{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:55:31Z","timestamp":1788170131581,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Basolateral amygdala (BLA) deep brain stimulation (DBS) has been shown to alleviate the symptoms of post-traumatic stress disorder (PTSD), but the specific mechanisms remain incompletely understood. The hippocampus, a brain region closely connected to the amygdala, plays a key role in the pathological processes of PTSD. The N6-methyladenosine (m6A) methylation of RNAs in the hippocampus is known to play a significant role in regulating the brain\u2019s response to stress and emotional disorders. Methods: This study aimed to comprehensively analyze the roles of transcriptome-wide m6A modifications of the hippocampus in the BLA DBS treatment of a PTSD mouse model using m6A sequencing. Results: Significant alterations in functional connectivity between the ventral hippocampus (vHPC) and BLA were observed in foot shock (FS) mice through functional magnetic resonance imaging (fMRI) analysis. Furthermore, we observed that the expression of the key m6A methyltransferase enzyme, METTL3, in the FS and BLA DBS groups was higher than that in the control group. At the same time, both FS and BLA DBS induced the widespread m6A methylation of RNAs in the vHPC. Gene ontology (GO) enrichment analysis revealed that FS altered methylation in metabolic, developmental, and cytoskeletal pathways, while BLA DBS targeted metabolic, cell cycle, and neuroplasticity-related genes. Additionally, BLA DBS reversed the aberrant methylation of genes associated with multiple functional pathways induced by FS, including those related to cholinergic transmission, sodium and calcium ion homeostasis, and stress hormone responsiveness. We identified a set of RNAs with methylation changes that were reversed by BLA DBS in the FS vs. Ctrl (control) comparison, including those associated with cholinergic transmission, sodium and calcium ion balance, and stress hormone response. Additionally, we detected several specific BLA DBS-related genes through MeRIP-qPCR, indicating that DBS influences crucial genes linked to calcium signaling and synaptic plasticity. Conclusions: We draw two conclusions from these findings: BLA DBS may alleviate PTSD-like symptoms by reversing FS-induced methylation changes and by altering the methylation levels of crucial genes. These findings indicate that epigenetic m6A modifications in the vHPC may play an important role in the amelioration of PTSD using BLA DBS.<\/jats:p>","DOI":"10.3390\/brainsci15050473","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T09:00:39Z","timestamp":1745917239000},"page":"473","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epitranscriptomic Analysis of the Ventral Hippocampus in a Mouse Model of Post-Traumatic Stress Disorder Following Deep Brain Stimulation Treatment of the Basolateral Amygdala"],"prefix":"10.3390","volume":"15","author":[{"given":"Mingxi","family":"Ma","sequence":"first","affiliation":[{"name":"Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Fan","sequence":"additional","affiliation":[{"name":"Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Yin","sequence":"additional","affiliation":[{"name":"Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Gao","sequence":"additional","affiliation":[{"name":"Center of Cognition and Brain Science, Beijing Institute of Basic Medical Sciences, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1056\/NEJMra1612499","article-title":"Post-Traumatic Stress Disorder","volume":"376","author":"Shalev","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8694","DOI":"10.1523\/JNEUROSCI.0703-18.2018","article-title":"Eye-Movement Intervention Enhances Extinction via Amygdala Deactivation","volume":"38","author":"Kanen","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.mcna.2022.04.003","article-title":"Post-traumatic Stress Disorder","volume":"107","author":"Merians","year":"2023","journal-title":"Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41582-018-0128-2","article-title":"Deep brain stimulation: Current challenges and future directions","volume":"15","author":"Lozano","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/s41398-023-02727-5","article-title":"Systematic review of rodent studies of deep brain stimulation for the treatment of neurological, developmental and neuropsychiatric disorders","volume":"14","author":"Zhang","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Staudt, M.D., Herring, E.Z., Gao, K., Miller, J.P., and Sweet, J.A. (2019). Evolution in the Treatment of Psychiatric Disorders: From Psychosurgery to Psychopharmacology to Neuromodulation. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.00108"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Carrillo-Ruiz, J.D., Carrillo-M\u00e1rquez, J.R., Beltr\u00e1n, J.Q., Jim\u00e9nez-Ponce, F., Garc\u00eda-Mu\u00f1oz, L., Navarro-Olvera, J.L., M\u00e1rquez-Franco, R., and Velasco, F. (2023). Innovative perspectives in limbic surgery using deep brain stimulation. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1167244"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sgambato-Faure, V., Alonso, P., Cuadras, D., Denys, D., Goodman, W., Greenberg, B.D., Jimenez-Ponce, F., Kuhn, J., Lenartz, D., and Mallet, L. (2015). Deep Brain Stimulation for Obsessive-Compulsive Disorder: A Meta-Analysis of Treatment Outcome and Predictors of Response. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133591"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hitti, F.L., Yang, A.I., Cristancho, M.A., and Baltuch, G.H. (2020). Deep Brain Stimulation Is Effective for Treatment-Resistant Depression: A Meta-Analysis and Meta-Regression. J. Clin. Med., 9.","DOI":"10.3390\/jcm9092796"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e82","DOI":"10.1016\/j.biopsych.2015.09.003","article-title":"Deep Brain Stimulation of the Basolateral Amygdala for Treatment-Refractory Posttraumatic Stress Disorder","volume":"79","author":"Langevin","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Langevin, J.P., Chen, J.W., Koek, R.J., Sultzer, D.L., Mandelkern, M.A., Schwartz, H.N., and Krahl, S.E. (2016). Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings. Brain Sci., 6.","DOI":"10.3390\/brainsci6030028"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/hipo.20102","article-title":"Bilateral hippocampal volume reduction in adults with post-traumatic stress disorder: A meta-analysis of structural MRI studies","volume":"15","author":"Smith","year":"2005","journal-title":"Hippocampus"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Mcnerney, M.W., Sheng, T., Nechvatal, J.M., Lee, A.G., Lyons, D.M., Soman, S., Liao, C.-P., O\u2019Hara, R., Hallmayer, J., and Taylor, J. (2018). Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192222"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.bpsgos.2023.07.001","article-title":"Structural Neuroimaging of Hippocampus and Amygdala Subregions in Posttraumatic Stress Disorder: A Scoping Review","volume":"4","author":"Korem","year":"2024","journal-title":"Biol. Psychiatry Glob. Open Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Postel, C., Mary, A., Dayan, J., Fraisse, F., Vall\u00e9e, T., Guillery-Girard, B., Viader, F., de la Sayette, V., Peschanski, D., and Eustache, F. (2021). Variations in response to trauma and hippocampal subfield changes. Neurobiol. Stress, 15.","DOI":"10.1016\/j.ynstr.2021.100346"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.neubiorev.2006.03.004","article-title":"A meta-analysis of structural brain abnormalities in PTSD","volume":"30","author":"Karl","year":"2006","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neuron.2009.11.031","article-title":"Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?","volume":"65","author":"Fanselow","year":"2010","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.neuropharm.2011.04.029","article-title":"Hippocampal dysfunction effects on context memory: Possible etiology for posttraumatic stress disorder","volume":"62","author":"Acheson","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103417","DOI":"10.1016\/j.nicl.2023.103417","article-title":"Altered Resting-State functional connectivity in the anterior and posterior hippocampus in Post-traumatic stress disorder: The central role of the anterior hippocampus","volume":"38","author":"Chaposhloo","year":"2023","journal-title":"Neuroimage Clin."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.neuron.2013.06.016","article-title":"BLA to vHPC Inputs Modulate Anxiety-Related Behaviors","volume":"79","author":"Seo","year":"2013","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/s41380-019-0549-3","article-title":"Successful treatment of post-traumatic stress disorder reverses DNA methylation marks","volume":"26","author":"Vinkers","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.neuron.2018.07.009","article-title":"The Role of m6A\/m-RNA Methylation in Stress Response Regulation","volume":"99","author":"Engel","year":"2018","journal-title":"Neuron"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, P.-F., Han, Q.-Q., Chen, F.-F., Shen, T.-T., Li, Y.-H., Cao, Y., Chen, J.-G., and Wang, F. (2021). Erasing m6A-dependent transcription signature of stress-sensitive genes triggers antidepressant actions. Neurobiol. Stress, 15.","DOI":"10.1016\/j.ynstr.2021.100390"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1038\/s41467-024-48730-2","article-title":"Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice","volume":"15","author":"Guo","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/s41586-018-0666-1","article-title":"m6A facilitates hippocampus-dependent learning and memory through YTHDF1","volume":"563","author":"Shi","year":"2018","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1093\/ijnp\/pyac068","article-title":"M6A RNA Methylation-Based Epitranscriptomic Modifications in Plasticity-Related Genes via miR-124-C\/EBP\u03b1-FTO-Transcriptional Axis in the Hippocampus of Learned Helplessness Rats","volume":"25","author":"Roy","year":"2022","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1007\/s11011-024-01485-7","article-title":"Unlocking NAC\u2019s potential ATF4 and m6A dynamics in rescuing cognitive impairments in PTSD","volume":"40","author":"Zhou","year":"2025","journal-title":"Metab. Brain Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.biopsych.2017.11.019","article-title":"Current Status of Animal Models of Posttraumatic Stress Disorder: Behavioral and Biological Phenotypes, and Future Challenges in Improving Translation","volume":"83","author":"Deslauriers","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113766","DOI":"10.1016\/j.celrep.2024.113766","article-title":"BLA DBS improves anxiety and fear by correcting weakened synaptic transmission from BLA to adBNST and CeL in a mouse model of foot shock","volume":"43","author":"Gao","year":"2024","journal-title":"Cell Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/s41398-020-0806-x","article-title":"Rodent models of post-traumatic stress disorder: Behavioral assessment","volume":"10","author":"Verbitsky","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"623753","DOI":"10.1155\/2012\/623753","article-title":"Anxiolytic Effects of Flavonoids in Animal Models of Posttraumatic Stress Disorder","volume":"2012","author":"Zhang","year":"2012","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12974-020-02069-9","article-title":"Microglial deletion and inhibition alleviate behavior of post-traumatic stress disorder in mice","volume":"18","author":"Li","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41583-018-0039-7","article-title":"Brain circuit dysfunction in post-traumatic stress disorder: From mouse to man","volume":"19","author":"Fenster","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/ner.12551","article-title":"Posttraumatic Stress Disorder: Perspectives for the Use of Deep Brain Stimulation","volume":"20","author":"Reznikov","year":"2017","journal-title":"Neuromodulation Technol. Neural Interface"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1159\/000521130","article-title":"Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature","volume":"100","author":"Meeres","year":"2022","journal-title":"Stereotact. Funct. Neurosurg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15057","DOI":"10.1038\/nrdp.2015.57","article-title":"Post-traumatic stress disorder","volume":"1","author":"Yehuda","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/hbm.26142","article-title":"Higher reliability and validity of Wavelet-ALFF of resting-state fMRI: From multicenter database and application to rTMS modulation","volume":"44","author":"Yue","year":"2022","journal-title":"Human. Brain Mapp."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cub.2021.12.015","article-title":"Unique spatiotemporal fMRI dynamics in the awake mouse brain","volume":"32","author":"Singh","year":"2022","journal-title":"Curr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hayes, J.P., Hayes, S.M., and Mikedis, A.M. (2012). Quantitative meta-analysis of neural activity in posttraumatic stress disorder. Biol. Mood Anxiety Disord., 2.","DOI":"10.1186\/2045-5380-2-9"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/da.22483","article-title":"Structural and Functional Connectivity in Posttraumatic Stress Disorder: Associations with Fkbp5","volume":"33","author":"Fani","year":"2016","journal-title":"Depress. Anxiety"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nature09742","article-title":"Synaptic potentiation onto habenula neurons in the learned helplessness model of depression","volume":"470","author":"Li","year":"2011","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.lfs.2003.09.024","article-title":"Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability","volume":"74","author":"Toews","year":"2003","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"12237","DOI":"10.1074\/jbc.275.16.12237","article-title":"Functional properties of a new voltage-dependent calcium channel alpha(2)delta auxiliary subunit gene (CACNA2D2)","volume":"275","author":"Gao","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"916","DOI":"10.2174\/1570159X21666230803101629","article-title":"Neurotensin and Neurotensin Receptors in Stress-related Disorders: Pathophysiology & Novel Drug Targets","volume":"22","author":"Kyriatzis","year":"2024","journal-title":"Curr. Neuropharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.neuron.2022.01.035","article-title":"Neuronal mitochondria transport Pink1 mRNA via synaptojanin 2 to support local mitophagy","volume":"110","author":"Harbauer","year":"2022","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/mp.2012.101","article-title":"Neuropeptide Y and posttraumatic stress disorder","volume":"18","author":"Sah","year":"2013","journal-title":"Mol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.neubiorev.2018.12.026","article-title":"Progress in brain cannabinoid CB(2) receptor research: From genes to behavior","volume":"98","author":"Jordan","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1515\/revneuro-2023-0009","article-title":"Pathway specific interventions reveal the multiple roles of ventral hippocampus projections in cognitive functions","volume":"34","author":"Bakoyiannis","year":"2023","journal-title":"Rev. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.celrep.2018.01.025","article-title":"Homeostatic Plasticity in the Hippocampus Facilitates Memory Extinction","volume":"22","author":"Mendez","year":"2018","journal-title":"Cell Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s12264-023-01129-3","article-title":"Memory Trace for Fear Extinction: Fragile yet Reinforceable","volume":"40","author":"Liu","year":"2023","journal-title":"Neurosci. Bull."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Almeida, F.B., Pinna, G., and Barros, H.M.T. (2021). The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115495"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.expneurol.2016.05.038","article-title":"Posttraumatic stress disorder: A metabolic disorder in disguise?","volume":"284","author":"Michopoulos","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.pnpbp.2018.10.010","article-title":"The hypothalamic-pituitary-adrenal axis in PTSD: Pathophysiology and treatment interventions","volume":"89","author":"Dunlop","year":"2019","journal-title":"Progress. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1176\/appi.ajp.2020.20121727","article-title":"Functional Neuroimaging in PTSD: From Discovery of Underlying Mechanisms to Addressing Diagnostic Heterogeneity","volume":"178","author":"Neria","year":"2021","journal-title":"Am. J. Psychiatry"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"105242","DOI":"10.1016\/j.psyneuen.2021.105242","article-title":"Oxytocin receptor is a potential biomarker of the hyporesponsive HPA axis subtype of PTSD and might be modulated by HPA axis reactivity traits in humans and mice","volume":"129","author":"Hofmann","year":"2021","journal-title":"Psychoneuroendocrinology"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/473\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:24:01Z","timestamp":1760030641000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":55,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["brainsci15050473"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15050473","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}