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Here, a zebrafish phenotypic screening with deep\u2010learning assisted multiplex cardiac functional analysis using motion videos of larval hearts is established. Through training the model on a dataset of 2125 labeled ventricular images, ZVSegNet and HRNet exhibit superior performance over previous methods. As a result of high\u2010content phenotypic screening, cyanidin chloride (CyCl) is identified as a potent suppressor of DIC. CyCl effectively rescues cardiac cell death and improves heart function in both in vitro and in vivo models of Doxorubicin (Dox) exposure. CyCl shows strong inhibitory effects on lipid peroxidation and mitochondrial damage and prevents ferroptosis and apoptosis\u2010related cell death. Molecular docking and thermal shift assay further suggest a direct binding between CyCl and Keap1, which may compete for the Keap1\u2010Nrf2 interaction, promote nuclear accumulation of Nrf2, and subsequentially transactivate Gpx4 and other antioxidant factors. Site\u2010specific mutation of R415A in Keap1 significantly attenuates the protective effects of CyCl against Dox\u2010induced cardiotoxicity. Taken together, the capability of deep\u2010learning\u2010assisted phenotypic screening in identifying promising lead compounds against DIC is exhibited, and new perspectives into drug discovery in the era of artificial intelligence are provided.<\/jats:p>","DOI":"10.1002\/advs.202301136","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T21:45:13Z","timestamp":1694123113000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Use of Deep\u2010Learning Assisted Assessment of Cardiac Parameters in Zebrafish to Discover Cyanidin Chloride as a Novel Keap1 Inhibitor Against Doxorubicin\u2010Induced Cardiotoxicity"],"prefix":"10.1002","volume":"10","author":[{"given":"Changtong","family":"Liu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang University  866 Yuhangtang Road, Xihu District Hangzhou 310058 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