{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:16:31Z","timestamp":1788308191671,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Key Medical Discipline of Jiangsu Province","award":["ZDXK202249"],"award-info":[{"award-number":["ZDXK202249"]}]},{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371462"],"award-info":[{"award-number":["82371462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Provincial Subsidy Funds for Pairing Assistance","award":["DHBFZ202505"],"award-info":[{"award-number":["DHBFZ202505"]}]},{"name":"Jiangsu Traditional Chinese Medicine","award":["PDJH2024027"],"award-info":[{"award-number":["PDJH2024027"]}]},{"name":"the Qing Lan Project of Jiangsu","award":["JS2023-27"],"award-info":[{"award-number":["JS2023-27"]}]},{"name":"the Traditional Chinese Medicine Science and Technology Development Plan Project of Zhejiang Province","award":["2024ZL140"],"award-info":[{"award-number":["2024ZL140"]}]},{"name":"the Hangzhou Medical and Health Science and Technology Project","award":["B20252321"],"award-info":[{"award-number":["B20252321"]}]},{"name":"the Yangzhou Polytechnic College Research Project","award":["2025XJ17"],"award-info":[{"award-number":["2025XJ17"]}]},{"name":"the Social Science Research Project on Yangzhou\u2019s Child-Friendly Initiative","award":["2025YFE-057"],"award-info":[{"award-number":["2025YFE-057"]}]},{"name":"the Yangzhou City Basic Research Program (Joint Special Project)\u2014Health and Wellness Category","award":["2025-3-26"],"award-info":[{"award-number":["2025-3-26"]}]},{"name":"the Yangzhou City Basic Research Program (Joint Special Project)\u2014Health and Wellness Category","award":["2025-3-36"],"award-info":[{"award-number":["2025-3-36"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>With rapid industrial expansion, air pollution\u2019s adverse neurological effects have gained increasing attention. Children face a greater risk of neurological damage because of their higher breathing rates, developing brains, and limited ability to detoxify harmful substances. Fine particulate matter has been identified as a primary neurotoxic contributor affecting developing brains. Strong evidence connects environmental pollutant exposure to the prevalence of Autism Spectrum Disorder (ASD), a neurodevelopmental condition marked by lasting difficulties with social communication and interaction. This study explores the association between long-term PM2.5 exposure and ASD symptom exacerbation, investigating underlying mechanisms. We hypothesize that long-term PM2.5 exposure exacerbates ASD symptoms through neuroinflammatory activation, leading to neuronal damage and impaired synaptic plasticity. Our investigation employs three complementary approaches: First, integrated analysis combining Global Burden of Disease data with Mendelian randomization demonstrates a significant association between PM2.5 exposure and increased ASD severity risk. Second, utilizing the China High-Resolution Air Pollution Database in conjunction with cohort studies, we provide evidence that ambient air pollution substantially influences autism severity, with PM2.5 identified as the predominant environmental determinant. Third, through network toxicology, single-cell transcriptomics, and animal experimentation, we demonstrate that chronic PM2.5 exposure exacerbates valproic acid-induced autism-like behaviors in murine models, identifying CTNNB1, PTEN, CCR2, AKT1, and mTOR as potential core mediating genes. Importantly, these findings represent preliminary results. Several potential confounding factors such as co-exposure to other pollutants and socioeconomic variables have not been fully addressed. While our multi-modal approach provides converging lines of evidence, further validation in larger, more diverse populations with refined control of confounders will be essential to establish causality and elucidate mechanisms. Nonetheless, these early insights advance our understanding of PM2.5-induced neurotoxicity in the context of ASD and offer timely, albeit preliminary, evidence to inform public health policy.<\/jats:p>","DOI":"10.3390\/toxics13110922","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T03:44:39Z","timestamp":1761795879000},"page":"922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the Effects of Long-Term Fine Particulate Matter Exposure on Autism Spectrum Disorder Severity: Evidence from Multiple Analytical Approaches"],"prefix":"10.3390","volume":"13","author":[{"given":"Jianrui","family":"Dou","sequence":"first","affiliation":[{"name":"Department of Occupational Safety and Health, Center for Disease Control and Prevention of Yangzhou, Yangzhou 225000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Occupational Safety and Health, Center for Disease Control and Prevention of Yangzhou, Yangzhou 225000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2499-8509","authenticated-orcid":false,"given":"Ruijin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqin","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Occupational Safety and Health, Center for Disease Control and Prevention of Yangzhou, Yangzhou 225000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linpei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3812-3164","authenticated-orcid":false,"given":"Chenyu","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, MN 55905, USA"},{"name":"School of Public Health, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7608-0164","authenticated-orcid":false,"given":"Yueying","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"124913","DOI":"10.1016\/j.envpol.2024.124913","article-title":"PM2.5 induces developmental neurotoxicity in cortical organoids","volume":"361","author":"Han","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"131827","DOI":"10.1016\/j.jhazmat.2023.131827","article-title":"Neurotoxicity of the air-borne particles: From molecular events to human diseases","volume":"457","author":"Liu","year":"2023","journal-title":"J. Hazard. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121715","DOI":"10.1016\/j.envres.2025.121715","article-title":"Air pollution and hypertension in rural versus urban children: Lipidomic insights into PM2.5 impacts","volume":"278","author":"Liu","year":"2025","journal-title":"Environ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17004","DOI":"10.1289\/EHP11155","article-title":"Prenatal Exposure to PM2.5 Oxidative Potential and Lung Function in Infants and Preschool- Age Children: A Prospective Study","volume":"131","author":"Marsal","year":"2023","journal-title":"Environ. Health Perspect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"118320","DOI":"10.1016\/j.envpol.2021.118320","article-title":"PM2.5 exposure in association with AD-related neuropathology and cognitive outcomes","volume":"292 Pt A","author":"Thiankhaw","year":"2022","journal-title":"Environ. Pollut."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114764","DOI":"10.1016\/j.intimp.2025.114764","article-title":"Andrographolide attenuates PM2.5-induced blood-brain barrier damage via antioxidant and PI3K\/AKT\/mTOR\/NRF2 pathways","volume":"157","author":"Kang","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, L., Wang, B., Wu, C., Wang, J., and Sun, M. (2023). Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031819"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jpsychires.2024.02.012","article-title":"ASD and ADHD: Divergent activating patterns of prefrontal cortex in executive function tasks?","volume":"172","author":"Li","year":"2024","journal-title":"J. Psychiatr. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25f15878","DOI":"10.4088\/JCP.25f15878","article-title":"Autism Spectrum Disorder, 1: Genetic and Environmental Risk Factors","volume":"86","author":"Andrade","year":"2025","journal-title":"J. Clin. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1016\/j.ajhg.2024.09.006","article-title":"MARK2 variants cause autism spectrum disorder via the downregulation of WNT\/\u03b2-catenin signaling pathway","volume":"111","author":"Gong","year":"2024","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e70429","DOI":"10.1111\/cns.70429","article-title":"Calcitriol Modulates Hippocampal Axon Guidance Through Enhanced EfnA4-Mediated PI3K\/AKT Signaling in an Autism Mouse Model","volume":"31","author":"Gong","year":"2025","journal-title":"CNS Neurosci. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41398-023-02563-7","article-title":"Bidirectional genetic overlap between autism spectrum disorder and cognitive traits","volume":"13","author":"Hope","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1001\/jamapsychiatry.2019.4160","article-title":"Cognitive Behavioral Treatments for Anxiety in Children With Autism Spectrum Disorder: A Randomized Clinical Trial","volume":"77","author":"Wood","year":"2020","journal-title":"JAMA Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18566","DOI":"10.1021\/acs.est.4c05563","article-title":"Prenatal Exposure to Source-Specific Fine Particulate Matter and Autism Spectrum Disorder","volume":"58","author":"Luglio","year":"2024","journal-title":"Environ. Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"135814","DOI":"10.1016\/j.jhazmat.2024.135814","article-title":"Investigating the potential risk of cadmium exposure on seizure severity and anxiety-like behaviors through the ferroptosis pathway in epileptic mice: An integrated multi-omics approach","volume":"480","author":"Chang","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"170317","DOI":"10.1016\/j.scitotenv.2024.170317","article-title":"Effects of chronic low-level lead (Pb) exposure on cognitive function and hippocampal neuronal ferroptosis: An integrative approach using bioinformatics analysis, machine learning, and experimental validation","volume":"917","author":"Cao","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1016\/S0140-6736(24)00769-4","article-title":"Findings from the Global Burden of Disease Study 2021","volume":"403","author":"Murray","year":"2024","journal-title":"Lancet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"168578","DOI":"10.1016\/j.scitotenv.2023.168578","article-title":"PM(2.5) exposure exacerbates seizure symptoms and cognitive dysfunction by disrupting iron metabolism and the Nrf2-mediated ferroptosis pathway","volume":"910","author":"Mei","year":"2024","journal-title":"Sci. Total Environ."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jare.2020.07.007","article-title":"Quercetin alleviates acute kidney injury by inhibiting ferroptosis","volume":"28","author":"Wang","year":"2021","journal-title":"J. Adv. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123091","DOI":"10.1016\/j.envpol.2023.123091","article-title":"Association of household solid fuel use and long-term exposure to ambient air pollution with estimated 10-year high cardiovascular disease risk among postmenopausal women","volume":"342","author":"Chen","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"14193","DOI":"10.1021\/acs.est.4c00599","article-title":"Integrated Benefits of Synergistically Reducing Air Pollutants and Carbon Dioxide in China","volume":"58","author":"Li","year":"2024","journal-title":"Environ. Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"118686","DOI":"10.1016\/j.ecoenv.2025.118686","article-title":"Exploring the potential associations between single and mixed volatile compounds and preserved ratio impaired spirometry using five different approaches","volume":"302","author":"Deng","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.scitotenv.2014.11.007","article-title":"Spatial and seasonal variations of PM2.5 mass and species during 2010 in Xi\u2019an, China","volume":"508","author":"Wang","year":"2015","journal-title":"Sci. Total Environ."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108883","DOI":"10.1016\/j.envint.2024.108883","article-title":"Particulate matter induces depression-like behavior through systemic inflammation and brain-derived neurotrophic factors","volume":"194","author":"Li","year":"2024","journal-title":"Environ. Int."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fan, X., Dong, T., Yan, K., Ci, X., and Peng, L. (2023). PM2.5 increases susceptibility to acute exacerbation of COPD via NOX4\/Nrf2 redox imbalance-mediated mitophagy. Redox Biol., 59.","DOI":"10.1016\/j.redox.2022.102587"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"118741","DOI":"10.1016\/j.ecoenv.2025.118741","article-title":"Association between long-term exposure of polystyrene microplastics and exacerbation of seizure symptoms: Evidence from multiple approaches","volume":"302","author":"Xie","year":"2025","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41398-023-02307-7","article-title":"Fecal microbiota transplantation improves VPA-induced ASD mice by modulating the serotonergic and glutamatergic synapse signaling pathways","volume":"13","author":"Wang","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jibon, M.D.K., Islam, M.A., Hosen, M.E., Faruqe, M.O., Zaman, R., Acharjee, U.K., Sikdar, B., Tiruneh, Y.K., Khalekuzzaman, M., and Jawi, M. (2025). In-silico analysis of deleterious non-synonymous SNPs in the human AVPR1a gene linked to autism. BMC Genomics, 26.","DOI":"10.1186\/s12864-025-11655-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eadp6182","DOI":"10.1126\/sciadv.adp6182","article-title":"Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition","volume":"10","author":"Lebas","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0100242024","DOI":"10.1523\/JNEUROSCI.0100-24.2024","article-title":"Sex-Specific Mechanisms Underlie Long-Term Potentiation at Hippocampus\u2192Medium Spiny Neuron Synapses in the Medial Shell of the Nucleus Accumbens","volume":"44","author":"Copenhaver","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"138105","DOI":"10.1016\/j.jhazmat.2025.138105","article-title":"Air pollution increases the risk of frailty: China Health and Retirement Longitudinal Study (CHARLS)","volume":"492","author":"Chen","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1186\/s12967-023-04218-z","article-title":"Exploring the molecular mechanism of comorbidity of autism spectrum disorder and inflammatory bowel disease by combining multiple data sets","volume":"21","author":"Zhu","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eadi3647","DOI":"10.1126\/sciadv.adi3647","article-title":"ATP1A3 as a target for isolating neuron-specific extracellular vesicles from human brain and biofluids","volume":"9","author":"You","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41586-022-05369-7","article-title":"Adenylate cyclase activity of TIR1\/AFB auxin receptors in plants","volume":"611","author":"Qi","year":"2022","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"D596","DOI":"10.1093\/nar\/gkab1020","article-title":"DISCO: A database of Deeply Integrated human Single-Cell Omics data","volume":"50","author":"Li","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"107706","DOI":"10.1016\/j.envint.2022.107706","article-title":"Diesel exhaust PM2.5 greatly deteriorates fibrosis process in pre-existing pulmonary fibrosis via ferroptosis","volume":"171","author":"Yue","year":"2023","journal-title":"Environ. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s12993-024-00251-0","article-title":"Assessing sociability using the Three-Chamber Social Interaction Test and the Reciprocal Interaction Test in a genetic mouse model of ASD","volume":"20","author":"Celec","year":"2024","journal-title":"Behav. Brain Funct."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1212\/WNL.0000000000201630","article-title":"Impacts of Climate Change and Air Pollution on Neurologic Health, Disease, and Practice: A Scoping Review","volume":"100","author":"Louis","year":"2023","journal-title":"Neurology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.neuro.2022.10.011","article-title":"Air pollution, depressive and anxiety disorders, and brain effects: A systematic review","volume":"93","author":"Zundel","year":"2022","journal-title":"Neurotoxicology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lamanna, J., and Meldolesi, J. (2024). Autism Spectrum Disorder: Brain Areas Involved, Neurobiological Mechanisms, Diagnoses and Therapies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042423"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"116222","DOI":"10.1016\/j.ecoenv.2024.116222","article-title":"Early-life exposure to PM2.5 leads to ASD-like phenotype in male offspring rats through activation of PI3K-AKT signaling pathway","volume":"274","author":"Li","year":"2024","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1038\/s42255-024-01121-9","article-title":"Organization of a functional glycolytic metabolon on mitochondria for metabolic efficiency","volume":"6","author":"Wang","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Gholipour, P., Ebrahimi, Z., Mohammadkhani, R., Ghahremani, R., Salehi, I., Sarihi, A., Komaki, A., and Karimi, S.A. (2024). Effects of (S)-3,4-DCPG, an mGlu8 receptor agonist, on hippocampal long-term potentiation at perforant pathway-dentate gyrus synapses in prenatal valproic acid-induced rat model of autism. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-63728-y"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Koek, L.A., Sanderson, T.M., Georgiou, J., and Collingridge, G.L. (2024). The role of calcium stores in long-term potentiation and synaptic tagging and capture in mouse hippocampus. Philos. Trans. R. Soc. Lond. B Biol. Sci., 379.","DOI":"10.1098\/rstb.2023.0241"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jare.2022.01.004","article-title":"Mechanical overloading induces GPX4-regulated chondrocyte ferroptosis in osteoarthritis via Piezo1 channel facilitated calcium influx","volume":"41","author":"Wang","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12967-023-04793-1","article-title":"The SOX4\/EZH2\/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury","volume":"22","author":"Yan","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.cell.2015.06.034","article-title":"FOXG1-Dependent Dysregulation of GABA\/Glutamate Neuron Differentiation in Autism Spectrum Disorders","volume":"162","author":"Mariani","year":"2015","journal-title":"Cell"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhao, H., Mao, X., Zhu, C., Zou, X., Peng, F., Yang, W., Li, B., Li, G., Ge, T., and Cui, R. (2021). GABAergic System Dysfunction in Autism Spectrum Disorders. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.781327"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1038\/s41380-022-01506-w","article-title":"Genetics of glutamate and its receptors in autism spectrum disorder","volume":"27","author":"Nisar","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1093\/hmg\/ddae058","article-title":"Identification of a molecular network regulated by multiple ASD high risk genes","volume":"33","author":"Wan","year":"2024","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pallar\u00e8s-Sastre, M., Amayra, I., Pulido, R., Nunes-Xavier, C.E., Ba\u00f1uelos, S., Cavaliere, F., and Garc\u00eda, M. (2025). Novel CTNNB1 Gene Variants in Spanish CTNNB1 Syndrome Patients: Clinical and Psychological Manifestations. J. Autism Dev. Disord., 1\u201315.","DOI":"10.1007\/s10803-025-06829-5"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"101021","DOI":"10.1016\/j.gendis.2023.04.041","article-title":"The molecular genetics of PI3K\/PTEN\/AKT\/mTOR pathway in the malformations of cortical development","volume":"11","author":"Ma","year":"2024","journal-title":"Genes Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.2174\/1871527320666210806165430","article-title":"Valproic Acid and Propionic Acid Modulated Mechanical Pathways Associated with Autism Spectrum Disorder at Prenatal and Neonatal Exposure","volume":"21","author":"Sharma","year":"2022","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Huang, W., Wu, D., Cai, C., Yao, H., Tian, Z., Yang, Y., Pang, M., Rong, L., and Liu, B. (2024). Inhibition of MST1 ameliorates neuronal apoptosis via GSK3\u03b2\/\u03b2-TrCP\/NRF2 pathway in spinal cord injury accompanied by diabetes. Redox Biol., 71.","DOI":"10.1016\/j.redox.2024.103104"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"155073","DOI":"10.1016\/j.phymed.2023.155073","article-title":"Network pharmacology analysis and animal experiment validation of neuroinflammation inhibition by total ginsenoside in treating CSM","volume":"126","author":"Li","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Moreno, R.J., Azzam, Y.W., Eng, S., Rose, D., and Ashwood, P. (2025). Altered Monocyte Populations and Activation Marker Expression in Children with Autism and Co-Occurring Gastrointestinal Symptoms. Biomolecules, 15.","DOI":"10.3390\/biom15020207"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Alshamrani, A.A., Alshehri, S., Alqarni, S.S., Ahmad, S.F., Alghibiwi, H., Al-Harbi, N.O., Alqarni, S.A., Al-Ayadhi, L.Y., Attia, S.M., and Alfardan, A.S. (2023). DNA Hypomethylation Is Associated with Increased Inflammation in Peripheral Blood Neutrophils of Children with Autism Spectrum Disorder: Understanding the Role of Ubiquitous Pollutant Di(2-ethylhexyl) Phthalate. Metabolites, 13.","DOI":"10.3390\/metabo13030458"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ibneur.2023.11.009","article-title":"Anethole via increase in the gene expression of PI3K\/AKT\/mTOR mitigates the autistic-like behaviors induced by maternal separation stress in mice","volume":"16","author":"Vanani","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s11481-024-10111-3","article-title":"IL-6 Enhances the Activation of PI3K-AKT\/mTOR-GSK-3\u03b2 by Upregulating GRPR in Hippocampal Neurons of Autistic Mice","volume":"19","author":"Li","year":"2024","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102409","DOI":"10.1016\/j.eclinm.2023.102409","article-title":"Identification and validation of an explainable prediction model of acute kidney injury with prognostic implications in critically ill children: A prospective multicenter cohort study","volume":"68","author":"Hu","year":"2024","journal-title":"eClinicalMedicine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","article-title":"Mendelian randomization","volume":"2","author":"Sanderson","year":"2022","journal-title":"Nat. Rev. Methods Primers"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lin, L., Zhang, R., Huang, H., Zhu, Y., Li, Y., Dong, X., Shen, S., Wei, L., Chen, X., and Christiani, D.C. (2021). Mendelian Randomization With Refined Instrumental Variables From Genetic Score Improves Accuracy and Reduces Bias. Front. Genet., 12.","DOI":"10.3389\/fgene.2021.618829"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zhu, M., Li, X., Lin, W., Zeng, D., Yang, P., Ni, W., Chen, Z., Lin, B., Lai, L., and Ouyang, Z. (2024). Microplastic Particles Detected in Fetal Cord Blood, Placenta, and Meconium: A Pilot Study of Nine Mother\u2013Infant Pairs in South China. Toxics, 12.","DOI":"10.3390\/toxics12120850"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"146979","DOI":"10.1016\/j.scitotenv.2021.146979","article-title":"Selection of microplastics by Nile Red staining increases environmental sample throughput by micro-Raman spectroscopy","volume":"783","author":"Prata","year":"2021","journal-title":"Sci. Total. Environ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"161155","DOI":"10.1016\/j.scitotenv.2022.161155","article-title":"Quantification analysis of microplastics released from disposable polystyrene tableware with fluorescent polymer staining","volume":"864","author":"Zheng","year":"2022","journal-title":"Sci. Total. Environ."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41398-023-02456-9","article-title":"Effect of psilocybin on marble burying in ICR mice: Role of 5-HT1A receptors and implications for the treatment of obsessive-compulsive disorder","volume":"13","author":"Singh","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Horii-Hayashi, N., Masuda, K., Kato, T., Kobayashi, K., Inutsuka, A., Nambu, M.F., Tanaka, K.Z., Inoue, K., and Nishi, M. (2024). Entrance-sealing behavior in the home cage: A defensive response to potential threats linked to the serotonergic system and manifestation of repetitive\/stereotypic behavior in mice. Front. Behav. Neurosci., 17.","DOI":"10.3389\/fnbeh.2023.1289520"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Samra, A.I., Kamel, A.S., Abdallah, D.M., El Fattah, M.A.A., Ahmed, K.A., and El-Abhar, H.S. (2023). Preclinical Evidence for the Role of the Yin\/Yang Angiotensin System Components in Autism Spectrum Disorder: A Therapeutic Target of Astaxanthin. Biomedicines, 11.","DOI":"10.3390\/biomedicines11123156"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12974-022-02400-6","article-title":"Edaravone ameliorates epressive and anxiety-like behaviors via Sirt1\/Nrf2\/HO-1\/Gpx4 pathway","volume":"19","author":"Dang","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Lee, J.-H., Yun, J.Y., Gregory, A., Hogarth, P., and Hayflick, S.J. (2020). Brain MRI Pattern Recognition in Neurodegeneration With Brain Iron Accumulation. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.01024"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.freeradbiomed.2022.09.001","article-title":"Quercetin alleviates kainic acid-induced seizure by inhibiting the Nrf2-mediated ferroptosis pathway","volume":"191","author":"Xie","year":"2022","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7174287","DOI":"10.1155\/2021\/7174287","article-title":"The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells","volume":"2021","author":"Xie","year":"2021","journal-title":"Neural Plast."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Xie, Q., and Hu, B. (2023). Effects of gut microbiota on prostatic cancer: A two-sample Mendelian randomization study. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1250369"}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/11\/922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T16:47:05Z","timestamp":1765212425000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/13\/11\/922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":73,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["toxics13110922"],"URL":"https:\/\/doi.org\/10.3390\/toxics13110922","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,28]]}}}