Metabolic gene-based clustering identifies the role of acyl-CoA synthetase long-chain family member 1 in sepsis

assays demonstrate that osthole, a natural coumarin derivative, directly targets ACSL1, reducing lipid peroxidation and ferroptosis in septic PBMCs. Single-cell RNA sequencing reveals that ACSL1 is predominantly overexpressed in a pathogenic monocyte subset, driving sepsis progression. These findings suggest that metabolic stratification can distinguish clinically relevant subtypes of sepsis, with ACSL1 representing a key therapeutic target. Furthermore, osthole shows potential as a targeted intervention by inhibiting ACSL1-mediated ferroptosis in PBMCs from sepsis patients.