Ferroptosis Profiling of Outcome-Associated Monocyte Subsets and the Potential Regulatory Role of LDHA in Early Sepsis.

Objective: Sepsis carries high morbidity and mortality, and early precise intervention is critical for improving outcomes. The heterogeneity of circulating immune cells, particularly at the monocyte subset level, remains a major barrier to early risk stratification. This study aimed to identify prognosis-associated monocyte subsets and their key regulators in early sepsis, providing potential clues for early prognostic assessment and targeted intervention. Methods: We analyzed single-cell transcriptomic profiles of peripheral blood mononuclear cells (PBMCs) from patients with early sepsis and healthy controls in the GSE167363 dataset to define myeloid subsets associated with clinical outcomes. Core regulatory molecules were prioritized by intersecting differentially expressed genes (DEGs) with cell death-related gene sets, and their expression patterns were examined in bulk transcriptomic cohorts. The lead candidate was further evaluated through in vitro functional experiments and in vivo survival studies using the cecal ligation and puncture (CLP) mouse model. Results: A transitional monocyte subset defined by high Conclusion: This study identifies an outcome-associated monocyte subset with a ferroptosis signature in early sepsis and suggests a potential regulatory role for LDHA in monocyte ferroptosis.