Journal of Liposome Research最新文献

{"title":"Preparation of multivesicular liposomes for the loco-regional delivery of Vancomycin hydrochloride using active loading method: drug release and antimicrobial properties.","authors":"Melody Vatankhah, Simin Dadashzadeh, Arash Mahboubi, Azadeh Haeri, Kimia Jandaghi Alaee, Seyed Baubak Mostafavi Naeini, Zahra Abbasian","doi":"10.1080/08982104.2023.2220805","DOIUrl":"10.1080/08982104.2023.2220805","url":null,"abstract":"<p><p>Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. <i>In vitro</i> antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"77-87"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9646277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phthalocyanine-based glucose-responsive nanocochleates for dynamic prevention of β-cell damage in diabetes.","authors":"Sharayu Govardhane, Pravin Shende","doi":"10.1080/08982104.2023.2209642","DOIUrl":"10.1080/08982104.2023.2209642","url":null,"abstract":"<p><p>Phthalocyanine is a blue-colored macrocyclic compound with excellent anti-oxidant and lipid-peroxidation abilities due to its intermolecular π-π stacking structure. Antioxidants inhibit intracellular reactive oxygen species formation and decrease oxidation defense ability of the enzymes in diabetes management. The present study aimed to fabricate concanavalin A conjugated phthalocyanine-loaded cochleates (Formulation PhConA) as a glucose-sensitive lipidic system and estimate its efficacy in streptozotocin-induced male Sprague Dawley diabetic rats for 28 days. Thin-film hydration and trapping methods were used in the preparation of liposomes and cochleates, respectively, whereas the surface was modified for concanavalin A conjugation using EDAC: NHS (1:1). Formulation PhConA with rod-shaped structures showed particle size of 415.7 ± 0.46 nm, PdI value of 0.435 ± 0.09, encapsulation efficiency of 85.64 ± 0.34%, and 84.55 ± 0.29% release of phthalocyanine for 56 h. The circular dichroism study displayed a slight deviation after the conjugation effect of concanavalin A to cochleates. The <i>in-vivo</i> studies of the formulation PhConA improved the blood glucose levels along with defensive effect on the liver to overcome the hyperlipidemic effect. The rigid structure of cochleates prolongs the drug elimination from systemic circulation and extends its effect for a longer duration by decreasing the blood glucose level. Thus, the glucose-sensitive formulation PhConA showed significant improvement in diabetic rats within the period of 28 days by improving the oxidative defense and protecting the pancreatic β-cells.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"44-59"},"PeriodicalIF":4.4,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9452465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astragaloside IV-induced BMSC exosomes promote neovascularization and protect cardiac function in myocardial infarction mice via the miR-411/HIF-1α axis","authors":"Lei Yang, Nuan Liu, Yang Yang","doi":"10.1080/08982104.2023.2293844","DOIUrl":"https://doi.org/10.1080/08982104.2023.2293844","url":null,"abstract":"This study focused on investigating the mechanism of the astragaloside IV-induced bone marrow mesenchymal stem cell exosome (AS-IV-MSC-exo)/microRNA(miR)-411/HIF-1α axis in affecting vascular neova...","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":"180 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138680041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of tLyP-1 functionalized nanoliposomes with tunable internal water phase for glioma targeting.","authors":"Yajing Wang, Ziwei Ding, Shiqun Lv, Jie Liu, Jie Pan, Yingcong Yu, Jun Gao, Xianfeng Huang","doi":"10.1080/08982104.2023.2191718","DOIUrl":"10.1080/08982104.2023.2191718","url":null,"abstract":"<p><p>tLyP-1 peptide is verified to recognize neuropilin (NRP) receptors overexpressed on the surface of both glioma cells and endothelial cells of angiogenic blood vessels. In the present study, tLyP-1 was conjugated with DSPE-PEG2000 to prepare tLyP-1-DSPE-PEG2000, which was further employed to prepare tLyP-1 functionalized nanoliposome (tLyP-1-Lip) to achieve enhancing target of glioblastoma. Process parameters were systematically studied to investigate the feasibility of tuning the internal water phase of nanoliposomes and encapsulating more Temozolomide (TMZ). The particle size, Zeta potential, and encapsulation efficiency of tLyP-1-Lip/TMZ were fully characterized in comparison with conventional nanoliposomes (Lip-TMZ) and PEGylated nanoliposomes (PEG-Lip/TMZ). The release behaviors of TMZ from PEG-Lip/TMZ and tLyP-1-Lip/TMZ are similar and slower than TMZ-Lip in acidic solutions. The tLyP-1-Lip/TMZ demonstrated the strongest cytotoxicity in comparison with TMZ-Lip and PEG-Lip/TMZ in both U87 and HT22 cells, and displayed the highest cellular internalization. The pharmacokinetic studies in rats revealed that tLyP-1-Lip/TMZ showed a 1.4-fold (<i>p</i><b> </b><<b> </b>0.001) increase in AUC_{INF_obs} and a 1.4-fold decrease (<i>p</i><b> </b><<b> </b>0.01) in clearance compared with PEG-Lip/TMZ. We finally confirmed by <i>in vivo</i> imaging that tLyP-1-Lip were able to penetrate the brains and tumors of mice.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"353-367"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9193097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosticating the effect of temperature and pH parameters on size and stability of the nanoliposome system based on thermodynamic modeling.","authors":"Fardin Rahimi, Pari Hajizadeh, Ghassem Amoabediny, Bahman Ebrahimi, Mansoor Khaledi, Fatemeh Sameni, Hamed Afkhami, Shahriar Bakhti, Elham Rafiee Taqanaki, Mahdi Zafari","doi":"10.1080/08982104.2023.2203250","DOIUrl":"10.1080/08982104.2023.2203250","url":null,"abstract":"<p><p>The main challenge of using nanoliposome systems is controlling their size and stability. In order to overcome this challenge, according to the research conducted at the Research Centre for New Technologies of Biological Engineering, University of Tehran, a model for predicting the size and stability of nanoliposome systems based on thermodynamic relations has been presented. In this model, by using the presented equations and without performing many experiments in the laboratory environment, the effect of temperature, ionic power and different pH can be considered simultaneously whereas examining the components of size, stability and any feature were considered before. Synthesis and application of liposomal nanocarriers in different operating conditions can be investigated and predicted, and due to the change in temperature and pH, the smallest size of th system can be obtained. In this study, we were able to model the synthesis and storage conditions of liposomal nanocarriers at different temperatures and acidic, neutral and alkaline pHs, based on the calculation of mathematical equations. This model also indicates that with increasing temperature, the radius increases but with increasing pH, the radius first increases and then decreases. Therefore, this model can be used to predict size and stability in different operating conditions. In fact, with this modelling method, there is no need to study through laboratory methods and analysis to determine the size, stability and surface loads, and in terms of Accuracy, time and cost savings are affordable.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"392-409"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9452464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MC3/SAINT-O-Somes, a novel liposomal delivery system for efficient and safe delivery of siRNA into endothelial cells.","authors":"Yutong He, Mees Barlag, Josée A Plantinga, Grietje Molema, Jan A A M Kamps","doi":"10.1080/08982104.2023.2187821","DOIUrl":"10.1080/08982104.2023.2187821","url":null,"abstract":"<p><p>Increased understanding of chronic inflammatory diseases and the role of endothelial cell (EC) activation herein, have urged interest in sophisticated strategies to therapeutically intervene in activated EC to treat these diseases. Liposome-mediated delivery of therapeutic siRNA in inflammation-activated EC is such a strategy. In this study, we describe the design and characterisation of two liposomal siRNA delivery systems formulated with the cationic MC3 lipid or MC3/SAINT mixed lipids, referred to as MC3-O-Somes (MOS) and MC3/SAINT-O-Somes (MSS). The two formulations showed comparable physicochemical properties, except for better siRNA encapsulation efficiency in the MSS formulation. Antibody-mediated VCAM-1 targeting (Ab_VCAM-1) increased the association of the targeted MOS and MSS with activated EC, although the targeted MOS showed a significantly higher VCAM-1 specific association than the targeted MSS. Ab_VCAM-1 MSS containing RelA siRNA achieved significant downregulation of RelA expression, while Ab_VCAM-1 MOS containing RelA siRNA did not downregulate RelA expression in activated EC. Additionally, Ab_VCAM-1 MSS containing RelA siRNA showed low cytotoxicity in EC and at the same time prohibited endothelial inflammatory activation by reducing expression of cell adhesion molecules. The Ab_VCAM-1 MSS formulation is a novel siRNA delivery system based on a combination of the cationic lipids MC3 and SAINT, that shows good physicochemical characteristics, enhanced endothelial cell association, improved transfection activity, low toxicity and significant anti-inflammatory effect, thereby complying with the requirements for future in vivo investigations.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"328-337"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal drug delivery to the lungs: a post covid-19 scenario.","authors":"S Swathi Krishna, M S Sudheesh, Vidya Viswanad","doi":"10.1080/08982104.2023.2199068","DOIUrl":"10.1080/08982104.2023.2199068","url":null,"abstract":"<p><p>High local delivery of anti-infectives to the lungs is required for activity against infections of the lungs. The present pandemic has highlighted the potential of pulmonary delivery of anti-infective agents as a viable option for infections like Covid-19, which specifically causes lung infections and mortality. To prevent infections of such type and scale in the future, target-specific delivery of drugs to the pulmonary region is a high-priority area in the field of drug delivery. The suboptimal effect of oral delivery of anti-infective drugs to the lungs due to the poor biopharmaceutical property of the drugs makes this delivery route very promising for respiratory infections. Liposomes have been used as an effective delivery system for drugs due to their biocompatible and biodegradable nature, which can be used effectively for target-specific drug delivery to the lungs. In the present review, we focus on the use of liposomal drug delivery of anti-infectives for the acute management of respiratory infections in the wake of Covid-19 infection.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"410-424"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9420297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced protection against hypoxia/reoxygenation-induced apoptosis in H9c2 cells by puerarin-loaded liposomes modified with matrix metalloproteinases-targeting peptide and triphenylphosphonium.","authors":"Fengmei Li, Yan Wang, Wenqun Li, Junyong Wu, Shengnan Li, Xiongbin Hu, Tiantian Tang, Xinyi Liu","doi":"10.1080/08982104.2023.2193845","DOIUrl":"10.1080/08982104.2023.2193845","url":null,"abstract":"<p><p>Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"378-391"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9241762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N'-(3-Aminopropyl)-N-(3'-(carbamoyl cholesteryl) propyl)-glycine amide liposomes for delivery of pTRAIL-EGFP.","authors":"Wanlop Weecharangsan, Nuttapon Apiratikul, Jantana Yahuafai","doi":"10.1080/08982104.2023.2193638","DOIUrl":"10.1080/08982104.2023.2193638","url":null,"abstract":"<p><p>In this study, N'-(3-aminopropyl)-N-(3'-(carbamoyl cholesteryl) propyl)-glycine amide (A) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, D) (AD) liposomes were synthesised at molar ratios of 50:25 (AD5025), 50:50 (AD5050) and 50:75 (AD5075) and complexed with plasmid, pTRAIL-EGFP. AD liposome/pTRAIL-EGFP were evaluated for their complex ability, particle size, polydispersity index, zeta potential, expression of pTRAIL-EGFP, cytotoxicity, cell growth inhibition and apoptosis induction in KB cells. AD liposomes complexed completely with pTRAIL-EGFP at AD liposome/DNA ratios of above 4.5/1. The particle size of AD liposome/pTRAIL-EGFP ranged from 180 ± 8 to 1,072 ± 657 nm depending on the proportion of lipid composition and liposome/DNA ratio. The extent of gene expression of pTRAIL-EGFP via AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP and depended on the AD liposome/DNA ratio. Cytotoxicity of AD liposomes was dependent on A and D molar ratio. Cell growth inhibition of AD liposome/pTRAIL-EGFP was significantly higher than that of the cells treated with pTRAIL-EGFP. The amount of late apoptotic and dead cells of AD liposome/pTRAIL-EGFP was significantly higher than that of cells treated with pTRAIL-EGFP. From this study that one can conclude that AD liposomes can carry and deliver pTRAIL-EGFP into KB cells resulting in cell growth inhibition and cell death.</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"368-377"},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9188610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: <i>in vitro</i> and <i>in vivo</i> evaluation.","authors":"Shi-Yi Xu, Wei-Wei Wang, Zi-Hui Qu, Xiang-Ke Zhang, Ming Chen, Xin-Yu Zhang, Nan-Nan Xing, Hui Su, Xue-Ying Wang, Ming-Yu Cui, Xue-Ying Yan, Wei Ma","doi":"10.1080/08982104.2023.2190810","DOIUrl":"10.1080/08982104.2023.2190810","url":null,"abstract":"<p><p>Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity <i>in vitro</i>. However, <i>in vivo</i> pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip <i>in vivo</i> was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).</p>","PeriodicalId":16286,"journal":{"name":"Journal of Liposome Research","volume":" ","pages":"338-352"},"PeriodicalIF":4.4,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9971950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}