{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T09:50:58Z","timestamp":1772272258059,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Administration of Traditional Chinese Medicine high-level key discipline construction project","award":["No.zyyzdxk-2023186"],"award-info":[{"award-number":["No.zyyzdxk-2023186"]}]},{"name":"Science and Technology Research Project of Traditional Chinese Medicine and Ethnic Medicine of Guizhou Administration of Traditional Chinese Medicine","award":["QZYY-2025-092"],"award-info":[{"award-number":["QZYY-2025-092"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Blumea balsamifera (L.) DC. (Miao Medicine: Diangd vob bvid), a medicinal plant with a long ethnopharmacological history in Southwest China, is widely used by the Miao, Li, and Zhuang ethnic groups to treat rheumatic diseases. While previous studies indicated that the ethyl acetate fraction of B. balsamifera (BBEA) possesses potent anti-inflammatory properties, its specific bioactive material basis and the underlying molecular mechanisms against rheumatoid arthritis (RA) remain elusive. Methods: In this study, an integrated strategy combining chemical profiling, network pharmacology, and experimental validation was employed. First, UPLC-Q-Exactive-MS\/MS analysis was conducted to characterize the chemical constituents of BBEA. Subsequently, network pharmacology and molecular docking were utilized to predict potential active compounds and core signaling pathways. Finally, the therapeutic effects and mechanisms were validated in vivo using a collagen-induced arthritis (CIA) rat model and in vitro using lipopolysaccharide (LPS)-induced RAW264.7 macrophages. Results: A total of 25 active constituents, including Genkwanin and Luteolin, were identified in BBEA via UPLC-Q-Exactive-MS\/MS. Network pharmacology analysis predicted that the PI3K\/AKT signaling pathway is critical for BBEA\u2019s anti-RA activity, and molecular docking confirmed strong binding affinities between key components (e.g., Genkwanin) and core targets (SRC, AKT1). In vivo experiments demonstrated that BBEA significantly reduced the Arthritis Index (AI) and paw swelling, reversed weight loss, and ameliorated synovial hyperplasia in CIA rats (p &lt; 0.05). Furthermore, BBEA markedly downregulated the levels of pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6, and IL-17) both in serum and synovial tissues. Mechanistically, Western blot analysis verified that BBEA inhibited the phosphorylation of PI3K and AKT in a dose-dependent manner. Conclusions: This study systematically reveals that BBEA alleviates RA symptoms and synovial inflammation primarily by inhibiting the PI3K\/AKT signaling pathway. These findings provide a scientific basis for the traditional application of B. balsamifera and suggest BBEA as a promising candidate for RA therapy.<\/jats:p>","DOI":"10.3390\/ph19030359","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Blumea balsamifera Alleviates Rheumatoid Arthritis by Suppressing Synovial Inflammation via the PI3K\/AKT Signaling Pathway: From Chemical Profiling to Molecular Mechanism"],"prefix":"10.3390","volume":"19","author":[{"given":"Tianyu","family":"Tang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kailang","family":"Mu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyue","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Sha","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuehua","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiwei","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingli","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanfei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanchi","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxin","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"Blumea Research Center, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Smolen, J.S., Aletaha, D., Barton, A., Burmester, G.R., Emery, P., Firestein, G.S., Kavanaugh, A., McInnes, I.B., Solomon, D.H., and Strand, V. (2018). Rheumatoid arthritis. Nat. Rev. Dis. Primers, 4.","DOI":"10.1038\/nrdp.2018.1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, W., Wang, J., Xu, Z., Huang, F., Qian, W., Ma, J., Wee, H.B., Lewis, G.S., June, R.R., and Schafer, P.H. (2018). Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01662"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Qian, X., Zai, Z., Tao, Y., Lv, H., Hao, M., Zhang, L., Zhang, X., Xu, Y., Zhang, Y., and Chen, F. (2025). Acidosis regulates immune progression in rheumatoid arthritis by promoting the expression of cytokines and co-stimulatory molecules in synovial fibroblasts. Mol. Med., 31.","DOI":"10.1186\/s10020-025-01181-x"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zeng, H., Yuan, Z., Wu, R.-T., and Huang, Z. (2025). Research progress on complications of rheumatoid arthritis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1561926"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, L., He, X., Zhi, D., Xue, Y., Gong, X., Dong, K., and Tian, Y. (2024). Melittin promotes dexamethasone in the treatment of adjuvant rheumatoid arthritis in rats. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1338432"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Shen, J., Fang, Y., Xu, N., Chen, H., Zhu, M., Li, D., Chu, Z., Sunagawa, M., Liu, Y., and Wang, H. (2025). Exploring the mechanism of triptolide inhibiting the motility of fibroblast-like synoviocytes in rheumatoid arthritis via RhoA\/Rho-associated kinase axis, based on network pharmacology, molecular docking and molecular dynamics simulations. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1545514"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wei, X., and Zheng, S.G. (2025). Immunomodulatory role of natural products in treating rheumatoid arthritis. Int. Immunopharmacol., 164.","DOI":"10.1016\/j.intimp.2025.115369"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cheema, K.S., Mansour, A.B., and Raychaudhuri, S.P. (2025). What\u2019s new on the horizon for rheumatoid arthritis management. Best Pr. Res. Clin. Rheumatol., 39.","DOI":"10.1016\/j.berh.2025.102038"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1001\/jama.2023.26504","article-title":"Disease-Modifying Drugs for Adult-Onset Rheumatoid Arthritis","volume":"331","author":"Faison","year":"2024","journal-title":"JAMA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1302\/2046-3758.98.BJR-2019-0301.R1","article-title":"Promising targets and drugs in rheumatoid arthritis","volume":"9","author":"Li","year":"2020","journal-title":"Bone Jt. Res."},{"key":"ref_11","first-page":"417","article-title":"Neuropsychiatric adverse drug reactions associated with low dose methotrexate in rheumatoid arthritis patients","volume":"21","author":"Bakker","year":"2021","journal-title":"Expert Opin Drug Saf."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Khoroshun, K., Bantel, C., Hoffmann, F., and Jobski, K. (2025). Methotrexate-related drug reactions on kidneys and liver in rheumatoid arthritis: An analysis of spontaneous reports in EudraVigilance. Arthritis Res. Ther., 27.","DOI":"10.1186\/s13075-025-03551-6"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"A1099","DOI":"10.1136\/annrheumdis-2013-eular.3172","article-title":"AB0850-HPR Side effect profile in patients with rheumatoid arthritis on leflunomide with and without loading dose","volume":"72","author":"Arava","year":"2013","journal-title":"Ann. Rheum. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lin, Y.-J., Anzaghe, M., and Sch\u00fclke, S. (2020). Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis. Cells, 9.","DOI":"10.3390\/cells9040880"},{"key":"ref_15","first-page":"3","article-title":"Classification and Treatment Methods for Rheumatic Diseases in Western Miao Medicine","volume":"6","author":"Du","year":"2006","journal-title":"J. Med. Pharm. Chin."},{"key":"ref_16","first-page":"53","article-title":"Research Progress of Miao Medicine in the Treatment of Rheumatoid Arthritis","volume":"20","author":"Li","year":"2024","journal-title":"Asia-Pac. Tradit. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9453","DOI":"10.3390\/molecules19079453","article-title":"Blumea balsamifera\u2014A Phytochemical and Pharmacological Review","volume":"19","author":"Pang","year":"2014","journal-title":"Molecules"},{"key":"ref_18","first-page":"219","article-title":"Epidemiological investigation of resident with rheumatoid arthritis in rural minorities from 20 to 79 years old in Qiannan, Guizhou","volume":"47","author":"He","year":"2020","journal-title":"Mod. Prev. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1136\/ard-2023-224080","article-title":"Country-level socioeconomic status relates geographical latitude to the onset of RA: A worldwide cross-sectional analysis in the METEOR registry","volume":"82","author":"Bergstra","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.14202\/vetworld.2021.1185-1196","article-title":"Phytochemical composition and health properties of Sembung plant (Blumea balsamifera): A review","volume":"14","author":"Widhiantara","year":"2021","journal-title":"Vet. World"},{"key":"ref_21","first-page":"1810","article-title":"Antibacterial Activity of Flavonoids from Blumea balsamifera","volume":"40","author":"Wang","year":"2019","journal-title":"Chin. J. Trop. Crops"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Huang, X.-L., Wang, D.-W., Liu, Y.-Q., and Cheng, Y.-X. (2022). Diterpenoids from Blumea balsamifera and Their Anti-Inflammatory Activities. Molecules, 27.","DOI":"10.3390\/molecules27092890"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gao, Y., Liu, F., Fang, L., Cai, R., Zong, C., and Qi, Y. (2014). Genkwanin Inhibits Proinflammatory Mediators Mainly through the Regulation of miR-101\/MKP-1\/MAPK Pathway in LPS-Activated Macrophages. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096741"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1007\/s10753-020-01248-3","article-title":"Alpinetin Protects Chondrocytes and Exhibits Anti-Inflammatory Effects via the NF-\u03baB\/ERK Pathway for Alleviating Osteoarthritis","volume":"43","author":"Gao","year":"2020","journal-title":"Inflammation"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sun, Y.-W., Bao, Y., Yu, H., Chen, Q.-J., Lu, F., Zhai, S., Zhang, C.-F., Li, F., Wang, C.-Z., and Yuan, C.-S. (2020). Anti-rheumatoid arthritis effects of flavonoids from Daphne genkwa. Int. Immunopharmacol., 83.","DOI":"10.1016\/j.intimp.2020.106384"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41584-020-0413-5","article-title":"Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes","volume":"16","author":"Nygaard","year":"2020","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1007\/s10753-020-01246-5","article-title":"Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K\/AKT Signaling Pathway","volume":"43","author":"Li","year":"2020","journal-title":"Inflammation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1002\/1878-0261.12558","article-title":"Disruption of the RICTOR\/mTORC2 complex enhances the response of head and neck squamous cell carcinoma cells to PI3K inhibition","volume":"13","author":"Ruicci","year":"2019","journal-title":"Mol. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.4155\/fmc.15.55","article-title":"The PI3K\/Akt\/PTEN\/mTOR Pathway: A Fruitful Target for Inducing Cell Death in Rheumatoid Arthritis?","volume":"7","author":"Malemud","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5969","DOI":"10.1093\/rheumatology\/keaf363","article-title":"The role of ITIH4 in regulating the PI3K\/Akt signalling in rheumatoid arthritis","volume":"64","author":"Joshi","year":"2025","journal-title":"Rheumatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cbi.2019.04.002","article-title":"Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K\/AKT pathway in complete Freund\u2019s adjuvant-induced arthritis in mice","volume":"306","author":"Qi","year":"2019","journal-title":"Chem. Interact."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Shao, W., Liu, F., Zhu, L., Qian, W., Meng, Q., Zhang, A., Jin, S., Lu, J., and Yan, S.G. (2024). Ferroportin inhibits the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via regulating ROS\/PI3K\/AKT signaling pathway. Eur. J. Pharmacol., 987.","DOI":"10.1016\/j.ejphar.2024.177205"},{"key":"ref_33","first-page":"1332","article-title":"Study on the pharmacodynamics and mechanism of Blumea balsamifera total flavonoids against acute myocardial infarction model rats","volume":"34","author":"Lv","year":"2023","journal-title":"China Pharm."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1080\/17425247.2025.2580443","article-title":"Targeted immunomodulation for chronic diseases through advanced delivery platforms","volume":"23","author":"Girela","year":"2025","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The Pathogenesis of Rheumatoid Arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3694","DOI":"10.1111\/febs.15715","article-title":"More than just protein building blocks: How amino acids and related metabolic pathways fuel macrophage polarization","volume":"288","author":"Kieler","year":"2021","journal-title":"FEBS J."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kondo, N., Kuroda, T., and Kobayashi, D. (2021). Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222010922"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1136\/annrheumdis-2018-214783","article-title":"TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: Transcriptomic and epigenomic analysis","volume":"78","author":"Loh","year":"2019","journal-title":"Ann. Rheum. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Li, L., Li, J., Ren, J., and Yao, J. (2025). Isorhamnetin Exhibits Hypoglycemic Activity and Targets PI3K\/AKT and COX-2 Pathways in Type 1 Diabetes. Nutrients, 17.","DOI":"10.3390\/nu17203201"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Viviano, M.T., Provini, A., Mazzanti, C., Nistic\u00f2, S.P., Patruno, C., Cannarozzo, G., Bennardo, S., Fusco, I., and Bennardo, L. (2022). Clinical Evaluation on the Performance and Safety of a Non-Ablative Fractional 1340 nm Laser for the Treatment of Stretch Marks in Adolescents and Young Adults: A Case Series. Bioengineering, 9.","DOI":"10.3390\/bioengineering9040139"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yan, J., Zhang, Z., Chen, M., Wu, X., and Ma, S. (2022). Immunosuppressive Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii Hook. f.. Molecules, 27.","DOI":"10.3390\/molecules27217274"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7941684","DOI":"10.1155\/2016\/7941684","article-title":"Periploca forrestii Saponin Ameliorates Murine CFA-Induced Arthritis by Suppressing Cytokine Production","volume":"2016","author":"Liu","year":"2016","journal-title":"Mediat. Inflamm."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Luo, J.-F., Yu, Y., Yao, Y.-D., Zhang, C., Liu, J.-X., Lio, C., Qian, H.-B., and Zhou, H. (2026). Sinomenine treats Rheumatoid Arthritis by regulating IL-6 Gene Promoter Methylation. Phytomedicine.","DOI":"10.2139\/ssrn.5525651"},{"key":"ref_44","first-page":"1112","article-title":"Study on the chemical constituents from the aerial parts of Blumea balsamifera DC. and their antioxidant and tyrosinase inhibitory activities","volume":"33","author":"Zhou","year":"2021","journal-title":"Nat. Prod. Res. Dev."},{"key":"ref_45","first-page":"1105","article-title":"Exploration on Action Characteristics of the Stems and Leaves of Melicope ptelefolia on the Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking","volume":"34","author":"Chen","year":"2023","journal-title":"Tradit. Chin. Drug Res. Clin. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Huang, J., Tang, H., Cao, S., He, Y., Feng, Y., Wang, K., and Zheng, Q. (2017). Molecular Targets and Associated Potential Pathways of Danlu Capsules in Hyperplasia of Mammary Glands Based on Systems Pharmacology. Evid.-Based Complement. Altern. Med., 2017.","DOI":"10.1155\/2017\/1930598"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Xu, S., Yu, Y., Xie, Q., Liu, X., Zhang, A., Tang, H., Zhu, Z., Bian, X., and Guo, L. (2025). Revealing the molecular mechanism of Buzhong Yiqi Decoction for tendon bone healing on the basis of network pharmacology, molecular docking and experimental validation. J. Ethnopharmacol., 347.","DOI":"10.1016\/j.jep.2025.119726"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yao, L., Cheng, S., Yang, J., Xiang, F., Zhou, Z., Zhang, Q., Pang, Y., Zhou, W., and Abliz, Z. (2022). Metabolomics reveals the intervention effect of Zhuang medicine Longzuantongbi granules on a collagen-induced arthritis rat model by using UPLC-MS\/MS. J. Ethnopharmacol., 294.","DOI":"10.1016\/j.jep.2022.115325"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Chi, P., Zhang, H., Chen, Y., Xie, J., Ayixianmuguli, Y., Wu, C., and Liu, M. (2025). Investigating the underlying mechanisms of the ethanol extract of saussureae involucratae herba in anti-rheumatoid arthritis effect based on sphingolipidomics. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1549437"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/359\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T05:13:55Z","timestamp":1772255635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/3\/359"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":49,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ph19030359"],"URL":"https:\/\/doi.org\/10.3390\/ph19030359","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]}}}