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Future efforts should focus on second/third generation highly selective RIPK1/3 inhibitors, combined with COPD-specific pharmacokinetic and safety evaluations, to truly answer whether necroptosis inhibition has an acceptable risk-benefit ratio. In terms of targeting pyroptosis/GSDMD, Disulfiram, a classic alcohol deterrent, has recently been found to covalently modify the key cysteine residue of GSDMD, blocking the insertion of the GSDMD-N terminal into membranes to form pores, thereby inhibiting pyroptosis and the release of IL-1 and IL-18 (263, 264)

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Additionally, for Randomized Controlled Trials (RCTs), we applied the JBI critical appraisal checklist specific to RCTs (21) (see Supplementary material 1)

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