Effects of acute PM_2.5 purification on cognitive function and underlying mechanisms: Evidence from integrating...

The relationship between fine particulate matter (PM_2.5) and cognition has been extensively investigated. However, the causal impact of acute PM_2.5 purification on cognition improvement and the underlying biological mechanisms remain relatively opaque. Our double-blinded randomized controlled trial assessed the impact of acute PM_2.5 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 PM_2.5 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 PM_2.5 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 PM_2.5 purification and provide mechanistic understandings of PM_2.5-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.