Effects of acute PM2.5 purification on cognitive function and underlying mechanisms: Evidence from integrating alternative splicing into multi-omics.

The relationship between fine particulate matter (PM2.5) and cognition has been extensively investigated. However, the causal impact of acute PM2.5 purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM2.5 purification on executive function, underpinned by multi-omics approaches including alternative splicing (AS) analysis. A total of 93 participants experienced a two-hour exposure to either reduced and normal PM2.5 levels. We measured the cognition of healthy young adults, collected peripheral blood before and after intervention, and performed multi-omics analysis including transcriptomics, metabolomics, and proteomics. Results indicated that reducing PM2.5 by 1 μg/m3 was associated with a 0.10 % (95 % CI: [0.18 %, 0.01 %]; p = 0.031) improvement in executive function. Notably, we identified 96 AS events without concurrent transcriptional amount alterations. Multi-layered omics analyses revealed disrupted pathways in hypoxia, mitochondrial function and energy metabolism, and immune responses, validated by ELISA and biochemical assay. These findings demonstrated short-term improvements of cognition following PM2.5 purification and provide mechanistic understandings of PM2.5-induced cognition alterations. This study underscores the significance of incorporating AS in the molecular framework of multi-omics research by exploring variable exon splicing, which could enrich multi-omics analysis methodologies and expose to broader audience.