{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:11:53Z","timestamp":1792789913545,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Cancer Association","award":["20240164"],"award-info":[{"award-number":["20240164"]}],"id":[{"id":"https:\/\/ror.org\/03yxd7304","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Israel Cancer Association","award":["20251130"],"award-info":[{"award-number":["20251130"]}],"id":[{"id":"https:\/\/ror.org\/03yxd7304","id-type":"ROR","asserted-by":"crossref"}]},{"award":["20240164"],"award-info":[{"award-number":["20240164"]}],"id":[{"id":"https:\/\/ror.org\/03yxd7304","id-type":"ROR","asserted-by":"publisher"}]},{"award":["20251130"],"award-info":[{"award-number":["20251130"]}],"id":[{"id":"https:\/\/ror.org\/03yxd7304","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hadassah France"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes, most patients do not respond to treatment or fail to achieve durable responses. Histone deacetylase inhibitors (HDACi) have emerged as promising immunomodulatory agents, with the potential to sensitize tumors to ICIs. We investigated the immunomodulatory effects of entinostat, a class I HDACi, in combination with dual ICI (anti-PD-1 and anti-CTLA-4) as well as with T-cell receptor (TCR) engineered T cells in preclinical NSCLC models. Methods: We employed human NSCLC cell lines and the immunogenic KRASG12D\/p53-mutant KPN1.1 murine NSCLC cell line. In vitro, we assessed entinostat-induced changes in MHC class I and PD-L1 expression. In addition, we evaluated the effects of entinostat on a KRASG12D-specific TCR. In vivo, therapeutic efficacy and immune modulation were assessed by transplanting KPN1.1 cells subcutaneously and orthotopically into immunocompetent mice, followed by treatment with dual ICI, with or without entinostat. Immune populations in the spleen and blood were subsequently analyzed. Results: In vitro, entinostat induced the upregulation of MHC-I and PD-L1 expression in both human and murine NSCLC cell lines. In addition, entinostat treatment significantly enhanced antigen-specific tumor recognition and killing by T cells engineered to express a KRASG12D-specific TCR. In vivo, the addition of entinostat to dual immune checkpoint inhibition showed an incremental trend toward improved tumor growth control. Notably, entinostat plus dual ICI enhanced systemic immune activation, increasing circulating and splenic T-cell populations and significantly expanding both antigen-specific and overall effector CD8+ T cells. Consistently, the ex vivo co-culture of splenocytes from KPN1.1-bearing mice with KPN1.1 tumor cells demonstrated enhanced CD8+ antigen-specific T-cell recognition. Conclusions: In human and murine NSCLC models, entinostat potentiates TCR- and ICI-mediated tumor recognition through tumor-intrinsic and systemic immune modulation. These effects were reflected by increased MHC-I expression, expansion of antigen-specific effector CD8+ T cells, and enhanced CD8+ T-cell tumor recognition. These findings support a further evaluation of entinostat as a strategy to improve immunotherapy efficacy in NSCLC.<\/jats:p>","DOI":"10.3390\/ph19071034","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T14:51:25Z","timestamp":1783003885000},"page":"1034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Entinostat Enhances Antigen-Specific CD8 T-Cell Response to Immunotherapies in Lung Cancer Models"],"prefix":"10.3390","volume":"19","author":[{"given":"Esti","family":"Porush","sequence":"first","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5688-5712","authenticated-orcid":false,"given":"Johnathan","family":"Arnon","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 10117 Berlin, Germany"},{"name":"Institute of Cancer Immunology, Charit\u00e9 Universit\u00e4tsmedizin Campus Buch, 13125 Berlin, Germany"},{"name":"Sharett Institute of Oncology, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Baruch","family":"Pinchover","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Esther","family":"Stern","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Oz","family":"Shapira","sequence":"additional","affiliation":[{"name":"Department of General Thoracic Surgery, Division of Cardiothoracic Surgery, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5823-7404","authenticated-orcid":false,"given":"Didier","family":"Jean","sequence":"additional","affiliation":[{"name":"INSERM, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, Centre de Recherche des Cordeliers, F-75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9374-2489","authenticated-orcid":false,"given":"Galia","family":"Blum","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, The Hebrew University, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Evalyn","family":"Yakobovich","sequence":"additional","affiliation":[{"name":"The Institute for Drug Research, The School of Pharmacy, The Faculty of Medicine, The Hebrew University, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Hanna","family":"Wald","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4973-2829","authenticated-orcid":false,"given":"Amnon","family":"Peled","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Zhangman","family":"Wang","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 10117 Berlin, Germany"},{"name":"Institute of Cancer Immunology, Charit\u00e9 Universit\u00e4tsmedizin Campus Buch, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Elmehdi","family":"Belbaraka","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Christian","family":"Friese","sequence":"additional","affiliation":[{"name":"Institute of Cancer Immunology, Charit\u00e9 Universit\u00e4tsmedizin Campus Buch, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Thomas","family":"Blankenstein","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3309-5141","authenticated-orcid":false,"given":"Thomas","family":"Kammertoens","sequence":"additional","affiliation":[{"name":"Max Delbr\u00fcck Center for Molecular Medicine in the Helmholtz Association (MDC), 10117 Berlin, Germany"},{"name":"Institute of Cancer Immunology, Charit\u00e9 Universit\u00e4tsmedizin Campus Buch, 13125 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Ori","family":"Wald","sequence":"additional","affiliation":[{"name":"Gene Therapy Institute, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"Department of General Thoracic Surgery, Division of Cardiothoracic Surgery, Hadassah Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zakaria, N., Satar, N.A., Abu Halim, N.H., Ngalim, S.H., Yusoff, N.M., Lin, J., and Yahaya, B.H. (2017). Targeting Lung Cancer Stem Cells: Research and Clinical Impacts. Front. Oncol., 7.","DOI":"10.3389\/fonc.2017.00080"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1056\/NEJMoa1801005","article-title":"Pembrolizumab plus Chemotherapy in Metastatic Non\u2013Small-Cell Lung Cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1056\/NEJMoa2202170","article-title":"Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer","volume":"386","author":"Forde","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1056\/NEJMoa2302983","article-title":"Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer","volume":"389","author":"Wakelee","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1007\/s11912-023-01443-z","article-title":"Cellular Therapy in NSCLC: Between Myth and Reality","volume":"25","author":"Imbimbo","year":"2023","journal-title":"Curr. Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.2217\/fon-2016-0526","article-title":"Entinostat: A promising treatment option for patients with advanced breast cancer","volume":"13","author":"Connolly","year":"2017","journal-title":"Future Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00262-007-0402-4","article-title":"Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells","volume":"57","author":"Khan","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7390","DOI":"10.18632\/oncotarget.7180","article-title":"Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype to enhance T-cell mediated lysis of prostate and breast carcinoma cells","volume":"7","author":"Gameiro","year":"2016","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1158\/1078-0432.CCR-15-2584","article-title":"HDAC inhibitors enhance T cell chemokine expression and augment response to PD-1 immunotherapy in lung adenocarcinoma","volume":"22","author":"Zheng","year":"2016","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1158\/1078-0432.CCR-17-0741","article-title":"Entinostat Neutralizes Myeloid-Derived Suppressor Cells and Enhances the Antitumor Effect of PD-1 Inhibition in Murine Models of Lung and Renal Cell Carcinoma","volume":"23","author":"Orillion","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1158\/2326-6066.CIR-18-0070","article-title":"Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs","volume":"6","author":"Christmas","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1158\/1078-0432.CCR-20-3305","article-title":"Entinostat plus pembrolizumab in patients with metastatic NSCLC previously treated with anti-PD-(L)1 therapy","volume":"27","author":"Hellmann","year":"2020","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5828","DOI":"10.1158\/1078-0432.CCR-20-5017","article-title":"Phase 1 Study of Entinostat and Nivolumab with or without Ipilimumab in Advanced Solid Tumors (ETCTN-9844)","volume":"27","author":"Torres","year":"2021","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"ref_16","first-page":"196","article-title":"Pharmacogenomic Characterization of a Large Cohort of Patient-Derived Cell Lines Identifies Therapeutic Strategies for Pleural Mesothelioma","volume":"86","author":"Meiller","year":"2025","journal-title":"Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1016\/j.jtcvs.2010.11.056","article-title":"Interaction between neoplastic cells and cancer-associated fibroblasts through the CXCL12\/CXCR4 axis: Role in non-small cell lung cancer tumor proliferation","volume":"141","author":"Wald","year":"2011","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"eadf3700","DOI":"10.1126\/sciadv.adf3700","article-title":"TCR-engineered T cell therapy in solid tumors: State of the art and perspectives","volume":"9","author":"Baulu","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.1056\/NEJMoa2119662","article-title":"Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer","volume":"386","author":"Leidner","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.ccell.2020.08.004","article-title":"Challenges and Opportunities for Pancreatic Cancer Immunotherapy","volume":"38","author":"Bear","year":"2020","journal-title":"Cancer Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4365","DOI":"10.1038\/s41467-021-24562-2","article-title":"Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting","volume":"12","author":"Bear","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100084","DOI":"10.1016\/j.crmeth.2021.100084","article-title":"Systematic discovery and validation of T cell targets directed against oncogenic KRAS mutations","volume":"1","author":"Choi","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.1158\/1078-0432.CCR-21-0849","article-title":"Identification and Validation of T-cell Receptors Targeting RAS Hotspot Mutations in Human Cancers for Use in Cell-based Immunotherapy","volume":"27","author":"Levin","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100080","DOI":"10.1016\/j.crmeth.2021.100080","article-title":"A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma","volume":"1","author":"Fitzgerald","year":"2021","journal-title":"Cell Rep. Methods"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41587-020-0613-1","article-title":"Inducible de novo expression of neoantigens in tumor cells and mice with NINJA","volume":"39","author":"Damo","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/JTO.0000000000000367","article-title":"In the Hunt for Therapeutic Targets: Mimicking the Growth, Metastasis, and Stromal Associations of Early-Stage Lung Cancer Using a Novel Orthotopic Animal Model","volume":"10","author":"Weiss","year":"2015","journal-title":"J. Thorac. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/path.6435","article-title":"Development and characterisation of improved unifocal primary mouse lung cancer models with metastatic potential","volume":"266","author":"Pedrosa","year":"2025","journal-title":"J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1466018","DOI":"10.1080\/2162402X.2018.1466018","article-title":"Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types","volume":"7","author":"Hicks","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9801","DOI":"10.1038\/s41467-024-52528-7","article-title":"Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: A phase 2 clinical trial","volume":"15","author":"Baretti","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/s43018-024-00729-w","article-title":"Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: A phase Ib trial","volume":"5","author":"Torres","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.21037\/tlcr-24-552","article-title":"Emerging insights into STK11, KEAP1 and KRAS mutations: Implications for immunotherapy in patients with advanced non-small cell lung cancer","volume":"13","author":"Krawczyk","year":"2024","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"eadd3243","DOI":"10.1126\/sciadv.add3243","article-title":"HDAC3 is critical in tumor development and therapeutic resistance in Kras-mutant non\u2013small cell lung cancer","volume":"9","author":"Eichner","year":"2023","journal-title":"Sci. Adv."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1034\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:37:33Z","timestamp":1792147053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/7\/1034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ph19071034"],"URL":"https:\/\/doi.org\/10.3390\/ph19071034","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]}}}