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Metabolic analysis tends to be powerful for precisely detection and mechanism exploration since most of diseases including cataracts are accompanied by metabolic disorder. Herein, a layered binary co\u2010ionizers assisted aqueous humor metabolic analysis tool is proposed for potentially etiological typing and detection of cataracts, including age\u2010related cataracts (ARC), cataracts with diabetes mellitus (CDM), and cataracts with high myopia (CHM). Startlingly, taking advantage of the optimal machine learning algorithm and all metabolic fingerprints, 100% of accuracy, precision, and recall rates are achieved for arbitrary comparison between groups. Moreover, 11, 9, and 7 key metabolites with explicit identities are confirmed as markers of discriminating CDM from ARC, CHM from ARC, and CDM from CHM, and the corresponding area under the curve values of validation cohorts are 0.985, 1.000, and 1.000. Finally, the critical impact of diabetes\/high myopia on cataracts is revealed by excavating the change levels and metabolic pathways of key metabolites. This work updates the insights of prevention and treatment about cataracts at metabolic level and throws out huge surprises and progresses metabolic diagnosis toward a reality.<\/jats:p>","DOI":"10.1002\/advs.202105905","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T09:02:06Z","timestamp":1653555726000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Precise Detection of Cataracts with Specific High\u2010Risk Factors by Layered Binary Co\u2010Ionizers Assisted Aqueous Humor Metabolic Analysis"],"prefix":"10.1002","volume":"9","author":[{"given":"Chenjie","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Chemistry Institue of Metabolism and Integrate Biology (IMIB) Zhongshan Hospital Fudan University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aizhu","family":"Miao","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye &amp; ENT Hospital Fudan University  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaochao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institue of Metabolism and Integrate Biology (IMIB) Zhongshan Hospital Fudan University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuwen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital Fudan University  Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institue of Metabolism and Integrate Biology (IMIB) Zhongshan Hospital Fudan University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye &amp; ENT Hospital Fudan University  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-7543","authenticated-orcid":false,"given":"Chunhui","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Chemistry Institue of Metabolism and Integrate Biology (IMIB) Zhongshan Hospital Fudan University  Shanghai 200433 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianrong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Zhongshan Hospital Fudan University  Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-020-00543-9"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30544-5"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0238081"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2015.06.035"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.3390\/nu12113534"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-27535"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2015.12.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/ceo.12696"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2018.04.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30393-5"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3310\/hta25060"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/582060"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112032"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4101"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-019-0108-4"},{"key":"e_1_2_8_10_3","doi-asserted-by":"publisher","DOI":"10.1038\/425905a"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107872"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.07.010"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2015.10.015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3745"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.06.013"},{"key":"e_1_2_8_14_2","doi-asserted-by":"crossref","first-page":"300060520934658","DOI":"10.1177\/0300060520934658","volume":"48","author":"Jin J.","year":"2020","journal-title":"J. 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