Journal of Controlled Release最新文献

{"title":"Transdermal psoriasis treatment inspired by tumor microenvironment-mediated immunomodulation and advanced by exosomal engineering","authors":"Jieru Yang ,&nbsp;Jiaojiao Zhu ,&nbsp;Shan Lu ,&nbsp;Hong Qin ,&nbsp;Wenhu Zhou","doi":"10.1016/j.jconrel.2025.113664","DOIUrl":"10.1016/j.jconrel.2025.113664","url":null,"abstract":"<div><div>Psoriasis, characterized by aberrant T cell activation and epidermal hyperplasia, lacks safe and effective localized transdermal treatments. Drawing on the divergent pathologies of psoriasis and malignancies, we explored whether immunosuppressive mechanisms from the tumor microenvironment could be repurposed for psoriasis therapy. Utilizing B16-F10 melanoma cells as a model, we found that topical application of inactivated melanoma tissue homogenate alleviated psoriatic lesions in mice, primarily mediated by melanoma-derived exosomes. These exosomes exert therapeutic effects by modulating IL-17 signaling through miRNAs, effectively reducing T cell activation and proliferation. We discovered key miRNAs, mmu-miR-320-3p and mmu-miR-126-5p, that target IL-17a. Additionally, we demonstrated that these exosomes, enriched with RhoA protein, enhance transcytosis across epidermal barriers. Based on these insights, we developed ‘ExoLipo,’ a biomimetic exosomal formulation incorporating RhoA and loaded with mmu-miR-320-3p, inheriting the native exosomes' transdermal and immunomodulatory capacities. This formulation exhibited significant preventive and therapeutic effects on psoriasis mice models with an excellent safety profile. Our findings highlight the potential of repurposing tumor-derived immunosuppressive strategies for inflammatory diseases and offer a groundbreaking approach for managing psoriasis.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113664"},"PeriodicalIF":10.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A “three-in-one” thermosensitive gel system that enhances mucus and biofilm penetration for the treatment of vulvovaginal candidiasis","authors":"Yameng Wang,&nbsp;Zhiyuan Wang,&nbsp;Qibin Li,&nbsp;Yangjun Feng,&nbsp;Jinling Li,&nbsp;Yuxiang Lu,&nbsp;JingYing Zhang,&nbsp;Xue Ke","doi":"10.1016/j.jconrel.2025.113666","DOIUrl":"10.1016/j.jconrel.2025.113666","url":null,"abstract":"<div><div>The special physiological barriers of women, such as vaginal mucus and self-cleaning behavior, pose great challenges for the treatment of vulvovaginal candidiasis (<em>VVC</em>), and the drug resistance caused by fungal biofilms limits the application of existing antifungal drugs. Based on this, we designed a “three-in-one” thermosensitive gel system (AF/BP Gel) loaded with antibiofilm nanoparticles (AF NPs) and mucus penetration-assisting nanoparticles (BP NPs) to achieve vaginal adhesion while enhancing mucus and biofilm penetration. AF NPs were loaded with farnesol (FAR) and amphotericin B (AMB), and FAR is one of quorum sensing molecules which can interfere with biofilm-related genes such as <em>ALS3</em>, <em>HWP1</em>, <em>RAS1</em>, <em>CPH1</em>, <em>EFG1</em>, <em>NRG1</em>, <em>TUP1</em>, <em>UME6</em>, and disperse mature biofilm, thus playing a synergic antibiofilm role with AMB. BP NPs was loaded with bromelain (BRO), which cleared the mucus barrier for AF NPs and help it penetrate deep into the infection. These two kinds of nanoparticles use the thermosensitive gel matrix to reach the surface of the vaginal mucosa uniformly and persistently to overcome the obstacle of vaginal self-cleaning. AF/BP Gel showed great anti-<em>candida albicans</em> activity <em>in vitro</em> and <em>in vivo</em>, and greatly improved the inflammatory conditions in <em>VVC</em> mice. Overall, this “three-in-one” thermosensitive gel system can overcome multiple physiological barriers and resist different periods of biofilm, providing a new platform for treating vagina-associated infections.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113666"},"PeriodicalIF":10.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A fusion protein that targets antigen-loaded extracellular vesicles to B cells enhances antigen-specific T cell expansion","authors":"Annemarijn Offens ,&nbsp;Loes Teeuwen ,&nbsp;Gozde Gucluler Akpinar ,&nbsp;Loïc Steiner ,&nbsp;Sander Kooijmans ,&nbsp;Doste Mamand ,&nbsp;Hannah Weissinger ,&nbsp;Alexander Käll ,&nbsp;Maria Eldh ,&nbsp;Oscar P.B. Wiklander ,&nbsp;Samir El-Andaloussi ,&nbsp;Mikael C.I. Karlsson ,&nbsp;Pieter Vader ,&nbsp;Susanne Gabrielsson","doi":"10.1016/j.jconrel.2025.113665","DOIUrl":"10.1016/j.jconrel.2025.113665","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have the potential to modulate immune responses <em>via</em> their cargo molecules and are being explored as vehicles in cancer immunotherapy. Dendritic cell-derived EVs can induce antigen-specific immune responses leading to reduced tumor burden. This response was shown to depend partially on B cells. EVs can be targeted to certain cells or tissues, and EVs from Epstein-Barr Virus (EBV) infected cells were shown to carry the EBV glycoprotein GP350 on their surface and target human CD21 (hCD21) on B cells. We therefore investigated whether targeting EVs to B cells <em>via</em> this mechanism could improve antigen-specific immune responses. A soluble fusion protein containing the phosphatidylserine-binding domain (C1C2) of lactadherin and hCD21-binding domain (D123) of GP350 was used to decorate and target EVs to B cells. D123-decorated EVs increased <em>in vitro</em> B cell targeting 5-fold compared to EVs decorated with a non-targeting control protein or undecorated EVs. Furthermore, <em>in vivo,</em> D123-decoration did not alter the biodistribution of EVs across organs but specifically targeted them to B cells in the spleen, blood and lymph nodes of hCD21-transgenic mice. Immunization with hCD21-targeted, OVA-loaded EVs resulted in a higher percentage of antigen-specific CD8⁺ T cells compared to untargeted EVs. Our data show that D123-decorated EVs efficiently target B cells and improve antigen-specific T cell responses <em>in vivo</em>, which could be explored in future therapeutic applications.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113665"},"PeriodicalIF":10.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143703486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Innovative injectable, self-healing, exosome cross-linked biomimetic hydrogel for cartilage regeneration’ [Journal of Controlled Release, Volume 381 (2025), 113608].","authors":"Chenlin Tu ,&nbsp;Xiang Gao ,&nbsp;Hong Zheng ,&nbsp;Rui Huang ,&nbsp;Fengkai Yang ,&nbsp;Yeying Dong ,&nbsp;Kaipeng Jing ,&nbsp;Thomas Groth ,&nbsp;Mingyan Zhao","doi":"10.1016/j.jconrel.2025.113636","DOIUrl":"10.1016/j.jconrel.2025.113636","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113636"},"PeriodicalIF":10.5,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of a novel neuroprotective compound to the retina in rat and rabbit animal models","authors":"Meredith Garrett ,&nbsp;Stacy Curry ,&nbsp;Sherri Feris ,&nbsp;Yan Lu ,&nbsp;Qi Gu ,&nbsp;Abe Clark ,&nbsp;Stephen F. Martin ,&nbsp;Michail Kastellorizios","doi":"10.1016/j.jconrel.2025.113659","DOIUrl":"10.1016/j.jconrel.2025.113659","url":null,"abstract":"<div><div>Posterior segment-related diseases are among the leading causes of irreversible blindness and loss of vision globally. These diseases are extremely difficult to treat due to the drug delivery barriers posed by the eye, among other challenges. One delivery method that bypasses many of these obstacles, albeit not without risk, is ocular injections, and long-acting formulations such as implants can improve patient compliance by allowing for longer intervals between injections. Here, we report our development of a preclinical <em>in situ</em>-forming implant dosage form that provides sustained release of a novel compound, DKR-1677, with a target in the retina. An <em>in situ</em>-forming implant based on polylactic co glycolic acid (PLGA) was chosen in this preclinical stage because it is readily translatable to a preformed implant product. The formulations were tested <em>in vitro</em>, in rat and rabbit animal models for drug release and pharmacokinetics. A two-step <em>in vitro</em> dissolution method with implant formation in a biorelevant gel followed by incubation in release media showed a 30-day three-phase release profile with an initial burst release of 36.04 ± 4.23 %, a plateau, and a controlled release up to 93.75 ± 4.68 % at day 30, typical of PLGA-based implant formulations. Immediate and controlled-release formulations were tested in rat and rabbit animal models and confirmed that DKR-1677 is taken up by the retina after intravitreal administration. Furthermore, the <em>in situ</em>-forming implant was found to prolong drug presence in the retina to 30 days following a single administration, confirming that a PLGA-based implant is a viable approach for this drug candidate.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113659"},"PeriodicalIF":10.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracellular redistribution of cell-penetrating peptide p28: A mechanism for enhanced anti-cancer activity","authors":"Duy Binh Tran ,&nbsp;Konstantin Christov ,&nbsp;Sunam Mander ,&nbsp;Albert Green ,&nbsp;Anne Shilkaitis ,&nbsp;Tapas K. Das Gupta ,&nbsp;Tohru Yamada","doi":"10.1016/j.jconrel.2025.113660","DOIUrl":"10.1016/j.jconrel.2025.113660","url":null,"abstract":"<div><div>Cell-penetrating peptides (CPPs) have been studied as they provide an efficient strategy for the intracellular delivery of bioactive molecules in various biomedical applications such as cancer diagnosis and therapy. We have developed an anionic CPP, p28, that can preferentially enter cancer cells and induce cell cycle arrest and apoptotic cell death preclinically and that showed preliminary efficacy in humans. Yet, the underlying intracellular fate after cell entry remains largely uncharacterized. To better understand the intracellular trafficking of p28, we investigated more closely the role of endosomal acidification and retrograde transport in cancer cells. Here, we show that agents such as chloroquine (CQ), NH₄Cl, and nordihydroguaiaretic acid (NDGA) that alter discrete steps of endocytosis or Golgi-mediated transport remarkably increased p28 access to the cytosol and nucleus. Moreover, CQ significantly improved the antiproliferative effects induced by p28. Our findings suggest that inadequate intracellular localization is the major limiting factor for the efficacy of CPPs such as p28. Taken together, these results indicate that the effective and adequate alternation of intracellular localization of CPPs can be a promising drug-delivery strategy to specifically deliver the therapeutic molecule to its intracellular therapeutic active site or organelle that leads to potentiate the efficacy for cancer diagnosis and therapy.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113660"},"PeriodicalIF":10.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly-lysine-modified recombinant protein nanocages for effective delivery of small activating RNA","authors":"Lixing Xu ,&nbsp;Shanshan Li ,&nbsp;Shen Wan ,&nbsp;Zhikuan Liu ,&nbsp;Yuxin Zhong ,&nbsp;Xiaoyang Qian ,&nbsp;Jiayi Qin ,&nbsp;Liangliang Cai ,&nbsp;Haiqin Huang","doi":"10.1016/j.jconrel.2025.113638","DOIUrl":"10.1016/j.jconrel.2025.113638","url":null,"abstract":"<div><div>Small activating RNA (saRNA) holds significant promise as a therapeutic platform for various diseases. However, the development of efficient nanocarriers that can overcome existing delivery challenges and ensure effective cellular uptake remains a critical hurdle. In this study, we aimed to address this issue by genetically modifying four lysine residues at the N-terminus of the FTH gene through gene recombinant technology, resulting in the creation of poly-lysine-H-apoferrin (4LF) vectors. These vectors were designed to efficiently deliver saRNA encoding the Sirtuin1 (Sirt1) protein to chondrocytes, thereby mitigating cartilage damage. The poly-lysine modification conferred the ability of 4LF@saRNA nanoparticles (NPs) to escape from lysosomes <em>via</em> proton sponge effects and to release saRNA into the cytoplasm through the pH-induced degradation of the 4LF vector, ultimately activating the target gene. To enhance the retention of NPs within the joint cavity and facilitate intra-articular delivery, we incorporated the 4LF@saRNA NPs into a thermosensitive self-healing hydrogel composed of chitosan, oxidized chondroitin sulfate (OCS), and sodium β-glycerophosphate (β-GP). Experimental results demonstrated that the chitosan/OCS/β-GP-4LF@saRNA (OCCG-4LF@saRNA) delivery system effectively delivered the 4LF@saRNA NPs to chondrocytes both <em>in vitro</em> and <em>in vivo</em>, resulting in a significant increase in Sirt1 protein expression. This upregulation led to a reduction in chondrocyte apoptosis, enhanced cell migration, and improved cartilage protection, effectively alleviating symptoms of osteoarthritis. In conclusion, our findings suggested that the 4LF-based delivery system hold considerable potential for effective intracellular saRNA delivery, demonstrating promising biocompatibility, stability, and delivery efficiency, with significant therapeutic implications for cartilage repair.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113638"},"PeriodicalIF":10.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acetyl-lysine human serum albumin nanoparticles activate CD44 receptors, with preferential uptake by cancer stem cells, leading to tumor eradication","authors":"Guojun Xiong ,&nbsp;Andreas G. Schätzlein ,&nbsp;Ijeoma F. Uchegbu","doi":"10.1016/j.jconrel.2025.113632","DOIUrl":"10.1016/j.jconrel.2025.113632","url":null,"abstract":"<div><div>CD44 receptors in cancer stem cells (CSCs) are a key biomarker associated with cancer recurrence, progression, and metastasis. Acetylation is a post-translational modification used to regulate protein function at the end of protein synthesis. In this study, we found that acetylated human serum albumin (Ac-HSA) acts an uptake ligand on CD44 receptors. This promising finding motivated us to develop an Ac-HSA-based nanocarrier for cancer chemotherapy. By conjugating maleimide-polylactic acid (MAL-PLA) with Ac-HSA, the resulting amphiphile formed nanoparticles (Ac-HSA-PLA NPs) which were shown to rapidly enter CD44+ cancer cells and cancer stem cells via CD44-mediated endocytosis. This contrasts with the comparatively slow uptake of CD44 antibodies. Abraxane®, an approved human serum albumin (HSA) nanoparticle formulation of paclitaxel (PTX) demonstrates that PTX may be delivered by HSA nanoparticles. However, Abraxane® is not clinically superior to solvent-based PTX formulations. In a CD44+ tumor model, PTX-loaded Ac-HSA-PLA NPs outperformed Abraxane®, achieving complete tumor elimination without recurrence, two months post-treatment, while Abraxane treated tumors continued to grow (tumor volume increased five fold). The Ac-HSA-PLA (PTX) NPs also demonstrated minimal systemic toxicity, suggesting that Ac-HSA could be a promising alternative for targeted cancer therapy in CD44-expressing cancers.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113632"},"PeriodicalIF":10.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered vesicular cancer vaccines for immunosuppressive microenvironment reversion and in situ vaccine generation","authors":"Yang Li ,&nbsp;Yulin Yu ,&nbsp;Bin Xia ,&nbsp;Siyu Zhao ,&nbsp;Xiaonan Li ,&nbsp;Qian Hu ,&nbsp;Yinmei Tian ,&nbsp;Yi Wang ,&nbsp;Yixuan Zhou ,&nbsp;Conglian Yang ,&nbsp;Dan Zhang ,&nbsp;Zhiping Zhang ,&nbsp;Li Kong","doi":"10.1016/j.jconrel.2025.113658","DOIUrl":"10.1016/j.jconrel.2025.113658","url":null,"abstract":"<div><div>It is crucial to reverse immunosuppressive tumor microenvironment (TME) and effectively activate both cellular and humoral immunity in cancer immunotherapy. We have found that decitabine, an epigenetic regulator, can increase antigen exposure and induce double-stranded RNA (dsRNA) accumulation in tumor cells. The corresponding cell-derived nanovesicles (NV) have the ability to stimulate both cellular and humoral immunity due to the internal dsRNA. However, the efficacy of dsRNA-containing NV (dsRNA@NV) remains constrained by the inadequate activation efficiency of immune cells in immunosuppressive TME. In this study, CD40L, an immune cell regulator, was incorporated on the surface of dsRNA@NV (dsRNA@NV_CD40L) through lentiviral transfection to further reverse the immunosuppressive TME, by activating dendritic cells and regulating macrophages phenotypes <em>via</em> CD40-CD40L interaction. In addition, CD40L could induce immunogenic death of tumor cells, and the administration of dsRNA@NV_CD40L effectively elicited an <em>in situ</em> cancer vaccine response in B16-OVA tumor. This proposed NV-based vaccine was expected to solve the problems of low immunogenicity, insufficient activation of immune responses and lack of effective regulation of immunosuppressive TME of existing tumor vesicular vaccines.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113658"},"PeriodicalIF":10.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyaminoglycoside nanosystem expressing antimicrobial peptides for multistage chronic wound management","authors":"Rui Ju,&nbsp;Yang Li,&nbsp;Dandan Sui,&nbsp;Fu-Jian Xu","doi":"10.1016/j.jconrel.2025.113657","DOIUrl":"10.1016/j.jconrel.2025.113657","url":null,"abstract":"<div><div>Chronic wounds are difficult to heal due to pathogenic microbial colonization and dysregulation of healing cascades, necessitating novel therapeutic strategies. This study developed a multifunctional nanosystem by integrating the antimicrobial peptide LL37 with cationic polyaminoglycoside (SS-HPT), constructing a self-sustaining \"AMP factory” to achieve multi-stage modulation of the wound healing. Validation through cell-level experiments and <em>in vivo</em> dual models (mechanical injury and bacterial infection) in immunocompromised rats demonstrated the system's unique dual intracellular-extracellular pathogen-killing capability, significantly accelerating the wound healing process. Transcriptomic analysis revealed that its mechanism involves the dual effects of suppressing pro-inflammatory factor expression and activating tissue repair pathways. Histological evidence confirmed that the system promotes angiogenesis, enhances re-epithelialization rates, and guides orderly collagen fiber deposition. This nanosystem, combining efficient AMP delivery and integrated therapeutic strategies, achieves three-dimensional synergy in microbial clearance, immune microenvironment regulation, and tissue matrix remodeling, providing theoretical and technical foundations for a paradigm shift in chronic wound treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"382 ","pages":"Article 113657"},"PeriodicalIF":10.5,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}