Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-03-20DOI: 10.1016/j.vesic.2025.100072
Ye Zhang, Bo Zhao, Jing Wang, Zeyi Zhang, Meiping Shen, Chengjie Ren, Mimi Li, Melanie Liu, Zhicheng You, Ping Li
{"title":"Therapeutic potential of Lycium barbarum-derived exosome-like nanovesicles in combating photodamage and enhancing skin barrier repair","authors":"Ye Zhang, Bo Zhao, Jing Wang, Zeyi Zhang, Meiping Shen, Chengjie Ren, Mimi Li, Melanie Liu, Zhicheng You, Ping Li","doi":"10.1016/j.vesic.2025.100072","DOIUrl":"10.1016/j.vesic.2025.100072","url":null,"abstract":"<div><div>In this study, the efficacy of <em>Lycium barbarum</em> L.-derived exosome-like nanovesicles (LB-EVs) in reinforcing skin barrier function were evaluated. Using a 3D skin model, expression levels of skin barrier proteins such as filaggrin, loricrin and claudin-1 were found to be modulated favorably upon treatment with LB-EVs, suggesting a role in maintaining cutaneous homeostasis. Additionally, we observed upregulated aquaporin 3 (AQP3) expression and increased natural moisturizing factor (NMF) components, indicating improved skin hydration. A split-face clinical trial involving individuals with sensitive skin revealed that incorporating LB-EVs into a cosmetic serum matrix led to reduced facial redness and transepidermal water loss (TEWL) compared to the control group. Two-photon imaging further demonstrated thickening of the stratum corneum on the treated side after 14 days of application, suggesting enhanced barrier integrity. The findings from this study highlight the potential of LB-EVs to fortify the skin's protective barrier, providing a novel therapeutic strategy for the management of photodamage and the enhancement of skin health.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-04-21DOI: 10.1016/j.vesic.2025.100080
Vanessa YiRan Li , Nicole Rosas , Sharon Fleischer , Gordana Vunjak-Novakovic , Ke Cheng
{"title":"MicroRNAs won the Nobel Prize. Now, can extracellular vesicles help them become drugs?","authors":"Vanessa YiRan Li , Nicole Rosas , Sharon Fleischer , Gordana Vunjak-Novakovic , Ke Cheng","doi":"10.1016/j.vesic.2025.100080","DOIUrl":"10.1016/j.vesic.2025.100080","url":null,"abstract":"<div><div>The 2024 Nobel Prize recognized microRNAs (miRNAs) as transformative regulators of gene expression. However, their clinical potential has been constrained by instability and delivery challenges. Extracellular vesicles (EVs), as natural carriers of miRNAs, address these limitations by protecting miRNAs from degradation and enabling their precise targeting. As such, harnessing EVs for miRNA delivery has the potential to redefine therapeutic approaches and offer innovative strategies to tackle the most challenging diseases of the 21st century. In this perspective, we examine the advantages and hurdles of EV-mediated miRNA delivery, from state-of-the-art research to its path toward commercialization. This article aims to inspire readers with the promise of EVs and miRNAs as revolutionary tools for future medicine.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2025-06-01Epub Date: 2025-03-06DOI: 10.1016/j.vesic.2025.100070
Worawan B. Limpitikul , Michael G. Silverman , Nedyalka Valkov , Jeong-Gun Park , Ashish Yeri , Fernando Camacho Garcia , Guoping Li , Priyanka Gokulnath , Marta Garcia-Contreras , Eric Alsop , Elizabeth Hutchins , Michail Spanos , Claire Lin , Kriti Bomb , Anthony Rosenzweig , Raymond Kwong , Kendall van-Keuren Jensen , James L. Januzzi Jr. , Ravi Shah , David A. Morrow , Saumya Das
{"title":"Plasma extracellular vesicle cargo microRNAs are associated with heart failure and cardiovascular death following acute coronary syndrome","authors":"Worawan B. Limpitikul , Michael G. Silverman , Nedyalka Valkov , Jeong-Gun Park , Ashish Yeri , Fernando Camacho Garcia , Guoping Li , Priyanka Gokulnath , Marta Garcia-Contreras , Eric Alsop , Elizabeth Hutchins , Michail Spanos , Claire Lin , Kriti Bomb , Anthony Rosenzweig , Raymond Kwong , Kendall van-Keuren Jensen , James L. Januzzi Jr. , Ravi Shah , David A. Morrow , Saumya Das","doi":"10.1016/j.vesic.2025.100070","DOIUrl":"10.1016/j.vesic.2025.100070","url":null,"abstract":"<div><h3>Background and aims</h3><div>Patients with acute coronary syndromes (ACS) are at risk for long-term sequelae related to adverse ventricular remodeling including heart failure (HF) and cardiovascular death. Circulating microRNAs (miRNAs) have the potential to serve as biomarkers associated with the pathogenesis of ventricular remodeling. This study aims to identify and characterize plasma miRNAs associated with HF and cardiovascular death.</div></div><div><h3>Methods</h3><div>The association between 21 candidate miRNAs and HF or cardiovascular death was evaluated in 4541 patients from the Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial using samples from the time of index hospitalization for ACS. Associations between each miRNA and the composite endpoint of hospitalization for HF or cardiovascular death (HHF/CVD) were estimated in Cox proportional hazards models. The top candidate miRNAs were validated in an independent cohort of patients hospitalized for ACS using complementary methods for isolation of extracellular RNA carriers.</div></div><div><h3>Results</h3><div>Over 12 months in MERLIN-TIMI 36, 313 individuals met the primary endpoint. In total, 11 miRNAs were associated with HHF/CVD. After adjustment for clinical factors and established biomarkers, miR-223-3p (hazard ratio 0.81 [95% confidence interval: 0.60–1.09], 0.62 [0.45–0.87], and 0.61 [0.43–0.85] for the 2nd, 3rd, and 4th quartiles, respectively) and miR-378c (0.96 [0.65–1.42], 1.14 [0.78–1.66], and 1.39 [0.97–1.98], for the 2nd, 3rd, and 4th quartiles, respectively) were independently associated with the risk of HHF/CVD. In an independent validation cohort of 27 patients hospitalized with ACS, we found that both miRNAs were identified in different RNA-carrying extracellular particles in plasma, including extracellular vesicles (EVs) and nonvesicular extracellular nanoparticles (NVEPs) including exomeres and supermeres. Both miR-223-3p and 378c were more enriched in small EVs (sEVs) compared to NVEPs. In concordance with the direction of the associations observed in MERLIN-TIMI 36 with HHF, the level of miR-223-3p in sEVs and exomeres was positively associated with left ventricular ejection fraction (LVEF) post-ACS while the level of miR-378c in sEVs was negatively associated with LVEF in the acute phase.</div></div><div><h3>Conclusion</h3><div>Circulating miRNAs 223-3p and 378c were associated with the risk of HHF/CVD after adjustment for clinical factors and established cardiovascular biomarkers. Carrier-specific measurement of these miRNAs may emerge as novel minimally invasive biomarkers for post-ACS cardiac remodeling and shed light on potentially new targetable pathways.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"5 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-12-11DOI: 10.1016/j.vesic.2024.100061
Kaiyue Zhang , Jingxuan Hu , Yilan Hu
{"title":"Visualization strategies of extracellular vesicles: Illuminating the invisible ‘dust’ in theranostics","authors":"Kaiyue Zhang , Jingxuan Hu , Yilan Hu","doi":"10.1016/j.vesic.2024.100061","DOIUrl":"10.1016/j.vesic.2024.100061","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), lipid bilayer vesicles with diameters of 30-150 nm derived from nearly all cell types, were once dismissed as “platelet dust” but are now recognized as key mediators of intercellular communication, playing vital roles in both physiological and pathophysiological processes. However, the clinical applications of EVs in theranostics remain limited by the challenge of effectively visualizing them at high resolution both <em>in vitro</em> and <em>in vivo</em>, primarily due to their nanoscale size. To address this limitation, researchers worldwide are developing innovative methods for labeling and visualizing EVs, aiming to unlock their full potential in optimized theranostic applications. This review provides a comprehensive overview of current strategies for EV labeling across various experimental settings and highlights their promising theranostic applications of diverse diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-09-17DOI: 10.1016/j.vesic.2024.100050
Richard J.R. Kelwick , Alexander J. Webb , Paul S. Freemont
{"title":"Accelerating extracellular vesicle research and biotechnological applications using synthetic biology approaches","authors":"Richard J.R. Kelwick , Alexander J. Webb , Paul S. Freemont","doi":"10.1016/j.vesic.2024.100050","DOIUrl":"10.1016/j.vesic.2024.100050","url":null,"abstract":"<div><p>Can a combination of the extracellular vesicle (EV) research community’s latest consensus guidance (MISEV2023) along with synthetic biology’s engineering approaches and responsible innovation framework help to accelerate future EV-based industrial and medical applications?</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100050"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041724000179/pdfft?md5=720e1cb2e048bcb19c26bb9c90ec5840&pid=1-s2.0-S2773041724000179-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-07-25DOI: 10.1016/j.vesic.2024.100047
Zhigang Wang , Yufei Yan , Rui Li, Ying Zhu, Gen Yang
{"title":"Artificially engineered vesicular vehicles for targeted therapy","authors":"Zhigang Wang , Yufei Yan , Rui Li, Ying Zhu, Gen Yang","doi":"10.1016/j.vesic.2024.100047","DOIUrl":"10.1016/j.vesic.2024.100047","url":null,"abstract":"<div><p>Vesicular vehicles have been one of the most potential platforms for therapeutic delivery. Here, we commentate on recent advances in the development of therapeutic vesicular delivery platforms, emphasizing two intriguing works, namely, the chimeric nanobody-decorated immunoliposomes (Wan et al.) and the retrovirus-like capsids incorporated extracellular vesicles (Jiang et al.). In the work of Wan et al., the researchers proposed a novel strategy for antitumor immunoliposome construction by the one-step self-assembly of lipids with rationally designed chimeric nanobody that comprises a nanobody against human epidermal growth factor receptor 2, a flexible peptide linker, and a human single transmembrane domain. By leveraging the natural cell systems (e.g., <em>E coli.</em>) to synthesize the chimeric nanobody, this technique provides a facile and robust strategy for producing immunoliposome platforms, ensuring suitability for industrial manufacturing and distribution, regulatory compliance, and clinical use. In the work of Jiang et al., taking advantage of the natural extracellular vesicle biogenesis system, the researchers introduced the activity-regulated cytoskeleton-associated protein inside the vesicle lumen and thus constructed endogenous retrovirus-like vesicles for mRNA drug delivery to neurons. This technique offers a significative strategy for developing sophisticated delivery platforms, manifesting broad application potential for different disease therapeutics. Overall, these two works have represented two typical paradigms for the artificial construction of vesicular vesicles. Considering their complementary merits, in the future, the integration of artificial engineering technologies and natural biosynthesis systems is anticipated to be a promising strategy to expedite the development of potent delivery systems.</p></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100047"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2773041724000143/pdfft?md5=892695f80d592b8b035d791f34e79689&pid=1-s2.0-S2773041724000143-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141960705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-11-26DOI: 10.1016/j.vesic.2024.100057
Junyao Deng , Qishan Li , Fei Wang
{"title":"Novel administration strategies for tissue-specific delivery of extracellular vesicles","authors":"Junyao Deng , Qishan Li , Fei Wang","doi":"10.1016/j.vesic.2024.100057","DOIUrl":"10.1016/j.vesic.2024.100057","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are nanoparticles released by cells with bilayer lipid membranes that have been demonstrated to regulate biological activities. The potential of EVs as a novel therapeutic or drug delivery platform has already been identified in emerging research. The therapeutic efficacy of EVs is contingent upon the quantity of EVs internalized by target cells, which necessitates the enhanced retention of EVs in target organs. Accordingly, various novel administration strategies for the targeted delivery of therapeutic EVs into specific tissues were developed. This review presents a comprehensive overview of the latest developments in EV delivery routes for brain-, heart-, lung-, skin-, eye-, and gastrointestinal tract-specific applications. We believe that the emergence of innovative EV administration strategies will contribute to the future clinical trials and eventual applicability of EV-based therapeutics.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-10-23DOI: 10.1016/j.vesic.2024.100054
Carla Martin Perez , Xiuming Liang , Dhanu Gupta , Emily R. Haughton , Mariana Conceição , Imre Mäger , Samir EL Andaloussi , Matthew J.A. Wood , Thomas C. Roberts
{"title":"An extracellular vesicle delivery platform based on the PTTG1IP protein","authors":"Carla Martin Perez , Xiuming Liang , Dhanu Gupta , Emily R. Haughton , Mariana Conceição , Imre Mäger , Samir EL Andaloussi , Matthew J.A. Wood , Thomas C. Roberts","doi":"10.1016/j.vesic.2024.100054","DOIUrl":"10.1016/j.vesic.2024.100054","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are promising therapeutic delivery vehicles, although their potential is limited by a lack of efficient engineering strategies to enhance loading and functional cargo delivery. Using an in-house bioinformatics analysis, we identified N-glycosylation as a putative EV-sorting feature. PTTG1IP (a small, N-glycosylated, single-spanning transmembrane protein) was found to be a suitable scaffold for EV loading of therapeutic cargoes, with loading dependent on its N-glycosylation at two arginine residues. Chimeric proteins consisting of PTTG1IP fused with various cargo proteins, and separated by self-cleaving sequences (to promote cargo release), were shown to enable highly efficient functional delivery of Cre protein to recipient cell cultures and mouse xenograft tumors, and delivery of Cas9-sgRNA complexes to recipient reporter cells. The favorable membrane topology of PTTG1IP enabled facile engineering of further variants with improved properties, highlighting its versatility and potential as a platform for EV-based therapeutics.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Extracellular vesiclePub Date : 2024-12-01Epub Date: 2024-10-04DOI: 10.1016/j.vesic.2024.100053
Ruotong Huang , Jiajun Zhu , Ru Fan , Yiting Tang , Lianlong Hu , HaeJu Lee , Shuying Chen
{"title":"Extracellular vesicle-based drug delivery systems in cancer","authors":"Ruotong Huang , Jiajun Zhu , Ru Fan , Yiting Tang , Lianlong Hu , HaeJu Lee , Shuying Chen","doi":"10.1016/j.vesic.2024.100053","DOIUrl":"10.1016/j.vesic.2024.100053","url":null,"abstract":"<div><div>Extracellular vesicles are lipid bilayer-enclosed extracellular membrane vesicles secreted from cells that have gradually shown promise in cancer treatment. As an essential intercellular communication mediator, extracellular vesicles carry bioactive molecules including proteins, lipids, and nucleic acids, which aid in the control and reprogramming of cell signals and ultimately accelerate the spread of cancer. Simultaneously, extracellular vesicles have become a highly desirable option for drug delivery carriers because of the special capacity to cross boundaries and low immunogenicity. Bypassing the endosomal pathway and lysosomal degradation, they can provide medications directly, increasing their effectiveness and decreasing their negative effects. We review the extracellular vesicles’ development, drug loading techniques, and discuss their potential in clinical applications to provide new avenues for precise and targeted treatment strategies. Additionally, engineering modifications of extracellular vesicles can enhance their ability to target specific cells, improving the stability and effectiveness of cargoes, further driving the development of cancer therapy. In this review, we particularly highlight new therapeutic applications of extracellular vesicles, including the latest progress in extracellular vesicle vaccines in tumors. Nonetheless, there are still a lot of obstacles to be overcome before extracellular vesicles may be used to treat cancer. Future research needs to focus on the characteristics of extracellular vesicles from various sources and explore their specific roles in disease treatment to fully leverage the potential of extracellular vesicles in clinical applications such as drug delivery.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects and challenges of targeted extracellular vesicles drug delivery for cancer treatment","authors":"Fatemeh Maher , Ali Samadi , Peyman Asadi , Isabella Jodoin","doi":"10.1016/j.vesic.2024.100059","DOIUrl":"10.1016/j.vesic.2024.100059","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have the ability to alter the phenotypes and functions of other cells as well as reflect the state of the cell from whence they originated.</div><div>Extracellular vesicles, or EVs, are membrane-bound nanostructures released into the extracellular environment. Under both normal and pathological circumstances, they are widely discharged from cells and display a variety of sizes, contents, and surface marks. These EVs are abundant in human serum, yet it might be difficult to separate them from non-EV lipid particles and serum proteins. These vesicles influence several physiological and pathological processes, including those that occur in the tumor microenvironment (TME), by transporting different cellular constituents such as proteins, mRNAs, miRNAs, DNA, and lipids across distances. EVs are potential possibilities for therapeutic agents, medication delivery methods, and disease biomarkers due to their crucial functions in cellular communication. EV detection has the potential to serve as a diagnostic biomarker and can facilitate early identification, particularly in the context of cancer diagnosis. Furthermore, EV subtypes may be clinically significant as different subtypes are emerging as targeted medication delivery methods. There is still a need for non-invasive biomarkers to track biological processes for treatment and diagnosis. In the future, utilizing EVs' distinct composition may open up new possibilities for enhanced diagnosis and treatment.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}