Journal of extracellular biology最新文献

{"title":"Hepatocyte-derived extracellular vesicles regulate liver regeneration through a negative feedback mechanism","authors":"Mina McGinn,&nbsp;Christopher Rabender,&nbsp;Ross Mikkelsen,&nbsp;Vasily Yakovlev","doi":"10.1002/jex2.70023","DOIUrl":"https://doi.org/10.1002/jex2.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>While significant progress has been made in understanding various aspects of liver regeneration, the molecular mechanisms responsible for the initiation and termination of cell proliferation in the liver following massive tissue loss or injury of liver remain unknown. As it was previously shown, the loss of liver mass affects putative hepatocyte-specific mitogenic inhibitors in the blood. Although the presence of these putative inhibitors regulating precise liver regeneration has been described in numerous publications, they have never been identified. Extracellular vesicles (EVs) are nano-sized, membrane-limited structures secreted by cells into the extracellular space. Their proposed role is stable intercellular carriers of proteins and RNAs, predominantly micro-RNA, from secreted to recipient cells. Upon uptake by the recipient cells, EVs can significantly modulate their biological functions. In the present study, using in vivo and in vitro models, we demonstrate that hepatocyte proliferation and liver regeneration are regulated by EVs secreted by hepatocytes into the bloodstream. This regulation occurs through a negative feedback mechanism, which explains the precise regeneration of liver tissue after massive damage. We also demonstrate that an essential component of this mechanism is RNA carried by hepatocyte-derived EVs. Our findings open up a new and unexplored area of liver biology regarding the mechanisms involved in the precise regulation of liver regeneration after a massive tissue loss or injury. Further study of this mechanism will have a great influence on the development of new approaches to liver transplantation, various liver pathologies, and hepatic tumors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142642244","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":"New perspectives of the role of skeletal muscle derived extracellular vesicles in the pathogenesis of amyotrophic lateral sclerosis: the ‘dying back’ hypothesis","authors":"Carolina Sbarigia,&nbsp;Sophie Rome,&nbsp;Luciana Dini,&nbsp;Stefano Tacconi","doi":"10.1002/jex2.70019","DOIUrl":"10.1002/jex2.70019","url":null,"abstract":"<p>Amyotrophic lateral sclerosis (ALS), is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord, and is characterized by muscle weakness, paralysis and ultimately, respiratory failure. The exact causes of ALS are not understood, though it is believed to combine genetic and environmental factors. Until now, it was admitted that motor neurons (MN) in the brain and spinal cord degenerate, leading to muscle weakness and paralysis. However, as ALS symptoms typically begin with muscle weakness or stiffness, a new hypothesis has recently emerged to explain the development of the pathology, that is, the ‘dying back hypothesis’, suggesting that this degeneration starts at the connections between MN and muscles, resulting in the loss of muscle function. Over time, this damage extends along the length of the MN, ultimately affecting their cell bodies in the spinal cord and brain. While the dying back hypothesis provides a potential framework for understanding the progression of ALS, the exact mechanisms underlying the disease remain complex and not fully understood. In this review, we are positioning the role of extracellular vesicles as new actors in ALS development.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634162","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":"Challenging the conventional wisdom: Re-evaluating Smpd3's role in extracellular vesicle biogenesis","authors":"Marlies Burgelman,&nbsp;Pieter Dujardin,&nbsp;Anthony Willems,&nbsp;Tino Hochepied,&nbsp;Griet Van Imschoot,&nbsp;Elien Van Wonterghem,&nbsp;Lien Van Hoecke,&nbsp;Charysse Vandendriessche,&nbsp;Roosmarijn E. Vandenbroucke","doi":"10.1002/jex2.70015","DOIUrl":"10.1002/jex2.70015","url":null,"abstract":"<p>Extracellular vesicles (EVs) are pivotal in intercellular communication, impacting diverse physiological and pathological processes. Current in vitro EV biogenesis studies often utilize pharmacological inhibitors, inducing off-target effects and overlooking cell-specific production nuances. Addressing these limitations, we utilized CRISPR/Cas9 to generate heterozygous full-body and conditional sphingomyelin phosphodiesterase 3 (Smpd3) knockout (KO) transgenic mice. <i>Smpd3</i>, also known as neutral sphingomyelinase 2 (nSMase2), triggers membrane curvature through sphingomyelin hydrolysis to ceramide, thereby influencing exosome release. Intriguingly, <i>Smpd3</i> deficiency demonstrated no impact on EV release both in vitro and in vivo, underscoring its potential cell-type-specific role in EV biogenesis. Notably, bone marrow derived macrophages (BMDMs) did exhibit reduced EV release upon <i>Alix</i> deletion. Our findings open avenues for subsequent inquiries, enriching our knowledge of EV biogenesis and illuminating intercellular communication in health and disease.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634156","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":"Proteome characterization of extracellular vesicles from human milk: Uncovering the surfaceome by a lipid-based protein immobilization technology","authors":"Emelie Ahlberg,&nbsp;Maria C. Jenmalm,&nbsp;Anders Karlsson,&nbsp;Roger Karlsson,&nbsp;Lina Tingö","doi":"10.1002/jex2.70020","DOIUrl":"10.1002/jex2.70020","url":null,"abstract":"<p>Breast milk is an essential source of nutrition and hydration for the infant. In addition, this highly complex fluid is rich in extracellular vesicles (EVs). Here, we have applied a microfluidic technology, lipid-based protein immobilization (LPI) and liquid chromatography with tandem mass spectrometry (LC-MS/MS) to characterize the proteome of human milk EVs. Mature milk from six mothers was subjected to EV isolation by ultracentrifugation followed by size exclusion chromatography. Three of the samples were carefully characterized; suggesting a subset enriched by small EVs. The EVs were digested by trypsin in an LPI flow cell and in-solution digestion, giving rise to two fractions of peptides originating from the surface proteome (LPI fraction) or the complete proteome (in-solution digestion). LC-MS/MS recovered peptides corresponding to 582 proteins in the LPI fraction and 938 proteins in the in-solution digested samples; 400 of these proteins were uniquely found in the in-solution digested samples and were hence denoted “cargo proteome”. GeneOntology overrepresentation analysis gave rise to distinctly different functional predictions of the EV surfaceome and the cargo proteome. The surfaceome tends to be overrepresented in functions and components of relevance for the immune system, while the cargo proteome primarily seems to be associated with EV biogenesis.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606761","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":"Mechanisms of extracellular vesicle uptake and implications for the design of cancer therapeutics","authors":"Stephanie R. Jackson Cullison,&nbsp;Joseph P. Flemming,&nbsp;Kubra Karagoz,&nbsp;Peter J. Wermuth,&nbsp;Mỹ G. Mahoney","doi":"10.1002/jex2.70017","DOIUrl":"https://doi.org/10.1002/jex2.70017","url":null,"abstract":"<p>The translation of pre-clinical anti-cancer therapies to regulatory approval has been promising, but slower than hoped. While innovative and effective treatments continue to achieve or seek approval, setbacks are often attributed to a lack of efficacy, failure to achieve clinical endpoints, and dose-limiting toxicities. Successful efforts have been characterized by the development of therapeutics designed to specifically deliver optimal and effective dosing to tumour cells while minimizing off-target toxicity. Much effort has been devoted to the rational design and application of synthetic nanoparticles to serve as targeted therapeutic delivery vehicles. Several challenges to the successful application of this modality as delivery vehicles include the induction of a protracted immune response that results in their rapid systemic clearance, manufacturing cost, lack of stability, and their biocompatibility. Extracellular vesicles (EVs) are a heterogeneous class of endogenous biologically produced lipid bilayer nanoparticles that mediate intercellular communication by carrying bioactive macromolecules capable of modifying cellular phenotypes to local and distant cells. By genetic, chemical, or metabolic methods, extracellular vesicles (EVs) can be engineered to display targeting moieties on their surface while transporting specific cargo to modulate pathological processes following uptake by target cell populations. This review will survey the types of EVs, their composition and cargoes, strategies employed to increase their targeting, uptake, and cargo release, and their potential as targeted anti-cancer therapeutic delivery vehicles.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555478","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":"Choice of blood collection methods influences extracellular vesicles counts and miRNA profiling","authors":"Vivian Tran,&nbsp;Getulio Pereira de Oliveira-Jr,&nbsp;Stephanie Chidester,&nbsp;Shulin Lu,&nbsp;Michelle L. Pleet,&nbsp;Alexander R. Ivanov,&nbsp;John Tigges,&nbsp;Moua Yang,&nbsp;Steven Jacobson,&nbsp;Maria C. B. Gonçalves,&nbsp;Alec A. Schmaier,&nbsp;Jennifer Jones,&nbsp;Ionita C. Ghiran","doi":"10.1002/jex2.70008","DOIUrl":"10.1002/jex2.70008","url":null,"abstract":"<p>Circulating RNAs have been investigated systematically for over 20 years, both as constituents of circulating extracellular vesicles (EVs) or, more recently, non-EV RNA carriers, such as exomeres and supermeres. The high level of variability and low reproducibility rate of EV/extracellular RNA (exRNA) results generated even on the same biofluids promoted several efforts to limit pre-analytical variability by standardizing sample collection and sample preparation, along with instrument validation, setup and calibration. Anticoagulants (ACs) are often chosen based on the initial goal of the study and not necessarily for the later EV and/or exRNA analyses. We show the effects of blood collection on EV size, abundance, and antigenic composition, as well on the miRNAs. Our focus of this work was on the effect of ACs on the number and antigenic composition of circulating EVs and on a set of circulating miRNA species, which were shown to be relevant as disease markers in several cancers and Alzheimer's disease. Results show that while the number of plasma EVs, their relative size, and post-fluorescence labeling profile varied with each AC, their overall antigenic composition, with few exceptions, did not change significantly. However, the number of EVs expressing platelet and platelet-activation markers increased in serum samples. For overall miRNA expression levels, EDTA was a better AC, although this may have been associated with stimulation of cells in the blood collection tube. Citrate and serum rendered better results for a set of miRNAs that were described as circulating markers for Alzheimer's disease, colon, and papillary thyroid cancers.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514202","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":"Comparison of nanoimaging and nanoflow based detection of extracellular vesicles at a single particle resolution","authors":"Shihan Xu,&nbsp;Zhengrong Zhang,&nbsp;Bridgette C. Melvin,&nbsp;Nibedita Basu Ray,&nbsp;Seiko Ikezu,&nbsp;Tsuneya Ikezu","doi":"10.1002/jex2.70016","DOIUrl":"https://doi.org/10.1002/jex2.70016","url":null,"abstract":"<p>The characterization of single extracellular vesicle (EV) has been an emerging tool for the early detection of various diseases despite there being challenges regarding how to interpret data with different protocols or instruments. In this work, standard EV particles were characterized for single CD9⁺, single CD81⁺ or double CD9⁺/CD81⁺ tetraspanin molecule positivity with two single EV analytic technologies in order to optimize their EV sample preparation after antibody labelling and analysis methods: NanoImager for direct stochastic optical reconstruction microscopy (dSTORM)-based EV imaging and characterization, and Flow NanoAnalyzer for flow-based EV quantification and characterization. False positives from antibody aggregates were found during dSTORM-based NanoImager imaging. Analysis of particle radius with lognormal fittings of probability density histogram enabled the removal of antibody aggregates and corrected EV quantification. Furthermore, different machine learning models were trained to differentiate antibody aggregates from EV particles and correct EV quantification with increased double CD9⁺/CD81⁺ population. With Flow NanoAnalyzer, EV samples were prepared with different dilution or fractionation methods, which increased the detection rate of CD9⁺/CD81⁺ EV population. Comparing the EV phenotype percentages measured by two instruments, differences in double positive and single positive particles existed after percentage correction, which might be due to the different detection limit of each instrument. Our study reveals that the characterization of individual EVs for tetraspanin positivity varies between two platforms—the NanoImager and the Flow NanoAnalyzer—depending on the EV sample preparation methods used after antibody labelling. Additionally, we applied machine learning models to correct for false positive particles identified in imaging-based results by fitting size distribution data.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443446","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":"Small extracellular vesicles contain metals and transfer metal intercellularly","authors":"Adityas Purnianto,&nbsp;Celeste Mawal,&nbsp;Mitali M. Kulkarni,&nbsp;Huaqi Su,&nbsp;Tiana F. Koukoulis,&nbsp;Patricia Wongsodirdjo,&nbsp;Ya Hui Hung,&nbsp;Scott Ayton,&nbsp;Ashley I. Bush,&nbsp;Kevin J. Barnham,&nbsp;Laura J. Vella","doi":"10.1002/jex2.70012","DOIUrl":"https://doi.org/10.1002/jex2.70012","url":null,"abstract":"<p>Cells have developed a highly regulated system for the uptake, transport, utilization, storage, and export of metals, ensuring the maintenance of cellular homeostasis. Small extracellular vesicles (sEVs) function as a mechanism through which a cell can export its cargo and transfer it to recipient cells. However, in contrast to the other molecular cargo associated with sEVs, the metal content of sEVs is not well characterized. To address this gap in knowledge, we measured the levels of nine essential metals (copper, iron, zinc, manganese, magnesium, potassium, calcium, chromium, cobalt) and six non-essential metals (nickel, rubidium, titanium, aluminium, lithium, lead) in sEVs originating from multiple in vitro and <i>ex vivo</i> sources. Our findings reveal that, beyond containing redox-active essential metals and those involved in redox reactions, sEVs also exhibit the capability to export and transfer non-physiological, potentially toxic metals.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435605","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":"Shining a light on fluorescent EV dyes: Evaluating efficacy, specificity and suitability by nano-flow cytometry","authors":"Joseph Brealey,&nbsp;Rebecca Lees,&nbsp;Robert Tempest,&nbsp;Alice Law,&nbsp;Sonia Guarnerio,&nbsp;Rawan Maani,&nbsp;Soozana Puvanenthiran,&nbsp;Nick Peake,&nbsp;Ryan Pink,&nbsp;Ben Peacock","doi":"10.1002/jex2.70006","DOIUrl":"https://doi.org/10.1002/jex2.70006","url":null,"abstract":"<p>Extracellular vesicles (EVs) are mediators of intercellular communication, recently recognised for their clinical applications. Accurate characterisation and quantification of EVs are critical for understanding of their function and clinical relevance. Many platforms utilise fluorescence for EV characterisation, frequently labelling surface proteins to identify EVs. The heterogeneity of EVs and the lack of a universal protein marker encourages the use of generic EV labelling methods, including membrane labelling. Using nano-flow cytometry, we evaluated six membrane dyes, including MemGlow and CellMask. Evaluation criteria included EV labelling efficacy, non-specific labelling of very low-density lipoproteins (VLDLs), brightness and dye aggregation. Significant variation was observed in dye performance, with certain dyes showing poor EV labelling efficacy or high affinity to VLDLs. Importantly, several promising candidates were identified for further investigation. Overall, this study highlights the importance of selecting appropriate membrane dyes for EV staining tailored to the aims of the study and the EV origin. MemGlow and CellMask proved favourable, allowing bright, sensitive staining of EV membranes with minimal aggregation. However, MemGlow showed an affinity to VLDLs, and CellMask requires additional sample handling for optimal labelling. These results contribute to deepening our understanding of EV membrane dyes, allowing for better dye selection and EV identification in future studies.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142429931","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":"Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach","authors":"Ofir Bar,&nbsp;Angel Porgador,&nbsp;Tomer Cooks","doi":"10.1002/jex2.70011","DOIUrl":"https://doi.org/10.1002/jex2.70011","url":null,"abstract":"<p>Cancer therapy is a dynamically evolving field, witnessing the emergence of innovative approaches that offer a promising outlook for patients grappling with persistent disease. Within the realm of therapeutic exploration, chimeric antigen receptor (CAR) T cells as well as CAR NK cells, have surfaced as novel approaches, each possessing unique attributes and transformative potential. Immune cells engineered to express CARs recognizing tumour-specific antigens, have shown remarkable promise in treating terminal cancers by combining the precision of antibody specificity with the potent cytotoxic function of T cells. However, their application in solid tumours is still in its nascent stages, presenting unique major challenges. On the same note, CAR NK cells offer a distinct immunotherapeutic approach, utilizing CARs on NK cells, providing advantages in safety, manufacturing simplicity, and a broader scope for cancer treatment. Extracellular vesicles (EVs) have emerged as promising therapeutic agents due to their ability to carry crucial biomarkers and biologically active molecules, serving as vital messengers in the intercellular communication network. In the context of cancer, the therapeutic potential of EVs lies in delivering tumour-suppressing proteins, nucleic acid components, or targeting drugs with precision, thereby redefining the paradigm of precision medicine. The fusion of CAR technology with the capabilities of EVs has given rise to a new therapeutic frontier. CAR T EVs and CAR NK EVs, leveraging the power of EVs, have the potential to alleviate challenges associated with live-cell therapies. EVs are suggested to reduce the side effects linked to CAR T cell therapy and hold the potential to revolutionize the penetrance in solid tumours. EVs act as carriers of pro-apoptotic molecules and RNA components, enhancing immune responses and thereby expanding their therapeutic potential. In this review article, we navigate dynamic landscapes, with our objective being to evaluate comparative efficacy, safety profiles, manufacturing complexities, and clinical applicability.</p>","PeriodicalId":73747,"journal":{"name":"Journal of extracellular biology","volume":"3 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jex2.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324673","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}