Related Experiment Video
Updated: Aug 5, 2026
09:10
Multimodal Analysis of Microplastics in Drinking Water using a Silicon Nanomembrane Analysis Pipeline
Published on: June 13, 2025
Polyamide-66 microplastics and early-onset ischemic stroke: a systems toxicology, multi-omics, and molecular dynamics
Qiu-Han Xu1, Zhao-Hui Chai1, Jian-Cheng Jin2
1Department of Neurosurgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.
Molecular Diversity
|July 30, 2026
Summary
Polyamide-66 (PA66) microplastics may drive early-onset ischemic stroke by disrupting astrocytic EPHX2-sphingolipid pathways. This research offers a mechanistic link between microplastic exposure and stroke risk, aiding hazard assessment.
Area of Science:
- Environmental Health
- Toxicology
- Neuroscience
Background:
- Early-onset ischemic stroke (EOS) rates are increasing, with microplastics identified as a novel risk factor.
- Polyamide-66 (PA66) microplastics are frequently detected in human arterial thrombi, correlating with stroke severity.
Purpose of the Study:
- To elucidate the molecular pathways linking PA66 microplastics to EOS using an in silico framework.
- To identify specific proteins and pathways affected by PA66 in the brain.
Main Methods:
- Integrated systems toxicology and multi-omics causal inference.
- Target prediction, Mendelian randomization (MR) using brain protein-QTL and sc-eQTL data.
- Molecular docking and dynamics simulations, mouse model phenome queries, and single-cell RNA-seq.
Main Results:
- Identified EPHX2 as a shared protein linking PA66 and EOS, with higher genetically proxied brain EPHX2 associated with lower EOS risk, particularly for small-artery occlusion.
- Confirmed an astrocytic association for EPHX2 expression and implicated downstream metabolites (glycosyl-N-ceramide) in EOS.
- Molecular docking showed PA66 binding to soluble epoxide hydrolase (EPHX2), and mouse models revealed disrupted lipid metabolism and Ephx2 downregulation in astrocytes post-stroke.
Conclusions:
- An astrocytic EPHX2-sphingolipid axis is proposed as a mechanism by which PA66 microplastics promote premature stroke.
- These findings provide a mechanistic basis for assessing and mitigating the neurovascular risks associated with PA66 microplastic exposure.
