{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:23:18Z","timestamp":1788337398381,"version":"build-2803163510"},"reference-count":41,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","award":["2018ZX10302205-002"],"award-info":[{"award-number":["2018ZX10302205-002"]}],"id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic hepatitis B virus (CHB) infection is one of the primary risk factors associated with the development of hepatocellular carcinoma (HCC). Despite having been extensively studied, diagnosing early-stage HCC remains challenging, and diagnosed patients have a poor (3\u20135%) survival rate. Identifying new approaches to detect changes in the serum metabolic profiles of patients with CHB and liver cirrhosis (LC) may provide a valuable approach to better detect HCC at an early stage when it is still amenable to treatment, thereby improving patient prognosis and survival. In the present study, we, therefore, employed a liquid chromatography-mass spectrometry (LC-MS)-based approach to evaluate the serum metabolic profiles of 30 CHB patients, 29 LC patients, and 30 HCC patients. We then employed appropriate statistical methods to identify those metabolites that were best able to distinguish HCC cases from LC and CHB controls. A mass-based database was then used to putatively identify these metabolites. We then confirmed the identities of a subset of these metabolites through comparisons with the MS\/MS fragmentation patterns and retention times of reference standards. The serum samples were then reanalyzed to quantify the levels of these selected metabolites and of other metabolites that have previously been identified as potential HCC biomarkers. Through this approach, we observed clear differences in the metabolite profiles of the CHB, LC, and HCC patient groups in both positive- and negative-ion modes. We found that the levels of taurodeoxy cholic acid (TCA) and 1,2-diacyl-3-\u03b2-d-galactosyl-sn-glycerol rose with the progression from CHB to LC to HCC, whereas levels of 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid were gradually reduced with liver disease progression in these groups. The ROC analysis showed that taurodeoxy cholic acid (TCA), 1,2-diacyl-3-\u03b2-d-galactosyl-sn-glycerol, 5-hydroxy-6E,8Z,11Z,14Z,17Z-eicosapentaenoic acid, and glycyrrhizic acid had a diagnosis performance with liver disease progression. These four metabolites have a significant correlation with alpha fetal protein (AFP) level and age. Our results highlight novel metabolic biomarkers that have the potential to be used for differentiating between CHB, LC, and HCC patients, thereby facilitating the identification and treatment of patients with early-stage HCC.<\/jats:p>","DOI":"10.1021\/acsomega.0c04259","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T13:55:58Z","timestamp":1609768558000},"page":"1160-1170","source":"Crossref","is-referenced-by-count":28,"title":["LC\/MS-Based Global Metabolomic Identification of Serum\nBiomarkers Differentiating Hepatocellular Carcinoma from Chronic Hepatitis\nB and Liver Cirrhosis"],"prefix":"10.1021","volume":"6","author":[{"given":"Hong Y.","family":"Pan","sequence":"first","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing Q.","family":"Wu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]},{"name":"Zhejiang Chinese Medical University , , No. 548 Binwen Road , , ,","place":["Hangzhou, Zhejiang, China, 310053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao Q.","family":"Yin","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]},{"name":"Bengbu Medical College , No. 2600 Donghai Road , , ,","place":["Bengbu, Anhui, China, 233030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-1381","authenticated-orcid":true,"given":"Yi N.","family":"Dai","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi C.","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian C.","family":"Hui","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]},{"name":"Bengbu Medical College , No. 2600 Donghai Road , , ,","place":["Bengbu, Anhui, China, 233030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei J.","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming S.","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia J.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai J.","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-4402","authenticated-orcid":true,"given":"Yong X.","family":"Tong","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial People\u2019s Hospital, People\u2019s Hospital of Hangzhou Medical College , , No. 158 Shangtang Road , , ,","place":["Hangzhou, Zhejiang, China, 310014"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"2026090204044019900_cit1","first-page":"549","article-title":"Liver resection\nand transplantation in the management of hepatocellular carcinoma:\na review","volume":"4","author":"Kassahun","year":"2006","journal-title":"Exp. Clin. Transplant."},{"key":"2026090204044019900_cit2","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.1053\/j.gastro.2007.04.061","article-title":"Hepatocellular carcinoma:\nepidemiology and molecular\ncarcinogenesis","volume":"132","author":"El-Serag","year":"2007","journal-title":"Gastroenterology"},{"key":"2026090204044019900_cit3","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1056\/NEJM199903113401001","article-title":"Rising incidence\nof hepatocellular carcinoma in the\nUnited States","volume":"340","author":"El-Serag","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"2026090204044019900_cit4","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1046\/j.1365-2559.2001.01188.x","article-title":"Hepatocellular\ncarcinoma: an overview","volume":"39","author":"Anthony","year":"2001","journal-title":"Histopathology"},{"key":"2026090204044019900_cit5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1620\/tjem.176.203","article-title":"Hepatocellular\ncarcinoma cases with\nfive-year survival and prognostic factors affecting the survival time","volume":"176","author":"Onodera","year":"1995","journal-title":"Tohoku J. Exp. Med."},{"key":"2026090204044019900_cit6","doi-asserted-by":"publisher","first-page":"E208","DOI":"10.9778\/cmajo.20140118","article-title":"Trends\nin relative survival in patients with a diagnosis\nof hepatocellular carcinoma in Ontario: a population-based retrospective\ncohort study","volume":"3","author":"Thein","year":"2015","journal-title":"CMAJ Open"},{"key":"2026090204044019900_cit7","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1111\/ajt.12774","article-title":"Waiting time\nand explant pathology in transplant recipients with hepatocellular\ncarcinoma: a novel study using national data","volume":"14","author":"Bittermann","year":"2014","journal-title":"Am. J. Transplant."},{"key":"2026090204044019900_cit8","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1080\/004982599238047","article-title":"\u2019Metabonomics\u2019:\nunderstanding\nthe metabolic responses of living systems to pathophysiological stimuli\nvia multivariate statistical analysis of biological NMR spectroscopic\ndata","volume":"29","author":"Nicholson","year":"1999","journal-title":"Xenobiotica"},{"key":"2026090204044019900_cit9","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1023\/A:1013713905833","article-title":"Metabolomics--the\nlink between genotypes and phenotypes","volume":"48","author":"Fiehn","year":"2002","journal-title":"Plant\nMol. Biol."},{"key":"2026090204044019900_cit10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trac.2011.08.009","article-title":"Metabolite\nidentification and quantitation\nin LC-MS\/MS-based metabolomics","volume":"32","author":"Xiao","year":"2012","journal-title":"TrAC, Trends\nAnal. Chem."},{"key":"2026090204044019900_cit11","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.4155\/bio.11.122","article-title":"Sample preparation\nprior to the LC-MS-based metabolomics\/metabonomics\nof blood-derived samples","volume":"3","author":"Gika","year":"2011","journal-title":"Bioanalysis"},{"key":"2026090204044019900_cit12","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1021\/pr901058t","article-title":"Characterization of urinary biomarkers\nof hepatocellular carcinoma using magnetic resonance spectroscopy\nin a Nigerian population","volume":"9","author":"Shariff","year":"2010","journal-title":"J. Proteome Res."},{"key":"2026090204044019900_cit13","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.004945","article-title":"Serum and urine metabolite profiling\nreveals potential biomarkers of human hepatocellular carcinoma","volume":"10","author":"Chen","year":"2011","journal-title":"Mol. Cell. Proteomics"},{"key":"2026090204044019900_cit14","doi-asserted-by":"publisher","first-page":"E359","DOI":"10.9778\/cmajo.20150109","article-title":"Correction:\nTrends in relative survival in patients with a diagnosis\nof hepatocellular carcinoma in Ontario: a population-based retrospective\ncohort study","volume":"3","year":"2015","journal-title":"CMAJ Open"},{"key":"2026090204044019900_cit15","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.aca.2011.02.038","article-title":"Fecal metabolome\nprofiling of liver cirrhosis and hepatocellular\ncarcinoma patients by ultra performance liquid chromatography-mass\nspectrometry","volume":"691","author":"Cao","year":"2011","journal-title":"Anal. Chim. Acta"},{"key":"2026090204044019900_cit16","doi-asserted-by":"publisher","first-page":"6590","DOI":"10.1158\/0008-5472.CAN-11-0885","article-title":"Aberrant\nlipid metabolism in hepatocellular carcinoma revealed by plasma metabolomics\nand lipid profiling","volume":"71","author":"Patterson","year":"2011","journal-title":"Cancer Res."},{"key":"2026090204044019900_cit17","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1111\/j.1349-7006.2009.01086.x","article-title":"Application\nof 1H NMR-based metabonomics in the study of metabolic\nprofiling of human hepatocellular carcinoma and liver cirrhosis","volume":"100","author":"Gao","year":"2009","journal-title":"Cancer Sci."},{"key":"2026090204044019900_cit18","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1093\/carcin\/bgz154","article-title":"Plasma hsa_circ_0027089\nis a diagnostic biomarker for hepatitis B virus-related hepatocellular\ncarcinoma","volume":"41","author":"Zhu","year":"2020","journal-title":"Carcinogenesis"},{"key":"2026090204044019900_cit19","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.hbpd.2020.01.003","article-title":"Human microbiome is a diagnostic\nbiomarker in hepatocellular carcinoma","volume":"19","author":"Rao","year":"2020","journal-title":"Hepatobiliary\nPancreatic Dis. Int."},{"key":"2026090204044019900_cit20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3390\/jcm9010281","article-title":"Serum Exosomal MicroRNA,\nmiR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular\nCarcinoma","volume":"9","author":"Cho","year":"2020","journal-title":"J. Clin. Med."},{"key":"2026090204044019900_cit21","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.3748\/wjg.v24.i18.1978","article-title":"Laparoscopic gastrojejunostomy for\ngastric outlet obstruction in patients with unresectable hepatopancreatobiliary\ncancers: A personal series and systematic review of the literature","volume":"24","author":"Manuel-Va\u0301zquez","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"2026090204044019900_cit22","doi-asserted-by":"publisher","first-page":"G91","DOI":"10.1152\/ajpgi.00027.2015","article-title":"Bile acids\npromote diethylnitrosamine-induced hepatocellular carcinoma via increased\ninflammatory signaling","volume":"311","author":"Sun","year":"2016","journal-title":"Am. J. Physiol.: Gastrointest.\nLiver Physiol."},{"key":"2026090204044019900_cit23","doi-asserted-by":"publisher","first-page":"2480","DOI":"10.1002\/hep.26251","article-title":"Hepatocyte\nnuclear\nfactor 4 alpha deletion promotes diethylnitrosamine-induced hepatocellular\ncarcinoma in rodents","volume":"57","author":"Walesky","year":"2013","journal-title":"Hepatology"},{"key":"2026090204044019900_cit24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007954","article-title":"Promotion and induction of liver cancer by gut microbiome-mediated\nmodulation of bile acids","volume":"15","author":"Jia","year":"2019","journal-title":"PLoS Pathog."},{"key":"2026090204044019900_cit25","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1021\/pr050364w","article-title":"High performance liquid chromatography-mass\nspectrometry for metabonomics:\npotential biomarkers for acute deterioration of liver function in\nchronic hepatitis B","volume":"5","author":"Yang","year":"2006","journal-title":"J. Proteome Res."},{"key":"2026090204044019900_cit26","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1039\/b820224a","article-title":"A metabonomic study\nof hepatitis B-induced liver cirrhosis and hepatocellular carcinoma\nby using RP-LC and HILIC coupled with mass spectrometry","volume":"5","author":"Yin","year":"2009","journal-title":"Mol. BioSyst."},{"key":"2026090204044019900_cit27","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/0005-2736(91)90253-5","article-title":"Specific binding of\nglycyrrhetinic acid to the rat liver membrane","volume":"1066","author":"Negishi","year":"1991","journal-title":"Biochim. Biophys. Acta, Biomembr."},{"key":"2026090204044019900_cit28","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.2147\/DDDT.S81722","article-title":"A novel glycyrrhetinic\nacid-modified oxaliplatin liposome for liver-targeting and in vitro\/vivo\nevaluation","volume":"9","author":"Chen","year":"2015","journal-title":"Drug Des., Dev. Ther."},{"key":"2026090204044019900_cit29","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/872139","article-title":"Glycyrrhizic\nacid in the treatment of liver diseases: literature review","volume":"2014","author":"Li","year":"2014","journal-title":"BioMed Res. Int."},{"key":"2026090204044019900_cit30","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.biochi.2011.04.011","article-title":"Selective toxicity\nof glycyrrhetinic acid against tumorigenic r\/m HM-SFME-1 cells is\npotentially attributed to downregulation of glutathione","volume":"93","author":"Yamaguchi","year":"2011","journal-title":"Biochimie"},{"key":"2026090204044019900_cit31","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1055\/s-0034-1390487","article-title":"Enhanced Cellular Cytotoxicity and\nAntibacterial Activity of 18-beta-Glycyrrhetinic Acid by Albumin-conjugated\nPLGA Nanoparticles","volume":"65","author":"Darvishi","year":"2015","journal-title":"Drug Res."},{"key":"2026090204044019900_cit32","doi-asserted-by":"publisher","first-page":"553","DOI":"10.3109\/10717544.2013.853850","article-title":"A wogonin-loaded glycyrrhetinic\nacid-modified liposome for hepatic targeting with anti-tumor effects","volume":"21","author":"Tian","year":"2014","journal-title":"Drug Delivery"},{"key":"2026090204044019900_cit33","doi-asserted-by":"publisher","first-page":"191","DOI":"10.3109\/10428190109057970","article-title":"Lamivudine\nand glycyrrhizin for treatment\nof chemotherapy-induced hepatitis B virus (HBV) hepatitis in a chronic\nHBV carrier with non-Hodgkin lymphoma","volume":"41","author":"Matsuo","year":"2001","journal-title":"Leuk.\nLymphoma"},{"key":"2026090204044019900_cit34","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1111\/j.1365-2125.2012.04374.x","article-title":"Omega-3\npolyunsaturated fatty acids and inflammatory processes: nutrition\nor pharmacology?","volume":"75","author":"Calder","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"2026090204044019900_cit35","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1093\/carcin\/bgx112","article-title":"Eicosapentaenoic\nacid attenuates\nobesity-related hepatocellular carcinogenesis","volume":"39","author":"Inoue-Yamauchi","year":"2018","journal-title":"Carcinogenesis"},{"key":"2026090204044019900_cit36","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-018-1326-z","article-title":"Omega-6-derived\noxylipin changes in serum of patients with hepatitis B virus-related\nliver diseases","volume":"14","author":"Lu","year":"2018","journal-title":"Metabolomics"},{"key":"2026090204044019900_cit37","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.3390\/cancers11101497","article-title":"Comprehensive Metabolomic\nSearch\nfor Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma\nfrom Cirrhosis","volume":"11","author":"Kim","year":"2019","journal-title":"Cancers"},{"key":"2026090204044019900_cit38","doi-asserted-by":"publisher","first-page":"17217","DOI":"10.1039\/c7ra00698e","article-title":"Metabolomic applications in hepatocellular\ncarcinoma: toward the exploration of therapeutics and diagnosis through\nsmall molecules","volume":"7","author":"Xie","year":"2017","journal-title":"RSC Adv."},{"key":"2026090204044019900_cit39","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1002\/0471250953.bi1324s46","article-title":"Employing ProteoWizard to Convert\nRaw Mass Spectrometry Data","volume":"46","author":"Holman","year":"2014","journal-title":"Curr. Protoc. Bioinf."},{"key":"2026090204044019900_cit40","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-395","article-title":"MZmine 2: modular framework\nfor processing, visualizing, and analyzing mass spectrometry-based\nmolecular profile data","volume":"11","author":"Pluskal","year":"2010","journal-title":"BMC Bioinf."},{"key":"2026090204044019900_cit41","doi-asserted-by":"publisher","first-page":"D608","DOI":"10.1093\/nar\/gkx1089","article-title":"HMDB 4.0: the human\nmetabolome database for 2018","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids\nRes."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c04259","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/2\/1160\/67657325\/acsomega.0c04259.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/6\/2\/1160\/67657325\/acsomega.0c04259.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:05:00Z","timestamp":1788336300000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/6\/2\/1160\/384884\/LC-MS-Based-Global-Metabolomic-Identification-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":41,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1,4]]},"published-print":{"date-parts":[[2021,1,19]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c04259","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]}}}