{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T06:29:16Z","timestamp":1770964156922,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"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>This study aimed to determine the effect of three widely used radiopharmaceuticals with intestinal excretion on selected relevant bacteria that are part of the human gut microbiota, using an ex vivo approach. Fecal samples obtained from healthy volunteers were analyzed. Each sample was divided into four smaller aliquots. One served as the non-irradiated control. The other three were homogenized with three radiopharmaceutical solutions ([131I]NaI, [99mTc]NaTcO4, and [223Ra]RaCl2). Relative quantification of each taxa was determined by the 2\u2212\u0394\u0394C method, using the ribosomal gene 16S as an internal control (primers 534\/385). Twelve fecal samples were analysed: three controls and nine irradiated. Our experiment showed fold changes in all analyzed taxa with all radiopharmaceuticals, but results were more significant with I-131, ranging from 1.87\u201383.58; whereas no relevant differences were found with Tc-99m and Ra-223, ranging from 0.98\u20131.58 and 0.83\u20131.97, respectively. This study corroborates limited existing research on how ionizing radiation changes the gut microbiota composition, providing novel data regarding the ex vivo effect of radiopharmaceuticals. Our findings justify the need for future larger scale projects.<\/jats:p>","DOI":"10.3390\/ijms231810809","type":"journal-article","created":{"date-parts":[[2022,9,18]],"date-time":"2022-09-18T23:39:22Z","timestamp":1663544362000},"page":"10809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Ionizing Radiation from Radiopharmaceuticals and the Human Gut Microbiota: An Ex Vivo Approach"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-8050","authenticated-orcid":false,"given":"Ana","family":"Fernandes","sequence":"first","affiliation":[{"name":"Department Nuclear Medicine, Centro Hospitalar e Universit\u00e1rio de S\u00e3o Jo\u00e3o, E.P.E., 4200-319 Porto, Portugal"}]},{"given":"Ana","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department Nuclear Medicine, Centro Hospitalar e Universit\u00e1rio de S\u00e3o Jo\u00e3o, E.P.E., 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3277-7821","authenticated-orcid":false,"given":"Carla","family":"Guedes","sequence":"additional","affiliation":[{"name":"Laboratory of Medical and Industrial Biotechnology, Instituto Polit\u00e9cnico do Porto, 4200-465 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3984","authenticated-orcid":false,"given":"R\u00faben","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Medical and Industrial Biotechnology, Instituto Polit\u00e9cnico do Porto, 4200-465 Porto, Portugal"},{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Faculdade de Ci\u00eancias da Sa\u00fade da Universidade Fernando Pessoa, 4200-150 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9157-5541","authenticated-orcid":false,"given":"Raquel","family":"Soares","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Department of Biomedicine, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4537-5450","authenticated-orcid":false,"given":"Pedro","family":"Barata","sequence":"additional","affiliation":[{"name":"i3S\u2014Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Faculdade de Ci\u00eancias da Sa\u00fade da Universidade Fernando Pessoa, 4200-150 Porto, Portugal"},{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio do Porto, 4099-001 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"ref_1","first-page":"247","article-title":"Targeted and non-targeted effects of ionizing radiation","volume":"8","author":"Desouky","year":"2015","journal-title":"J. Radiat. Res. Appl. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/09553009414550041","article-title":"Free radicals in biology: Oxidative stress and the effects of ionizing radiation","volume":"65","author":"Riley","year":"1994","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1126\/science.3.72.726","article-title":"A new form of radiation","volume":"3","year":"1896","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/jhered\/esx059","article-title":"Gut Microbiomics-A Solution to Unloose the Gordian Knot of Biological Effects of Ionizing Radiation","volume":"109","author":"Zhang","year":"2018","journal-title":"J. Hered."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1136\/gut.2004.062596","article-title":"Gastrointestinal complications of pelvic radiotherapy: Are they of any importance?","volume":"54","author":"Andreyev","year":"2005","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1136\/flgastro-2014-100468","article-title":"Guidance: The practical management of the gastrointestinal symptoms of pelvic radiation disease","volume":"6","author":"Andreyev","year":"2015","journal-title":"Frontline Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"Av173","DOI":"10.1667\/RRAV13.1","article-title":"The nature of intestinal radiation death","volume":"178","author":"Quastler","year":"2012","journal-title":"Radiat. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/gutjnl-2017-313789","article-title":"Radiation induces proinflammatory dysbiosis: Transmission of inflammatory susceptibility by host cytokine induction","volume":"67","author":"Blatt","year":"2018","journal-title":"Gut"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The Human Intestinal Microbiome in Health and Disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kumagai, T., Rahman, F., and Smith, A.M. (2018). The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis. Nutrients, 10.","DOI":"10.3390\/nu10101405"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0140-6736(03)12489-0","article-title":"Gut flora in health and disease","volume":"361","author":"Guarner","year":"2003","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature11319","article-title":"Gut microbiota composition correlates with diet and health in the elderly","volume":"488","author":"Claesson","year":"2012","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.tem.2019.05.008","article-title":"Microbiota and Thyroid Interaction in Health and Disease","volume":"30","author":"Frohlich","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1111\/j.1572-0241.2008.01868.x","article-title":"The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea","volume":"103","author":"Manichanh","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, A., Ling, Z., Yang, Z., Kiela, P.R., Wang, T., Wang, C., Cao, L., Geng, F., Shen, M., and Ran, X. (2015). Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: A pilot study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126312"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Johnson, L.B., Riaz, A.A., Adawi, D., Wittgren, L., Back, S., Thornberg, C., Osman, N., Gadaleanu, V., Thorlacius, H., and Jeppsson, B. (2004). Radiation enteropathy and leucocyte-endothelial cell reactions in a refined small bowel model. BMC Surg., 4.","DOI":"10.1186\/1471-2482-4-10"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.anaerobe.2015.01.004","article-title":"High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy","volume":"33","author":"Kim","year":"2015","journal-title":"Anaerobe"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nam, Y.D., Kim, H.J., Seo, J.G., Kang, S.W., and Bae, J.W. (2013). Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082659"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1158\/1078-0432.CCR-20-3445","article-title":"Gut Microbiome Components Predict Response to Neoadjuvant Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Prospective, Longitudinal Study","volume":"27","author":"Yi","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e7683","DOI":"10.7717\/peerj.7683","article-title":"Effect of radiotherapy on the gut microbiome in pediatric cancer patients: A pilot study","volume":"7","author":"Sahly","year":"2019","journal-title":"PeerJ"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3365","DOI":"10.1007\/s00259-021-05345-9","article-title":"EANM position paper on the role of radiobiology in nuclear medicine","volume":"48","author":"Aerts","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1007\/s00259-019-04334-3","article-title":"Call to arms: Need for radiobiology in molecular radionuclide therapy","volume":"46","author":"Terry","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.semradonc.2020.07.002","article-title":"The Radiobiology of Radiopharmaceuticals","volume":"31","author":"Morris","year":"2021","journal-title":"Semin. Radiat. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fmed.2015.00012","article-title":"Introduction to radiobiology of targeted radionuclide therapy","volume":"2","author":"Pouget","year":"2015","journal-title":"Front. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"448","DOI":"10.15252\/emmm.201606932","article-title":"Faecal microbiota transplantation protects against radiation-induced toxicity","volume":"9","author":"Cui","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1667\/RR2691.1","article-title":"Intestinal microbiota as novel biomarkers of prior radiation exposure","volume":"177","author":"Lam","year":"2012","journal-title":"Radiat. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11070","DOI":"10.1073\/pnas.0504978102","article-title":"Obesity alters gut microbial ecology","volume":"102","author":"Ley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1242\/dmm.017400","article-title":"How informative is the mouse for human gut microbiota research?","volume":"8","author":"Nguyen","year":"2015","journal-title":"Dis. Models Mech."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_30","first-page":"364","article-title":"Dysbiosis in ukrainian children with irritable bowel syndrome affected by natural radiation","volume":"22","author":"Kuznetsova","year":"2012","journal-title":"Iran. J. Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13568-019-0763-z","article-title":"Altered diversity and composition of the gut microbiome in patients with cervical cancer","volume":"9","author":"Wang","year":"2019","journal-title":"AMB Express"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"El Alam, M.B., Sims, T.T., Kouzy, R., Biegert, G.W.G., Jaoude, J., Karpinets, T.V., Yoshida-Court, K., Wu, X., Delgado-Medrano, A.Y., and Mezzari, M.P. (2021). A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247905"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S103","DOI":"10.2307\/3583517","article-title":"Biochemistry of DNA lesions","volume":"8","author":"Ward","year":"1985","journal-title":"Radiat. Res. Suppl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0079-6603(08)60611-X","article-title":"DNA damage produced by ionizing radiation in mammalian cells: Identities, mechanisms of formation, and reparability","volume":"35","author":"Ward","year":"1988","journal-title":"Prog. Nucleic Acid Res. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1667\/RR14306.1","article-title":"An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis","volume":"186","author":"Goudarzi","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1039\/c5tx00222b","article-title":"Key mechanisms involved in ionizing radiation-induced systemic effects. A current review","volume":"5","author":"Mavragani","year":"2015","journal-title":"Toxicol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1191\/0960327104ht418oa","article-title":"The radiation-induced bystander effect: Evidence and significance","volume":"23","author":"Azzam","year":"2004","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_38","unstructured":"Radswiki, T., and Worsley, C. (2022, January 24). Tc-99m Pertechnetate. Reference Article. Available online: https:\/\/radiopaedia.org\/articles\/15559."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/MNM.0000000000000132","article-title":"Adverse effects of radioactive iodine-131 treatment for differentiated thyroid carcinoma","volume":"35","author":"Fallahi","year":"2014","journal-title":"Nucl. Med. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4103\/1450-1147.174703","article-title":"Gastrointestinal Side Effects of the Radioiodine Therapy for the Patients with Differentiated Thyroid Carcinoma Two Days after Prescription","volume":"15","author":"Pashnehsaz","year":"2016","journal-title":"World J. Nucl. Med."},{"key":"ref_41","first-page":"362","article-title":"False-positive uptake on radioiodine whole-body scintigraphy: Physiologic and pathologic variants unrelated to thyroid cancer","volume":"2","author":"Oh","year":"2012","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1007\/s00259-017-3900-4","article-title":"EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer","volume":"45","author":"Poeppel","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"20160748","DOI":"10.1259\/bjr.20160748","article-title":"Imaging and dosimetry for radium-223: The potential for personalized treatment","volume":"90","author":"Flux","year":"2017","journal-title":"Br. J. Radiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"345","DOI":"10.7555\/JBR.29.20140069","article-title":"Internal radiation therapy: A neglected aspect of nuclear medicine in the molecular era","volume":"29","author":"Lin","year":"2015","journal-title":"J. Biomed. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1128\/AEM.66.5.2263-2266.2000","article-title":"Quantification of bacterial groups within human fecal flora by oligonucleotide probe hybridization","volume":"66","author":"Sghir","year":"2000","journal-title":"Appl. Env. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4153","DOI":"10.1128\/AEM.71.7.4153-4155.2005","article-title":"Colonic microbiota signatures across five northern European countries","volume":"71","author":"Lay","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1574-6968.2009.01514.x","article-title":"Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine","volume":"294","author":"Louis","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1093\/jrr\/rrz002","article-title":"Short-term follow-up of intestinal flora in radiation-exposed mice","volume":"60","author":"Yamanouchi","year":"2019","journal-title":"J. Radiat. Res."},{"key":"ref_49","first-page":"1908","article-title":"Effect of a mixture of inulin and fructo-oligosaccharide on Lactobacillus and Bifidobacterium intestinal microbiota of patients receiving radiotherapy: A randomised, double-blind, placebo-controlled trial","volume":"27","author":"Velasco","year":"2012","journal-title":"Nutr. Hosp."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"106696","DOI":"10.1016\/j.jenvrad.2021.106696","article-title":"A new era of radiation resistance bacteria in bioremediation and production of bioactive compounds with therapeutic potential and other aspects: An in-perspective review","volume":"237","author":"Nayak","year":"2021","journal-title":"J. Environ. Radioact."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"fnz180","DOI":"10.1093\/femsle\/fnz180","article-title":"Community structure and functional genes in radionuclide contaminated soils in Chernobyl and Fukushima","volume":"366","author":"Courbert","year":"2019","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/SHK.0b013e3182a2c5b5","article-title":"Intestinal barrier disruption as a cause of mortality in combined radiation and burn injury","volume":"40","author":"Carter","year":"2013","journal-title":"Shock"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1038\/bjc.2013.491","article-title":"Radiation-induced bowel injury: The impact of radiotherapy on survivorship after treatment for gynaecological cancers","volume":"109","author":"Kuku","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1245\/s10434-012-2827-z","article-title":"Effect of preoperative radio(chemo)therapy on long-term functional outcome in rectal cancer patients: A systematic review and meta-analysis","volume":"20","author":"Loos","year":"2013","journal-title":"Ann. Surg. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41571-018-0046-7","article-title":"Safety of combining radiotherapy with immune-checkpoint inhibition","volume":"15","author":"Hwang","year":"2018","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/aem.59.3.695-700.1993","article-title":"Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA","volume":"59","author":"Muyzer","year":"1993","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Gonzalez-Hernandez, L.A., Ruiz-Briseno, M.D.R., Sanchez-Reyes, K., Alvarez-Zavala, M., Vega-Magana, N., Lopez-Iniguez, A., Diaz-Ramos, J.A., Martinez-Ayala, P., Soria-Rodriguez, R.A., and Ramos-Solano, M. (2019). Alterations in bacterial communities, SCFA and biomarkers in an elderly HIV-positive and HIV-negative population in western Mexico. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3867-9"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e02106","DOI":"10.1128\/AEM.02106-17","article-title":"Porcine Small and Large Intestinal Microbiota Rapidly Hydrolyze the Masked Mycotoxin Deoxynivalenol-3-Glucoside and Release Deoxynivalenol in Spiked Batch Cultures In Vitro","volume":"84","author":"Gratz","year":"2018","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.femsec.2004.03.001","article-title":"Temporal stability analysis of the microbiota in human feces by denaturing gradient gel electrophoresis using universal and group-specific 16S rRNA gene primers","volume":"48","author":"Vanhoutte","year":"2004","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"7220","DOI":"10.1128\/AEM.70.12.7220-7228.2004","article-title":"Use of 16S rRNA gene-targeted group-specific primers for real-time PCR analysis of predominant bacteria in human feces","volume":"70","author":"Matsuki","year":"2004","journal-title":"Appl. Environ. Microbiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10809\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:32:48Z","timestamp":1760142768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/18\/10809"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":60,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms231810809"],"URL":"https:\/\/doi.org\/10.3390\/ijms231810809","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]}}}