When activated by HMGB1, NLRP3 can activate caspase-1 through recruiting nucleotide-binding domain and leucine-rich repeat (NLR) family, caspase recruitment domain (CARD) containing 4 (NLRC4), apoptosis associated speck like protein (ASC), and finally initiating a canonical pathway of pyroptosis and prompting the production of inflammatory factors in sepsis (41). The gene discussed is HMGB1; the disease is Sepsis.