{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:03:48Z","timestamp":1784545428946,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"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":["22525704"],"award-info":[{"award-number":["22525704"]}],"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":["92478120"],"award-info":[{"award-number":["92478120"]}],"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":["22374010"],"award-info":[{"award-number":["22374010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["Z220023"],"award-info":[{"award-number":["Z220023"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021187","name":"Beijing National Laboratory for Molecular Sciences","doi-asserted-by":"publisher","award":["BNLM\u2010CXTD\u2010202401"],"award-info":[{"award-number":["BNLM\u2010CXTD\u2010202401"]}],"id":[{"id":"10.13039\/501100021187","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2243300002"],"award-info":[{"award-number":["2243300002"]}],"id":[{"id":"10.13039\/501100012226","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":[[2026,7,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The dynamic and tissue\u2010specific nature of protein secretion underlies a wide range of physiological and pathological processes, yet tools for profiling the in vivo secretome with high spatial and temporal resolution remain limited. Here, we present\n                    <jats:bold>STePTag<\/jats:bold>\n                    (\n                    <jats:styled-content>S<\/jats:styled-content>\n                    patio\u2010\n                    <jats:styled-content>Te<\/jats:styled-content>\n                    mporal\n                    <jats:styled-content>P<\/jats:styled-content>\n                    rotein\n                    <jats:styled-content>Tag<\/jats:styled-content>\n                    ging), a conditional proximity labeling (PL) system for profiling secreted proteins in live animals.\n                    <jats:bold>STePTag<\/jats:bold>\n                    integrates the rapid labeling kinetics of the PL enzyme TurboID with a destabilized dihydrofolate reductase (DHFR) domain, enabling tight post\u2010translational control of labeling activity through the small\u2010molecule stabilizer trimethoprim (TMP). Targeting\n                    <jats:bold>STePTag<\/jats:bold>\n                    to the endoplasmic reticulum (ER) confines labeling to the secretory pathway and enables robust labeling within 10\u00a0min of TMP administration. Furthermore, we design tissue\u2010specific lipid nanoparticles (tsLNPs) to enable programmable, in vivo delivery of\n                    <jats:bold>STePTag<\/jats:bold>\n                    to the mouse liver. Using this approach, we identified 93 liver\u2010derived secretory proteins under physiological conditions and uncovered 40 dynamically regulated proteins in a model of acetaminophen\u2010induced acute liver injury (ALI), including Aldh1a1, which we functionally validated as a protective factor in ALI. Together,\n                    <jats:bold>STePTag<\/jats:bold>\n                    provides a versatile platform for spatiotemporally resolved secretome profiling, enabling the discovery of context\u2010dependent biomarkers and tissue\u2010derived signaling molecules in native physiological environments.\n                  <\/jats:p>","DOI":"10.1002\/anie.5498199","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T16:11:16Z","timestamp":1779811876000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatiotemporally Resolved Protein Tagging for Dynamic and Tissue\u2010Specific Secretome Profiling In Vivo"],"prefix":"10.1002","volume":"65","author":[{"given":"Qizhen","family":"Zheng","sequence":"first","affiliation":[{"name":"Beijing National Laboratory For Molecular Sciences CAS Key Laboratory of Analytical Chemistry For Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yao","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory For Molecular Sciences CAS Key Laboratory of Analytical Chemistry For Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory For Molecular Sciences CAS Key Laboratory of Analytical Chemistry For Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory For Molecular Sciences CAS Key Laboratory of Analytical Chemistry For Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-1768","authenticated-orcid":false,"given":"Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Chemistry Beijing Normal University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2783-9426","authenticated-orcid":false,"given":"Ming","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory For Molecular Sciences CAS Key Laboratory of Analytical Chemistry For Living Biosystems Institute of Chemistry Chinese Academy of Sciences  Beijing China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010024\u201008225\u2010y"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14336"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201066508\u2010y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.036"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201057767\u2010w"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010025\u201001973\u20106"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c13183"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.2c00061"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.ado5088"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4201"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3179"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596\u2010020\u20100399\u20100"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201046034\u2010z"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.05.044"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025546\u2010y"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-020-00698-y"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.04.011"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.220149"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2005134118"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201022599\u2010x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102926\u20100"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1919528117"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010023\u201001880\u20105"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2025299118"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.801644"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010024\u201002375\u20107"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41589\u2010024\u201001603\u20107"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.206.Supp.15.06"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.202204947"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.3c00597"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010021\u201001325\u20106"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022483"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1520244113"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9CC04517A"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202009572"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201006112\u2010w"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587\u2010021\u201001156\u20103"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102009\u201010\u201011\u2010r130"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adv0185"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathmechdis\u2010051122\u2010094016"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.01.020"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfq380"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2020.1812597"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfz222"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2019.05.012"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2018.04.004"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.07.036"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2757"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010020\u20102334\u20102"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5498199","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.5498199","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.5498199","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:15:46Z","timestamp":1784542546000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.5498199"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":50,"journal-issue":{"issue":"30","published-print":{"date-parts":[[2026,7,20]]}},"alternative-id":["10.1002\/anie.5498199"],"URL":"https:\/\/doi.org\/10.1002\/anie.5498199","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]},"assertion":[{"value":"2026-02-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e5498199"}}