{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:49:08Z","timestamp":1782136148991,"version":"3.54.5"},"reference-count":73,"publisher":"Wiley","issue":"26","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22422407"],"award-info":[{"award-number":["22422407"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFA1509600"],"award-info":[{"award-number":["2024YFA1509600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004945","name":"Nankai University","doi-asserted-by":"publisher","award":["020\u201363261151"],"award-info":[{"award-number":["020\u201363261151"]}],"id":[{"id":"10.13039\/501100004945","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    D\u2010Cysteine (D\u2010Cys) is critically involved in regulating redox homeostasis within the brain, and its dysregulation has been closely related to the pathogenesis of various neurological disorders. However, the precise mapping of cerebral D\u2010Cys levels in situ remains a formidable challenge due to the lack of specific detection tools. Herein, we report a new class of fluorinated firefly luciferase prosubstrates for sensitive and noninvasive detection of D\u2010Cys in the brain via nitrile\u2010aminothiol bioorthogonal reaction. The lipophilic\n                    <jats:bold>7'F\u2010CBT<\/jats:bold>\n                    exhibits enhanced blood\u2010brain barrier (BBB) permeability and reacts with endogenous D\u2010Cys to form a luciferin analog in situ, generating prolonged and intense bioluminescence. It sensitively detected D\u2010Cys in vitro, achieving a detection limit of 1.37\u00a0nM, and successfully imaged endogenous D\u2010Cys in the mouse brain with a high signal\u2010to\u2010noise ratio (60:1) after intravenous administration. Furthermore,\n                    <jats:bold>7'F\u2010CBT<\/jats:bold>\n                    enabled unprecedented video\u2010rate visualization of D\u2010Cys in freely moving glioblastoma\u2010bearing mice. More importantly, by leveraging BBB\u2010permeable\n                    <jats:bold>7'F\u2010CBT<\/jats:bold>\n                    , we revealed a precipitous reduction of brain D\u2010Cys levels in a drug\u2010induced Parkinson's disease (PD) mouse model for the first time. This study paves the way for diagnosing D\u2010Cys\u2010related brain diseases and provides a novel diagnostic tool.\n                  <\/jats:p>","DOI":"10.1002\/anie.5604948","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T10:16:51Z","timestamp":1777976211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Blood\u2010Brain\u2010Barrier\u2010Crossing Fluorinated Luciferase Prosubstrates Enable Sensitive Monitoring of D\u2010Cysteine Levels in Brain Diseases"],"prefix":"10.1002","volume":"65","author":[{"given":"Yuexia","family":"Yang","sequence":"first","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ma","sequence":"additional","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoming","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Zheng","sequence":"additional","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4969-8158","authenticated-orcid":false,"given":"Hu","family":"Xiong","sequence":"additional","affiliation":[{"name":"Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular Recognition Frontiers Science Center For New Organic Matter College of Chemistry Nankai University  Nankai District Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.01.008"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9070597"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.08.021"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2020.05.001"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00156"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2018.02.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2015.04.004"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201704084"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.1c01945"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2110610118"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/chir.23562"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.70083"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2371"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04\u20101815fje"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2019.112841"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bios.2023.115631"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.0c03481"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b12845"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aca.2017.09.031"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b04407"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.2c01372"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5CC01321F"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cc45519j"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2sc20540h"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2017.06.166"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2018.11.056"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b01878"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b05211"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nantod.2024.102401"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2017.03.012"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2018.05.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS01492C"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201031673\u2010x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202314468"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1012864107"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac502396g"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201507530"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.7b01103"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b00198"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c00008"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.1c00317"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b00682"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.126968"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5b03712"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5b03636"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b03877"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.4c01462"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb300194b"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010023\u201001265\u2010x"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b04357"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6CS00296J"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.5b00195"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312159110"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.08.073"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.480"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja309078t"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.57.2.4"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568\u2010019\u20100205\u2010x"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578\u2010021\u201000394\u2010w"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200903627"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4OB02529F"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b11737"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201200142"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201509460"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb3007314"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202203235"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1039\/C2CS35249D"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2019.05.002"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010anchem\u2010061318\u2010115027"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21613"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094\u2010016\u20101497\u2010x"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(13)70054\u20101"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.342"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5604948","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.5604948","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5604948","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:03:55Z","timestamp":1782133435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.5604948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":73,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2026,6,22]]}},"alternative-id":["10.1002\/anie.5604948"],"URL":"https:\/\/doi.org\/10.1002\/anie.5604948","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2026-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5604948"}}