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In macrophage models, -KG promotes JMJD3-mediated H3K27me3 demethylation, thereby favoring the expression of M2-related genes, whereas succinate accumulation can inhibit demethylase activity and sustain a pro-inflammatory transcriptional state ( It should be noted that most current evidence regarding amino acid-mediated regulation of macrophage polarization is derived from in vitro cell models or animal experiments, whereas systematic validation in human clinical samples remains relatively limited