{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:53:10Z","timestamp":1791571990514,"version":"4.3.4"},"reference-count":48,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"22","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21877030"],"award-info":[{"award-number":["21877030"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22174042"],"award-info":[{"award-number":["22174042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research and Development Program of Hunan Province, China","award":["2023SK2039"],"award-info":[{"award-number":["2023SK2039"]}]},{"name":"Key Research and Development Program of Hunan Province, China","award":["2022GK2017"],"award-info":[{"award-number":["2022GK2017"]}]},{"name":"Hunan Science and Technology Innovation Plan","award":["2025ZYJ003"],"award-info":[{"award-number":["2025ZYJ003"]}]},{"name":"the Fundamental and Interdisciplinary Disciplines Breakthrough Plan of the Ministry of Education of China","award":["JYB2025XDXM602"],"award-info":[{"award-number":["JYB2025XDXM602"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:p>\n                    The ability to interrogate complex biological environments without prior target knowledge is a key challenge in chemical sensing. Conventional methods are limited in discovering previously unidentified biomarkers. To overcome this, we developed CEMs-SELEX (cell extracellular mixtures\u2013systematic evolution of ligands by exponential enrichment), a de novo selection platform that screens for functional DNAzymes responsive to disease-specific CEMs. Applied to tongue squamous cell carcinoma (TSCC), we identified C502, a DNAzyme activated by tumor secretions with high affinity (\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    \u00a0=\u00a024.49 nanomolar) and fast catalytic turnover (\n                    <jats:italic toggle=\"yes\">K<\/jats:italic>\n                    <jats:sub>cat<\/jats:sub>\n                    \u00a0=\u00a047.56 per second). Integrated multiomics and affinity pull-down identified annexin A2 (ANXA2) as its target, and molecular docking with mutagenesis elucidated the recognition mechanism. Engineering C502 into a DNA Walker enabled ultrasensitive detection of ANXA2 in clinical serum and saliva. In 80 individuals, the assay clearly differentiated patients with TSCC from healthy donors, highlighting its potential as a noninvasive diagnostic framework. Collectively, this work closes the loop from functional probe discovery to clinical assay, offering a generalizable platform for noninvasive cancer diagnostics.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee7184","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:00:46Z","timestamp":1780077646000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["CEMs-SELEX: DNAzyme-powered de novo biomarker discovery and noninvasive cancer diagnosis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5937-0343","authenticated-orcid":true,"given":"Wei","family":"Cui","sequence":"first","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing, Hunan University, Changsha 410082, China."},{"name":"College of Biology, Hunan University, Changsha 410082, China."},{"name":"Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3390-3141","authenticated-orcid":true,"given":"Hang","family":"Xiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing, Hunan University, Changsha 410082, China."},{"name":"Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China."},{"name":"College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7408-4155","authenticated-orcid":true,"given":"Xiaohong","family":"Wen","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, P. 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-682X","authenticated-orcid":true,"given":"Jin","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Chemo and Biosensing, Hunan University, Changsha 410082, China."},{"name":"Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha 410082, China."},{"name":"College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay9040"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02855"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-018-0378-6"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-024-03141-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4CS00370E"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.113844"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-023-00633-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0390-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1155-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b06728"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00240F"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202504363"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja801951p"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201510125"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202306272"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201100477"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-023-01328-5"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-22-2124"},{"key":"e_1_3_2_20_2","first-page":"e18138","article-title":"Global burden of lip, oral, and pharyngeal cancer across three decades: An age-adjusted GBD analysis","volume":"43","author":"Hamza K.","year":"2025","unstructured":"K. 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