{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:45:57Z","timestamp":1792784757139,"version":"4.5.0"},"reference-count":47,"publisher":"American Chemical Society (ACS)","issue":"37","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2026-RISE-01-022-02"],"award-info":[{"award-number":["2026-RISE-01-022-02"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2024-00406240"],"award-info":[{"award-number":["RS-2024-00406240"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-NR077138"],"award-info":[{"award-number":["RS-2023-NR077138"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00464032"],"award-info":[{"award-number":["RS-2024-00464032"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-16063568"],"award-info":[{"award-number":["RS-2025-16063568"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-18362970"],"award-info":[{"award-number":["RS-2025-18362970"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2026-25512726"],"award-info":[{"award-number":["RS-2026-25512726"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010446","name":"Institute for Basic Science","doi-asserted-by":"publisher","award":["IBS-R026-D1"],"award-info":[{"award-number":["IBS-R026-D1"]}],"id":[{"id":"10.13039\/501100010446","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2E33190"],"award-info":[{"award-number":["2E33190"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003693","name":"Korea Institute of Science and Technology","doi-asserted-by":"publisher","award":["2E33191"],"award-info":[{"award-number":["2E33191"]}],"id":[{"id":"10.13039\/501100003693","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Technology Innovation Program","award":["RS-2025-08672969"],"award-info":[{"award-number":["RS-2025-08672969"]}]},{"name":"InnoCORE program","award":["N10260097"],"award-info":[{"award-number":["N10260097"]}]},{"name":"Yonsei University Research Fund","award":["2025-12-0195"],"award-info":[{"award-number":["2025-12-0195"]}],"id":[{"id":"https:\/\/ror.org\/01wjejq96","id-type":"ROR","asserted-by":"crossref"}]},{"name":"STEAM Research Programs","award":["RS-2024-00460364"],"award-info":[{"award-number":["RS-2024-00460364"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Early identification of the pre-disease state is critical for effective intervention and improved outcomes in chronic kidney disease. However, current diagnostic approaches mainly rely on serum-based biomarkers, which are limited in capturing dynamic physiological changes or enabling real-time monitoring. Here, we present a smart contact lens (SCL) platform capable of real-time, non-invasive monitoring of tear uric acid (TUA) levels. The system integrates an electrochemical biosensor and wireless communication module, offering high sensitivity, stability, and selectivity. Using a hyperuricemic nephropathy (HN) rabbit model, we continuously tracked TUA levels and applied dynamic network biomarker (DNB) theory to identify the critical transition point preceding irreversible disease onset. The DNB-derived composite index enabled personalized identification of critical transition periods and detection of the reversible pre-disease state before progression to HN. Furthermore, longitudinal analysis revealed progressive shortening of the blood-to-tear diffusion lag time during disease progression, introducing transport kinetics as an additional dynamic biomarker associated with pathological changes. Continuous tear-derived dynamic signatures enabled more sensitive detection of early disease transitions than static serum biomarkers, highlighting the value of waveform-based analysis for pre-disease monitoring. Together, this work provides a framework for wearable, tear-based early warning signal detection and personalized monitoring of kidney dysfunction.<\/jats:p>","DOI":"10.1021\/acsnano.6c11068","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T16:01:43Z","timestamp":1789228903000},"page":"25660-25673","source":"Crossref","is-referenced-by-count":0,"title":["Tear-Based Dynamic\nNetwork Biomarkers for Pre-Disease\nDetection of Hyperuricemic Nephropathy via Smart Contact Lens"],"prefix":"10.1021","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6026-3094","authenticated-orcid":true,"given":"Hayoung","family":"Song","sequence":"first","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeon-Mi","family":"Hong","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1094-5167","authenticated-orcid":true,"given":"Dayeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonho","family":"Paek","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0795-8097","authenticated-orcid":true,"given":"Wonjung","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-9766","authenticated-orcid":true,"given":"Hunkyu","family":"Seo","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-7361","authenticated-orcid":true,"given":"Jakyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihui","family":"Lee","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongwook","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-8478","authenticated-orcid":true,"given":"Jayoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1522-4958","authenticated-orcid":true,"given":"Jang-Ung","family":"Park","sequence":"additional","affiliation":[{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Institute for Basic Science (IBS) , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Yonsei University , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Yonsei University College of Medicine , , ,","place":["Seoul, Republic of Korea, 03722"]},{"name":"Yonsei-KIST Convergence Research Institute , ,","place":["Seoul, Republic of Korea, 03722"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"2026092210081982200_cit1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41551-025-01605-3","article-title":"A Filamentary Soft Robotic Probe\nfor Multimodal in Utero Monitoring of Fetal Health","author":"Bai","year":"2026","journal-title":"Nat. Biomed. Eng."},{"key":"2026092210081982200_cit2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2024.116769","article-title":"Calibration-Free\nand Ready-to-Use Wearable Electroanalytical Reporting System (r-WEAR)\nfor Long-Term Remote Monitoring of Electrolytes Markers","volume":"267","author":"Wang","year":"2025","journal-title":"Biosens. Bioelectron."},{"issue":"4","key":"2026092210081982200_cit3","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41587-019-0045-y","article-title":"Wearable Biosensors\nfor Healthcare Monitoring","volume":"37","author":"Kim","year":"2019","journal-title":"Nat. Biotechnol."},{"issue":"2","key":"2026092210081982200_cit4","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/s41587-019-0321-x","article-title":"A Laser-Engraved Wearable\nSensor for Sensitive Detection of Uric Acid and Tyrosine in Sweat","volume":"38","author":"Yang","year":"2020","journal-title":"Nat. Biotechnol."},{"issue":"8","key":"2026092210081982200_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.device.2025.100781","article-title":"A Wireless\nForehead E-Tattoo for Mental Workload Estimation","volume":"3","author":"Huh","year":"2025","journal-title":"Device"},{"issue":"8095","key":"2026092210081982200_cit6","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41586-025-09819-w","article-title":"Quantifying the Global Eco-Footprint of Wearable Healthcare\nElectronics","volume":"649","author":"Yang","year":"2026","journal-title":"Nature"},{"issue":"1","key":"2026092210081982200_cit7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55790-x","article-title":"Thermoelectric Porous\nLaser-Induced Graphene-Based Strain-Temperature Decoupling and Self-Powered\nSensing","volume":"16","author":"Yang","year":"2025","journal-title":"Nat. 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Mater."},{"key":"2026092210081982200_cit11","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/s41578-025-00819-w","article-title":"Materials\nDesign and Integration Strategies for Soft Bioelectronics in Digital\nHealthcare","volume":"10","author":"Kim","year":"2025","journal-title":"Nat. Rev. Mater."},{"issue":"1","key":"2026092210081982200_cit12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47123-9","article-title":"In-Depth\nCorrelation Analysis between Tear Glucose and Blood Glucose Using\na Wireless Smart Contact Lens","volume":"15","author":"Park","year":"2024","journal-title":"Nat. Commun."},{"issue":"1","key":"2026092210081982200_cit13","doi-asserted-by":"publisher","DOI":"10.1002\/admt.201900728","article-title":"Recent Advances in Smart Contact Lenses","volume":"5","author":"Kim","year":"2020","journal-title":"Adv. Mater. Technol."},{"issue":"7","key":"2026092210081982200_cit14","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1038\/s41551-021-00719-8","article-title":"A Soft\nand Transparent Contact Lens for the Wireless Quantitative Monitoring\nof Intraocular Pressure","volume":"5","author":"Kim","year":"2021","journal-title":"Nat. Biomed. Eng."},{"issue":"19","key":"2026092210081982200_cit15","doi-asserted-by":"publisher","first-page":"11488","DOI":"10.1021\/acs.chemrev.3c00290","article-title":"Smart Contact\nLenses as Wearable Ophthalmic Devices for Disease Monitoring and Health\nManagement","volume":"123","author":"Seo","year":"2023","journal-title":"Chem. Rev."},{"issue":"27","key":"2026092210081982200_cit16","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202313848","article-title":"Self-Lubricating, Living Contact\nLenses","volume":"36","author":"Puertas-Bartolome\u0301","year":"2024","journal-title":"Adv. Mater."},{"issue":"26","key":"2026092210081982200_cit17","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aee8506","article-title":"Smart Contact Lens\u2013Trained\nDigital Twin for\nDevice-Free Personalized Uric Acid Prediction","volume":"12","author":"Song","year":"2026","journal-title":"Sci. Adv."},{"issue":"7260","key":"2026092210081982200_cit18","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/nature08227","article-title":"Early-Warning Signals for Critical Transitions","volume":"461","author":"Scheffer","year":"2009","journal-title":"Nature"},{"issue":"2","key":"2026092210081982200_cit19","doi-asserted-by":"publisher","DOI":"10.1186\/1755-8794-6-S2-S8","article-title":"Detecting Early-Warning Signals of\nType 1 Diabetes and Its Leading Biomolecular Networks by Dynamical\nNetwork Biomarkers","volume":"6","author":"Liu","year":"2013","journal-title":"BMC Med. Genomics"},{"issue":"2","key":"2026092210081982200_cit20","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s40484-013-0008-0","article-title":"Dynamical\nNetwork Biomarkers for\nIdentifying Critical Transitions and Their Driving Networks of Biologic\nProcesses","volume":"1","author":"Liu","year":"2013","journal-title":"Quant. Biol."},{"issue":"26","key":"2026092210081982200_cit21","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aec9837","article-title":"AI-Driven\nTripartite Classification for Optimizing Wearable Bioelectronics in\nDepression Management","volume":"12","author":"Lee","year":"2026","journal-title":"Sci. Adv."},{"issue":"6","key":"2026092210081982200_cit22","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1053\/j.ajkd.2018.03.028","article-title":"Distant Organ Dysfunction\nin Acute Kidney Injury: A Review","volume":"72","author":"Lee","year":"2018","journal-title":"Am. J. Kidney\nDis."},{"issue":"6","key":"2026092210081982200_cit23","first-page":"623","article-title":"Studies on\nthe Relation of the Kidney to Cardiovascular Disease","volume":"12","author":"Winternitz","year":"1940","journal-title":"Yale J. Biol. Med."},{"issue":"4","key":"2026092210081982200_cit24","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1111\/j.1523-1755.2005.00551.x","article-title":"Cardiovascular Risk\nFactors in Chronic Kidney Disease","volume":"68","author":"Menon","year":"2005","journal-title":"Kidney Int."},{"issue":"9","key":"2026092210081982200_cit25","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1093\/ndt\/gft029","article-title":"Uric Acid and Chronic Kidney Disease:\nWhich Is Chasing Which?","volume":"28","author":"Johnson","year":"2013","journal-title":"Nephrol., Dial., Transplant."},{"key":"2026092210081982200_cit26","article-title":"BUN and Creatinine","volume-title":"Clinical Methods: The History, Physical, and Laboratory\nExaminations","author":"Hosten","year":"1990"},{"issue":"8","key":"2026092210081982200_cit27","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1002\/bmc.1376","article-title":"Tear Analysis of Ascorbic Acid, Uric\nAcid and Malondialdehyde with Capillary Electrophoresis","volume":"24","author":"Georgakopoulos","year":"2010","journal-title":"Biomed. Chromatogr."},{"issue":"2","key":"2026092210081982200_cit28","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1111\/j.1755-3768.2008.01215.x","article-title":"Determination of Uric Acid Concentrations\nin Human Tear Fluid, Aqueous Humour and Serum","volume":"87","author":"Horwath-Winter","year":"2009","journal-title":"Acta Ophthalmol."},{"key":"2026092210081982200_cit29","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2022.121326","article-title":"Quantification\nof Uric Acid Concentration in Tears by Using PDMS Inverse Opal Structure\nSurface-Enhanced Raman Scattering Substrates: Application in Hyperuricemia","volume":"278","author":"Li","year":"2022","journal-title":"Spectrochim. Acta, Part A"},{"issue":"5","key":"2026092210081982200_cit30","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1097\/ICL.0b013e318268610a","article-title":"Blepharo-Tensiometer:\nNew Eyelid Pressure Measurement System Using Tactile Pressure Sensor","volume":"38","author":"Sakai","year":"2012","journal-title":"Eye Contact Lens"},{"issue":"10","key":"2026092210081982200_cit31","doi-asserted-by":"publisher","first-page":"3763","DOI":"10.1073\/pnas.1320393111","article-title":"Evolutionary\nHistory and Metabolic Insights of Ancient Mammalian Uricases","volume":"111","author":"Kratzer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. 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Nurs."},{"issue":"4","key":"2026092210081982200_cit37","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/S0272-6386(04)00934-5","article-title":"Significance\nof Hyperuricemia as a Risk Factor for\nDeveloping ESRD in a Screened Cohort","volume":"44","author":"Iseki","year":"2004","journal-title":"Am. J.\nKidney Dis."},{"issue":"6","key":"2026092210081982200_cit38","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1016\/j.surg.2015.12.029","article-title":"ROC-Ing along:\nEvaluation and Interpretation\nof Receiver Operating Characteristic Curves","volume":"159","author":"Carter","year":"2016","journal-title":"Surgery"},{"issue":"1","key":"2026092210081982200_cit39","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s00011-020-01409-y","article-title":"Uric Acid Drives Intestinal Barrier\nDysfunction through TSPO-Mediated\nNLRP3 Inflammasome Activation","volume":"70","author":"Lv","year":"2021","journal-title":"Inflamm. Res."},{"issue":"1","key":"2026092210081982200_cit40","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1080\/0886022X.2021.1944875","article-title":"Curcumin Modulates\nGut Microbiota and Improves Renal Function in Rats with Uric Acid\nNephropathy","volume":"43","author":"Xu","year":"2021","journal-title":"Renal Failure"},{"issue":"8","key":"2026092210081982200_cit41","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1080\/02713683.2018.1457164","article-title":"Tear Film\nStability and Tear Break Up Time (TBUT) in Laboratory Rabbits\u2500A\nSystematic Review","volume":"43","author":"Doughty","year":"2018","journal-title":"Curr. 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