{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:21:13Z","timestamp":1788434473038,"version":"build-2803163510"},"reference-count":48,"publisher":"American Chemical Society (ACS)","issue":"34","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22134004"],"award-info":[{"award-number":["22134004"]}],"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":["22374092"],"award-info":[{"award-number":["22374092"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"the Project of Shandong Provincial Center for Fundamental Science Research","doi-asserted-by":"publisher","award":["YDZX2024150"],"award-info":[{"award-number":["YDZX2024150"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The antioxidant treatment for atherosclerosis has presented a paradox: theoretically feasible but clinically ineffective. In this study, we developed an \u201coxidative stress clock\u201d nanoprobe to dynamically monitor oxidative stress at different stages of atherosclerosis, thereby dissecting the optimal time window for antioxidant intervention. This probe could simultaneously and specifically recognize hydrogen peroxide, protein sulfenylation, and protein phosphorylation in vitro and in vivo, enabling accurate mapping of the evolution of oxidative stress during disease progression. Using this probe, we discovered that the effective window for antioxidant intervention is limited to the stage of reversible protein oxidative modification. However, clinical ultrasound imaging identifies plaques well after this critical window, which directly contributes to the clinical failure of antioxidant therapy. Furthermore, the underlying molecular mechanism driving oxidative stress-mediated atherosclerosis progression (ox-LDL\u2192H2O2\u2192EGFR\/Src\/PTP1B-SOH\u2192p-MAPK\u2192atherosclerosis) was uncovered.<\/jats:p>","DOI":"10.1021\/acsnano.6c09224","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T05:06:14Z","timestamp":1787375174000},"page":"23992-24003","source":"Crossref","is-referenced-by-count":0,"title":["An\n\u201cOxidative\nStress Clock\u201d Nanoprobe Reveals the Therapeutic Time Window\nfor Antioxidant Intervention in Atherosclerosis"],"prefix":"10.1021","volume":"20","author":[{"given":"Xia","family":"Zhang","sequence":"first","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guocheng","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Yin","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Zhong","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-8749","authenticated-orcid":true,"given":"Wei","family":"Pan","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhua","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-6672","authenticated-orcid":true,"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-7025","authenticated-orcid":true,"given":"Bo","family":"Tang","sequence":"additional","affiliation":[{"name":"Shandong Normal University , , ,","place":["Jinan, P. R. China, 250014"]},{"name":"Laoshan Laboratory , ,","place":["Qingdao, P. R. China, 266237"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026090306592668300_cit1","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/s41569-024-01016-y","article-title":"Canonical and non-canonical\nroles of complement in atherosclerosis","volume":"21","author":"Maffia","year":"2024","journal-title":"Nat.\nRev. Cardiol."},{"key":"2026090306592668300_cit2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41569-018-0073-1","article-title":"Nanoimmunotherapy to treat ischaemic\nheart disease","volume":"16","author":"Duivenvoorden","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"2026090306592668300_cit3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202514547","article-title":"Self-Assembled\nMetal-Polyphenol Colchicine Nanoparticles Targeting Oxidative Stress\nand Inflammation for Treatment of Atherosclerosis","volume":"65","author":"Centurion","year":"2026","journal-title":"Angew. Chem. Int. Ed."},{"key":"2026090306592668300_cit4","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/s41569-021-00668-4","article-title":"Therapeutic strategies targeting inflammation and immunity\nin atherosclerosis: how to proceed?","volume":"19","author":"Engelen","year":"2022","journal-title":"Nat. Rev.\nCardiol."},{"key":"2026090306592668300_cit5","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh1037","article-title":"Oxidative\nstress biomarker triggered multiplexed tool for auxiliary diagnosis\nof atherosclerosis","volume":"9","author":"Ma","year":"2023","journal-title":"Sci. Adv."},{"key":"2026090306592668300_cit6","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/s41392-023-01560-y","article-title":"NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress,\ninflammation and apoptosis in ApoE knockout mice","volume":"8","author":"Cheng","year":"2023","journal-title":"Sig. Transduct. Target. Ther."},{"key":"2026090306592668300_cit7","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s11883-017-0678-6","article-title":"Oxidative Stress in Atherosclerosis","volume":"19","author":"Kattoor","year":"2017","journal-title":"Curr. Atheroscler. Rep."},{"key":"2026090306592668300_cit8","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1038\/s41573-021-00233-1","article-title":"Targeting Oxidative\nStress in Disease: Promise and Limitations of Antioxidant Therapy","volume":"20","author":"Forman","year":"2021","journal-title":"Nat. Rev. Drug Disc."},{"key":"2026090306592668300_cit9","doi-asserted-by":"publisher","first-page":"103332","DOI":"10.1016\/j.redox.2024.103332","article-title":"Oxidative Stress-Mediated Protein Sulfenylation in Human Diseases:\nPast, Present, and Future","volume":"76","author":"Mu","year":"2024","journal-title":"Redox Biol."},{"key":"2026090306592668300_cit10","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/j.cell.2020.02.012","article-title":"A Quantitative\nTissue-Specific Landscape of Protein Redox Regulation during Aging","volume":"180","author":"Xiao","year":"2020","journal-title":"Cell"},{"key":"2026090306592668300_cit11","doi-asserted-by":"publisher","first-page":"101934","DOI":"10.1016\/j.redox.2021.101934","article-title":"Structural Insights into Redox-Active\nCysteine Residues of the Src Family Kinases","volume":"41","author":"Heppner","year":"2021","journal-title":"Redox Biol."},{"key":"2026090306592668300_cit12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nchembio.736","article-title":"Peroxide-Dependent\nSulfenylation of the EGFR Catalytic Site Enhances Kinase Activity","volume":"8","author":"Paulsen","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"2026090306592668300_cit13","doi-asserted-by":"publisher","first-page":"17444","DOI":"10.1021\/jacs.8b06354","article-title":"Oxidative Post-Tanslational Modifications\nAccelerate Proteolytic Degradation of Calprotectin","volume":"140","author":"Stephan","year":"2018","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306592668300_cit14","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1038\/s41586-021-03513-3","article-title":"A Lysine-Cysteine Redox Switch with\nan NOS Bridge Regulates Enzyme Function","volume":"593","author":"Wensien","year":"2021","journal-title":"Nature"},{"key":"2026090306592668300_cit15","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1038\/s41467-022-29512-0","article-title":"Citrullination of glucokinase is linked to autoimmune\ndiabetes","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"key":"2026090306592668300_cit16","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41570-020-00223-8","article-title":"Deciphering\nprotein post-translational modifications using chemical biology tools","volume":"4","author":"Conibear","year":"2020","journal-title":"Nat. Rev. Chem."},{"key":"2026090306592668300_cit17","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/s41581-024-00837-x","article-title":"Post-translational\nmodifications in kidney diseases and associated cardiovascular risk","volume":"20","author":"Noels","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"2026090306592668300_cit18","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/s41420-023-01560-5","article-title":"Research progress on post-translational modification of proteins\nand cardiovascular diseases","volume":"9","author":"Cheng","year":"2023","journal-title":"Cell Death Discov"},{"key":"2026090306592668300_cit19","doi-asserted-by":"publisher","first-page":"4582","DOI":"10.1021\/acs.jafc.5c15753","article-title":"Protocatechuic Acid, a Gut-Derived\nDietary Metabolite, Attenuates Endothelial Dysfunction via GPER-Mediated\nNO Signaling","volume":"74","author":"Lee","year":"2026","journal-title":"J. Agric. Food Chem."},{"key":"2026090306592668300_cit20","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1093\/cvr\/cvv250","article-title":"Pim1 kinase promotes\nangiogenesis through phosphorylation of endothelial nitric oxide synthase\nat Ser-633","volume":"109","author":"Chen","year":"2016","journal-title":"Cardiovasc. Res."},{"key":"2026090306592668300_cit21","doi-asserted-by":"publisher","first-page":"3691","DOI":"10.1016\/j.molcel.2021.08.018","article-title":"Redox Metabolism: ROS as Specific Molecular Regulators\nof Cell Signaling and Function","volume":"81","author":"Lennicke","year":"2021","journal-title":"Mol. Cell"},{"key":"2026090306592668300_cit22","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/s41418-024-01316-3","article-title":"EGFR inhibits TNF-\u03b1-mediated\npathway by phosphorylating TNFR1 at tyrosine 360 and 401","volume":"31","author":"Nam","year":"2024","journal-title":"Cell Death Differ."},{"key":"2026090306592668300_cit23","doi-asserted-by":"publisher","first-page":"4522","DOI":"10.1038\/s41467-018-06790-1","article-title":"Direct Cysteine\nSulfenylation Drives Activation of the Src Kinase","volume":"9","author":"Heppner","year":"2018","journal-title":"Nat. Commun."},{"key":"2026090306592668300_cit24","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1182\/blood-2014-01-453134","article-title":"Src Family Kinases: at the Forefront of Platelet Activation","volume":"124","author":"Senis","year":"2014","journal-title":"Blood"},{"key":"2026090306592668300_cit25","doi-asserted-by":"publisher","first-page":"11190","DOI":"10.1021\/acs.analchem.5c00911","article-title":"AIE-Active Probe for\nUnveiling the Role of Protein Sulfenylation In Vivo: Specific Imaging\nand Therapeutic Insights","volume":"97","author":"Zhang","year":"2025","journal-title":"Anal. Chem."},{"key":"2026090306592668300_cit26","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1182\/blood-2016-04-636456","article-title":"Vascular Thiol Isomerases","volume":"128","author":"Flaumenhaft","year":"2016","journal-title":"Blood"},{"key":"2026090306592668300_cit27","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1016\/j.jtha.2023.03.034","article-title":"Sulfenylation Links Oxidative Stress\nto Protein Disulfide Isomerase Oxidase Activity and Thrombus Formation","volume":"21","author":"Yang","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"2026090306592668300_cit28","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202506728","article-title":"A \u201cCocktail\u201d\nFluorescent Probe for Multi-ROS Imaging Unveils Ferroptosis-Driven\nLiver Fibrosis Development","volume":"64","author":"Wang","year":"2025","journal-title":"Angew. Chem. Int.\nEd."},{"key":"2026090306592668300_cit29","doi-asserted-by":"publisher","first-page":"114480","DOI":"10.1016\/j.bios.2022.114480","article-title":"Simultaneous fluorescence imaging of Golgi O2\u2022\u2013 and Golgi H2O2 in mice with hypertension","volume":"213","author":"Wang","year":"2022","journal-title":"Biosens. Bioelectron."},{"key":"2026090306592668300_cit30","doi-asserted-by":"publisher","first-page":"6166","DOI":"10.1021\/acs.analchem.0c00989","article-title":"Multiplex Optical Urinalysis for Early Detection of\nDrug-Induced Kidney Injury","volume":"92","author":"Cheng","year":"2020","journal-title":"Anal. Chem."},{"key":"2026090306592668300_cit31","doi-asserted-by":"publisher","first-page":"12656","DOI":"10.1021\/jacs.4c02070","article-title":"Bienzyme-Locked Activatable Fluorescent Probes for Specific Imaging\nof Tumor-Associated Mast Cells","volume":"146","author":"Hu","year":"2024","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026090306592668300_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301625","article-title":"A Tandem-Locked Fluorescent NETosis Reporter for the\nPrognosis Assessment of Cancer Immunotherapy","volume":"62","author":"Cheng","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"2026090306592668300_cit33","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202319780","article-title":"A Tandem-Locked\nChemiluminescent Probe for Imaging of Tumor-Associated Macrophage\nPolarization","volume":"136","author":"Huang","year":"2024","journal-title":"Angew. Chem. Int. Ed."},{"key":"2026090306592668300_cit34","doi-asserted-by":"publisher","first-page":"21267","DOI":"10.1021\/jacs.0c10442","article-title":"Construction of Molecular Sensing and Logic Systems Based on Site-Occupying\nEffect-Modulated MOF\u2013DNA Interaction","volume":"142","author":"Yu","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306592668300_cit35","doi-asserted-by":"publisher","first-page":"8952","DOI":"10.1021\/acs.analchem.0c00925","article-title":"Evaluating Hyperthyroidism-Induced\nLiver Injury Based on In Situ Fluorescence Imaging of Glutathione\nand Phosphate via Nano-MOFs Sensor","volume":"92","author":"Zhang","year":"2020","journal-title":"Anal. Chem."},{"key":"2026090306592668300_cit36","doi-asserted-by":"publisher","first-page":"2412498","DOI":"10.1002\/advs.202412498","article-title":"Macrophage\nHM13\/SPP Enhances Foamy Macrophage Formation and Atherogenesis","volume":"12","author":"Cao","year":"2025","journal-title":"Adv. Sci."},{"key":"2026090306592668300_cit37","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1124\/pr.118.017178","article-title":"Targeting Foam Cell Formation in Atherosclerosis: Therapeutic\nPotential of Natural Products","volume":"71","author":"Wang","year":"2019","journal-title":"Pharmacol. Rev."},{"key":"2026090306592668300_cit38","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202204518","article-title":"In-Sequence High-Specificity Dual-Reporter\nUnlocking of Fluorescent Probe Enables the Precise Identification\nof Atherosclerotic Plaques","volume":"61","author":"Ye","year":"2022","journal-title":"Angew. Chem. Int.\nEd."},{"key":"2026090306592668300_cit39","doi-asserted-by":"publisher","first-page":"102159","DOI":"10.1016\/j.redox.2021.102159","article-title":"The role of NADPH oxidases in infectious\nand inflammatory diseases","volume":"48","author":"Taylor","year":"2021","journal-title":"Redox Biol."},{"key":"2026090306592668300_cit40","doi-asserted-by":"publisher","first-page":"1430293","DOI":"10.3389\/fphar.2024.1430293","article-title":"The Relationship\nof Redox Signaling with the Risk for Atherosclerosis","volume":"15","author":"Lei","year":"2024","journal-title":"Front. Pharmacol."},{"key":"2026090306592668300_cit41","doi-asserted-by":"publisher","first-page":"17868","DOI":"10.1021\/acs.analchem.4c04559","article-title":"Synergistically Activated Aggregation-Induced\nEmission Probe for Precise In Situ Staining of Lipids in Atherosclerotic\nPlaques","volume":"96","author":"Li","year":"2024","journal-title":"Anal. Chem."},{"key":"2026090306592668300_cit42","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/nature01681","article-title":"Oxidation State of the Active-Site Cysteine in Protein Tyrosine Phosphatase\n1B","volume":"423","author":"van Montfort","year":"2003","journal-title":"Nature"},{"key":"2026090306592668300_cit43","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41467-017-00503-w","article-title":"Assay to visualize specific protein\noxidation reveals spatio-temporal regulation of SHP2","volume":"8","author":"Tsutsumi","year":"2017","journal-title":"Nat. Commun."},{"key":"2026090306592668300_cit44","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1021\/acs.chemrev.7b00105","article-title":"Regulatory Mechanisms\nand Novel Therapeutic Targeting Strategies for Protein Tyrosine Phosphatases","volume":"118","author":"Yu","year":"2018","journal-title":"Chem. Rev."},{"key":"2026090306592668300_cit45","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1126\/science.add7859","article-title":"Architecture of\nthe MKK6-p38\u03b1 Complex Defines the Basis of MAPK Specificity\nand Activation","volume":"381","author":"Juyoux","year":"2023","journal-title":"Science"},{"key":"2026090306592668300_cit46","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1038\/s41584-023-00966-w","article-title":"Matrix Metalloproteinases in Arthritis: Towards Precision\nMedicine","volume":"19","author":"Grillet","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"2026090306592668300_cit47","doi-asserted-by":"publisher","first-page":"17881","DOI":"10.1021\/jacs.3c04981","article-title":"Rational\nDesign of a Double-Locked Photoacoustic Probe for Precise In Vivo\nImaging of Cathepsin B in Atherosclerotic Plaques","volume":"145","author":"Ma","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"2026090306592668300_cit48","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1021\/jacs.5c17549","article-title":"A PET-Driven Strategy for Ultrasensitive Mapping of Lipid Microenvironment\nHeterogeneity in Dual Organelles during Metabolic Stress and Atherosclerosis","volume":"148","author":"Xie","year":"2026","journal-title":"J. Am. Chem. Soc."}],"container-title":["ACS Nano"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsnano.6c09224","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/34\/23992\/66966048\/acsnano.6c09224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancac3\/article-pdf\/20\/34\/23992\/66966048\/acsnano.6c09224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:59:33Z","timestamp":1788433173000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancac3\/article\/20\/34\/23992\/5284275\/An-Oxidative-Stress-Clock-Nanoprobe-Reveals-the"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":48,"journal-issue":{"issue":"34","published-online":{"date-parts":[[2026,8,21]]},"published-print":{"date-parts":[[2026,9,1]]}},"URL":"https:\/\/doi.org\/10.1021\/acsnano.6c09224","relation":{},"ISSN":["1936-0851","1936-086X"],"issn-type":[{"value":"1936-0851","type":"print"},{"value":"1936-086X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]}}}