{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:24:20Z","timestamp":1787073860885,"version":"build-2736575974"},"reference-count":49,"publisher":"American Chemical Society (ACS)","issue":"19","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Shaanxi Province","award":["2024SF-ZDCYL-03-27"],"award-info":[{"award-number":["2024SF-ZDCYL-03-27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Allosteric modulators represent a novel paradigm to therapeutically target G-protein-coupled receptors (GPCRs), but the discovery of novel allosteric ligands from natural products remains challenging. Here, we developed a high-performance affinity chromatography method for screening allosteric ligands toward the human calcium-sensing receptor (CaSR) by immobilizing an extracellular domain-deleted CaSR truncation (\u0394CaSR) onto silica gels as solid-phase materials for column packing. The immobilized \u0394CaSR column demonstrated the greatest allosteric responsive feature when cinacalcet at 0.50 \u03bcM or NPS2143 at 0.25 \u03bcM was included in the mobile phase, suggesting that the binding affinity of Ca2+ was increased 8% by cinacalcet and was decreased 77% by NPS2143. The column was applied to screen allosteric ligands from Epimedii Folium, which were identified as epimedin B, epimedin C, and icariin using HPLC-MS. The allosteric binding of the screened compounds was testified through competitive experiments, and their allosteric effects were verified by CaSR downstream signaling events, like the intracellular Ca2+ levels and cAMP production. Our observations indicated that the three compounds exerted an allosteric effect similar to that of cinacalcet and might be potential allosteric ligands. The proposed approach features the immobilization of headless GPCR truncations, in which the transmembrane domain is exposed to interact directly with the ligands, realizing the highly selective discovery of allosteric ligands from complex herbal extracts.<\/jats:p>","DOI":"10.1021\/acsomega.5c01504","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T03:58:56Z","timestamp":1746503936000},"page":"19887-19902","source":"Crossref","is-referenced-by-count":2,"title":["The Highly Selective\nDiscovery of Allosteric Ligands\nfrom Herbal Extracts through Their Direct Interactions with the Immobilized\nHeadless CaSR Truncation"],"prefix":"10.1021","volume":"10","author":[{"given":"XianGang","family":"Shi","sequence":"first","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru","family":"Xu","sequence":"additional","affiliation":[{"name":"Xi\u2019an International University , ,","place":["Xi\u2019an, PR China, 710077"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MeiZhi","family":"Jiao","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YaoKun","family":"Han","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ShouCheng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiLong","family":"Chen","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"YiYing","family":"Xu","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"FengWu","family":"Li","sequence":"additional","affiliation":[{"name":"Xi\u2019an Food and Drug Inspection Institute , , ,","place":["Xi\u2019an, PR China, 710127"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1372-3414","authenticated-orcid":true,"given":"ChaoNi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Northwest University , , ,","place":["Xi\u2019an, PR China, 710069"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"issue":"6","key":"2026081811231775600_cit1","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.bcp.2010.12.012","article-title":"Strategies for the\nidentification of allosteric modulators of G-protein-coupled receptors","volume":"81","author":"Burford","year":"2011","journal-title":"Biochem. Pharmacol."},{"issue":"2","key":"2026081811231775600_cit2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1124\/pr.54.2.323","article-title":"G protein-coupled receptor\nallosterism and complexing","volume":"54","author":"Christopoulos","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"2026081811231775600_cit3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.pharmtox.47.120505.105159","article-title":"Allosteric\nmodulation of G protein-coupled receptors","volume":"47","author":"May","year":"2007","journal-title":"Annu.\nRev. Pharmacol. Toxicol."},{"issue":"2","key":"2026081811231775600_cit4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2012.09.008","article-title":"Technology\ncombination to address\nGPCR allosteric modulator drug-discovery pitfalls","volume":"10","author":"Schann","year":"2013","journal-title":"Drug Discovery Today: Technol."},{"issue":"24","key":"2026081811231775600_cit5","doi-asserted-by":"publisher","first-page":"8775","DOI":"10.1021\/jm101069m","article-title":"Chemical Switch of\na Metabotropic Glutamate Receptor 2 Silent Allosteric Modulator into\nDual Metabotropic Glutamate Receptor 2\/3 Negative\/Positive Allosteric\nModulators","volume":"53","author":"Schann","year":"2010","journal-title":"J. Med. Chem."},{"key":"2026081811231775600_cit6","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.ddtec.2021.10.005","article-title":"Drug discovery\nfrom natural products using affinity\nselection-mass spectrometry","volume":"40","author":"Muchiri","year":"2021","journal-title":"Drug Discovery\nToday: Technol."},{"issue":"12","key":"2026081811231775600_cit7","doi-asserted-by":"publisher","first-page":"3192","DOI":"10.1039\/C7SC04698G","article-title":"High-throughput\nidentification of G protein-coupled receptor modulators through affinity\nmass spectrometry screening","volume":"9","author":"Qin","year":"2018","journal-title":"Chem. Sci."},{"issue":"8","key":"2026081811231775600_cit8","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1111\/bph.14961","article-title":"Negative allosteric\nmodulators of the human calcium-sensing receptor\nbind to overlapping and distinct sites within the 7-transmembrane\ndomain","volume":"177","author":"Josephs","year":"2020","journal-title":"Br. J. Pharmacol."},{"issue":"8","key":"2026081811231775600_cit9","doi-asserted-by":"publisher","first-page":"7254","DOI":"10.1074\/jbc.M307191200","article-title":"Homology\nmodeling of the transmembrane domain of the human calcium sensing\nreceptor and localization of an allosteric binding site","volume":"279","author":"Miedlich","year":"2004","journal-title":"J. Biol. Chem."},{"issue":"18","key":"2026081811231775600_cit10","doi-asserted-by":"publisher","first-page":"18990","DOI":"10.1074\/jbc.M400724200","article-title":"Positive and negative\nallosteric modulators of the Ca2+-sensing receptor interact\nwithin overlapping but not identical binding\nsites in the transmembrane domain","volume":"279","author":"Petrel","year":"2004","journal-title":"J. Biol.\nChem."},{"issue":"21","key":"2026081811231775600_cit11","doi-asserted-by":"publisher","first-page":"18908","DOI":"10.1074\/jbc.M202113200","article-title":"Evidence for\ndistinct cation and calcimimetic compound\n(NPS 568) recognition domains in the transmembrane regions of the\nhuman Ca2+ receptor","volume":"277","author":"Ray","year":"2002","journal-title":"J. Biol. Chem."},{"issue":"2","key":"2026081811231775600_cit12","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S1043-2760(98)00119-2","article-title":"Calcimimetic Compounds: a Direct Approach to Controlling Plasma Levels\nof Parathyroid Hormone in Hyperparathyroidism","volume":"10","author":"Nemeth","year":"1999","journal-title":"Trends Endocrinol. Metab."},{"issue":"1","key":"2026081811231775600_cit13","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S0022-3565(24)29333-2","article-title":"Calcilytic compounds: Potent and\nselective Ca2+ receptor\nantagonists that stimulate secretion of parathyroid hormone","volume":"299","author":"Nemeth","year":"2001","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2026081811231775600_cit14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-3-0348-8012-1_1","article-title":"Chemical and pharmacological\ninvestigations of Epimedium species: A survey","volume-title":"Progress In Drug Research","author":"Wu","year":"2003"},{"key":"2026081811231775600_cit15","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202400846","article-title":"Epimedium Linn: A Comprehensive Review\nof Phytochemistry Pharmacology, Clinical\nApplications and Quality Control","volume":"21","author":"Chen","year":"2024","journal-title":"Chem. Biodivers."},{"issue":"1\u20132","key":"2026081811231775600_cit16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.diff.2012.11.002","article-title":"The expression\nof calcium-sensing receptor in mouse embryonic stem cells (mESCs)\nand its influence on differentiation of mESC into cardiomyocytes","volume":"85","author":"Sun","year":"2013","journal-title":"Differentiation"},{"issue":"5","key":"2026081811231775600_cit17","doi-asserted-by":"publisher","first-page":"1831","DOI":"10.23812\/20-228-L","article-title":"Therapeutic effect\nand mechanism of icariin combined\nwith calcium sensitive receptor on mouse gastric cancer cells","volume":"34","author":"Sun","year":"2020","journal-title":"J. Biol. Regul. Homeostatic Agents"},{"issue":"24","key":"2026081811231775600_cit18","doi-asserted-by":"publisher","first-page":"7187","DOI":"10.1021\/ac048910c","article-title":"G-protein-coupled\nreceptor chromatographic stationary phases. 2. Ligand-induced conformational\nmobility in an immobilized beta(2)-adrenergic receptor","volume":"76","author":"Beigi","year":"2004","journal-title":"Anal. Chem."},{"key":"2026081811231775600_cit19","doi-asserted-by":"publisher","first-page":"115253","DOI":"10.1016\/j.jpba.2023.115253","article-title":"A rapid\napproach\nto capture the potential bioactive compounds from Rhizoma Drynariae,\nutilizing disease-associated mutation in calcium sensing receptor\nto alter the binding affinity for agonists","volume":"226","author":"Meng","year":"2023","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"17","key":"2026081811231775600_cit20","doi-asserted-by":"publisher","first-page":"4480","DOI":"10.1021\/ac034385q","article-title":"Syntheses of immobilized\nG protein-coupled receptor\nchromatographic stationary phases: Characterization of immobilized\n\u03bc and \u03ba opioid receptors","volume":"75","author":"Beigi","year":"2003","journal-title":"Anal.\nChem."},{"key":"2026081811231775600_cit21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.chroma.2014.03.017","article-title":"Exploring drug-protein\ninteractions using the relationship between injection volume and capacity\nfactor","volume":"1339","author":"Zhao","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"2026081811231775600_cit22","doi-asserted-by":"publisher","first-page":"116192","DOI":"10.1016\/j.jpba.2024.116192","article-title":"The screened compounds\nfrom Ligustri Lucidi Fructus using the immobilized calcium sensing\nreceptor column exhibit osteogenic activity in vitro","volume":"245","author":"Jiao","year":"2024","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"10","key":"2026081811231775600_cit23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078745","article-title":"Snap-, CLIP-\nand Halo-Tag Labelling of Budding Yeast Cells","volume":"8","author":"Stagge","year":"2013","journal-title":"PLoS One"},{"key":"2026081811231775600_cit24","doi-asserted-by":"publisher","first-page":"123409","DOI":"10.1016\/j.jchromb.2022.123409","article-title":"Extracellular\ndomain of human calcium sensing receptor immobilized to silica beads\nas biomaterial: A rapid chromatographic method for recognizing ligands\nfrom complex matrix\u2019Shuangdan\u2019","volume":"1208","author":"Xu","year":"2022","journal-title":"J. Chromatogr. B"},{"issue":"1","key":"2026081811231775600_cit25","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1007\/s00604-023-06092-4","article-title":"Solid-phase extraction with the functionalization\nof calcium-sensing receptors onto magnetic microspheres as an affinity\nprobe can capture ligands selectively from herbal extract","volume":"191","author":"Cheng","year":"2024","journal-title":"Microchim. Acta"},{"key":"2026081811231775600_cit26","doi-asserted-by":"publisher","first-page":"1154374","DOI":"10.3389\/fphys.2023.1154374","article-title":"Inhibition of the\ncalcium-sensing receptor by extracellular phosphate ions and by intracellular\nphosphorylation","volume":"14","author":"Centeno","year":"2023","journal-title":"Front. Physiol."},{"issue":"44","key":"2026081811231775600_cit27","doi-asserted-by":"publisher","first-page":"37013","DOI":"10.1074\/jbc.M506681200","article-title":"Calindol, a positive allosteric modulator of the human\nCa 2+ receptor, activates an extracellular ligand-binding\ndomain-deleted rhodopsin-like seven-transmembrane structure in the\nabsence of Ca2+","volume":"280","author":"Ray","year":"2005","journal-title":"J. Biol. Chem."},{"issue":"23","key":"2026081811231775600_cit28","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg1483","article-title":"Structural basis for\nactivation and\nallosteric modulation of full-length calcium-sensing receptor","volume":"7","author":"Wen","year":"2021","journal-title":"Sci. Adv."},{"issue":"4","key":"2026081811231775600_cit29","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1016\/S0026-895X(24)23025-X","article-title":"Domains\ndetermining ligand specificity for Ca2+ receptors","volume":"55","author":"Hammerland","year":"1999","journal-title":"Mol. Pharmacol."},{"key":"2026081811231775600_cit30","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/978-1-4939-2914-6_15","article-title":"High-Throughput\nScreening for Allosteric Modulators of GPCRs","volume":"1335","author":"Bertekap","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"2026081811231775600_cit31","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13662","article-title":"Structural\nmechanism of ligand activation in human\ncalcium-sensing receptor","volume":"5","author":"Geng","year":"2016","journal-title":"Elife"},{"issue":"5","key":"2026081811231775600_cit32","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1600241","article-title":"Structural basis for regulation of human calcium-sensing\nreceptor by magnesium ions and an unexpected tryptophan derivative\nco-agonist","volume":"2","author":"Zhang","year":"2016","journal-title":"Sci. Adv."},{"issue":"5","key":"2026081811231775600_cit33","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/cr.2016.36","article-title":"Towards a structural understanding\nof allosteric drugs at the human calcium-sensing receptor","volume":"26","author":"Leach","year":"2016","journal-title":"Cell Res."},{"key":"2026081811231775600_cit34","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.ijms.2018.09.026","article-title":"Flavonoids in natural\nand tissue cultured materials of Epimedium alpinum identified by using UHPLC-Q-TOF-MS\/MS","volume":"434","author":"Pilepic","year":"2018","journal-title":"Int.\nJ. Mass Spectrom."},{"issue":"3","key":"2026081811231775600_cit35","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/j.jpba.2009.09.033","article-title":"Identification of\nprenyl flavonoid\nglycosides and phenolic acids in Epimedium koreanum Nakai by Q-TOF-MS combined with selective enrichment on \u2033click\noligo (ethylene glycol)\u2033 column","volume":"51","author":"Wang","year":"2010","journal-title":"J. Pharm.\nBiomed. Anal."},{"issue":"1\u20132","key":"2026081811231775600_cit36","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.chroma.2008.02.109","article-title":"Analysis of phenolic\ncompounds in Epimedium plants using liquid chromatography\ncoupled with electrospray ionization mass spectrometry","volume":"1190","author":"Zhao","year":"2008","journal-title":"J. Chromatogr. A"},{"key":"2026081811231775600_cit37","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.pharmthera.2016.01.015","article-title":"Preclinical studies\nand clinical evaluation of compounds from the genus Epimedium for\nosteoporosis and bone health","volume":"162","author":"Indran","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"2026081811231775600_cit38","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jep.2015.11.007","article-title":"Anti-osteoporosis\neffect of Epimedium\nvia an estrogen-like mechanism based on a system-level approach","volume":"177","author":"Xu","year":"2016","journal-title":"J. Ethnopharmacol."},{"issue":"35","key":"2026081811231775600_cit39","doi-asserted-by":"publisher","first-page":"21711","DOI":"10.1073\/pnas.1922231117","article-title":"Illuminating\nthe allosteric modulation\nof the calcium-sensing receptor","volume":"117","author":"Liu","year":"2020","journal-title":"Proc. Natl.\nAcad. Sci. U. S. A."},{"issue":"10","key":"2026081811231775600_cit40","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1359\/jbmr.1998.13.10.1530","article-title":"Mouse osteoblastic cell line (MC3T3-E1)\nexpresses extracellular calcium (Ca2+o)-sensing receptor and its agonists\nstimulate chemotaxis and proliferation of MC3T3-E1 cells","volume":"13","author":"Yamaguchi","year":"1998","journal-title":"J. Bone Miner. Res."},{"issue":"1","key":"2026081811231775600_cit41","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S8756-3282(00)00288-X","article-title":"Extracellular\ncalcium-sensing-receptor (CaR)-mediated\nopening of an outward K+ channel in murine MC3T3-E1 osteoblastic cells:\nEvidence for expression of a functional CaR","volume":"27","author":"Ye","year":"2000","journal-title":"Bone"},{"issue":"3","key":"2026081811231775600_cit42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00229.2004","article-title":"Involvement\nof calcium-sensing receptor in osteoblastic differentiation of mouse\nMC3T3-E1 cells","volume":"288","author":"Yamauchi","year":"2005","journal-title":"Am. J. Physiol.-Endocrinol.\nMetab."},{"key":"2026081811231775600_cit43","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.coemr.2020.06.007","article-title":"Calcium-sensing\nreceptor signaling - How human disease informs biology","volume":"16","author":"Gorvin","year":"2021","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"issue":"3","key":"2026081811231775600_cit44","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1124\/jpet.112.197210","article-title":"Strontium\nIs a Biased Agonist of\nthe Calcium-Sensing Receptor in Rat Medullary Thyroid Carcinoma 6\u201323\nCells","volume":"343","author":"Thomsen","year":"2012","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"3","key":"2026081811231775600_cit45","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1210\/en.2012-1887","article-title":"Impact of Clinically Relevant Mutations on the Pharmacoregulation\nand Signaling Bias of the Calcium-Sensing Receptor by Positive and\nNegative Allosteric Modulators","volume":"154","author":"Leach","year":"2013","journal-title":"Endocrinology"},{"issue":"2","key":"2026081811231775600_cit46","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.ceca.2011.11.009","article-title":"Biased agonism of the\ncalcium-sensing receptor","volume":"51","author":"Thomsen","year":"2012","journal-title":"Cell Calcium"},{"issue":"12","key":"2026081811231775600_cit47","doi-asserted-by":"publisher","first-page":"103803","DOI":"10.1016\/j.drudis.2023.103803","article-title":"Pharmacologically targeting intracellular\nallosteric sites of GPCRs for drug discovery","volume":"28","author":"Zhang","year":"2023","journal-title":"Drug Discovery Today"},{"key":"2026081811231775600_cit48","doi-asserted-by":"publisher","first-page":"107574","DOI":"10.1016\/j.phrs.2024.107574","article-title":"Targeting cryptic allosteric sites of G protein-coupled receptors\nas a novel strategy for biased drug discovery","volume":"212","author":"Qiao","year":"2025","journal-title":"Pharmacol. Res."},{"issue":"1","key":"2026081811231775600_cit49","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41392-024-01803-6","article-title":"G protein-coupled receptors (GPCRs):\nadvances in structures, mechanisms,\nand drug discovery","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target.\nTher."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.5c01504","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/10\/19\/19887\/40829640\/ao5c01504.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/10\/19\/19887\/40829640\/ao5c01504.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:25:54Z","timestamp":1787070354000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/10\/19\/19887\/3654240\/The-Highly-Selective-Discovery-of-Allosteric"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":49,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2025,5,6]]},"published-print":{"date-parts":[[2025,5,20]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.5c01504","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]}}}