{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:08:21Z","timestamp":1779253701194,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tamoxifen remains the standard treatment for estrogen receptor alpha (ER \u03b1) positive breast cancer (BC) cases. However, a significant proportion of patients develop chemoresistance, leading to disease recurrence. The Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), coded by NFE2L2 gene, has emerged as a key player in chemoresistance and tumoral progression across multiple cancer types, including BC. This study aimed to analyze the role of Nrf2 in metastasis-related processes in a tamoxifen-metabolite-resistant BC cell variant (MCF-7Var-H) and to assess the impact of Nrf2 modulation. We analyzed Nrf2 expression and nuclear localization and observed that both were increased in endocrine-chemoresistant MCF-7Var-H cells compared with MCF-7 parental cells. Critically, we assessed the effects of Nrf2 on migration, invasion, and metalloproteinase secretion capacity using wound-healing assays, Boyden chamber assays, and zymography, respectively. Our results suggest that Nrf2 actively promotes metastatic behaviors in the resistant variant. To further explore its pharmacological relevance, we designed and synthesized small interfering RNAs (siRNAs) targeting NFE2L2 mRNA in its coding region by heterogeneous-phase chemical synthesis. Transfection with these siRNAs significantly inhibited metastasis-related functions such as migration in MCF-7Var-H cells. Overall, siRNAs targeting Nrf2 may be promising tools for treating chemoresistant and metastatic breast cancer.<\/jats:p>","DOI":"10.3390\/ijms27104506","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"4506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nrf2 Is Associated with Metastasis-Related Processes in a Chemoresistant Breast Cancer Model: Insights from siRNA Modulation"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2715-9811","authenticated-orcid":false,"given":"Andrea","family":"Mu\u00f1oz-Ayala","sequence":"first","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Humberto Torres Sangin\u00e9s S\/N, Centro C\u00edvico, Mexicali 21000, BC, Mexico"},{"name":"Laboratorio Multidisciplinario de Estudios Metab\u00f3licos y C\u00e1ncer, Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-3985","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Seraf\u00edn-Higuera","sequence":"additional","affiliation":[{"name":"Facultad de Odontolog\u00eda Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Centro de Ciencias de la Salud Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8543-5676","authenticated-orcid":false,"given":"Ana Gabriela","family":"Leija-Montoya","sequence":"additional","affiliation":[{"name":"Centro de Ciencias de la Salud Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Centro de Innovaci\u00f3n e Investigaci\u00f3n en Salud, CIIS, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-7551","authenticated-orcid":false,"given":"Octavio","family":"Galindo-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Humberto Torres Sangin\u00e9s S\/N, Centro C\u00edvico, Mexicali 21000, BC, Mexico"},{"name":"Laboratorio Multidisciplinario de Estudios Metab\u00f3licos y C\u00e1ncer, Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Centro de Innovaci\u00f3n e Investigaci\u00f3n en Salud, CIIS, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luis","family":"Vique-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Ciencias de la Salud Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Centro de Innovaci\u00f3n e Investigaci\u00f3n en Salud, CIIS, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-5683","authenticated-orcid":false,"given":"Ra\u00fal","family":"D\u00edaz-Molina","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Humberto Torres Sangin\u00e9s S\/N, Centro C\u00edvico, Mexicali 21000, BC, Mexico"},{"name":"Laboratorio Multidisciplinario de Estudios Metab\u00f3licos y C\u00e1ncer, Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Departamento de Educaci\u00f3n e Investigaci\u00f3n, Servicios de Salud del Instituto Mexicano del Seguro Social para el Bienestar (IMSS-BIENESTAR), Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8660-7393","authenticated-orcid":false,"given":"Santiago","family":"Villafa\u00f1a","sequence":"additional","affiliation":[{"name":"Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-3730","authenticated-orcid":false,"given":"Victor","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Humberto Torres Sangin\u00e9s S\/N, Centro C\u00edvico, Mexicali 21000, BC, Mexico"},{"name":"Laboratorio Multidisciplinario de Estudios Metab\u00f3licos y C\u00e1ncer, Facultad de Medicina y Nutrici\u00f3n Mexicali, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"},{"name":"Centro de Innovaci\u00f3n e Investigaci\u00f3n en Salud, CIIS, Universidad Aut\u00f3noma de Baja California, Mexicali 21000, BC, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.soc.2017.08.005","article-title":"Molecular Subtypes and Local-Regional Control of Breast Cancer","volume":"27","author":"Fragomeni","year":"2018","journal-title":"Surg. Oncol. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s12672-021-00411-y","article-title":"Tamoxifen and oxidative stress: An overlooked connection","volume":"12","author":"Ahmed","year":"2021","journal-title":"Discov. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10549-024-07431-6","article-title":"Receptor Discordance in Metastatic Breast Cancer; a review of clinical and genetic subtype alterations from primary to metastatic disease","volume":"207","author":"Dowling","year":"2024","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The Hallmarks of Cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12943-025-02338-2","article-title":"Epithelial\u2014To\u2014Mesenchymal transition (EMT) and cancer metastasis: The status quo of methods and experimental models 2025","volume":"24","author":"Allgayer","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"McGrath, E., Logue, S., Mnich, K., Deegan, S., J\u00e4ger, R., Gorman, A., and Samali, A. (2018). The Unfolded Protein Response in Breast Cancer. Cancers, 10.","DOI":"10.3390\/cancers10100344"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lindholm, D., Korhonen, L., Eriksson, O., and K\u00f5ks, S. (2017). Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease. Front. Cell Dev. Biol., 5.","DOI":"10.3389\/fcell.2017.00048"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2174\/1566524016666160523143937","article-title":"The Role of the PERK\/eIF2\u03b1\/ATF4\/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress","volume":"16","author":"Pytel","year":"2016","journal-title":"Curr. Mol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"67506","DOI":"10.18632\/oncotarget.18724","article-title":"ROS-independent Nrf2 activation in prostate cancer","volume":"8","author":"Bellezza","year":"2017","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20108","DOI":"10.1074\/jbc.M314219200","article-title":"PERK-dependent Activation of Nrf2 Contributes to Redox Homeostasis and Cell Survival following Endoplasmic Reticulum Stress","volume":"279","author":"Cullinan","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sarcinelli, C., Dragic, H., Piecyk, M., Barbet, V., Duret, C., Barthelaix, A., Ferraro-Peyret, C., Fauvre, J., Renno, T., and Chaveroux, C. (2020). ATF4-Dependent NRF2 Transcriptional Regulation Promotes Antioxidant Protection during Endoplasmic Reticulum Stress. Cancers, 12.","DOI":"10.3390\/cancers12030569"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"BSR20240444","DOI":"10.1042\/BSR20240444","article-title":"Tamoxifen metabolites treatment promotes ER\u03b1+ transition to triple negative phenotype in vitro, effects of LDL in chemoresistance","volume":"44","year":"2024","journal-title":"Biosci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8592348","DOI":"10.1155\/2019\/8592348","article-title":"Potential applications of NRF2 inhibitors in cancer therapy","volume":"2019","author":"Panieri","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the Hallmarks of Cancer","volume":"34","author":"Chapman","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s10549-019-05494-4","article-title":"The prognostic value of NRF2 in breast cancer patients: A systematic review with meta-analysis","volume":"179","author":"Almeida","year":"2020","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"36603","DOI":"10.18632\/oncotarget.16622","article-title":"Suppression of radiation-induced migration of NSCLC through inhibition of Nrf2-Notch Axis","volume":"8","author":"Zhao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gao, L., Morine, Y., Yamada, S., Saito, Y., Ikemoto, T., Tokuda, K., Takasu, C., Miyazaki, K., and Shimada, M. (2021). Nrf2 signaling promotes cancer stemness, migration, and expression of abc transporter genes in sorafenib-resistant hepatocellular carcinoma cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0256755"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40170-023-00304-4","article-title":"Tamoxifen induces radioresistance through NRF2-mediated metabolic reprogramming in breast cancer","volume":"11","author":"Reinema","year":"2023","journal-title":"Cancer Metab."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Duong, H.-Q., You, K.S., Oh, S., Kwak, S.J., and Seong, Y.S. (2017). Silencing of NRF2 Reduces the Expression of ALDH1A1 and ALDH3A1 and Sensitizes to 5-FU in Pancreatic Cancer Cells. Antioxidants, 6.","DOI":"10.3390\/antiox6030052"},{"key":"ref_21","first-page":"116","article-title":"The Impact of Nrf2 Silencing on Nrf2-PD-L1 Axis to Overcome Oxaliplatin Resistance and Migration in Colon Cancer Cells","volume":"13","author":"Payandeh","year":"2021","journal-title":"Avicenna J. Med. Biotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"116822","DOI":"10.1016\/j.ejmech.2024.116822","article-title":"NRF2 inhibitors: Recent progress, future design and therapeutic potential","volume":"279","author":"Lv","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/s12951-023-02147-z","article-title":"Engineering siRNA therapeutics: Challenges and strategies","volume":"21","author":"Fatima","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_24","first-page":"3147","article-title":"The story of MCF-7 breast cancer cell line: 40 Years of experience in research","volume":"35","author":"Raica","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1089\/nat.2014.0494","article-title":"Effect of siRNA with an Asymmetric RNA\/dTdT Overhang on RNA Interference Activity","volume":"24","author":"Park","year":"2014","journal-title":"Nucleic Acid. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"zcab027","DOI":"10.1093\/narcan\/zcab027","article-title":"A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells","volume":"3","author":"Sahoo","year":"2021","journal-title":"NAR Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pulido-Capiz, A., Chimal-Vega, B., Avila-Barrientos, L.P., Campos-Valenzuela, A., D\u00edaz-Molina, R., Mu\u00f1iz-Salazar, R., Mu\u00f1iz-Salazar, R., Galindo-Hern\u00e1ndez, O., and Garc\u00eda-Gonz\u00e1lez, V. (2024). Auraptene Boosts the Efficacy of the Tamoxifen Metabolites Endoxifen and 4-OH-Tamoxifen in a Chemoresistant ER+ Breast Cancer Model. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16091179"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41598-025-31313-6","article-title":"The translation factor eIF4E is a key mediator of doxorubicin resistance: Insights from a triple-negative breast cancer model","volume":"16","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"S\u00e1nchez-Ortega, M., Carrera, A.C., and Garrido, A. (2021). Role of NRF2 in Lung Cancer. Cells, 10.","DOI":"10.3390\/cells10081879"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10122","DOI":"10.1038\/s41598-018-28074-w","article-title":"Glucose starvation induces LKB1-AMPK-mediated MMP-9 expression in cancer cells","volume":"8","author":"Endo","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5734","DOI":"10.1111\/bph.70215","article-title":"Pathway-level mutational signatures predict breast cancer outcomes and reveal therapeutic targets","volume":"182","author":"Posta","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lin, Y.C., Ku, C.C., Wuputra, K., Wu, D.C., and Yokoyama, K.K. (2024). Vulnerability of Antioxidant Drug Therapies on Targeting the Nrf2-Trp53-Jdp2 Axis in Controlling Tumorigenesis. Cells, 13.","DOI":"10.20944\/preprints202409.0612.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7605","DOI":"10.2147\/IJN.S436038","article-title":"A Comprehensive Review of Small Interfering RNAs (siRNAs): Mechanism, Therapeutic Targets, and Delivery Strategies for Cancer Therapy","volume":"18","author":"Zhang","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic siRNA: State of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, C., Zhen, D., Yang, L., and Li, G. (2025). Clinical development prospects of siRNA drugs for tumor therapy: Analysis of clinical trial registration data from 2004 to 2024. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1637958"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Neumeier, J., and Meister, G. (2021). siRNA Specificity: RNAi Mechanisms and Strategies to Reduce Off-Target Effects. Front. Plant Sci., 11.","DOI":"10.3389\/fpls.2020.526455"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13442","DOI":"10.1038\/s41598-017-13880-5","article-title":"A Novel \u03b2-adaptin\/c-Myc Complex Formation Modulated by Oxidative Stress in the Control of the Cell Cycle in Macrophages and its Implication in Atherogenesis","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4158","DOI":"10.1002\/jcb.27701","article-title":"Protein translation associated to PERK arm is a new target for regulation of metainflammation: A connection with hepatocyte cholesterol","volume":"120","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Valencia, J., Garc\u00eda-Villarreal, R., Rodr\u00edguez-Jim\u00e9nez, M., Hern\u00e1ndez-Avalos, A.D., Rivero, I.A., Vique-S\u00e1nchez, J.L., Chimal-Vega, B., Pulido-Capiz, A., and Garc\u00eda-Gonz\u00e1lez, V. (2025). Lapatinib-Resistant HER2+ Breast Cancer Cells Are Associated with Dysregulation of MAPK and p70S6K\/PDCD4 Pathways and Calcium Management, Influence of Cryptotanshinone. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083763"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1038\/nprot.2006.339","article-title":"Clonogenic assay of cells in vitro","volume":"1","author":"Franken","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"9649","DOI":"10.1007\/s13277-015-3711-9","article-title":"Extracellular vesicles from women with breast cancer promote an epithelial-mesenchymal transition-like process in mammary epithelial cells MCF10A","volume":"36","author":"Salazar","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"G\u00f3nzalez-Ortiz, A., Pulido-Capiz, A., Casta\u00f1eda-S\u00e1nchez, C.Y., Ibarra-L\u00f3pez, E., Galindo-Hernandez, O., Calder\u00f3n-Fern\u00e1ndez, M.A., L\u00f3pez-Cossio, L.Y., D\u00edaz-Molina, R., Chimal-Vega, B., and Seraf\u00edn-Higuera, N. (2022). eIF4E\/PDCD4 Pathway, a Factor for Doxorubicin Chemoresistance in a Triple-Negative Breast Cancer Cell Model. Cells, 11.","DOI":"10.3390\/cells11244069"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"W521","DOI":"10.1093\/nar\/gkae241","article-title":"The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024","volume":"52","author":"Madeira","year":"2024","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4506\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:29:47Z","timestamp":1779251387000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":43,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104506"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104506","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}