{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:44:15Z","timestamp":1792784655193,"version":"4.5.0"},"reference-count":34,"publisher":"American Chemical Society (ACS)","issue":"36","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","award":["B2024206003"],"award-info":[{"award-number":["B2024206003"]}],"id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["22404040"],"award-info":[{"award-number":["22404040"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["82473752"],"award-info":[{"award-number":["82473752"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hepatic ischemia-reperfusion injury (HIRI) represents a severe complication in liver surgery and transplantation, thus early identification of ischemic damage, specifically the hallmark hypoxia, is pivotal for prognosis. However, the specific tools for detecting ischemic injury remain scarce. Herein, we present the first nitroreductase (NTR)-activatable, self-referenced surface-enhanced Raman scattering (SERS) nanoprobe (Au@MBN@Au@4-NTP, AMAN) for the quantitative monitoring of NTR activity, a key hypoxia biomarker, during hepatic ischemia. The nanoprobe integrates a physically shielded internal standard (4-mercaptobenzonitrile, 4-MBN) and an NTR-responsive reporter (4-nitrothiophenol, 4-NTP). Uniquely, the internal standard exhibits distinct vibrational fingerprints exclusively within the biologically Raman-silent window (1800\u20132800 cm\u20131), which substantially reduces spectral interference from complex endogenous biological matrices. Upon NTR activation, the reporter signal of 4-NTP at \u223c1325 cm\u20131 diminishes, while the internal standard signal at 2217 cm\u20131 remains unchanged, yielding a robust ratiometric readout (I1325\/I2217). This enables accurate quantification of NTR with a low detection limit of 0.406 \u03bcg\/mL. Using this nanoprobe, we achieve accurate and sensitive quantification of hypoxia-induced NTR upregulation in living cells. More importantly, the nanoprobe realizes real-time monitoring of dynamic NTR fluctuations during hepatic ischemia in both 2D and 3D cellular models. This work establishes a novel, interference-free SERS strategy for accurate NTR quantification, providing a powerful tool for the real-time diagnosis and progression assessment of hypoxia-related pathologies.<\/jats:p>","DOI":"10.1021\/acs.analchem.6c03979","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:02:03Z","timestamp":1788573723000},"page":"26947-26956","source":"Crossref","is-referenced-by-count":0,"title":["Self-Referenced\nSERS Nanoprobe for Accurate and Real-Time\nMonitoring of Nitroreductase Activity in Hepatic Ischemia"],"prefix":"10.1021","volume":"98","author":[{"given":"Chi","family":"Wang","sequence":"first","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenning","family":"Fan","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3499-8337","authenticated-orcid":true,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1833-3539","authenticated-orcid":true,"given":"Yanting","family":"Shen","sequence":"additional","affiliation":[{"name":"Hebei Medical University , , , ,","place":["Shijiazhuang, Hebei Province, P. R. China, 050017"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"issue":"2","key":"2026091511070697700_cit1","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/nrgastro.2012.225","article-title":"Ischemia-reperfusion\ninjury in liver transplantation--from bench to bedside","volume":"10","author":"Zhai","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"issue":"44","key":"2026091511070697700_cit2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202212721","article-title":"Tracking hepatic ischemia-reperfusion\ninjury in real time with a reversible NIR-IIb fluorescent redox probe","volume":"61","author":"Song","year":"2022","journal-title":"Angew. Chem., Int. Ed."},{"issue":"1","key":"2026091511070697700_cit3","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nm.4451","article-title":"An\nALOX12\u201312-HETE-GPR31 signaling axis is a\nkey mediator of hepatic ischemia-reperfusion injury","volume":"24","author":"Zhang","year":"2018","journal-title":"Nat. Med."},{"issue":"36","key":"2026091511070697700_cit4","doi-asserted-by":"publisher","first-page":"19662","DOI":"10.1021\/jacs.3c04303","article-title":"Unveiling the crucial roles of O2\u2022- and ATP in hepatic ischemia-reperfusion injury using dual-color\/reversible\nfluorescence imaging","volume":"145","author":"Liu","year":"2023","journal-title":"J. Am. 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Bioelectron."},{"issue":"10","key":"2026091511070697700_cit19","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303472","article-title":"Intracellular\nnitroreductase-triggered\n\u201con\u201d and \u201cenhanced\u201d photoacoustic signals\nfor sensitive imaging of tumor hypoxia","volume":"13","author":"Sun","year":"2024","journal-title":"Adv.\nHealthcare Mater."},{"issue":"51","key":"2026091511070697700_cit20","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202411636","article-title":"A nitroreductase-activatable\nmetabolic reporter for\ncovalent labeling of pathological hypoxic cells in tumorigenesis","volume":"63","author":"Wang","year":"2024","journal-title":"Angew. Chem., Int. 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Bioelectron."},{"issue":"8","key":"2026091511070697700_cit34","doi-asserted-by":"publisher","first-page":"3926","DOI":"10.1021\/ac400750r","article-title":"Nitroreductase\ndetection and hypoxic tumor cell imaging by a designed sensitive and\nselective fluorescent probe, 7-[(5-nitrofuran-2-yl)methoxy]-3H-phenoxazin-3-one","volume":"85","author":"Li","year":"2013","journal-title":"Anal. 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