Channels (Austin, Tex.)最新文献

{"title":"Astrocytic abnormalities in brain-specific <i>Cacna1c</i>-deficient mice: Implications for BBB impairment in neuropsychiatric diseases associated with <i>CACNA1C</i> mutations.","authors":"Yeojung Koh, Maria Noterman-Soulinthavong, Anusha Bangalore, Uapingena P Kandjoze, Zea Bud, Kamryn L Noel, Hami Lee, Kathryn Franke, Coral J Cintrón-Pérez, Anjali M Rajadhyaksha, Eric B Taylor, Andrew A Pieper","doi":"10.1080/19336950.2025.2523788","DOIUrl":"10.1080/19336950.2025.2523788","url":null,"abstract":"<p><p>Intronic genetic variants within the <i>CACNA1C</i> gene, which encodes the pore-forming alpha 1c subunit of the Ca_v1.2 L-type calcium channel, are significant risk factors for a multitude of neuropsychiatric disorders. In most cases, these intronic SNPs have been associated with reduced <i>CACNA1C</i> expression. Here, we demonstrate that targeted genetic deletion of <i>Cacna1c</i> in mouse brain leads to increased astrocyte reactivity, increased expression of aquaporin 4 (AQP4) in astrocytes adjacent to the blood-brain barrier (BBB), and neuroinflammation, including changes in the levels of brain chemokines and inflammatory cytokines. Astrocytes are vital for maintaining BBB integrity, with AQP4 predominantly expressed in astrocytic endfeet where it regulates water balance in the brain. This function is critical to brain health, and deterioration of the BBB is a major feature of virtually all forms of neuropsychiatric disease. Our results highlight a previously unrecognized role for <i>CACNA1C</i> in astrocytes at the BBB, which could be a major factor in how intronic <i>CACNA1C</i> SNPs broadly increase the risk of multiple forms of major neuropsychiatric disease.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2523788"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144509826","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":"Genetic silencing of K_Ca3.1 inhibits atherosclerosis in ApoE null mice.","authors":"P Alam, D L Tharp, H J Bowles, L A Grisanti, H Bui, S B Bender, D K Bowles","doi":"10.1080/19336950.2025.2538864","DOIUrl":"10.1080/19336950.2025.2538864","url":null,"abstract":"<p><p>Increased expression of K_Ca3.1 has been found in vascular smooth muscle cells (SMC), macrophages, and T cells in atherosclerotic lesions from humans and mice. Pharmacological inhibition of K_Ca3.1 in limiting atherosclerosis has been demonstrated in mice and pigs, however direct, loss-of-function, i.e. gene silencing, studies are absent. Therefore, we generated K_Ca3.1^-/-Apoe^-/- (DKO) mice and assessed lesion development in the brachiocephalic artery (BCA) of DKO versus Apoe^-/- mice on a Western diet for 3 months. In BCAs of DKO mice, lesion size and relative stenosis were reduced by ~70% compared to Apoe^-/- mice, with no effect on medial or lumen area. Additionally, DKO mice exhibited a significant reduction in macrophage content within plaques compared to Apoe^-/- mice, independent of sex. <i>In vitro</i> migration assays showed a significant reduction in migration of bone marrow-derived macrophages (BMDMs) from DKO mice compared to those from Apoe^-/- mice. <i>In vitro</i> experiments using rat aortic smooth muscle cells revealed inhibition of PDGF-BB-induced MCP1/Ccl2 expression upon K_Ca3.1 inhibition, while activation of K_Ca3.1 further enhanced MCP1/Ccl2 expression. Both <i>in vivo</i> and <i>in vitro</i> analyses showed that silencing K_Ca3.1 had no significant effect on the collagen content of plaque. RNAseq analysis of BCA samples from DKO and Apoe^-/- mice revealed PPAR-dependent signaling as a potential key mediator of the reduction in atherosclerosis due to K_Ca3.1 silencing. Overall, this study provides the first genetic evidence that K_Ca3.1 is a critical regulator of atherosclerotic lesion development and composition and provides novel mechanistic insight into the link between K_Ca3.1 and atherosclerosis.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2538864"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12320860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777049","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":"Mechanotransduction mechanisms in human erythrocytes: Fundamental physiology and clinical significance.","authors":"Lennart Kuck, Lars Kaestner, Stéphane Egée, Virgilio L Lew, Michael J Simmonds","doi":"10.1080/19336950.2025.2556105","DOIUrl":"10.1080/19336950.2025.2556105","url":null,"abstract":"<p><p>The hallmarks of mechanosensitive ion channels have been observed for half a century in various cell lines, although their mechanisms and molecular identities remained unknown until recently. Identification of the bona fide mammalian mechanosensory Piezo channels resulted in an explosion of research exploring the translation of mechanical cues into biochemical signals and dynamic cell morphology responses. One of the Piezo isoforms - Piezo1 - is integral in the erythrocyte (red blood cell; RBC) membrane. The exceptional flexibility of RBCs and the absence of intracellular organelles provides a unique mechanical and biochemical environment dictating specific Piezo1-functionality. The Piezo1-endowed capacity of RBCs to sense the mechanical forces acting upon them during their continuous traversal of the circulatory system has solidified a brewing step-change in our fundamental understanding of RBC biology in health and disease; that is, RBCs are not biologically inert but rather capable of complex dynamic cellular signaling. Although several lines of investigation have unearthed various regulatory mechanisms of signaling pathway activation by RBC-Piezo1, these independent studies have not yet been synthesized into a cohesive picture. The aim of the present review is to thus summarize the progress in elucidating how Piezo1 functions in the unique cellular environment of RBCs, challenge classical views of this enucleated cell, and provoke developments for future work.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2556105"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12427448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034825","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":"Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.","authors":"Yuhan Wang, Tingting Zhou, Jiajing Zhao, Hongjun Zhu, Xiaodong Tan, Jiahao Chen, Zhuojun Zhang, Lijuan Shen, Shu Lu","doi":"10.1080/19336950.2025.2519545","DOIUrl":"10.1080/19336950.2025.2519545","url":null,"abstract":"<p><p>Calcium ions play a crucial role in cardiac excitation-contraction (EC) coupling, and disruptions in Ca²⁺ homeostasis are a key factor in the development of dilated cardiomyopathy (DCM). This review aims to systematically analyze how structural and functional remodeling of Ca²⁺-handling proteins drives DCM progression and to evaluate therapeutic strategies targeting these pathways. The movement of intracellular Ca²⁺, which is regulated by transporters like SERCA2a, ryanodine receptor 2 (RYR2), and L-type Ca²⁺ channels, affects the heart's contraction and relaxation. In DCM, both structural and functional changes in the Ca²⁺-handling machinery-including t-tubule remodeling, modifications to RYR2, and dysregulation of SERCA2a and phospholamban (PLN)-disrupt Ca²⁺ cycling, worsening systolic dysfunction and ventricular dilation. For instance, reduced affinity of SERCA2a for Ca²⁺ due to imbalances in the PLN-SERCA2a interaction impairs the heart's ability to reuptake Ca²⁺ during diastole. Meanwhile, abnormalities in RYR2 contribute to arrhythmogenic Ca²⁺ leaks. Targeting these pathways for treatment has two main challenges: too much Ca²⁺ modulation can cause arrhythmias, while insufficient correction may fail to improve heart contractility. Precision interventions demand structurally resolved targets, such as stabilizing RYR2 closed states or enhancing SERCA2a activity via gene therapy, to address DCM's heterogeneous pathophysiology. Emerging strategies leveraging t-tubule restoration or isoform-specific L-type channel modulation show promise in normalizing Ca²⁺ transients and halting adverse remodeling. This review compiles evidence that connects changes in EC coupling components to the progression of DCM and emphasizes the potential benefits of restoring Ca²⁺ balance as a treatment. By integrating molecular insights with clinical phenotypes, structurally informed Ca²⁺-targeted therapies could pave the way for personalized DCM management, balancing efficacy with minimized off-target effects.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2519545"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12184125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310832","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":"Graded activation of mutant K41C-KCNE1:KCNQ1 channel complexes by mefenamic acid.","authors":"Yundi Wang, Magnus Chan, Marc Pourrier, Jodene Eldstrom, David Fedida","doi":"10.1080/19336950.2025.2539494","DOIUrl":"10.1080/19336950.2025.2539494","url":null,"abstract":"<p><p>The <i>I</i>_<i>Ks</i> current formed by the co-assembly of KCNE1 and KCNQ1 plays an important role in cardiac repolarization. Mefenamic acid, an NSAID, is known to enhance <i>I</i>_<i>Ks</i> currents and has in turn been suggested as a therapeutic starting point for the development of compounds for the treatment of long QT syndrome. Our previous examinations of mefenamic acid's action revealed that residue K41 on KCNE1 was critical for mefenamic acid's activating effect on fully KCNE1 saturated, and partially saturated <i>I</i>_<i>Ks</i> channel complexes. The present study extends our previous work by incorporating the K41C-KCNE1 mutation into individual subunits to destabilize local mefenamic acid binding and explore how many of the remaining mefenamic acid-bound WT KCNE1-KCNQ1 subunits are required to support the activating action of the drug. Our results show that the potency of mefenamic acid action is reduced by the presence of K41C-KCNE1 subunits in a graded and stoichiometric, but non-linear manner. Modeling results are consistent with the idea that WT <i>I</i>_<i>Ks</i> subunits, in the presence of mefenamic acid, precede activation of K41C-<i>I</i>_<i>Ks</i> subunits due to their augmented voltage sensor kinetics.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2539494"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12309529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746321","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":"Role of the C-terminal domain in modifying pH-dependent regulation of Ca_v1.4 Ca²⁺ channels.","authors":"Juan de la Rosa Vázquez, Amy Lee","doi":"10.1080/19336950.2025.2473074","DOIUrl":"10.1080/19336950.2025.2473074","url":null,"abstract":"<p><p>In the retina, Ca²⁺ influx through Ca_v1.4 Ca²⁺ channels triggers neurotransmitter release from rod and cone photoreceptors. Changes in extracellular pH modify channel opening, enabling a feedback regulation of photoreceptor output that contributes to the encoding of color and contrast. However, the mechanisms underlying pH-dependent modulation of Ca_v1.4 are poorly understood. Here, we investigated the role of the C-terminal domain (CTD) of Ca_v1.4 in pH-dependent modulation of Ba²⁺ currents (<i>I</i>_<i>Ba</i>) in HEK293T cells transfected with the full length Ca_V1.4 (FL) or variants lacking portions of the CTD due to alternative splicing (Δe47) or a disease-causing mutation (K1591X). While extracellular alkalinization caused an increase in <i>I</i>_<i>Ba</i> for each variant, the magnitude of this increase was significantly diminished (~40-50%) for both CTD variants; K1591X was unique in showing no pH-dependent increase in maximal conductance. Moreover, the auxiliary α₂δ-4 subunit augmented the pH sensitivity of <i>I</i>_<i>Ba</i>, as compared to α₂δ-1 or no α₂δ, for FL and K1591X but not Δe47. We conclude that the CTD and α₂δ-4 are critical determinants of pH-dependent modulation of Ca_v1.4 and may influence the processing of visual information in normal and diseased states of the retina.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2473074"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11934190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671726","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":"The research progress into cellular mechanosensitive ion channels mediating cancer pain.","authors":"Chang Liu, Haiyan Li, Lihua Hang","doi":"10.1080/19336950.2025.2517109","DOIUrl":"10.1080/19336950.2025.2517109","url":null,"abstract":"<p><p>Cellular mechanotransduction refers to the process through which cells perceive mechanical stimuli and subsequently translate them into biochemical signals. Key mechanosensitive ion channels encompass PIEZO, TREK-1, and TRESK. These mechanosensitive ion channels are crucial in regulating specific pathophysiological conditions, including fibrosis, tumor progression, and cellular proliferation and differentiation. Recent research indicates that PIEZO, TREK-1, and TRESK are significant contributors to various types of cancer pain by sensing mechanical stimuli, which subsequently activate internal signaling pathways. Here concentrates on advancements in research concerning PIEZO, TREK-1, and TRESK in cancer pain research, aiming to lay the groundwork for creating new therapeutic drugs that address mechanosensitive ion channels for treating cancer pain.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"19 1","pages":"2517109"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12169045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295429","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":"The role and mechanism of vascular wall cell ion channels in vascular fibrosis remodeling.","authors":"Xiaolin Zhang, Hai Tian, Cheng Xie, Yan Yang, Pengyun Li, Jun Cheng","doi":"10.1080/19336950.2024.2418128","DOIUrl":"10.1080/19336950.2024.2418128","url":null,"abstract":"<p><p>Fibrosis is usually the final pathological state of many chronic inflammatory diseases and may lead to organ malfunction. Excessive deposition of extracellular matrix (ECM) molecules is a characteristic of most fibrotic tissues. The blood vessel wall contains three layers of membrane structure, including the intima, which is composed of endothelial cells; the media, which is composed of smooth muscle cells; and the adventitia, which is formed by the interaction of connective tissue and fibroblasts. The occurrence and progression of vascular remodeling are closely associated with cardiovascular diseases, and vascular remodeling can alter the original structure and function of the blood vessel. Dysregulation of the composition of the extracellular matrix in blood vessels leads to the continuous advancement of vascular stiffening and fibrosis. Vascular fibrosis reaction leads to excessive deposition of the extracellular matrix in the vascular adventitia, reduces vessel compliance, and ultimately alters key aspects of vascular biomechanics. The pathogenesis of fibrosis in the vasculature and strategies for its reversal have become interesting and important challenges. Ion channels are widely expressed in the cardiovascular system; they regulate blood pressure, maintain cardiovascular function homeostasis, and play important roles in ion transport, cell differentiation, proliferation. In blood vessels, different types of ion channels in fibroblasts, smooth muscle cells and endothelial cells may be relevant mediators of the development of fibrosis in organs or tissues. This review discusses the known roles of ion channels in vascular fibrosis remodeling and discusses potential therapeutic targets for regulating remodeling and repair after vascular injury.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2418128"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482288","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":"A phenylalanine at the extracellular side of Kir1.1 facilitates potassium permeation.","authors":"Henry Sackin, Mikheil Nanazashvili","doi":"10.1080/19336950.2023.2294661","DOIUrl":"10.1080/19336950.2023.2294661","url":null,"abstract":"<p><p>The Kir1.1 (ROMK) family of weak inward rectifiers controls K secretion in the renal CCT and K recycling in the renal TALH. A single point mutant of the inward rectifier, F127V-Kir1.1b was used to investigate the K transition between the selectivity filter and the outer mouth of the channel. We hypothesize that normally an aromatic <i>Phe</i> at the external entryway of Kir1.1b facilitates outward K secretion. We tested this by replacing F127-Kir1.1b with a small aliphatic <i>Val</i>. Results indicate that removal of the <i>Phe</i> at 127 suppresses outward currents that normally contribute to K secretion. Results with the F127V mutant could be explained by increased polyamine block and/or a decrease in the avidity of Kir1.1 for K ions near the outer mouth of the channel. The latter is supported by F127V-Kir1.1b having a lower affinity (K_m = 33 mM) for K than wild-type Kir1.1b (K_m = 7 mM) during external K elevation. Conversely, chelation of K with 18-Crown-6 ether reduced K conductance faster in F127V (half-time = 6s) than in wt-Kir1.1b (half-time = 120s), implying that F127V is less hospitable to external K. In other experiments, positive membrane potentials gated the F127V mutant channel closed at physiological levels of external Ca, possibly by electrostatically depleting K adjacent to the membrane, suggesting that the <i>Phe</i> residue is critical for outward K secretion at physiological Ca. We speculate that the avidity of wt-Kir1.1b for external K could result from a cation-Pi interaction between K and the aromatic F127.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2294661"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139111385","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":"A structural atlas of druggable sites on Na_v channels.","authors":"Zhangqiang Li, Qiurong Wu, Nieng Yan","doi":"10.1080/19336950.2023.2287832","DOIUrl":"10.1080/19336950.2023.2287832","url":null,"abstract":"<p><p>Voltage-gated sodium (Na_v) channels govern membrane excitability by initiating and propagating action potentials. Consistent with their physiological significance, dysfunction, or mutations in these channels are associated with various channelopathies. Na_v channels are thereby major targets for various clinical and investigational drugs. In addition, a large number of natural toxins, both small molecules and peptides, can bind to Na_v channels and modulate their functions. Technological breakthrough in cryo-electron microscopy (cryo-EM) has enabled the determination of high-resolution structures of eukaryotic and eventually human Na_v channels, alone or in complex with auxiliary subunits, toxins, and drugs. These studies have not only advanced our comprehension of channel architecture and working mechanisms but also afforded unprecedented clarity to the molecular basis for the binding and mechanism of action (MOA) of prototypical drugs and toxins. In this review, we will provide an overview of the recent advances in structural pharmacology of Na_v channels, encompassing the structural map for ligand binding on Na_v channels. These findings have established a vital groundwork for future drug development.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":"18 1","pages":"2287832"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10732651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464760","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}