Circulatory Molecular Atlas Reveals Dose- and Time-dependent Perturbation and Recovery Signatures after Acute PM _2.5 Exposure

Recent epidemiological and toxicological studies have linked exposure to ambient fine particulate matter (PM_2.5) to various diseases and adverse health outcomes. However, a comprehensive atlas of the molecular responses and underlying mechanisms that connect PM_2.5 exposure to long-term effects remains elusive. To bridge this gap, we established a dose- and time-dependent serum multiomics atlas in mice following a single PM_2.5 exposure by integrating biochemical indexes and proteomic, metabolomic, and lipidomic profiles collected at 3, 7, 14, and 21 days postexposure across 10, 50, and 150 μg doses. Across increasing PM_2.5 doses, systemic perturbations progressed from mild inflammatory activation to coordinated disruptions of hemostasis and metabolic homeostasis. Over time, trajectories shifted from acute injury and immune mobilization (3-7 days) to later metabolic remodeling and tissue repair (14-21 days). Multiomics integrative analyses revealed early hemostatic and inflammatory perturbations with later recovery processes, outlining a continuum from acute insult to long-term effects. This work provides novel mechanistic insights into the systemic pathophysiology of air pollution, establishing a foundation for elucidating the molecular transitions that link acute exposure to chronic health risks.