Matrix Biology Plus最新文献

{"title":"Endothelial glycocalyx degradation during sepsis: Causes and consequences","authors":"Ryan C. Sullivan ,&nbsp;Matthew D. Rockstrom ,&nbsp;Eric P. Schmidt ,&nbsp;Joseph A. Hippensteel","doi":"10.1016/j.mbplus.2021.100094","DOIUrl":"10.1016/j.mbplus.2021.100094","url":null,"abstract":"<div><p>The glycocalyx is a ubiquitous structure found on endothelial cells that extends into the vascular lumen. It is enriched in proteoglycans, which are proteins attached to the glycosaminoglycans heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. In health and disease, the endothelial glycocalyx is a central regulator of vascular permeability, inflammation, coagulation, and circulatory tonicity. During sepsis, a life-threatening syndrome seen commonly in hospitalized patients, the endothelial glycocalyx is degraded, significantly contributing to its many clinical manifestations. In this review we discuss the intrinsically linked mechanisms responsible for septic endothelial glycocalyx destruction: glycosaminoglycan degradation and proteoglycan cleavage. We then examine the consequences of local endothelial glycocalyx loss to several organ systems and the systemic consequences of shed glycocalyx constituents. Last, we explore clinically relevant non-modifiable and modifiable factors that exacerbate or protect against endothelial glycocalyx shedding during sepsis.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100094"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/bb/main.PMC8668992.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9699516","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":"Molecular conformations and dynamics in the extracellular matrix of mammalian structural tissues: Solid-state NMR spectroscopy approaches","authors":"Adrian Murgoci,&nbsp;Melinda Duer","doi":"10.1016/j.mbplus.2021.100086","DOIUrl":"10.1016/j.mbplus.2021.100086","url":null,"abstract":"<div><p>Solid-state NMR spectroscopy has played an important role in multidisciplinary studies of the extracellular matrix. Here we review how solid-state NMR has been used to probe collagen molecular conformations, dynamics, post-translational modifications and non-enzymatic chemical changes, and in calcified tissues, the molecular structure of bone mineral and its interface with collagen. We conclude that NMR spectroscopy can deliver vital information that in combination with data from structural imaging techniques, can result in significant new insight into how the extracellular matrix plays its multiple roles.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8a/e3/main.PMC8551230.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39598963","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":"Targeting the “sweet spot” in septic shock – A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2","authors":"Thorben Pape ,&nbsp;Anna Maria Hunkemöller ,&nbsp;Philipp Kümpers ,&nbsp;Hermann Haller ,&nbsp;Sascha David ,&nbsp;Klaus Stahl","doi":"10.1016/j.mbplus.2021.100095","DOIUrl":"10.1016/j.mbplus.2021.100095","url":null,"abstract":"<div><p>Sepsis is a life-threatening syndrome caused by a pathological host response to an infection that eventually, if uncontrolled, leads to septic shock and ultimately, death. In sepsis, a massive aggregation of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) cause a cytokine storm. The endothelial glycocalyx (eGC) is a gel like layer on the luminal side of the endothelium that consists of proteoglycans, glycosaminoglycans (GAG) and plasma proteins. It is synthesized by endothelial cells and plays an active role in the regulation of inflammation, permeability, and coagulation. In sepsis, early and profound injury of the eGC is observed and circulating eGC components correlate directly with clinical severity and outcome. The activity of the heparan sulfate (HS) specific glucuronidase Heparanase-1 (Hpa-1) is elevated in sepsis, resulting in shedding of heparan sulfate (HS), a main GAG of the eGC. HS induces endothelial barrier breakdown and accelerates systemic inflammation. Lipopolysaccharide (LPS), a PAMP mainly found on the surface of gram-negative bacteria, activates TLR-4, which results in cytokine production and further activation of Hpa-1. Hpa-1 shed HS fragments act as DAMPs themselves, leading to a vicious cycle of inflammation and end-organ dysfunction such as septic cardiomyopathy and encephalopathy. Recently, Hpa-1′s natural antagonist, Heparanase-2 (Hpa-2) has been identified. It has no intrinsic enzymatic activity but instead acts by reducing inflammation. Hpa-2 levels are reduced in septic mice and patients, leading to an acquired imbalance of Hpa-1 and Hpa-2 paving the road towards a therapeutic intervention. Recently, the synthetic antimicrobial peptide 19–2.5 was described as a promising therapy protecting the eGC by inhibition of Hpa-1 activity and HS shed fragments in animal studies. However, a recombinant Hpa-2 therapy does not exist to the present time. Therapeutic plasma exchange (TPE), a modality already tested in clinical practice, effectively removes injurious mediators, e.g., Hpa-1, while replacing depleted protective molecules, e.g., Hpa-2. In critically ill patients with septic shock, TPE restores the physiological Hpa-1/Hpa-2 ratio and attenuates eGC breakdown. TPE results in a significant improvement in hemodynamic instability including reduced vasopressor requirement. Although promising, further studies are needed to determine the therapeutic impact of TPE in septic shock.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100095"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/04/d2/main.PMC8669377.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39846194","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":"Conformational flexibility determines the Nf2/merlin tumor suppressor functions","authors":"Marina C. Primi,&nbsp;Erumbi S. Rangarajan,&nbsp;Dipak N. Patil,&nbsp;Tina Izard","doi":"10.1016/j.mbplus.2021.100074","DOIUrl":"10.1016/j.mbplus.2021.100074","url":null,"abstract":"<div><p>The Neurofibromatosis type 2 gene encodes the Nf2/merlin tumor suppressor protein that is responsible for the regulation of cell proliferation. Once activated, Nf2/merlin modulates adhesive signaling pathways and thereby inhibits cell growth. Nf2/merlin controls oncogenic gene expression by modulating the Hippo pathway. By responding to several physical and biochemical stimuli, Hippo signaling determines contact inhibition of proliferation as well as organ size. The large tumor suppressor (LATS) serine/threonine-protein kinase is the key enzyme in the highly conserved kinase cascade that negatively regulates the activity and localization of the transcriptional coactivators Yes-associated protein (YAP) and its paralogue transcriptional coactivator with PDZ-binding motif (TAZ). Nf2/merlin belongs to the band 4.1, ezrin, radixin, moesin (FERM) gene family that links the actin cytoskeleton to adherens junctions, remodels adherens junctions during epithelial morphogenesis and maintains organized apical surfaces on the plasma cell membrane. Nf2/merlin and ERM proteins have a globular <em>N</em>-terminal cloverleaf head domain, the FERM domain, that binds to the plasma membrane, a central α-helical domain, and a tail domain that binds to its head domain. Here we present the high-resolution crystal structure of Nf2/merlin bound to LATS1 which shows that LATS1 binding to Nf2/merlin displaces the Nf2/merlin tail domain and causes an allosteric shift in the Nf2/merlin α-helix that extends from its FERM domain. This is consistent with the fact that full-length Nf2/merlin binds LATS1 ~10-fold weaker compared to LATS1 binding to the Nf2/merlin-PIP₂ complex. Our data increase our understanding of Nf2/merlin biology by providing mechanistic insights into the Hippo pathway that are relevant to several diseases in particular oncogenic features that are associated with cancers.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100074"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100074","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39266772","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":"Biochemical and immuno-histochemical localization of type IIA procollagen in annulus fibrosus of mature bovine intervertebral disc","authors":"Audrey McAlinden ,&nbsp;David M. Hudson ,&nbsp;Aysel A. Fernandes ,&nbsp;Soumya Ravindran ,&nbsp;Russell J. Fernandes","doi":"10.1016/j.mbplus.2021.100077","DOIUrl":"10.1016/j.mbplus.2021.100077","url":null,"abstract":"<div><p>For next generation tissue-engineered constructs and regenerative medicine to succeed clinically, the basic biology and extracellular matrix composition of tissues that these repair techniques seek to restore have to be fully determined. Using the latest reagents coupled with tried and tested methodologies, we continue to uncover previously undetected structural proteins in mature intervertebral disc. In this study we show that the “embryonic” type IIA procollagen isoform (containing a cysteine-rich amino propeptide) was biochemically detectable in the annulus fibrosus of both calf and mature steer caudal intervertebral discs, but not in the nucleus pulposus where the type IIB isoform was predominantly localized. Specifically, the triple-helical type IIA procollagen isoform immunolocalized in the outer margins of the inner annulus fibrosus. Triple helical processed type II collagen exclusively localized within the inter-lamellae regions and with type IIA procollagen in the intra-lamellae regions. Mass spectrometry of the α1(II) collagen chains from the region where type IIA procollagen localized showed high 3-hydroxylation of Proline-944, a post-translational modification that is correlated with thin collagen fibrils as in the nucleus pulposus. The findings implicate small diameter fibrils of type IIA procollagen in select regions of the annulus fibrosus where it likely contributes to the organization of collagen bundles and structural properties within the type I-type II collagen transition zone.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100077"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mbplus.2021.100077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9358789","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":"Comprehensive quantitative characterization of the human term amnion proteome","authors":"Eva Avilla-Royo ,&nbsp;Katharina Gegenschatz-Schmid ,&nbsp;Jonas Grossmann ,&nbsp;Tobias Kockmann ,&nbsp;Roland Zimmermann ,&nbsp;Jess Gerrit Snedeker ,&nbsp;Nicole Ochsenbein-Kölble ,&nbsp;Martin Ehrbar","doi":"10.1016/j.mbplus.2021.100084","DOIUrl":"10.1016/j.mbplus.2021.100084","url":null,"abstract":"<div><p>The loss of fetal membrane (FM) integrity and function at an early time point during pregnancy can have devastating consequences for the fetus and the newborn. However, biomaterials for preventive sealing and healing of FMs are currently non-existing, which can be partly attributed to the current fragmentary knowledge of FM biology. Despite recent advances in proteomics analysis, a robust and comprehensive description of the amnion proteome is currently lacking. Here, by an optimized protein sample preparation and offline fractionation before liquid chromatography coupled to mass spectrometry (LC-MS) analysis, we present a characterization of the healthy human term amnion proteome, which covers more than 40% of the previously reported transcripts in similar RNA sequencing datasets and, with more than 5000 identifications, greatly outnumbers previous reports. Together, beyond providing a basis for the study of compromised and preterm ruptured FMs, this comprehensive human amnion proteome is a stepping-stone for the development of novel healing-inducing biomaterials. The proteomic dataset has been deposited in the ProteomeXchange Consortium with the identifier PXD019410.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/31/main.PMC8572956.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614108","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":"Deletion of type VIII collagen reduces blood pressure, increases carotid artery functional distensibility and promotes elastin deposition","authors":"Amanda L. Mohabeer ,&nbsp;Jeffrey T. Kroetsch ,&nbsp;Meghan McFadden ,&nbsp;Negin Khosraviani ,&nbsp;Thomas J. Broekelmann ,&nbsp;Guangpei Hou ,&nbsp;Hangjun Zhang ,&nbsp;Yu-Qing Zhou ,&nbsp;Minyao Wang ,&nbsp;Anthony O. Gramolini ,&nbsp;Robert P. Mecham ,&nbsp;Scott P. Heximer ,&nbsp;Steffen-Sebastian Bolz ,&nbsp;Michelle P. Bendeck","doi":"10.1016/j.mbplus.2021.100085","DOIUrl":"10.1016/j.mbplus.2021.100085","url":null,"abstract":"<div><p>Arterial stiffening is a significant predictor of cardiovascular disease development and mortality. In elastic arteries, stiffening refers to the loss and fragmentation of elastic fibers, with a progressive increase in collagen fibers. Type VIII collagen (Col-8) is highly expressed developmentally, and then once again dramatically upregulated in aged and diseased vessels characterized by arterial stiffening. Yet its biophysical impact on the vessel wall remains unknown. The purpose of this study was to test the hypothesis that Col-8 functions as a matrix scaffold to maintain vessel integrity during extracellular matrix (ECM) development. These changes are predicted to persist into the adult vasculature, and we have tested this in our investigation. Through our <em>in vivo</em> and <em>in vitro</em> studies, we have determined a novel interaction between Col-8 and elastin. Mice deficient in Col-8 (Col8^−/−) had reduced baseline blood pressure and increased arterial compliance, indicating an enhanced Windkessel effect in conducting arteries. Differences in both the ECM composition and VSMC activity resulted in Col8^−/− carotid arteries that displayed increased crosslinked elastin and functional distensibility, but enhanced catecholamine-induced VSMC contractility. <em>In vitro</em> studies revealed that the absence of Col-8 dramatically increased tropoelastin mRNA and elastic fiber deposition in the ECM, which was decreased with exogenous Col-8 treatment. These findings suggest a causative role for Col-8 in reducing mRNA levels of tropoelastin and the presence of elastic fibers in the matrix. Moreover, we also found that Col-8 and elastin have opposing effects on VSMC phenotype, the former promoting a synthetic phenotype, whereas the latter confers quiescence. These studies further our understanding of Col-8 function and open a promising new area of investigation related to elastin biology.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/39/d3/main.PMC8517381.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39556913","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":"Cooperation of cell adhesion and autophagy in the brain: Functional roles in development and neurodegenerative disease","authors":"Sarah J. Hernandez ,&nbsp;Gianna Fote ,&nbsp;Andrea M. Reyes-Ortiz ,&nbsp;Joan S. Steffan ,&nbsp;Leslie M. Thompson","doi":"10.1016/j.mbplus.2021.100089","DOIUrl":"10.1016/j.mbplus.2021.100089","url":null,"abstract":"<div><p>Cellular adhesive connections directed by the extracellular matrix (ECM) and maintenance of cellular homeostasis by autophagy are seemingly disparate functions that are molecularly intertwined, each regulating the other. This is an emerging field in the brain where the interplay between adhesion and autophagy functions at the intersection of neuroprotection and neurodegeneration. The ECM and adhesion proteins regulate autophagic responses to direct protein clearance and guide regenerative programs that go awry in brain disorders. Concomitantly, autophagic flux acts to regulate adhesion dynamics to mediate neurite outgrowth and synaptic plasticity with functional disruption contributed by neurodegenerative disease. This review highlights the cooperative exchange between cellular adhesion and autophagy in the brain during health and disease. As the mechanistic alliance between adhesion and autophagy has been leveraged therapeutically for metastatic disease, understanding overlapping molecular functions that direct the interplay between adhesion and autophagy might uncover therapeutic strategies to correct or compensate for neurodegeneration.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/fe/main.PMC8579148.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39630668","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":"Biomechanical properties of endothelial glycocalyx: An imperfect pendulum","authors":"Xi Zhuo Jiang ,&nbsp;Michael S. Goligorsky","doi":"10.1016/j.mbplus.2021.100087","DOIUrl":"10.1016/j.mbplus.2021.100087","url":null,"abstract":"<div><p>Endothelial glycocalyx plays a crucial role in hemodynamics in health and disease, yet studying it is met by multiple technical hindrances. We attempted to outline our views on some biomechanical properties of endothelial glycocalyx, which are potentially amenable to mathematical modeling. We start with the null-hypothesis ascribing to glycocalyx the properties of a pendulum and reject this hypothesis on the grounds of multiple obstacles for pendulum behavior, such as rich decoration with flexible negatively charged side-chains, variable length and density, fluid fixation to the plasma membrane. We next analyze the current views on membrane attachments to the cortical actin web, its pulsatile contraction-relaxation cycles which rebound to the changes in tension of the plasma membrane. Based on this, we consider the outside-in signaling, the basis for mechanotransduction, and the dampening action of the inside-out signaling. The aperiodic oscillatory motions of glycocalyx and cortical actin web underlie our prediction of two functional pacemakers. We next advance an idea that the glycocalyx, plasma membrane, and cortical actin web represent a structure-functional unit and propose the concept of tensegrity model. Finally, we present our recent data suggesting that erythrocytes are gliding or hovering and rotating over the surface of intact glycocalyx, whereas the rotational and hovering components of their passage along the capillaries are lost when glycocalyx of either is degraded. These insights into the mechanics of endothelial glycocalyx motions may be of value in crosspollination between biomechanics, physiology, and pathophysiology for deeper appreciation of its rich untapped resources in health and pharmacotherapy in disease.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100087"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f3/3e/main.PMC8596327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657247","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":"Biophotonic tools for probing extracellular matrix mechanics","authors":"B.E. Sherlock ,&nbsp;J. Chen ,&nbsp;J.C. Mansfield ,&nbsp;E. Green ,&nbsp;C.P. Winlove","doi":"10.1016/j.mbplus.2021.100093","DOIUrl":"10.1016/j.mbplus.2021.100093","url":null,"abstract":"<div><p>The complex, hierarchical and heterogeneous biomechanics of the extracellular matrix (ECM) are central to the health of multicellular organisms. Characterising the distribution, dynamics and above all else origins of ECM biomechanics are challenges that have captivated researchers for decades. Recently, a suite of biophotonics techniques have emerged as powerful new tools to investigate ECM biomechanics. In this mini-review, we discuss how the non-destructive, sub-micron resolution imaging capabilities of Raman spectroscopy and nonlinear microscopy are being used to interrogate the biomechanics of thick, living tissues. These high speed, label-free techniques are implemented during mechanical testing, providing unprecedented insight into the compositional and structural response of the ECM to changes in the mechanical environment.</p></div>","PeriodicalId":52317,"journal":{"name":"Matrix Biology Plus","volume":"12 ","pages":"Article 100093"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661043/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39746298","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}