{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:49:39Z","timestamp":1785937779147,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ZJUT-Jinhua Innovation Joint Research Institute","award":["KYY-HX-20250040"],"award-info":[{"award-number":["KYY-HX-20250040"]}]},{"name":"ZJUT-Jinhua Innovation Joint Research Institute","award":["KYY-HX-20220649"],"award-info":[{"award-number":["KYY-HX-20220649"]}]},{"name":"Key Research and Development Program of Lishui City Science and Technology Bureau","award":["2025zdyf04"],"award-info":[{"award-number":["2025zdyf04"]}]},{"award":["2025zdyf04"],"award-info":[{"award-number":["2025zdyf04"]}],"id":[{"id":"https:\/\/ror.org\/03vdbng75","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Valorizing agricultural byproducts into functional ingredients is highly desirable. Herein, plant-derived nanovesicles (PDNVs) from Paris polyphylla stems\/leaves (SL-EXO) exhibited potent anti-melanogenic properties, whereas root-derived PDNVs were ineffective. In vitro, SL-EXO achieved 92.66% cell-free tyrosinase inhibition, while \u03b1-arbutin was 49.78%. In vivo, SL-EXO ameliorated the pigmentation-driving oxidative\/senescent microenvironment in zebrafish and reduced macroscopic melanin by ~66%. Crucially, SL-EXO reversed \u03b1-MSH-induced hyperpigmentation in B16F10 cells while maintaining excellent biocompatibility up to 0.15 mg\/mL, displaying a vastly superior safety margin compared to \u03b1-arbutin (which induced cytotoxicity at 0.075 mg\/mL). To decode this, multi-omics profiling revealed that SL-EXO utilizes a chloroplast-derived biomimetic lipid architecture (enriched in MGDG\/DGDG) to efficiently deliver potent flavonoid payloads. Molecular docking demonstrated exceptional predictive structural affinities (binding energies up to \u221210.9 kcal\/mol) between these phytochemicals and AKT1. Finally, pharmacological rescue assays validated that SL-EXO arrests melanogenesis by targeting the AKT1 pathway, thereby downregulating the p-AKT\/p-GSK3\/MITF signaling cascade and silencing melanogenic genes. This study establishes a rigorous multi-omics paradigm for upcycling botanical wastes into exceptionally safe and efficacious natural anti-melanogenic nanotherapeutics.<\/jats:p>","DOI":"10.3390\/cells15151420","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"1420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Valorization of Paris polyphylla Byproducts: Integrated Multi-Omics and Molecular Docking Reveal the Anti-Melanogenic Mechanism of Plant-Derived Nanovesicles via the AKT\/GSK3\u03b2\/MITF Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Peishi","family":"Feng","sequence":"first","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"},{"name":"Zhejiang International Scientific & Technological Cooperation Base of Development and Utilization of Natural Products, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4471-6716","authenticated-orcid":false,"given":"Li","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"},{"name":"Zhejiang International Scientific & Technological Cooperation Base of Development and Utilization of Natural Products, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"},{"name":"Zhejiang International Scientific & Technological Cooperation Base of Development and Utilization of Natural Products, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yida","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang Provincial Key Laboratory of TCM for Innovative R & D and Digital Intelligent Manufacturing of TCM Great Health Products, Hangzhou 310014, China"},{"name":"Zhejiang International Scientific & Technological Cooperation Base of Development and Utilization of Natural Products, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102288","DOI":"10.1016\/j.mtbio.2025.102288","article-title":"Bioinspired nanoparticles prevent blue-light-induced skin hyperpigmentation via FZD2-TYR-melanin pathway","volume":"35","author":"Chen","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.freeradbiomed.2024.12.032","article-title":"Deciphering the role of skin aging in pigmentary disorders","volume":"227","author":"Yang","year":"2025","journal-title":"Free Radic. Biol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3424","DOI":"10.1021\/acsnano.3c10552","article-title":"Conjugated Network Supporting Highly Surface-Exposed Ru Site-Based Artificial Antioxidase for Efficiently Modulating Microenvironment and Alleviating Solar Dermatitis","volume":"18","author":"Yang","year":"2024","journal-title":"ACS Nano"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Negre-Salvayre, A., and Salvayre, R. (2022). Post-Translational Modifications Evoked by Reactive Carbonyl Species in Ultraviolet-A-Exposed Skin: Implication in Fibroblast Senescence and Skin Photoaging. Antioxidants, 11.","DOI":"10.3390\/antiox11112281"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s12276-024-01175-5","article-title":"Emerging roles of MITF as a crucial regulator of immunity","volume":"56","author":"Lee","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wang, W., Gao, Y., Wang, W.W., Zhang, J.Y., Yin, J.F., Le, T., Xue, J.J., Engelhardt, U.H., and Jiang, H.Y. (2022). Kojic Acid Showed Consistent Inhibitory Activity on Tyrosinase from Mushroom and in Cultured B16F10 Cells Compared with Arbutins. Antioxidants, 11.","DOI":"10.3390\/antiox11030502"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"115574","DOI":"10.1016\/j.bcp.2023.115574","article-title":"Targeting tyrosinase in hyperpigmentation: Current status, limitations and future promises","volume":"212","author":"Zolghadri","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2207826","DOI":"10.1002\/adma.202207826","article-title":"Plant-Derived Vesicle-Like Nanoparticles as Promising Biotherapeutic Tools: Present and Future","volume":"35","author":"Feng","year":"2023","journal-title":"Adv. Mater."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1080\/13543776.2023.2195093","article-title":"Purposing plant-derived exosomes-like nanovesicles for drug delivery: Patents and literature review","volume":"33","author":"Orefice","year":"2023","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Woith, E., Guerriero, G., Hausman, J.F., Renaut, J., Leclercq, C.C., Weise, C., Legay, S., Weng, A., and Melzig, M.F. (2021). Plant Extracellular Vesicles and Nanovesicles: Focus on Secondary Metabolites, Proteins and Lipids with Perspectives on Their Potential and Sources. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073719"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12793","DOI":"10.2147\/IJN.S496664","article-title":"Engineering Strategies of Plant-Derived Exosome-Like Nanovesicles: Current Knowledge and Future Perspectives","volume":"19","author":"Li","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Naselli, F., Volpes, S., Cardinale, P.S., Palumbo, F.S., Cancilla, F., Lopresti, F., Villanova, V., Girgenti, A., Nuzzo, D., and Caradonna, F. (2024). New Nanovesicles from Prickly Pear Fruit Juice: A Resource with Antioxidant, Anti-Inflammatory, and Nutrigenomic Properties. Cells, 13.","DOI":"10.3390\/cells13211756"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120402","DOI":"10.1016\/j.jep.2025.120402","article-title":"Revealing the chemical and pharmacological individualities of two pharmacopoeial Paris species for the purpose of precise medication","volume":"353","author":"Qiu","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e13810","DOI":"10.1111\/ppl.13810","article-title":"Comparative transcriptome analysis reveals key genes for polyphyllin difference in five Paris species","volume":"174","author":"Hou","year":"2022","journal-title":"Physiol. Plant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1039\/D6TB00396F","article-title":"Cucumber-derived exosome-like nanovesicles encapsulating epigallocatechin gallate for skin depigmentation: Molecular docking, stability, and efficacy in B16\/F10 cells and zebrafish","volume":"14","author":"Tao","year":"2026","journal-title":"J. Mater. Chem. B"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"101103","DOI":"10.1016\/j.mtbio.2024.101103","article-title":"Olea europaea leaf exosome-like nanovesicles encapsulated in a hyaluronic acid\/tannic acid hydrogel dressing with dual \u201cdefense-repair\u201d effects for treating skin photoaging","volume":"26","author":"Wang","year":"2024","journal-title":"Mater. Today Bio"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Hering, A., Stefanowicz-Hajduk, J., Dziomba, S., Halasa, R., Krzemieniecki, R., Sappati, S., Baginski, M., and Ochocka, J.R. (2023). Mangiferin Affects Melanin Synthesis by an Influence on Tyrosinase: Inhibition, Mechanism of Action and Molecular Docking Studies. Antioxidants, 12.","DOI":"10.3390\/antiox12051016"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107837","DOI":"10.1016\/j.phrs.2025.107837","article-title":"A TRPV1 agonist from the transcriptome profiling of Dipsastraea rotumana inhibits neuroinflammation in vivo through the NF-\u03baB and MAPK pathways","volume":"218","author":"Chen","year":"2025","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"139497","DOI":"10.1016\/j.jhazmat.2025.139497","article-title":"Amino-functionalized carbon dots disrupt lipid metabolism to impair zebrafish embryogenesis","volume":"496","author":"Zhang","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108244","DOI":"10.1016\/j.biotechadv.2023.108244","article-title":"Fidelity-oriented fluorescence imaging probes for beta-galactosidase: From accurate diagnosis to precise treatment","volume":"68","author":"Feng","year":"2023","journal-title":"Biotechnol. Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1039\/D2FO03105A","article-title":"Rapid screening of novel tyrosinase inhibitory peptides from a pearl shell meat hydrolysate by molecular docking and the anti-melanin mechanism","volume":"14","author":"Huang","year":"2023","journal-title":"Food Funct."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1093\/mp\/sst080","article-title":"A novel integrated method for large-scale detection, identification, and quantification of widely targeted metabolites: Application in the study of rice metabolomics","volume":"6","author":"Chen","year":"2013","journal-title":"Mol. Plant"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1021\/ac1003568","article-title":"Signature-Discovery Approach for Sample Matching of a Nerve-Agent Precursor Using Liquid Chromatography-Mass Spectrometry, XCMS, and Chemometrics","volume":"82","author":"Fraga","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1021\/acs.jproteome.5b00354","article-title":"Analysis of the Human Adult Urinary Metabolome Variations with Age, Body Mass Index, and Gender by Implementing a Comprehensive Workflow for Univariate and OPLS Statistical Analyses","volume":"14","author":"Roux","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1074\/mcp.TIR119.001720","article-title":"MaxQuant Software for Ion Mobility Enhanced Shotgun Proteomics","volume":"19","author":"Prianichnikov","year":"2020","journal-title":"Mol. Cell Proteom."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ab.2009.10.047","article-title":"Enrichment of serum low-molecular-weight proteins using C18 absorbent under urea\/dithiothreitol denatured environment","volume":"398","author":"Wu","year":"2010","journal-title":"Anal. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4541","DOI":"10.1021\/pr300330z","article-title":"Identification and confirmation of differentially expressed fucosylated glycoproteins in the serum of ovarian cancer patients using a lectin array and LC-MS\/MS","volume":"11","author":"Wu","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"126560","DOI":"10.1016\/j.foodchem.2020.126560","article-title":"Halophyte plants from sustainable marine aquaponics are a valuable source of omega-3 polar lipids","volume":"320","author":"Maciel","year":"2020","journal-title":"Food Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.1021\/acs.analchem.8b01331","article-title":"Development of a High Coverage Pseudotargeted Lipidomics Method Based on Ultra-High Performance Liquid Chromatography-Mass Spectrometry","volume":"90","author":"Xuan","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e00183","DOI":"10.1002\/pld3.183","article-title":"An efficient and comprehensive plant glycerolipids analysis approach based on high-performance liquid chromatography-quadrupole time-of-flight mass spectrometer","volume":"3","author":"Lu","year":"2019","journal-title":"Plant Direct"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13429","DOI":"10.1111\/1541-4337.13429","article-title":"Transplanting network pharmacology technology into food science research: A comprehensive review on uncovering food-sourced functional factors and their health benefits","volume":"23","author":"Shen","year":"2024","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"158187","DOI":"10.1016\/j.phymed.2026.158187","article-title":"Jingfang granules alleviate atopic dermatitis by restoring skin barrier function and inhibiting NF-\u03baB\/NLRP3 axis and JAK\/STAT3 axis","volume":"155","author":"Tai","year":"2026","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1186\/s13046-025-03531-3","article-title":"Bufalin inhibits hepatocellular carcinoma progression by blocking EGFR-mediated RAS-RAF-MEK-ERK pathway activation","volume":"44","author":"Liu","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.jare.2024.08.012","article-title":"Extracellular vesicle-derived miR-146a as a novel crosstalk mechanism for high-fat induced atherosclerosis by targeting SMAD4","volume":"73","author":"Zhai","year":"2025","journal-title":"J. Adv. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1186\/s13046-022-02377-3","article-title":"TEAD4 functions as a prognostic biomarker and triggers EMT via PI3K\/AKT pathway in bladder cancer","volume":"41","author":"Chi","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1038\/s41596-024-01095-8","article-title":"A consensus platform for antibody characterization","volume":"20","author":"Ayoubi","year":"2025","journal-title":"Nat. Protoc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7011","DOI":"10.1021\/acsnano.3c10142","article-title":"Targeted Liposomes Sensitize Plastic Melanoma to Ferroptosis via Senescence Induction and Coenzyme Depletion","volume":"18","author":"Fan","year":"2024","journal-title":"ACS Nano"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"108754","DOI":"10.1016\/j.pharmthera.2024.108754","article-title":"The pharmacodynamic and pharmacological mechanisms underlying nanovesicles of natural products: Developments and challenges","volume":"265","author":"Zhang","year":"2025","journal-title":"Pharmacol. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"107062","DOI":"10.1016\/j.phrs.2024.107062","article-title":"Bioactive compounds and biological functions of medicinal plant-derived extracellular vesicles","volume":"200","author":"Hao","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/bjd.20804","article-title":"An in vivo model of postinflammatory hyperpigmentation and erythema: Clinical, colorimetric and molecular characteristics","volume":"186","author":"Vellaichamy","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114097","DOI":"10.1016\/j.foodres.2024.114097","article-title":"Identification of tyrosinase inhibitors in defatted seeds of evening primrose (Oenothera biennis L.) by affinity-labeled molecular networking","volume":"180","author":"Wang","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"102108","DOI":"10.1016\/j.mtbio.2025.102108","article-title":"Topical application of Tea leaf-derived nanovesicles reduce melanogenesis by modulating the miR-828b\/MYB4 axis: Better permeability and therapeutic efficacy than conventional tea extracts","volume":"34","author":"Lin","year":"2025","journal-title":"Mater. Today Bio"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s12951-022-01308-w","article-title":"Continuous ZnO nanoparticle exposure induces melanoma-like skin lesions in epidermal barrier dysfunction model mice through anti-apoptotic effects mediated by the oxidative stress-activated NF-\u03baB pathway","volume":"20","author":"Wang","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114758","DOI":"10.1016\/j.jconrel.2026.114758","article-title":"The multiverse of zebrafish within the nanoworld","volume":"393","author":"Azuara","year":"2026","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1111\/pbi.70594","article-title":"Deciphering Cold Stress Resilience: Multiomics Insights in Contrasting Wheat Genotypes From the Western Himalayas","volume":"24","author":"Jan","year":"2026","journal-title":"Plant Biotechnol. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108681","DOI":"10.1016\/j.pharmthera.2024.108681","article-title":"Bioactive lipids in the skin barrier mediate its functionality in health and disease","volume":"260","author":"Nicolaou","year":"2024","journal-title":"Pharmacol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101264","DOI":"10.1016\/j.plipres.2023.101264","article-title":"The heterogeneity and complexity of skin surface lipids in human skin health and disease","volume":"93","author":"Mijaljica","year":"2024","journal-title":"Prog. Lipid Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eadg6007","DOI":"10.1126\/sciadv.adg6007","article-title":"Adoptive Treg therapy with metabolic intervention via perforated microneedles ameliorates psoriasis syndrome","volume":"9","author":"Zhang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4598","DOI":"10.7150\/thno.97096","article-title":"Exosome-like nanoparticles derived from fruits, vegetables, and herbs: Innovative strategies of therapeutic and drug delivery","volume":"14","author":"Zhao","year":"2024","journal-title":"Theranostics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41574-023-00822-7","article-title":"The G protein-coupled oestrogen receptor GPER in health and disease: An update","volume":"19","author":"Prossnitz","year":"2023","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1210\/endrev\/bnae034","article-title":"Endocrine Controls of Skin Aging","volume":"46","author":"Stegemann","year":"2025","journal-title":"Endocr. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"122104","DOI":"10.1016\/j.biomaterials.2023.122104","article-title":"Regulating T-cell metabolic reprogramming and blocking PD-1 co-promote personalized postoperative autologous nanovaccines","volume":"297","author":"Chang","year":"2023","journal-title":"Biomaterials"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10008","DOI":"10.1038\/s41467-024-54324-9","article-title":"Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3\u03b2\/\u03b2-Catenin\/MITF-axis","volume":"15","author":"Abrahamian","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8402","DOI":"10.1021\/acs.est.5c00093","article-title":"EPO Enhances Adaptation to Hypoxic Environment in the Freshwater Teleost (Micropterus salmoides) through the PI3K\/AKT Pathway","volume":"59","author":"Yan","year":"2025","journal-title":"Environ. Sci. Technol."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Yasar, M.M., Yasar, E., Yorulmaz, N., Gurses, G., Celik, H., Guney, M., Tas, A., Tanriverdi, Z., and Yentur Doni, N. (2026). Structural analysis of ITS 1 gene of Leishmania tropica and evaluation of a novel ligand, benzo[d][1,3]dioxol-5-yl 4-acetamidobenzenesulfonate, via molecular modeling methods. Front. Cell. Infect. Microbiol., 16.","DOI":"10.3389\/fcimb.2026.1743630"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:26:56Z","timestamp":1785936416000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,5]]},"references-count":56,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151420"],"URL":"https:\/\/doi.org\/10.3390\/cells15151420","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,5]]}}}