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Relevant investigations indicated that H2S plays a cytoprotective effect under endoplasmic reticulum stress. Currently, it is still a challenge to design effective methods for ratio detection of endoplasmic reticulum H2S. Herein we are the first to construct a ratiometric near-infrared fluorescent probe (M-H2S) for sensing H2S in the endoplasmic reticulum. M-H2S has high selectivity and sensitivity toward H2S (LOD = 39.1 nM). Additionally, M-H2S possessed an excellent endoplasmic reticulum targeting ability. Moreover, M-H2S was successfully utilized to visualize exogenous\/endogenous H2S in HeLa cells and zebrafish. Particularly important, endogenously produced H2S was observed under endoplasmic reticulum stress induced by tunicamycin.<\/jats:p>","DOI":"10.1021\/acs.analchem.0c01623","type":"journal-article","created":{"date-parts":[[2020,6,22]],"date-time":"2020-06-22T01:16:39Z","timestamp":1592788599000},"page":"9982-9988","source":"Crossref","is-referenced-by-count":135,"title":["An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent\nProbe for the Sensing of Hydrogen Sulfide in Living Cells and Zebrafish"],"prefix":"10.1021","volume":"92","author":[{"given":"Wei","family":"Shu","sequence":"first","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunping","family":"Zang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxu","family":"Gao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Jing","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-4685","authenticated-orcid":true,"given":"Xiaoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology , , ,","place":["Beijing, P. R. China, 100081"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,6,22]]},"reference":[{"key":"2026081803283049000_cit1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nrd2425","article-title":"Hydrogen sulphide\nand its therapeutic potential","volume":"6","author":"Szabo\u0301","year":"2007","journal-title":"Nat. Rev. Drug\nDiscovery"},{"key":"2026081803283049000_cit2","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1089\/152308603768295249","article-title":"The gasotransmitter\nrole of hydrogen sulfide","volume":"5","author":"Wang","year":"2003","journal-title":"Antioxid. Redox Signaling"},{"key":"2026081803283049000_cit3","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1016\/j.envpol.2016.03.035","article-title":"An emphasis\nof hydrogen sulfide-cysteine cycle on enhancing the tolerance to chromium\nstress in arabidopsis","volume":"213","author":"Fang","year":"2016","journal-title":"Environ. Pollut."},{"key":"2026081803283049000_cit4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nrm3391","article-title":"H2S signalling\nthrough protein sulfhydration\nand beyond","volume":"13","author":"Paul","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2026081803283049000_cit5","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cca.2014.10.037","article-title":"Hydrogen sulfide\nin signaling pathways","volume":"439","author":"Olas","year":"2015","journal-title":"Clin. Chim. Acta"},{"key":"2026081803283049000_cit6","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1038\/nchembio.1018","article-title":"Hydrogen sulfide anion\nregulates redox signaling via electrophile sulfhydration","volume":"8","author":"Nishida","year":"2012","journal-title":"Nat. Chem. Biol."},{"key":"2026081803283049000_cit7","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nchembio.1834","article-title":"Biogenesis of reactive sulfur species\nfor signaling by hydrogen sulfide oxidation pathways","volume":"11","author":"Mishanina","year":"2015","journal-title":"Nat. Chem. Biol."},{"key":"2026081803283049000_cit8","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.tips.2007.11.003","article-title":"Putative biological roles of hydrogen sulfide in health\nand disease: A breath of not so fresh air?","volume":"29","author":"Li","year":"2008","journal-title":"Trends Pharmacol. Sci."},{"key":"2026081803283049000_cit9","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.neuint.2007.05.016","article-title":"Hydrogen\nsulfide: Neurochemistry and neurobiology","volume":"52","author":"Qu","year":"2008","journal-title":"Neurochem.\nInt."},{"key":"2026081803283049000_cit10","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1002\/hep.20817","article-title":"The third\ngas: H2S regulates perfusion pressure in both the isolated\nand perfused normal rat liver and in cirrhosis","volume":"42","author":"Fiorucci","year":"2005","journal-title":"Hepatology"},{"key":"2026081803283049000_cit11","doi-asserted-by":"publisher","first-page":"6035","DOI":"10.1039\/C9SC01652J","article-title":"Fluorescent probes for organelle-targeted\nbioactive species imaging","volume":"10","author":"Gao","year":"2019","journal-title":"Chem. 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Commun."},{"key":"2026081803283049000_cit20","doi-asserted-by":"publisher","first-page":"1956","DOI":"10.1080\/15548627.2015.1091141","article-title":"ER stress: Autophagy\ninduction, inhibition and selection","volume":"11","author":"Rashid","year":"2015","journal-title":"Autophagy"},{"key":"2026081803283049000_cit21","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/nrd2755","article-title":"Cell death\nand endoplasmic reticulum stress: Disease\nrelevance and therapeutic opportunities","volume":"7","author":"Kim","year":"2008","journal-title":"Nat.\nRev. 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J."},{"key":"2026081803283049000_cit24","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.lfs.2015.11.025","article-title":"Hydrogen sulfide suppresses endoplasmic\nreticulum stress-induced endothelial-to-mesenchymal transition through\nSrc pathway","volume":"144","author":"Ying","year":"2016","journal-title":"Life Sci."},{"key":"2026081803283049000_cit25","doi-asserted-by":"publisher","first-page":"12234","DOI":"10.1039\/C4CC03312D","article-title":"Fluorescent\nprobes for hydrogen sulfide detection and\nbioimaging","volume":"50","author":"Yu","year":"2014","journal-title":"Chem. Commun."},{"key":"2026081803283049000_cit26","doi-asserted-by":"publisher","first-page":"7573","DOI":"10.1021\/acs.orglett.9b02844","article-title":"Hydrogen Sulfide\nMediated Tandem Reaction of Selenenyl Sulfides and Its Application\nin Fluorescent Probe Development","volume":"21","author":"Wang","year":"2019","journal-title":"Org. Lett."},{"key":"2026081803283049000_cit27","doi-asserted-by":"publisher","first-page":"17973","DOI":"10.1021\/jacs.9b09181","article-title":"An optical\/photoacoustic dual-modality probe: Ratiometric\nin\/ex vivo imaging for stimulated H2S upregulation in mice","volume":"141","author":"Chen","year":"2019","journal-title":"J. Am. Chem. Soc."},{"key":"2026081803283049000_cit28","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1021\/acs.analchem.9b04009","article-title":"Rational design of a targetable fluorescent probe for visualizing\nH2S production under golgi stress response elicited by\nmonensin","volume":"92","author":"Zhu","year":"2020","journal-title":"Anal. 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Chem. Lett."},{"key":"2026081803283049000_cit32","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1039\/C9AY02657F","article-title":"An ICT-based fluorescent\nprobe with bridging Si\u2013O\u2013Si bonds for visualizing hydrogen\nsulfide in lipid droplets and its application","volume":"12","author":"Wang","year":"2020","journal-title":"Anal. Methods"},{"key":"2026081803283049000_cit33","doi-asserted-by":"publisher","first-page":"5476","DOI":"10.1021\/acs.analchem.6b00956","article-title":"Mitochondria-targeted\nreaction-based fluorescent probe for hydrogen sulfide","volume":"88","author":"Pak","year":"2016","journal-title":"Anal. Chem."},{"key":"2026081803283049000_cit34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.snb.2017.03.135","article-title":"A mitochondrial-targeted\ntwo-photon fluorescent probe for imaging hydrogen sulfide in the living\ncells and mouse liver tissues","volume":"248","author":"Deng","year":"2017","journal-title":"Sens. Actuators,\nB"},{"key":"2026081803283049000_cit35","doi-asserted-by":"publisher","first-page":"126773","DOI":"10.1016\/j.snb.2019.126773","article-title":"Based \u2018successive\u2019\nnucleophilic substitution mitochondrial-targeted H2S red\nlight emissive fluorescent probe and its imaging in mice","volume":"297","author":"Wang","year":"2019","journal-title":"Sens. Actuators, B"},{"key":"2026081803283049000_cit36","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.talanta.2017.02.012","article-title":"A ratiometric two-photon fluorescent\nprobe for imaging hydrogen sulfide in lysosomes","volume":"167","author":"Feng","year":"2017","journal-title":"Talanta"},{"key":"2026081803283049000_cit37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.trac.2015.11.014","article-title":"Recent progress in the fluorescent\nprobes for the specific imaging of small molecular weight thiols in\nliving cells","volume":"76","author":"Chen","year":"2016","journal-title":"TrAC, Trends Anal. Chem."},{"key":"2026081803283049000_cit38","doi-asserted-by":"publisher","first-page":"2932","DOI":"10.1021\/acs.analchem.8b05116","article-title":"Single fluorescent\nprobe separately and continuously visualize H2S and hclo\nin lysosomes with different fluorescence signals","volume":"91","author":"Ren","year":"2019","journal-title":"Anal. Chem."},{"key":"2026081803283049000_cit39","doi-asserted-by":"publisher","first-page":"6257","DOI":"10.1039\/C7SC00423K","article-title":"A multi-signal\nfluorescent probe for simultaneously distinguishing and sequentially\nsensing cysteine\/homocysteine, glutathione, and hydrogen sulfide in\nliving cells","volume":"8","author":"He","year":"2017","journal-title":"Chem. Sci."},{"key":"2026081803283049000_cit40","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1039\/C8OB02998A","article-title":"An endoplasmic\nreticulum-targetable\nfluorescent probe for highly selective detection of hydrogen sulfide","volume":"17","author":"Zhang","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"2026081803283049000_cit41","doi-asserted-by":"publisher","first-page":"8778","DOI":"10.1039\/C9OB01750J","article-title":"Endoplasmic reticulum targeted fluorescent probe for the detection\nof hydrogen sulfide based on a twist-blockage strategy","volume":"17","author":"Zhang","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"2026081803283049000_cit42","doi-asserted-by":"publisher","first-page":"4185","DOI":"10.1039\/C4CS00280F","article-title":"Small molecule-based ratiometric\nfluorescence probes for cations, anions, and biomolecules","volume":"44","author":"Lee","year":"2015","journal-title":"Chem. Soc. Rev."},{"key":"2026081803283049000_cit43","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1039\/C9CS00243J","article-title":"Synthetic\nratiometric fluorescent probes for detection of ions","volume":"49","author":"Park","year":"2020","journal-title":"Chem. Soc. 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Biol."},{"key":"2026081803283049000_cit47","doi-asserted-by":"publisher","first-page":"10776","DOI":"10.1039\/C9CC03114F","article-title":"An ultrasensitive ratiometric fluorescent\nprobe based on the ICT-PET-FRET\nmechanism for the quantitative measurement of pH values in the endoplasmic\nreticulum (ER)","volume":"55","author":"Dong","year":"2019","journal-title":"Chem. Commun."},{"key":"2026081803283049000_cit48","doi-asserted-by":"publisher","first-page":"51749","DOI":"10.1074\/jbc.M303978200","article-title":"The endoplasmic\nreticulum (ER) translocon can differentiate\nbetween hydrophobic sequences allowing signals for glycosylphosphatidylinositol\nanchor addition to be fully translocated into the ER lumen","volume":"278","author":"Dalley","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2026081803283049000_cit49","doi-asserted-by":"publisher","first-page":"12945","DOI":"10.1021\/acs.analchem.7b03809","article-title":"Endoplasmic\nreticulum-directed ratiometric fluorescent probe for quantitive detection\nof basal H2O2","volume":"89","author":"Gao","year":"2017","journal-title":"Anal. Chem."},{"key":"2026081803283049000_cit50","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.snb.2018.09.081","article-title":"H2S2-triggered\noff-on fluorescent indicator with endoplasmic reticulum\ntargeting for imaging in cells and zebrafishes","volume":"278","author":"Zhou","year":"2019","journal-title":"Sens. Actuators, B"},{"key":"2026081803283049000_cit51","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.1039\/C8CC01332B","article-title":"Polysulfide-triggered fluorescent\nindicator suitable for super-resolution\nmicroscopy and application in imaging","volume":"54","author":"Hoskere","year":"2018","journal-title":"Chem.\nCommun."},{"key":"2026081803283049000_cit52","doi-asserted-by":"publisher","first-page":"13136","DOI":"10.1021\/acs.analchem.9b03383","article-title":"Nitrobenzoxadiazole\nether-based near-infrared fluorescent probe with unexpected high selectivity\nfor H2S imaging in living cells and mice","volume":"91","author":"Gong","year":"2019","journal-title":"Anal. Chem."}],"container-title":["Analytical Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.analchem.0c01623","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/92\/14\/9982\/8580513\/ac0c01623.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ancham\/article-pdf\/92\/14\/9982\/8580513\/ac0c01623.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T08:57:41Z","timestamp":1787043461000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ancham\/article\/92\/14\/9982\/827287\/An-Endoplasmic-Reticulum-Targeted-Ratiometric"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,22]]},"references-count":52,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2020,6,22]]},"published-print":{"date-parts":[[2020,7,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.analchem.0c01623","relation":{},"ISSN":["0003-2700","1520-6882"],"issn-type":[{"value":"0003-2700","type":"print"},{"value":"1520-6882","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,22]]}}}