Matters arising: cellular composition, regulatory directionality, and prognostic reproducibility in m6A-associated glycolytic reprogramming during sepsis

To the Editor,We read with interest the study by Liu and colleagues integrating public transcriptomic, perturbation, epitranscriptomic, and single-cell datasets to investigate N6-methyladenosine-associated glycolytic reprogramming in sepsis [1].The study provides a valuable hypothesis-generating framework linking an ALKBH5-associated transcriptional program with glycolytic activity and a four-gene mortality signature.The authors appropriately acknowledge major leukocyte shifts, weak within-lineage correlations, limited mechanistic validation, and constraints in external validation.Nevertheless, several specific internal inconsistencies and unresolved methodological details merit clarification, particularly where stronger mechanistic language in parts of the results and figures extends beyond the more cautious interpretation in the Conclusion and Discussion.First, the reported ρ = 0.592 represents the correlation between the M2 module eigengene and glycolytic