately leading to cellular apoptosis. Furthermore, high-concentration intermittent inhalation was more harmful than low-concentration continuous inhalation when the total mass of PM2.5 exposure was the same.

Ambient ozone exposure induces ROS related-mitophagy and pyroptosis via NLRP3 inflammasome activation in rat lung cells.

OBJECTIVE: To study the regulatory relationship between ozone-induced mitophagy and pyroptosis in lung epithelial cells. RESULTS: First, type I primary alveolar epithelial cells and male Wistar rats were treated with ozone at different dosages. The ATP content and mitochondrial membrane potential significantly decreased in type I primary alveolar epithelial cells. The mitophagy-related markers and PINK1/Parkin pathway-related proteins, and the co-localization of LC3, Parkin, and mitochondria in type I alveolar epithelial cells indicated that ozone exposure triggered mitophagy. On the other hand, the reactive oxygen species (ROS) inhibitor NAC could significantly alleviate mitophagy in epithelial cells. After treatment with the mitophagy inhibitor MDIVI-1, the levels of the NLRP3 inflammasome, cleaved caspase-1, and N-gasdermin D (N-GSDMD) significantly decreased in the cells. Altogether, these results indicated that mitophagy can be triggered by ozone exposure, and subsequently induces cell death mediated by the NLRP3 inflammasome. Finally, the overexpression and knockdown of NLRP3 confirmed this conclusion. CONCLUSION: Ozone exposure induced oxidative damage, leading to mitochondrial structural and functional damage. Ozone-induced ROS triggered mitophagy through the activation of the PINK1/Parkin signaling pathway, then pyroptosis through activation of the NLRP3 inflammasome.

Combined multi-omics analysis reveals oil mist particulate matter-induced lung injury in rats: Pathological damage, proteomics, metabolic disturbances, and lung dysbiosis.

Oil mist particulate matter (OMPM) causes acute and chronic diseases and exacerbations. Owing to the characteristics of poor ventilation, high oil mist concentration, and a relatively closed working environment, the existence of OMPM in the cabin is inevitable, and its impact on the health of occupations on ships cannot be ignored. However, compared with several studies that summarized the health effects of OMPM from traditional sources, few studies have focused on the occupational exposure risk of OMPM from oil pollution sources in ships. In this study, we collected OMPM from oil pollution in cabins and assessed the exposure to OMPM from oil pollution and the corresponding health risks through acute exposure experiments in rats. OMPM exposure induces protein regulation in the extracellular matrix and immune responses, leading to severe inflammatory responses. The abundance and composition of the lung microbial community changed significantly. It interferes with the lung metabolite levels. However, more research is needed to fully understand the extent of health risks associated with OMPM exposure. Further research on vulnerable groups exposed to OMPM from ships is needed to inform public health interventions.

Intestinal toxicity of micro- and nano-particles of foodborne titanium dioxide in juvenile mice: Disorders of gut microbiota-host co-metabolites and intestinal barrier damage.

The wide use of TiO2 particles in food and the high exposure risk to children have prompted research into the health risks of TiO2. We used the microbiome and targeted metabolomics to explore the potential mechanism of intestinal toxicity of foodborne TiO2 micro-/nanoparticles after oral exposure for 28 days in juvenile mice. Results showed that the gut microbiota-including the abundance of Bacteroides, Bifidobacterium, Lactobacillus, and Prevotella-changed dynamically during exposure. The organic inflammatory response was activated, and lipopolysaccharide levels increased. Intestinal toxicity manifested as increased mucosal permeability, impaired intestinal barrier, immune damage, and pathological changes. The expression of antimicrobial peptides, occludin, and ZO-1 significantly reduced, while that of JNK2 and Src/pSrc increased. Compared with micro-TiO2 particles, the nano-TiO2 particles had strong toxicity. Fecal microbiota transplant confirmed the key role of gut microbiota in intestinal toxicity. The levels of gut microbiota-host co-metabolites, including pyroglutamic acid, L-glutamic acid, phenylacetic acid, and 3-hydroxyphenylacetic acid, changed significantly. Significant changes were observed in the glutathione and propanoate metabolic pathways. There was a significant correlation between the changes in gut microbiota, metabolites, and intestinal cytokine levels. These, together with the intestinal barrier damage signaling pathway, constitute the network mechanism of the intestinal toxicity of TiO2 particles.

[Effect of epithelial-mesenchymal transition on cardiac fibrosis induced by oil mist particulate matter].

Objective: To investigate the effects of oil-mist particulate matter (OMPM) on cardiac tissue structure fibrosis in rats and the role of epithelial-mesenchymal transition (EMT). Methods: Six-week-old Wistar rats (half male and half female) were randomly divided into 3 groups: control group (without OMPM exposure), low-dose exposure group (50 mg/m3) and high-dose exposure group (100 mg/m3), 18 rats in each group, with 6.5 hours per day of dynamic inhalation exposure. After 42 days of continuous exposure, cardiac tissues were collected for morphological observation; Western blot was used to detect fibrosis markers collagen I and collagen III levels, epithelial marker E-cadherin levels, interstitial markers N-cadherin, fibronectin, vimentin, alpha-smooth muscle actin (α-SMA) levels, and EMT transcription factor Twist protein levels; Real-time polymerase chain reaction (RT-qPCR) was used to detect collagen I and collagen III mRNA levels. Results: After OMPM exposure, myocardial cell edema and collagen fiber deposition were increased gradually with increasing exposure dose. Western blot results showed that compared with the control group, the expression levels of collagen I, collagen III, N-Cadherin, fibronectin, vimentin, α-SMA, and Twist protein were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and protein expression levels were higher in the high-dose exposure group than those in the low-dose exposure group (P＜0.01). In contrast, E-Cadherin protein expression levels were decreased significantly, and lower in the high-dose exposure group (P＜0.01). RT-qPCR results showed that compared with the control group, collagen I and collagen III mRNA levels were increased significantly in the low-dose exposure group and the high-dose exposure group (P＜0.01), and were increased with increasing exposure dose. (P＜0.01). Conclusion: OMPM may induce cardiac fibrosis in rats by promoting EMT process.