Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Abstract Type 2 diabetes mellitus (T2DM) has become a worldwide epidemic, which poses a great threat to the global healthcare system. Based on review of publications pertaining to T2DM health management in urban communities, this article focuses on the health management models of T2DM in foreign urban communities, including insurance companies and medical institutions, self-management plans, community management, community and home hybrid services, artificial intelligence + big data management, social media and online community management, precision health management, and proposes suggestions for T2DM health management in Chinese urban communities based on currently available national management models, including increasing the standardization of the management level, improving the supporting facilities of professional talents, mobilizing social forces to support, improving the scientific and technological level of management tools, strengthening the advantages of traditional Chinese medicine and exploring novel personalized models, so as to provide insights into promoting the sustainable development of T2DM health management in Chinese urban communities.