Journal of Controlled Release最新文献

{"title":"Investigation of the impact of lipid nanoparticle compositions on the delivery and T cell response of circRNA vaccine","authors":"Yasir Alshehry ,&nbsp;Xiang Liu ,&nbsp;Yu Zhang ,&nbsp;Guizhi Zhu","doi":"10.1016/j.jconrel.2025.113617","DOIUrl":"10.1016/j.jconrel.2025.113617","url":null,"abstract":"<div><div>Circular RNA (circRNA) is an emerging class of vaccines for various diseases, such as cancer immunotherapy. For cancer therapeutic vaccines, it is critical to deliver circRNA to lymphoid tissues such as lymph nodes (LNs) and dendritic cells (DCs) and then elicit antigen-specific T cell responses. Lipid nanoparticles (LNPs) have shown great success for mRNA vaccines and may also have great potential as nanocarriers for circRNA vaccines. Here, we studied the impact of LNP composition on the efficiency of immune delivery, protein expression, and the T cell responses for circRNA vaccine. First, we used model mRNA and circRNA encoding firefly luciferase (mRNA-fLuc) to study protein expression and used two small circRNA vaccines to study T cell responses. We investigated a combination of six ionizable lipids, three helper lipids, and six different molar ratios of cholesterol and β-sitosterol for their impact on the physicochemical properties of RNA LNPs, <em>in vitro</em> DC transfection, <em>in vivo</em> protein expression in draining LNs, and antigen-specific T cell responses. Among these ionizable lipids, SM-102 was the most effective for DC transfection and enabling circRNA vaccines to elicit T cell responses. DOPE and β-sitosterol incorporation in LNPs resulted in efficient protein expression, albeit β-sitosterol incorporation appeared to be associated with reduced T cell response. Overall, circRNA was efficiently delivered to DCs and macrophages in mouse draining lymph nodes by LNPs of SM-102 (50 %), cholesterol (38.5 %), DOPE (10 %), and DMG-PEG2000 (1.5 %), resulting in the induction of potent antigen-specific CD8⁺ T cell response in mice. These findings may provide insights into designing the compositions of LNPs as the carrier for circRNA therapeutics and vaccines.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113617"},"PeriodicalIF":10.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635562","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":"Effects of silica nanoparticles with varied physicochemical properties on the survival and functionality of saturated macrophages","authors":"Sushanto Kumar Saha ,&nbsp;Cansu Umran Tunc ,&nbsp;Nitish Khurana ,&nbsp;Jason William Grunberger ,&nbsp;Hamidreza Ghandehari","doi":"10.1016/j.jconrel.2025.113640","DOIUrl":"10.1016/j.jconrel.2025.113640","url":null,"abstract":"<div><div>Silica nanoparticles (SNPs) have shown potential as nanocarriers in diagnostic, imaging, and drug delivery applications. To use SNPs for systemic drug delivery, it is important to have a detailed understanding of how these particles interact with the mononuclear phagocytic system (MPS). Whether or not SNPs may saturate the macrophages, thereby influencing their function and impairing innate immune responses, remains poorly understood. In this work, we defined macrophage saturation using RAW 264.7 macrophages as a model and studied four SNPs with variations in size and porosity. We further explored the downstream effects of SNP uptake by macrophages, including apoptosis/necrosis, cell cycle progression, membrane integrity, and phagocytic activity. The data demonstrate that SNPs do not alter major cellular functions at their respective nontoxic, saturating concentrations.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113640"},"PeriodicalIF":10.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635579","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":"In situ peptide assembly for cell membrane rewiring in tumor therapy","authors":"Yu Ma ,&nbsp;Qiaochu Jiang ,&nbsp;Xiaoyang Liu,&nbsp;Xianbao Sun,&nbsp;Gaolin Liang","doi":"10.1016/j.jconrel.2025.113637","DOIUrl":"10.1016/j.jconrel.2025.113637","url":null,"abstract":"<div><div>Peptide assembly on the cell membrane is capable of endowing cells with novel biological properties that are distinct from their original states, thereby playing a pivotal role in the regulation of diverse cellular biological events. In practical biomedical scenarios, in order to make peptide assembly more precisely meet the requirements of cells at different physiological stages and conditions to achieve desired effects of cell function regulation, it becomes particularly crucial to conduct precise <em>in situ</em> spatiotemporal control of peptide assembly on the cell membrane, thus attracting great attentions. Particularly for tumor treatment, this artificially manipulated cell surface engineering can achieve excellent anti-tumor effects by altering the cell membrane structure, influencing receptor clustering or interfering with relevant signal pathways. Of note, membrane-anchoring peptides play a key role in these processes. In this review, we focus on three main types of membrane-anchoring peptides, elaborating in detail on how their assembly regulation mechanisms influence the cell membrane remodeling effect, and further exert therapeutic effects on tumors. On this basis, we further introduce a variety of tumor treatment strategies combined with <em>in situ</em> peptide assembly on the cell membrane, and discuss the current opportunities and challenges in this field, aiming to present the overall research panorama and trend of <em>in situ</em> peptide self-assembly on the cell membrane for efficient tumor treatment.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113637"},"PeriodicalIF":10.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639967","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":"Evaluation of focused ultrasound modulation of the blood-brain barrier in gray and white matter","authors":"Alessandro De Maio ,&nbsp;Yuexi Huang ,&nbsp;Fa-Hsuan Lin ,&nbsp;Bojana Stefanovic ,&nbsp;Greg J. Stanisz ,&nbsp;Meaghan A. O'Reilly","doi":"10.1016/j.jconrel.2025.113631","DOIUrl":"10.1016/j.jconrel.2025.113631","url":null,"abstract":"<div><h3>Rationale</h3><div>Focused ultrasound (FUS) in combination with intravenous microbubbles is being studied clinically for modulation of the blood-brain barrier. Contrast-enhanced MRI can be used to visualize the enhanced permeability resulting from the treatment. However, contrast enhancement in the white matter (WM) are inconsistently observed compared to the gray matter (GM). Intrinsic tissue differences are believed to result in reduced treatment efficacy and insufficient drug delivery to the WM. In this study we evaluate the deposition of MRI contrast and clinically relevant antineoplastics in GM and WM tissues following single and repeated FUS and microbubble treatments.</div></div><div><h3>Methods</h3><div>The brains of Fischer-344 rats (<em>n</em> = 24) and Yorkshire pigs (<em>n</em> = 6) underwent FUS (rats: 580 kHz; pigs: 220 kHz) treatments targeting the internal capsule and thalamus, repeated at 30-min intervals. Definity microbubbles (rats: 20 μL/kg bolus; pigs: 4 μL/kg/5-min infusion) were administered intravenously for each sonication with MRI contrast to measure gadolinium-mediated signal change. Feedback-controlled algorithms were used to monitor treatments and modulate the pressure based on emitted microbubble signals to ensure safe and effective exposures. The delivery of methotrexate (MTX; 454.4 Da) and bevacizumab (BVZ; 149 kDa) was evaluated via immunofluorescence microscopy in rats, and respectively quantified via liquid chromatography mass spectrometry and enzyme-linked immunosorbent assay in pigs.</div></div><div><h3>Results</h3><div>Repeated FUS exposures successfully increased the vascular permeability of both gray and white matter tissues to MRI contrast and drugs of both small and large molecular sizes.</div><div>In rats, single treatments showed statistically significant higher enhancements in the GM (23.5 ± 4.3 %; WM: 4.68 ± 3.75 %), however following a second sonication there were no between-tissue differences (GM: 38.0 ± 6.4 %; WM: 34.0 ± 8.7 %).</div><div>In pigs, the smaller focus size relative to the brain enabled separate targeting of GM vs WM and the treatment controller used higher average power level in the WM to achieve the same cavitation dose. This resulted in no difference in gray and white matter permeability levels (to both contrast and pharmacological agents) after a single sonication. Repeated treatments sustained MRI enhancements for a longer time and enhanced drug deposition (MTX increased 6.5 and 8.3 folds after single and repeated treatment; BVZ increased 6.8 and 20.4 folds respectively).</div></div><div><h3>Conclusions</h3><div>Feedback-controlled algorithms and the possibility to individually target gray and white matter highlighted the impact of tissue composition on treatment outcomes. Repeated FUS-mediated modulation of the brain microvasculature achieved higher levels of permeabilization to contrast and pharmacological agents in both gray and white matter.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113631"},"PeriodicalIF":10.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631343","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":"Ion-paired moxifloxacin nanocrystal formulation improves treatment and prevention of ocular infection","authors":"Matthew B. Appell ,&nbsp;Kiersten Malmberg ,&nbsp;Ashwin Pasupathy ,&nbsp;Aditya Josyula ,&nbsp;Jairo Ortiz ,&nbsp;Peter J. McDonnell ,&nbsp;Nakul Shekhawat ,&nbsp;Kunal S. Parikh ,&nbsp;Laura M. Ensign","doi":"10.1016/j.jconrel.2025.113634","DOIUrl":"10.1016/j.jconrel.2025.113634","url":null,"abstract":"<div><div>Ocular infections may arise spontaneously or following penetrating globe injury or operation, such as corneal transplant or cataract extraction. Treatment and prophylaxis of bacterial infections using antibiotic eye drops requires a strict dosing regimen to avoid irreversible vision loss. At present, moxifloxacin eye drops are prescribed for use multiple times per day, leading to patient non-adherence, the emergence of bacterial resistance, and infection progression. The desire to avoid sub-lethal antibiotic dosing and visual impairment through inconsistent eye drop application motivates the development of a sustained release injectable formulation. Herein, we report the development of an ion-paired, nanocrystalline moxifloxacin formulation that provided increased intraocular antibiotic accumulation with a single subconjunctival injection compared to 3× daily eye drops. The sustained release functionality further led to improved or non-inferior prevention and treatment of <em>Staphylococcus aureus</em>-induced ocular infection in both rats and rabbits compared to gold standard intracameral moxifloxacin and moxifloxacin eye drops. By achieving therapeutically relevant moxifloxacin accumulation, this nanocrystalline moxifloxacin formulation may be a promising alternative to conventional therapies to achieve improved post-surgical infection prevention and bacterial keratitis treatment outcomes.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113634"},"PeriodicalIF":10.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631344","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":"Assembled granular hydrogels loaded with growth factors for enhanced mesenchymal stem cell therapy in abdominal wall defect repair","authors":"Liuxin Yang ,&nbsp;Fengya Jing ,&nbsp;Dandan Wei ,&nbsp;Xiaocong Zhao ,&nbsp;Yinghua Tao ,&nbsp;Tao Liu ,&nbsp;Tianzhu Zhang","doi":"10.1016/j.jconrel.2025.113630","DOIUrl":"10.1016/j.jconrel.2025.113630","url":null,"abstract":"<div><div>Abdominal wall defects caused by trauma, congenital rupture, and intra-abdominal infection remain challenging due to the large wound area and complex complications. Herein, an assembled mesenchymal stem cell (MSCs)-laden granular hydrogel (termed assembled GSD@FPs), loaded with basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), is developed. This hydrogel is constructed through dynamic covalent cross-linking (<em>via</em> borate ester bonds) among dopamine-grafted gelatin methacrylamide (GelMA-DA), phenylborate-modified hyaluronic acid (HA-PBA), and epigallocatechin-3-gallate (EGCG), serving as multifunctional bulk building blocks for cell delivery and abdominal wall repair. The designed assembled granular hydrogels possess good rheological properties, self-healing, injectability, and tissue-adhesion properties. Detailed <em>in vitro</em> cell experiments are conducted, revealing that the GSD@FPs granular hydrogels can effectively promote cell proliferation, cell migration and angiogenesis. Furthermore, in abdominal wall defects, assembled GSD@FPs significantly accelerates the tissue healing process by simultaneously inhibiting the inflammatory response, promoting collagen deposition, and promoting cell proliferation and angiogenesis. Importantly, the assembled GSD@FPs granular hydrogels can also provide mechanical support and increase the thickness of regenerated tissue (1727.8 ± 169.6 μm for the control group, 3204.2 ± 278.5 μm for the assembled GSD@FPs group at 14 d). Eventually, the GSD granular hydrogels biodegraded, facilitating tissue remodeling and generating new muscle tissues. Therefore, this study provides a promising strategy with great potential for application in abdominal wall repair.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113630"},"PeriodicalIF":10.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627645","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":"Inside back cover: Adrian Tabora Dychiao et al","authors":"","doi":"10.1016/S0168-3659(25)00226-3","DOIUrl":"10.1016/S0168-3659(25)00226-3","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Page IBC"},"PeriodicalIF":10.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609657","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":"Content list including Graphcal Abstracts","authors":"","doi":"10.1016/S0168-3659(25)00225-1","DOIUrl":"10.1016/S0168-3659(25)00225-1","url":null,"abstract":"","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"380 ","pages":"Pages II-XXIV"},"PeriodicalIF":10.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609655","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":"Blood-brain barrier crossing biopolymer targeting c-Myc and anti-PD-1 activate primary brain lymphoma immunity: Artificial intelligence analysis","authors":"Vladimir A. Ljubimov ,&nbsp;Tao Sun ,&nbsp;Jiawei Wang ,&nbsp;Lian Li ,&nbsp;Paul Z. Wang ,&nbsp;Alexander V. Ljubimov ,&nbsp;Eggehard Holler ,&nbsp;Keith L. Black ,&nbsp;Jindřich Kopeček ,&nbsp;Julia Y. Ljubimova ,&nbsp;Jiyuan Yang","doi":"10.1016/j.jconrel.2025.113611","DOIUrl":"10.1016/j.jconrel.2025.113611","url":null,"abstract":"<div><div>Primary Central Nervous System Lymphoma is an aggressive central nervous system neoplasm with poor response to pharmacological treatment, partially due to insufficient drug delivery across blood-brain barrier. In this study, we developed a novel therapy for this lymphoma by combining a targeted nanopolymer treatment with an immune checkpoint inhibitor antibody (anti-PD-1).</div><div>A <em>N</em>-(2-hydroxypropyl)methacrylamide copolymer-based nanoconjugate was designed to block tumor cell c-Myc oncogene expression by antisense oligonucleotide. Angiopep-2 peptide was conjugated to the copolymer to facilitate nanodrug crossing of the blood-brain barrier. Systemically administered polymeric nanodrug, alone or in combination with immune checkpoint inhibitor antibody anti-PD-1, was tested in syngeneic mouse model of A20 intracranial brain lymphoma. There was no significant survival difference between saline- and free anti-PD-1-treated groups. However, significant survival advantage <em>vs.</em> saline was observed upon treatment with nanodrug bearing Angiopep-2, H6 (6 histidines for endosome escape), and c-Myc antisense alone and especially when it was combined with anti-PD-1 antibody. Animal survival after combined treatment was also significantly increased <em>vs.</em> free anti-PD-1. Artificial Intelligence-assisted analysis of gene expression database after RNA-seq of tumors was used to find novel immune pathways, molecular targets and the most effective multifunctional drugs together with future drug prediction for brain lymphoma <em>in vivo</em> model. Spectral flow cytometry and RNA-seq analysis revealed a robust activation of tumor infiltrating T lymphocytes with enhanced interferon γ signaling and polarization to M1-type macrophages in treated tumors, which was confirmed by immunofluorescence staining.</div><div>In summary, a new effective blood-brain barrier crossing nano immuno therapeutic system was developed that effectively blocked tumor c-Myc acting in combination with immune checkpoint inhibitor anti-PD-1 to treat primary brain lymphoma. The treatment improved survival of tumor-bearing animals through activation of both the adaptive and innate immune responses.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113611"},"PeriodicalIF":10.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618584","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":"Codelivery Ce6 and curcumin in antibacterial poly(β-amino ester) for anti-inflammatory and photodynamic antimicrobial combination therapy","authors":"Chong Liu ,&nbsp;Lei Guo ,&nbsp;Penghan Yue ,&nbsp;Dayang Xie ,&nbsp;Jiahui Gao ,&nbsp;Yanwei Li ,&nbsp;Cong Liu ,&nbsp;Caina Xu ,&nbsp;Yanhui Li ,&nbsp;Huayu Tian","doi":"10.1016/j.jconrel.2025.113627","DOIUrl":"10.1016/j.jconrel.2025.113627","url":null,"abstract":"<div><div>Developing antimicrobial therapies not rely on antibiotics is an expective way to resolve the threat of drug-resistant bacteria, such as photodynamic antimicrobial therapy (APDT). However, the main antibacterial species in APDT are reactive oxygen species (ROS), and the overproduction of ROS will cause serious inflammatory and delay wound healing. Therefore, it is necessary to solve this contradiction in order to realize anti-inflammatory in the process of APDT. Here, we selected Ce6 as a photosensitizer for APDT, phenylboronic acid (PBA) was introduced on Ce6 (as Ce6-D-P) to get bacterial targeting, and then covalently grafted curcumin (Cur) on Ce6-D-P (as Ce6-D-P-C) to obtain anti-inflammatory ability. Finally, antibacterial poly(β-amino ester)(PBAE) was used as carrier to load Ce6-D-P-C to form nanoparticles Ce6-D-P-C@PBAE. Under light irradiation, ROS can be produced for APDT, and also, boroester bond on Ce6-D-P-C will broke to release small Cur molecules, and then released from Ce6-D-P-C@PBAE to perform anti-inflammatory. As a result, after ROS treatment, anti-inflammatory was achieved, forming stepwise antibacterial and anti-inflammatory therapy. The study showed that Ce6-D-P-C@PBAE was biosafe with good cell activity and also no hemolysis. The drug loading content of Cur in Ce6-D-P-C@PBAE can reach 11.2 %. When Ce6-D-P-C@PBAE was stimulated by light, the responsive release of Cur will achieve. <em>In vivo</em> studies, Ce6-D-P-C@PBEA can collaboratively kill bacteria and regulate inflammatory responses, as well as inhibiting and eliminating local inflammation, thereby promoting the healing of infected wounds. As a result, the Ce6-D-P-C@PBAE nanoparticles had both antibacterial and anti-inflammatory therapy abilities, which was important for combating bacterial infections and promoting wound healing.</div></div>","PeriodicalId":15450,"journal":{"name":"Journal of Controlled Release","volume":"381 ","pages":"Article 113627"},"PeriodicalIF":10.5,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618607","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}