New insights into the spleen injury by mitochondrial dysfunction of chicken under polystyrene microplastics stress.

Microplastics biological toxicity, environmental persistence and biological chemicals have been paid widespread attention. Microplastics exposed to chicken spleen injury of the specific mechanism is unclear. Thus, we randomly assigned chickens to 4 groups: C (normal diet), L-MPs (1 mg/L), M-MPs (10 mg/L), and H-MPs (100 mg/L), and assessed spleen damage after 42 d of exposure. Morphologically, the boundary between the red and white pulp of the spleen was blurred, along with the expansion of the white pulp. It was further speculated that microplastics induced mitochondrial dynamic homeostasis (Drp1 upgraded, Mfn1, Mfn2, and OPA1 reduced), and provoked the mitochondrial apoptotic pathway (Bcl-2/Bax decreased, cytc, caspase3, and caspase9 raised), resulting in redox imbalance and lipid peroxide accumulation (MDA increased, CAT, GSH, and T-AOC plummeted), and further stimulated ferroptosis (FTH1, GPX4, and SLC7A11 decreased). Here we explored the impact of polystyrene microplastics on the spleen, as well as the programmed death (apoptosis and ferroptosis) involved, and the regulative role of mitochondria in this process. This could be of significant importance in bridging the gap in laboratory research on microplastics-induced spleen injury in chicken.

Endoplasmic reticulum stress-induced NLRP3 inflammasome activation as a novel mechanism of polystyrene microplastics (PS-MPs)-induced pulmonary inflammation in chickens. / å† è´¨ç½‘åº”æ¿€è¯±å¯¼çš„NLRP3炎性体激活是聚苯乙烯微塑料（PS-MPs）诱导的鸡肺部炎症的新机制.

Microplastics (MPs) have attracted growing attention worldwide as an increasingly prevalent environmental pollutant. In addition, chicken meat is currently the most widely consumed kind of poultry in the global market. Consumer demand for chicken is on the rise both at home and abroad. As a result, the safety of chicken raising has also received significant attention. The lungs play an essential role in the physiological activities of chickens, and they are also the most vulnerable organs. Lung injury is difficult to repair after the accumulation of contaminants, and the mortality rate is high, which brings huge economic losses to farmers. The research on the toxicity of MPs has mainly focused on the marine ecosystem, while the mechanisms of toxicity and lung damage in chickens have been poorly studied. Thus, this study explored the effects of exposure to polystyrene microplastics (PS-MPs) at various concentrations for 42 d on chicken lungs. PS-MPs could cause lung pathologies and ultrastructural abnormalities, such as endoplasmic reticulum (ER) swelling, inflammatory cell infiltration, chromatin agglutination, and plasma membrane rupture. Simultaneously, PS-MPs increased the expression of genes related to the heat shock protein family (Hsp60, Hsp70, and Hsp90), ER stress signaling (activating transcription factor 6 (ATF6), ATF4, protein kinase RNA-like ER kinase (PERK), and eukaryotic translation initiation factor 2 subunit α (eIF2α)), pyroptosis-related genes (NOD-|, LRR- and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin-1ß (IL-1ß), cysteinyl aspartate-specific proteinase 1 (Caspase1), and gasdermin-D (GSDMD)), and the inflammatory signaling pathway (nuclear factor-|κB (NF-|κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)). The above results showed that PS-MP exposure could result in lung stress, ER stress, pyroptosis, and inflammation in broilers. Our findings provide new scientific clues for further research on the mechanisms of physical health and toxicology regarding MPs.

Assessing and mitigating foodborne acetochlor exposure induced ileum toxicity in broiler chicks: The role of omega-3 polyunsaturated fatty acids supplementation and molecular pathways analysis.

Excessive acetochlor residues present ecological and food safety challenges. Here, broiler chicks were exposed to varied acetochlor doses to first assess its effects on the gut. Subsequent dietary supplementation with omega-3 was used to assess its anti-contamination effects. Pathologically, acetochlor induced notable ileal lesions including inflammation, barrier disruption, tight junction loss, and cellular anomalies. Mechanistically, acetochlor stimulated the TNFα/TNFR1 and TLR4/NF-κB/NLRP3 pathways, promoting RIPK1/RIPK3 complex formation, MLKL phosphorylation, NLRP3 inflammasome activation, Caspase-1 activation, and GSDMD shearing with inflammatory factor release. These mechanisms elucidate ileal cell death patterns essential for understanding chicken enteritis. Omega-3 supplementation showed promise in mitigating inflammation, though its precise counteractive role remains unclear. Our findings suggest early omega-3 intervention offered protective benefits against acetochlor's adverse intestinal effects, emphasizing its potential poultry health management role. Harnessing dietary interventions' therapeutic potential will be pivotal in ensuring sustainable poultry production and food safety despite persistent environmental contaminants.

A new insight into fluoride induces cardiotoxicity in chickens: Involving the regulation of PERK/IRE1/ATF6 pathway and heat shock proteins.

Fluorosis poses a significant threat to human and animal health and is an urgent public safety concern in various countries. Subchronic exposure to fluoride has the potential to result in pathological damage to the heart, but its potential mechanism requires further investigation. This study investigated the effects of long-term exposure to sodium fluoride (0, 500, 1000, and 2000 mg/kg) on the hearts of chickens were investigated. The results showed that an elevated exposure dose of sodium fluoride led to congested cardiac tissue and disrupted myofiber organisation. Sodium fluoride exposure activated the ERS pathways of PERK, IRE1, and ATF6, increasing HSP60 and HSP70 and decreasing HSP90. The NF-κB pathway and the activation of TNF-α and iNOS elicited an inflammatory response. BAX, cytc, and cleaved-caspase3 were increased, triggering apoptosis and leading to cardiac injury. The abnormal expression of HSP90 and HSP70 affected the stability and function of RIPK1, RIPK3, and MLKL, which are crucial necroptosis markers. HSPs inhibited TNF-α-mediated necroptosis and apoptosis of the death receptor pathway. Sodium fluoride resulted in heart injury in chickens because of the ERS and variations in HSPs, inducing inflammation and apoptosis. Cardiac-adapted HSPs impeded the activation of necroptosis. This paper may provide a reference for examining the potential cardiotoxic effects of sodium fluoride.

Polystyrene microplastics mediate cell cycle arrest, apoptosis, and autophagy in the G2/M phase through ROS in grass carp kidney cells.

Microplastics (MPs) have attracted widespread worldwide attention as a new pollutant. However, the role of reactive oxygen species (ROS) and cell cycle in nephrotoxicity induced by different concentrations of polystyrene microplastics (PS-MPs) is unknown. This study used grass carp kidney cells (CIK) treated with different concentrations of PS-MPs (0, 0.012, 0.0625, and 0.5 mg L-1 ) as subjects. With the increase of PS-MPs concentration, the levels of ROS and malonaldehyde increased, while the level of total antioxidant capacity, superoxide Dismutase (SOD), and glutathione (GSH) activity decreased. The expression of BUB1 mitotic checkpoint serine/threonine kinase (BUB1), cyclin-dependent kinase (CDK1), CDK2, CyclinB1, cell division cycle 20 homolog (CDC20), and B-cell lymphoma-2, sequestosome 1 decreased significantly. Nevertheless, the expression of Caspase 3, Cleave-Caspase 3, cytochrome c (Cytc), BCL2-associated X, apoptosis regulator, poly ADP-ribose polymerase (PARP), Cleave-PARP, Caspase 9, autophagy immunoblot kit (LC3), and Beclin1 increased. Our research shows that PS-MPs can trigger oxidative stress and induce cell cycle arrest, apoptosis, and autophagy in CIK cells by regulating ROS. This work provides a theoretical basis for cellular biology and toxicology mechanisms and new insights into the potential risks to animals from MPs exposure in the environment.

Effects of environmentally relevant cypermethrin and sulfamethoxazole on intestinal health, microbiome, and liver metabolism in grass carp.

The incorrect use of antibiotics and pesticides poses significant risks of biological toxicity. Their simultaneous exposure could jeopardize fish health and hinder sustainable aquaculture. Here, we subjected grass carp to waterborne cypermethrin (0.65 µg/L) or/and sulfamethoxazole (0.30 µg/L) treatments for a duration of 6 weeks. We closely monitored the effects on intestinal function, the intestinal microbiome, and the liver metabolome. The results revealed that exposure to waterborne cypermethrin or/and sulfamethoxazole compromised intestinal barrier function and decreased the expression of intestinal tight junction proteins. Additionally, heightened levels of pro-inflammatory cytokines in the intestines and reduced antioxidant levels indicated systemic inflammation and oxidative stress, with more severe effects observed in the combined exposure group. 16S rRNA sequencing of intestinal tissues suggested Firmicutes play a key role in the intestinal microbiota. GC/MS metabolomics of the liver showed more differential metabolites (56) in the co-exposure group compared to cypermethrin (45) or sulfamethoxazole (32) alone, indicating greater toxicological effects with combined exposure. Our analyses also suggest that ATP-binding cassette transporters could serve as a novel endpoint for assessing the risk of pesticide and antibiotic mixtures in grass carp. In summary, this study underscores the potential ecological risks posed by antibiotics and pesticides to aquatic environments and products. It emphasizes the importance of the gut-liver axis as a comprehensive pathway for assessing the toxicity in fish exposed to environmental contaminants.

Perturbed Progressive Learning for Semisupervised Defect Segmentation.

Recently, with the development of intelligent manufacturing, the demand for surface defect inspection has been increasing. Deep learning has achieved promising results in defect inspection. However, due to the rareness of defect data and the difficulties of pixelwise annotation, the existing supervised defect inspection methods are too inferior to be implemented in practice. To solve the problem of defect segmentation with few labeled data, we propose a simple and efficient method for semisupervised defect segmentation (SSDS), named perturbed progressive learning (PPL). On the one hand, PPL decouples the predictions of student and teacher networks as well as alleviates overfitting on noisy pseudo-labels. On the other hand, PPL encourages consistency across various perturbations in a broader stagewise scope, alleviating drift caused by the noisy pseudo-labels. Specifically, PPL contains two training stages. In the first stage, the teacher network gives the unlabeled data with pseudo-labels that are divided into the easy and hard groups. The labeled data and the unlabeled data in the easy group with their perturbation are both used to train for a better-performing student network. In the second stage, the unlabeled data in the hard group are predicted by the obtained student network, so the refined pseudo-labeled data are enlarged. All the pseudo-labeling data and labeled data with their perturbation are used to retrain the student network, progressively improving the defect feature representation. We build a mobile screen defect dataset (MSDD-3) with three classes of defects. PPL is implemented on MSDD-3 as well as other public datasets. Extensive experimental results demonstrate that PPL significantly surpasses the state-of-the-art methods across all evaluation partition protocols.

Liver Injury Induced by Exposure to Polystyrene Microplastics Alone or in Combination with Cadmium in Mice Is Mediated by Oxidative Stress and Apoptosis.

Microplastics (MPs) have been considered an emerging environmental pollutant which, when combined with toxic metals, enter the circulatory system of mammals and eventually cause damage. Therefore, it is important to study the toxicity of the mixture of MPs and heavy metals for evaluating risk assessment of mammals. In the present study, the toxicological effects of different concentrations of polystyrene (PS)-MPs alone or in combination with cadmium chloride (CdCl2) during chronic exposure (8 weeks) were evaluated using intragastric administration in mice. Using comparative analysis, it was revealed that PS-MPs alone or in combination with Cd could destroy the normal structural morphology of liver tissue and increase the levels of two biochemical indicators of liver damage, thereby inducing changes in antioxidant and hyperoxide capacities. In addition, PS-MPs and/or Cd activated the antioxidant signaling pathway Nrf2-Keap1 and affected the endogenous apoptosis signaling pathway p53-Bcl-2/Bax, thus promoting apoptosis. These findings suggested that exposure to MPs alone or in combination with Cd led to adverse effects on the liver. Furthermore, it was revealed that co-exposure to MPs and Cd reduced Cd toxicity, thereby highlighting the possibility MPs may act as carriers of other toxic substances and coordinate with them. Therefore, evaluating the synergistic or anti-agonistic effects of MPs on the toxicity and bioavailability of xenobiotics is in the future critical in environmental toxicological studies.

Polystyrene microplastics mediate inflammatory responses in the chicken thymus by Nrf2/NF-κB pathway and trigger autophagy and apoptosis.

Microplastics (MPs) are a hot environmental contaminant now. However, researchers paid little attention to their effects on immune organs such as the thymus. Here, we exposed chickens to a concentration gradient of polystyrene microplastics (PS-MPs) and then followed the decrease in the thymus index. HE staining showed cellular infiltration in the thymus. The assay kit corroborated that PS-MPs impelled oxidative stress in the thymus: increased MDA levels, downregulated antioxidants such as SOD, CAT, and GSH, and significantly undermined total antioxidant capacity. Western blotting and qRT-PCR results showed that Nrf2/NF-κB, Bcl-2/Bax, and AKT signaling pathways were activated in the thymus after exposure to PS-MPs. It stimulated the increased expression of downstream such as IL-1ß, caspase-3, and Beclin1, triggering thymus inflammation, apoptosis, and autophagy. This study provides new insights into the field of microplastic immunotoxicity and highlights potential environmental hazards in poultry farming.

Fluoride induces neutrophil extracellular traps and aggravates brain inflammation by disrupting neutrophil calcium homeostasis and causing ferroptosis.

Endemic fluorosis (EF) has been listed as one of the serious public health problems in many countries. Long-term exposure to high fluoride can lead to severe neuropathological damage to the brain. Although long-term research has revealed the mechanism of some brain inflammation caused by excessive fluoride, the role of intercellular interactions, especially immune cells, in brain damage is still unclear. Fluoride can induce ferroptosis and inflammation in the brain in our study. A co-culture system of neutrophil extranets and primary neuronal cells showed that fluoride can aggravate neuronal cell inflammation by causing neutrophil extranets (NETs). In terms of the mechanism of action, we found that fluoride leads to the opening of calcium ion channels by causing neutrophil calcium imbalance, which in turn leads to the opening of L-type calcium ion channels (LTCC). Extracellular free iron enters the cell from the open LTCC, leading to neutrophil ferroptosis, which releases NETs. Blocking LTCC (nifedipine) rescued neutrophil ferroptosis and reduced the generation of NETs. Inhibition of ferroptosis (Fer-1) did not block cellular calcium imbalance. In summary, our study explores the role of NETs in fluoride-induced brain inflammation and suggests that blocking calcium channels may be one of the possibilities to rescue fluoride-induced ferroptosis.

Polystyrene microplastics promote liver inflammation by inducing the formation of macrophages extracellular traps.

Microplastics (MPs), a new and increasing environmental pollutant, can cause ongoing damage to organisms. Although recent studies have revealed mechanisms of action for some of the hepatotoxicity caused by MPs, the role-played by cellular interactions, particularly immune cells, in the process of liver injury has not been elucidated. In the present study, 5-µm polystyrene microplastics (PS-MPs) induced liver inflammation as well as the formation of Macrophage extracellular traps (METs). Macrophage and LMH cell co-culture systems confirmed that PS-MPs-induced METs promote inflammation in hepatocytes. Mechanistically, macrophages actively phagocytose particles after 4 h of exposure to PS-MPs. Subsequently PS-MPs elevated ROS levels and disrupt mitochondrial kinetic homeostasis. Further activation of mitochondrial autophagy and lysosomes. After phagocytosis of PS-MPs by macrophages for 12 h, continued autophagy and lysosome activation eventually lead to lysosome rupture and release of calcium ions to induce the formation of METs. Blocking ROS (NAC) and autophagy (3MA) partially alleviated mitochondrial and lysosomal damage and thus inhibited the formation of METs induced by PS-MPs. NAC also delayed the onset of respiratory burst to alleviate METs formation. In conclusion, our study reveals the mechanism of METs formation in liver inflammation induced by PS-MPs exposure and suggests that lysosomal damage may be one of the key players in the formation of METs induced by PS-MPs.

Polystyrene microplastics induce autophagy and apoptosis in birds lungs via PTEN/PI3K/AKT/mTOR.

Microplastics (MPs) seriously pollute and potentially threaten human health. Birds are sentinels of environmental pollutants, which respond quickly to contamination events and reveal current environmental exposure. Therefore, birds are good bioindicators for monitoring environmental pollutants. However, the mechanism of lung injury in birds and the role of the PTEN/PI3K/AKT axis are unknown. In this study, broilers treated with different polystyrene microplastics (PS-MPs) (0, 1, 10, and 100 mg/L) were exposed to drinking water for 6 weeks to analyze the effect of PS-MPs on lung injury of broilers. The results showed that with the increase of PS-MPs concentration, malonaldehyde (MDA) content increased, and catalase (CAT) and glutathione (GSH) activity decreased, further leading to oxidative stress. PS-MPs caused the PI3K/Akt/mTOR pathway to be inhibited by phosphorylation, and autophagy accelerated formation (LC3) and degradation (p62), causing autophagy. In PS-MPs exposed lung tissues, the expression of Bax/Bcl-2 and Caspase family increased, and MAPK signaling pathways (p38, ERK, and JNK) showed an increase in phosphorylation level, thus leading to cell apoptosis. Our research showed that PS-MPs could activate the antioxidant system. The antioxidant system unbalance-regulated Caspase family, and PTEN/PI3K/AKT pathways initiated apoptosis and autophagy, which in turn led to lung tissue damage in chickens. These results are of great significance to the toxicological study of PS-MPs and the protection of the ecosystem.

Novel pathways of fluoride-induced hepatotoxicity: P53-dependent ferroptosis induced by the SIRT1/FOXOs pathway and Nrf2/HO-1 pathway.

Fluoride (F) is an environmental pollutant that continues to threaten human health. Long-term or excessive fluoride exposure can cause a series of acute or chronic systemic and organ-specific diseases. The liver is considered to be one of the important target organs of fluoride poisoning, however, the specific cause of liver damage caused by fluoride is still unclear. In the present study, we identified ferroptosis as a key mechanism of fluoride-induced liver injury. Under fluorosis conditions, lipid peroxidation levels in the liver are significantly increased and iron overload is induced. Combined transcriptomic and metabolomic analysis revealed that activation of the SIRT1/FOXOs pathway is one of the main causes of fluorosis-induced liver damage. Further analysis by in vitro experiments showed that the SIRT1/FOXOs pathway can cause the activation of the Nrf2/HO-1 pathway under the condition of fluorosis, and can activate the P53-dependent ferroptosis pathway, leading to the occurrence of lipid peroxidation and iron accumulation, ultimately leading to ferroptosis. Our study provides insight into the mechanism of fluoride-induced liver injury, and our results also provide strategies for treatment to alleviate liver injury caused by fluorosis.

Dose-effect of polystyrene microplastics on digestive toxicity in chickens (Gallus gallus): Multi-omics reveals critical role of gut-liver axis.

INTRODUCTION: Microplastic pollution seriously threatens the health and safety of humans and wildlife. Avian is one of the main species endangered by microplastics. However, the damage mechanism of microplastics to the digestive system of avian is not clear. OBJECTIVES: The gut-liver axis is a bidirectional channel that regulates the exchange of information between the gut and the liver and is also a key target for tissue damage caused by pollutants. This study aimed to elucidate the digestive toxicity of microplastics in avian and the key role of the gut-liver axis in it. METHODS: We constructed an exposure model for microplastics in environmental concentrations and toxicological concentrations in chickens and reveal the digestive toxicity of polystyrene microplastics (PS-MPs) in avian by 16S rRNA, transcriptomics and metabolomics. RESULTS: PS-MPs changed the death mode from apoptosis to necrosis and pyroptosis by upregulating Caspase 8, disrupting the intestinal vascular barrier, disturbing the intestinal flora and promoting the accumulation of lipopolysaccharide. Harmful flora and metabolites were translocated to the liver through the liver-gut axis, eliciting hepatic immune responses and promoting hepatic lipid metabolism disorders and apoptosis. Liver injury involves multiple molecular effects of mitochondrial dynamics disturbance, oxidative stress, endoplasmic reticulum stress, and cell cycle disturbance. Furthermore, metabolomics suggested that caffeine and melanin metabolites may be potential natural resistance substances for microplastics. CONCLUSION: Taken together, our data demonstrate the digestive damage of PS-MPs in avian, revealing a critical role of the liver-gut axis in it. This will provide a reference for protecting the safety of avian populations.

Secondary brain injury after polystyrene microplastic-induced intracerebral hemorrhage is associated with inflammation and pyroptosis.

Unlike regular environmental pollutants, microplastics cannot dissolve in liquids. Physical contact of microplastic (MPs) with tissue can damage tissue structure, and it is unclear how this physical secondary injury affects brain tissue. Through CTD database analysis, it was determined that cerebral ischemia may be one of the main ways of brain tissue damage caused by MPs, and inflammatory response may play a key role in it. In the present study, PS-MPs (L-PS group:1 mg/L, M - PS group:10 mg/L, H-PS group: 100 mg/L in water) were assessed to brain tissue damage in chicken after six weeks of continuous exposure. Exposure to PS-MPs caused cerebral hemorrhage as well as generation of microthrombi and loss of Purkinje cells. Intracerebral hemorrhage caused a strong infiltration of inflammatory cells and activated the ASC-NLRP3-GSDMD signaling pathway to induce pyroptosis. Disruption of mitochondrial dynamics by PS-MPs exposure disrupts mitochondrial function and activates AMPK signaling. In conclusion, this study explored the mechanism regulation of subsequent brain injury from the perspective of physical injury (cerebral hemorrhage) of PS-MPs. To provide a reference for elucidating the neurotoxicity induced by microplastic exposure.

Endoplasmic reticulum stress-controlled autophagic pathway promotes polystyrene microplastics-induced myocardial dysplasia in birds.

In complex ecosystems, birds are generally long-lived and occupy high trophic positions, making them good bioindicators for monitoring environmental contaminants. The effects of microplastics (MPs) on myocardial development in bird is currently unknown. Chicks, as a high trophic level terrestrial bird, may be more affected by MPs exposure and. Therefore, we established an in vivo model of chicks exposed to different concentrations of polystyrene microplastics (PS-MPs) and selected 12-day-old chicken embryos in vitro to extract primary cardiomyocytes to further investigate the potential molecular mechanisms of the effect of PS-MPs on myocardial development in birds. Histopathological observations revealed that the PS-MPs treated exhibited loose and irregular myocardial arrangement, large cell gaps and broken myocardial fiber bundles. More mechanistically, TnnT2, Nkx2-5, Gata4, TBX5 and ACTN2 were down-regulated, endoplasmic reticulum (ER) stress markers GRP78, PERK, eIF2α, IRE1, ATF4, ATF6 and CHOP were overexpressed, autophagy-related genes LC3, ATG5, Beclin1 and P62 were down-expressed after PS-MPs exposure, and the addition of 4PBA effectively deregulated the above aberrant expression. Hence, our report indicated that PS-MPs induced myocardial dysplasia in birds is mainly attributed to the ER stress-mediated autophagic pathway. This provided data supporting the protection of birds from the health risks of MPs pollution. More critically, the study of cardiac developmental toxicity in birds may help to better explain or solve the problem of MPs pollution in complex ecosystems.

Polystyrene microplastics induce apoptosis in chicken testis via crosstalk between NF-κB and Nrf2 pathways.

Microplastics (MPs) are a new type of pollutants that are widespread in nature, and their toxic effects on humans or animals are receiving attention. Birds are in a higher ecological niche in nature, and MPs may have potential bioaccumulation and biomagnification risks to birds. The mechanisms underlying the reproductive toxicity of MPs to birds are mainly unknown. To study the reproductive toxicity of MPs to birds, we randomly divided chickens into six groups and exposed polystyrene microplastics (PS-MPs) through drinking water (0, 1, and 100 mg/L) for 28 and 42 days. We found that PS-MPs caused testicular inflammatory infiltration and interstitial hemorrhage, resulting in testicular tissue damage; the expression of Claudin3 and Occludin in the blood-testis barrier (BTB) decreased and may damage the integrity of the BTB. PS-MPs exposure inhibited the expression of the Nrf2-Keap1 pathway, which in turn reduced HO-1 and NQO1, simultaneous GSH and T-AOC were also reduced, resulting in an imbalance of the redox system; in addition, the NF-κB signaling pathway was activated, increasing the expression of TNF-α, COX-2 and iNOS. Under redox system imbalance and inflammatory stress, exposure to PS-MPs led to decreased expression of Bcl-2 and increased Bax, cytc, caspase-8, and caspase-3, etc., activating apoptosis, and ultimately causing testicular damage. These results suggested that PS-MPs exposure led to an imbalance of the redox system and an inflammatory response, inducing both endogenous and exogenous apoptosis, resulting in testicular tissue damage. Our study provides a theoretical basis for reproductive injury mechanisms in chicken.

Polystyrene microplastics induced oxidative stress, inflammation and necroptosis via NF-κB and RIP1/RIP3/MLKL pathway in chicken kidney.

Microplastics (MPs) are a novel environment pollutant widespread among the natural environment, also causing damage to aquatic animals and mammals. However, their effects on the kidney of poultry are still unclear. In this study, chickens were exposure to the different doses of PS-MPs (1, 10, 100 mg/L) for six weeks, with 1 mg/L being the environmental concentration. The effects of PS-MPs on renal tissue damage in chicken were analyzed. Our results suggested that MPs exposure causes mitochondrial morphology and dysbiosis (MFN1/2, OPA1, Drp1), mitochondrial structural damage by triggering imbalance in mitochondrial dynamics. Antioxidant enzyme (SOD, CAT, MDA, GSH, T-AOC) activity was significantly altered, which in turn caused oxidative stress. H&E staining results showed damage and inflammation of chicken kidney. Mechanistically, the inflammation featured by activated NF-κB P65 and increased expression of pro-inflammatory factors (TNFα, iNOs, IL-1ß and IL-6). Moreover, PS-MPs intake induced necroptosis through activated RIP1/RIP3/MLKL signaling pathway. In conclusion, our study was the first to show that oral intake of PS-MPs induced inflammation and necroptosis in chicken kidney and the differences in damage were linked to the concentration of PS-MPs. The purpose of this study provided theoretical support for the environmental risk assessment of PS-MPs.

Polystyrene microplastics-induced cardiotoxicity in chickens via the ROS-driven NF-κB-NLRP3-GSDMD and AMPK-PGC-1α axes.

Microplastics (MPs) pollution is getting increasingly prominent, and its dangers have attracted widespread attention. The heart is the central hub of the organism's survival, and the mechanism of MPs-induced heart injury in chickens is unknown. Here, we investigated the effects of 5 µm polystyrene microplastics (PS-MPs) on the heart and primary cardiomyocytes of chickens at varied concentrations. We observed that PS-MPs caused severe pathological damage and ultrastructural changes in heart, induced myocardial pyroptosis, inflammatory cell infiltration and mitochondrial lesions. PS-MPs evoked abnormal antioxidant enzyme content and ROS overproduction. Detailed mechanistic investigation indicated that PS-MPs triggered pyroptosis via NF-κB-NLRP3-GSDMD axis and exacerbated myocardial inflammation (NLRP3, Caspase-1, IL-1ß, IL-18, ASC, GSDMD, NF-κB, COX-2, iNOS and IL-6 overexpression). Additionally, PS-MPs induced mitochondrial damage (TFAM, OPA1, MFN1 and MFN2 down-expression, DRP1 and Fis1 overexpression) and energy metabolism disorders (HK2, PKM2, PDHX and LDH up-regulation) by inhibiting AMPK-PGC-1α pathway. Interestingly, NAC alleviated these aberrant manifestations in vitro. We suggested that PS-MPs driven alterations in NF-κB-NLRP3-GSDMD and AMPK-PGC-1α pathways via ROS overload, which in turn triggered oxidative stress, myocardial pyroptosis, inflammation, mitochondrial and energy metabolism dysfunction. This provided theoretical bases for protecting chickens from toxic injury by MPs.

Polystyrene microplastics up-regulates liver glutamine and glutamate synthesis and promotes autophagy-dependent ferroptosis and apoptosis in the cerebellum through the liver-brain axis.

Microplastics (MPs), which are emerging environmental pollutants, remain uncertainties in their toxic mechanism. MPs have been linked to severe liver metabolic disorders and neurotoxicity, but it is still unknown whether the abnormal metabolites induced by MPs can affect brain tissue through the liver-brain axis. Exposed to MPs of chickens results in liver metabolic disorders and increased glutamine and glutamate synthesis. The relative expression of glutamine in the C group was -0.862, the L-PS group was 0.271, and the H-PS group was 0.592. The expression of tight junction proteins in the blood-brain barrier (BBB) was reduced by PS-MPs. Occludin protein expression decreased by 35.8%-41.2%. Claudin 3 decreased by 19.6%-42.3%, and ZO-1 decreased by 28.3%-44.6%. Excessive glutamine and glutamate cooperated with PS-MPs to inhibit the Nrf2-Keap1-HO-1/NQO1 signaling pathway and triggered autophagy-dependent ferroptosis and apoptosis. GPX protein expression decreased by 30.9%-38%. LC3II/LC3I increased by 54%, and Caspase 3 increased by 45%. Eventually, the number of Purkinje cells was reduced, causing neurological dysfunction. In conclusion, this study provides new insights for revealing the mechanism of nervous system damaged caused by PS-MPs exposed in chickens.