Citations

ABSTRACT Microplastic pollution may influence neurodevelopment, yet its relationship with attention‐deficit/hyperactivity disorder (ADHD) remains unclear. We integrated a pediatric cohort, multi‐omics analyses, network toxicology, and animal experiments to investigate polyethylene (PE) microplastic exposure in ADHD vulnerability. Among 90 children, PE was the predominant polymer detected in blood and was more abundant in children with ADHD. Higher PE burden was associated with greater symptom severity, increased IL‐6, and reduced antioxidant capacity. Multi‐omics and network analyses converged on PI3K/AKT1/Nrf2 signaling. In a perinatal nicotine mouse model, developmental PE co‐exposure exacerbated ADHD‐like behaviors, dopaminergic dysfunction, and oxidative injury. Melatonin partially alleviated these abnormalities by restoring PI3K/AKT1/GSK3β and Nrf2 signaling, whereas AAV‐mediated PI3K knockdown weakened its protective effects. Collectively, the human findings identify circulating PE burden as an environmental correlate of ADHD‐related neurodevelopmental vulnerability, while the animal experiments provide evidence that developmental PE co‐exposure can aggravate ADHD‐like abnormalities in a susceptible background.

As an emerging tire wear-derived environmental contaminant, 6PPD-quinone (6PPDQ) has raised significant concerns regarding its neurotoxic potential, particularly for children exposed to recycled tire crumb rubber in playgrounds. However, the molecular mechanisms by which 6PPDQ influences neurological disorders such as epilepsy remain poorly understood. In this study, we employed an integrative framework combining network toxicology, bulk analysis of human epileptic brain tissues, Mendelian randomization, and molecular dynamics simulations to elucidate these mechanisms. Our findings, validated through CETSA-WB and SPR, identify 6PPDQ as a direct ligand that binds to and stabilizes neuronal TP53. Through a synergistic double-hit mechanism, 6PPDQ directly engages the TP53 pathway while simultaneously triggering microglial interleukin-6 secretion. These converging pathways lead to the suppression of the master antioxidant regulator Nrf2, resulting in glutathione depletion, excessive reactive oxygen species accumulation, and exacerbated neuronal damage under excitotoxic stress. Experimental validation using glutamate-induced HT22 cell models and microglia–neuron crosstalk systems confirmed that targeting the TP53/Nrf2 axis or scavenging ROS significantly attenuates 6PPDQ-induced neurotoxicity. Our findings highlight critical risks to pediatric neurological health posed by tire-derived contaminants and identify the TP53/Nrf2 axis as a promising therapeutic target. Furthermore, this work provides a robust scientific basis for refining risk assessment frameworks and developing regulatory strategies to mitigate environmental exposure to 6PPDQ.

Abstract Background The association between long-term use of benzodiazepines (BDZs) and cognitive function in patients with schizophrenia has not been fully characterized. This study aimed to investigate the relationship between long-term BDZs use and cognitive impairment in schizophrenia. Methods Data were derived from an observational study of treatment with atypical antipsychotics in Chinese patients with schizophrenia (SALT-C). Fifty-seven patients with long-term use of BDZs (≥ 60 days) were included, and 57 BDZs non-users were matched using propensity scores for age, sex, disease duration, and atypical antipsychotics received. Cognitive impairment was assessed using the Montreal Cognitive Assessment (MoCA); psychotic symptoms, illness severity, and psychosocial functioning were assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity (CGI-S) scale, and the Personal and Social Performance (PSP) scale. Between-group comparisons were performed using independent-samples t-tests or Mann–Whitney U tests. Multivariate analysis was performed using binary logistic regression. Results The long-term BDZs user group showed a significantly lower total MoCA score [16.02 (6.69)] than the BDZs non-user group [19.33 (7.11)] (P = 0.012). No significant between-group differences were observed in total scores on the PANSS, CGI-S, or PSP (all P > 0.05). Long-term BDZs use was independently associated with cognitive impairment (OR = 7.728, P = 0.017), whereas years of education was negatively associated with cognitive impairment (OR = 0.740, P = 0.007). Conclusions Long-term BDZs use is associated with poorer cognitive performance in patients with schizophrenia, suggesting that cognitive function should be monitored during BDZs treatment in this population.

With rapid industrial expansion, air pollution’s 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.