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Itaconate, derived from citrate produced in the TCA cycle, contains ,-unsaturated carboxylic acid, and covalently modifies at the Cys151 residue of Keap1 ( via oxidative phosphorylation-driven ROS generation in peritoneal tissue-resident macrophages and concomitant ROS-mediated mitogen-activated protein kinases (MAPKs) activation in tumor cells ( Nrf2 expression is significantly downregulated in peritoneal tissue-resident macrophages isolated from Immune-responsive gene 1 ( Irg1 ) shRNA-injected tumor-bearing mouse ( via Keap1 alkylation ( Figure 3 )

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