{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:24:48Z","timestamp":1790573088037,"version":"4.1.0"},"reference-count":102,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"708","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2023,8,9]]},"abstract":"<jats:p>\n            There is an urgent need to develop therapeutics for inflammatory bowel disease (IBD) because up to 40% of patients with moderate-to-severe IBD are not adequately controlled with existing drugs. Glutamate carboxypeptidase II (GCPII) has emerged as a promising therapeutic target. This enzyme is minimally expressed in normal ileum and colon, but it is markedly up-regulated in biopsies from patients with IBD and preclinical colitis models. Here, we generated a class of GCPII inhibitors designed to be gut-restricted for oral administration, and we interrogated efficacy and mechanism using in vitro and in vivo models. The lead inhibitor, (\n            <jats:italic>S<\/jats:italic>\n            )-IBD3540, was potent (half maximal inhibitory concentration = 4 nanomolar), selective, gut-restricted (AUC\n            <jats:sub>colon\/plasma<\/jats:sub>\n            &gt; 50 in mice with colitis), and efficacious in acute and chronic rodent colitis models. In dextran sulfate sodium\u2013induced colitis, oral (\n            <jats:italic>S<\/jats:italic>\n            )-IBD3540 inhibited &gt;75% of colon GCPII activity, dose-dependently improved gross and histologic disease, and markedly attenuated monocytic inflammation. In spontaneous colitis in interleukin-10 (IL-10) knockout mice, once-daily oral (\n            <jats:italic>S<\/jats:italic>\n            )-IBD3540 initiated after disease onset improved disease, normalized colon histology, and attenuated inflammation as evidenced by reduced fecal lipocalin 2 and colon pro-inflammatory cytokines\/chemokines, including tumor necrosis factor\u2013\u03b1 and IL-17. Using primary human colon epithelial air-liquid interface monolayers to interrogate the mechanism, we further found that (\n            <jats:italic>S<\/jats:italic>\n            )-IBD3540 protected against submersion-induced oxidative stress injury by decreasing barrier permeability, normalizing tight junction protein expression, and reducing procaspase-3 activation. Together, this work demonstrated that local inhibition of dysregulated gastrointestinal GCPII using the gut-restricted, orally active, small-molecule (\n            <jats:italic>S<\/jats:italic>\n            )-IBD3540 is a promising approach for IBD treatment.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.abn7491","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T17:58:40Z","timestamp":1691603920000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":19,"title":["A gut-restricted glutamate carboxypeptidase II inhibitor reduces monocytic inflammation and improves preclinical colitis"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4185-6203","authenticated-orcid":true,"given":"Diane E.","family":"Peters","sequence":"first","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren D.","family":"Norris","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6982-3545","authenticated-orcid":true,"given":"Luk\u00e1\u0161","family":"Tenora","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 160 00 Prague, Czechia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0831-4034","authenticated-orcid":true,"given":"Ivan","family":"\u0160najdr","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 160 00 Prague, Czechia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-5038","authenticated-orcid":true,"given":"Andr\u00e1s K.","family":"Ponti","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2733-242X","authenticated-orcid":true,"given":"Xiaolei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-551X","authenticated-orcid":true,"given":"Shinji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayabhaskar","family":"Veeravalli","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8710-0148","authenticated-orcid":true,"given":"Manisha","family":"Pradhan","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5440-7891","authenticated-orcid":true,"given":"Jesse","family":"Alt","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5922-5050","authenticated-orcid":true,"given":"Ajit G.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-6934","authenticated-orcid":true,"given":"Pavel","family":"Majer","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 160 00 Prague, Czechia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4059-2453","authenticated-orcid":true,"given":"Rana","family":"Rais","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-9487","authenticated-orcid":true,"given":"Christine","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9814-4157","authenticated-orcid":true,"given":"Barbara S.","family":"Slusher","sequence":"additional","affiliation":[{"name":"Johns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30333-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6542a3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000496739"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izz078"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/3108025"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/MEG.0000000000000378"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36185-9"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67054-1"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.2910620511"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02635.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.06.003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037139"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21263"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.MIB.0000437045.26036.00"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI75436"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307387"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab311"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.88634"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2017.01.036"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/crocol\/otz030"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2016.01.007"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02909-y"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00256.2016"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2012.11.017"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.02766-16"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.01.021"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00027.2007"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1864"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13333"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms3040641"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0689-3"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1159\/000199367"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-302578"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.14456"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.044"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(02)00412-3"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm049258g"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2013.08.028"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3845"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1998.00357.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i35.5272"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izy364"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.09.004"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02764"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.20753"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000468"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevImmunol.v32.i1.30"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2000.278.6.G829"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1965"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0246161"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.01182-18"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1254529"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0097699"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01969-20"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00981-19"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.015"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.01.042"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.1999.01439.x"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-011-0516-5"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044328"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/0192623316665927"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.8277"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.09.064"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-320022"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.45"},{"key":"e_1_3_2_67_2","first-page":"255","article-title":"The expanding role of anti-IL-12 and\/or anti-IL-23 antibodies in the treatment of inflammatory bowel disease","volume":"15","author":"Kashani A.","year":"2019","unstructured":"A.\u00a0Kashani, D. A.\u00a0Schwartz, The expanding role of anti-IL-12 and\/or anti-IL-23 antibodies in the treatment of inflammatory bowel disease. Gastroenterol. Hepatol (N Y) 15, 255\u2013265 (2019).","journal-title":"Gastroenterol. Hepatol (N Y)"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.1.65"},{"key":"e_1_3_2_69_2","first-page":"607","article-title":"Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course","volume":"9","author":"Guimbaud R.","year":"1998","unstructured":"R.\u00a0Guimbaud, V.\u00a0Abitbol, V.\u00a0Bertrand, G.\u00a0Quartier, L.\u00a0Chauvelot-Moachon, J.\u00a0Giroud, D.\u00a0Couturier, D. C.\u00a0Chaussade, Leukemia inhibitory factor involvement in human ulcerative colitis and its potential role in malignant course. Eur. Cytokine Netw. 9, 607\u2013612 (1998).","journal-title":"Eur. Cytokine Netw."},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201899595"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00073.2005"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65128-0"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303424"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.4.526"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.20904"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1RU0716-327R"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.967"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1746.2002.02791.x"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199610)180:2<152::AID-PATH649>3.0.CO;2-Y"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10350-004-6802-z"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21191"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13771"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.3892\/or.2010.869"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.07.058"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.09.002"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014121271"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01382-y"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.05.067"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-016-0251-1"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2015.10.035"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.77"},{"key":"e_1_3_2_92_2","first-page":"182","article-title":"NKX3.1 and PSMA are sensitive diagnostic markers for prostatic carcinoma in bone metastasis after decalcification of specimens","volume":"6","author":"Huang H.","year":"2018","unstructured":"H.\u00a0Huang, S. R.\u00a0Guma, J.\u00a0Melamed, M.\u00a0Zhou, P.\u00a0Lee, F. M.\u00a0Deng, NKX3.1 and PSMA are sensitive diagnostic markers for prostatic carcinoma in bone metastasis after decalcification of specimens. Am. J.\u00a0Clin. Exp. Urol. 6, 182\u2013188 (2018).","journal-title":"Am. J.\u00a0Clin. Exp. Urol."},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102020"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2018.00032"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0131861"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(02)00286-5"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)47823-4"},{"key":"e_1_3_2_98_2","first-page":"4557","article-title":"A guide to histomorphological evaluation of intestinal inflammation in mouse models","volume":"7","author":"Erben U.","year":"2014","unstructured":"U.\u00a0Erben, C.\u00a0Loddenkemper, K.\u00a0Doerfel, S.\u00a0Spieckermann, D.\u00a0Haller, M. M.\u00a0Heimesaat, M.\u00a0Zeitz, B.\u00a0Siegmund, A. A.\u00a0Kuhl, A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int. J.\u00a0Clin. Exp. Pathol. 7, 4557\u20134576 (2014).","journal-title":"Int. J.\u00a0Clin. Exp. Pathol."},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-019-09859-w"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1423221112"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306651"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314540"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.23311"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.abn7491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T17:50:56Z","timestamp":1705427456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.abn7491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,9]]},"references-count":102,"journal-issue":{"issue":"708","published-print":{"date-parts":[[2023,8,9]]}},"alternative-id":["10.1126\/scitranslmed.abn7491"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.abn7491","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,9]]},"assertion":[{"value":"2021-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabn7491"}}