Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-10-09DOI: 10.1080/19336950.2024.2402749
Tobias Korn, Ulf-Peter Hansen, Tobias Sebastian Gabriel, Oliver Rauh, Nils Drexler, Indra Schroeder
{"title":"Binding kinetics of quaternary ammonium ions in Kcv potassium channels.","authors":"Tobias Korn, Ulf-Peter Hansen, Tobias Sebastian Gabriel, Oliver Rauh, Nils Drexler, Indra Schroeder","doi":"10.1080/19336950.2024.2402749","DOIUrl":"10.1080/19336950.2024.2402749","url":null,"abstract":"<p><p>Kcv channels from plant viruses represent the autonomous pore module of potassium channels, devoid of any regulatory domains. These small proteins show very reproducible single-channel behavior in planar lipid bilayers. Thus, they are an optimum system for the study of the biophysics of ion transport and gating. Structural models based on homology modeling have been used successfully, but experimental structural data are currently not available. Here we determine the size of the cytosolic pore entrance by studying the blocker kinetics. Blocker binding and dissociation rate constants ranging from 0.01 to 1000 ms<sup>-1</sup> were determined for different quaternary ammonium ions. We found that the cytosolic pore entrance of Kcv<sub>NTS</sub> must be at least 11 Å wide. The results further indicate that the residues controlling a cytosolic gate in one of the Kcv isoforms influence blocker binding/dissociation as well as a second gate even when the cytosolic gate is in the open state. The voltage dependence of the rate constant of blocker release is used to test, which blockers bind to the same binding site.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395703","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}
{"title":"Ion channel-mediated mitochondrial volume regulation and its relationship with mitochondrial dynamics.","authors":"Yujia Zhuang, Wenting Jiang, Zhe Zhao, Wencui Li, Zhiqin Deng, Jianquan Liu","doi":"10.1080/19336950.2024.2335467","DOIUrl":"10.1080/19336950.2024.2335467","url":null,"abstract":"<p><p>The mitochondrion, one of the important cellular organelles, has the major function of generating adenosine triphosphate and plays an important role in maintaining cellular homeostasis, governing signal transduction, regulating membrane potential, controlling programmed cell death and modulating cell proliferation. The dynamic balance of mitochondrial volume is an important factor required for maintaining the structural integrity of the organelle and exerting corresponding functions. Changes in the mitochondrial volume are closely reflected in a series of biological functions and pathological changes. The mitochondrial volume is controlled by the osmotic balance between the cytoplasm and the mitochondrial matrix. Thus, any disruption in the influx of the main ion, potassium, into the cells can disturb the osmotic balance between the cytoplasm and the matrix, leading to water movement between these compartments and subsequent alterations in mitochondrial volume. Recent studies have shown that mitochondrial volume homeostasis is closely implicated in a variety of diseases. In this review, we provide an overview of the main influencing factors and research progress in the field of mitochondrial volume homeostasis.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140308160","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-03-06DOI: 10.1080/19336950.2024.2325032
Phuong Tran Nguyen, Brandon John Harris, Diego Lopez Mateos, Adriana Hernández González, Adam Michael Murray, Vladimir Yarov-Yarovoy
{"title":"Structural modeling of ion channels using AlphaFold2, RoseTTAFold2, and ESMFold.","authors":"Phuong Tran Nguyen, Brandon John Harris, Diego Lopez Mateos, Adriana Hernández González, Adam Michael Murray, Vladimir Yarov-Yarovoy","doi":"10.1080/19336950.2024.2325032","DOIUrl":"10.1080/19336950.2024.2325032","url":null,"abstract":"<p><p>Ion channels play key roles in human physiology and are important targets in drug discovery. The atomic-scale structures of ion channels provide invaluable insights into a fundamental understanding of the molecular mechanisms of channel gating and modulation. Recent breakthroughs in deep learning-based computational methods, such as AlphaFold, RoseTTAFold, and ESMFold have transformed research in protein structure prediction and design. We review the application of AlphaFold, RoseTTAFold, and ESMFold to structural modeling of ion channels using representative voltage-gated ion channels, including human voltage-gated sodium (Na<sub>V</sub>) channel - Na<sub>V</sub>1.8, human voltage-gated calcium (Ca<sub>V</sub>) channel - Ca<sub>V</sub>1.1, and human voltage-gated potassium (K<sub>V</sub>) channel - K<sub>V</sub>1.3. We compared AlphaFold, RoseTTAFold, and ESMFold structural models of Na<sub>V</sub>1.8, Ca<sub>V</sub>1.1, and K<sub>V</sub>1.3 with corresponding cryo-EM structures to assess details of their similarities and differences. Our findings shed light on the strengths and limitations of the current state-of-the-art deep learning-based computational methods for modeling ion channel structures, offering valuable insights to guide their future applications for ion channel research.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041077","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":"Clinical and genetic characteristics of myotonia congenita in Chinese population.","authors":"Yuting He, Yusen Qiu, Ying Xiong, Yu Shen, Kaiyan Jiang, Hancun Yi, Pengcheng Huang, Yu Zhu, Min Zhu, Meihong Zhou, Daojun Hong, Dandan Tan","doi":"10.1080/19336950.2024.2349823","DOIUrl":"10.1080/19336950.2024.2349823","url":null,"abstract":"<p><p>Myotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892497","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-05-19DOI: 10.1080/19336950.2024.2355150
Rua'a Al-Aqtash, Daniel M Collier
{"title":"Ionotropic purinergic receptor 7 (P2X7) channel structure and pharmacology provides insight regarding non-nucleotide agonism.","authors":"Rua'a Al-Aqtash, Daniel M Collier","doi":"10.1080/19336950.2024.2355150","DOIUrl":"10.1080/19336950.2024.2355150","url":null,"abstract":"<p><p>P2X7 is a member of the Ionotropic Purinergic Receptor (P2X) family. The P2X family of receptors is composed of seven (P2X1-7), ligand-gated, nonselective cation channels. Changes in P2X expression have been reported in multiple disease models. P2Xs have large complex extracellular domains that function as receptors for a variety of ligands, including endogenous and synthetic agonists and antagonists. ATP is the canonical agonist. ATP affinity ranges from nanomolar to micromolar for most P2XRs, but P2X7 has uniquely poor ATP affinity. In many physiological settings, it may be difficult to achieve the millimolar extracellular ATP concentrations needed for P2X7 channel activation; however, channel function is implicated in pain sensation, immune cell function, cardiovascular disease, cancer, and osteoporosis. Multiple high-resolution P2X7 structures have been solved in apo-, ATP-, and antagonist-bound states. P2X7 structural data reveal distinct allosteric and orthosteric antagonist-binding sites. Both allosteric and orthosteric P2X7 antagonists are well documented to inhibit ATP-evoked channel current. However, a growing body of evidence supports P2X7 activation by non-nucleotide agonists, including extracellular histone proteins and human cathelicidin-derived peptides (LL-37). Interestingly, P2X7 non-nucleotide agonism is not inhibited by allosteric antagonists, but is inhibited by orthosteric antagonists. Herein, we review P2X7 function with a focus on the efficacy of available pharmacology on P2X7 channel current activation by non-nucleotide agonists in effort to understand agonist/antagonist efficacy, and consider the impact of these data on the current understanding of P2X7 in physiology and disease given these limitations of P2X7-selective antagonists and incomplete knockout mouse models.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066102","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-02-14DOI: 10.1080/19336950.2024.2313323
Raúl Sánchez-Hernández, Miguel Benítez-Angeles, Ana M Hernández-Vega, Tamara Rosenbaum
{"title":"Recent advances on the structure and the function relationships of the TRPV4 ion channel.","authors":"Raúl Sánchez-Hernández, Miguel Benítez-Angeles, Ana M Hernández-Vega, Tamara Rosenbaum","doi":"10.1080/19336950.2024.2313323","DOIUrl":"10.1080/19336950.2024.2313323","url":null,"abstract":"<p><p>The members of the superfamily of Transient Receptor Potential (TRP) ion channels are physiologically important molecules that have been studied for many years and are still being intensively researched. Among the vanilloid TRP subfamily, the TRPV4 ion channel is an interesting protein due to its involvement in several essential physiological processes and in the development of various diseases. As in other proteins, changes in its function that lead to the development of pathological states, have been closely associated with modification of its regulation by different molecules, but also by the appearance of mutations which affect the structure and gating of the channel. In the last few years, some structures for the TRPV4 channel have been solved. Due to the importance of this protein in physiology, here we discuss the recent progress in determining the structure of the TRPV4 channel, which has been achieved in three species of animals (<i>Xenopus tropicalis</i>, <i>Mus musculus</i>, and <i>Homo sapiens</i>), highlighting conserved features as well as key differences among them and emphasizing the binding sites for some ligands that play crucial roles in its regulation.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139736869","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-08-22DOI: 10.1080/19336950.2024.2393088
Dingchang He, Xin Liu, Wenhao Yang, Taiyuan Guan, Guoyou Wang
{"title":"The role of mechanosensitive ion channel Piezo1 in knee osteoarthritis inflammation.","authors":"Dingchang He, Xin Liu, Wenhao Yang, Taiyuan Guan, Guoyou Wang","doi":"10.1080/19336950.2024.2393088","DOIUrl":"10.1080/19336950.2024.2393088","url":null,"abstract":"<p><p>Mechanosensitive ion channel Piezo1 is known to mediate a variety of inflammatory pathways and is also involved in the occurrence and development of many orthopedic diseases. Although its role in the inflammatory mechanism of knee osteoarthritis (KOA) has been reported, a systematic explanation is yet to be seen. This article aims to summarize the role of inflammatory responses in the pathogenesis of KOA and elucidate the mechanism by which the Piezo1-mediated inflammatory response contributes to the pathogenesis of KOA, providing a theoretical basis for the prevention and treatment of knee osteoarthritis. The results indicate that in the mechanism leading to knee osteoarthritis, Piezo1 can mediate the inflammatory response through chondrocytes and synovial cells, participating in the pathological progression of KOA. Piezo1 has the potential to become a new target for the prevention and treatment of this disease. Additionally, as pain is one of the most severe manifestations in KOA patients, the inflammatory response mediated by Piezo1, which causes the release of inflammatory mediators and pro-inflammatory factors leading to pain, can be further explored.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11346567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142019719","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-03-15DOI: 10.1080/19336950.2024.2327708
Bruce L Patton, Phillip Zhu, Assmaa ElSheikh, Camden M Driggers, Show-Ling Shyng
{"title":"Dynamic duo: Kir6 and SUR in K<sub>ATP</sub> channel structure and function.","authors":"Bruce L Patton, Phillip Zhu, Assmaa ElSheikh, Camden M Driggers, Show-Ling Shyng","doi":"10.1080/19336950.2024.2327708","DOIUrl":"10.1080/19336950.2024.2327708","url":null,"abstract":"<p><p>K<sub>ATP</sub> channels are ligand-gated potassium channels that couple cellular energetics with membrane potential to regulate cell activity. Each channel is an eight subunit complex comprising four central pore-forming Kir6 inward rectifier potassium channel subunits surrounded by four regulatory subunits known as the sulfonylurea receptor, SUR, which confer homeostatic metabolic control of K<sub>ATP</sub> gating. SUR is an ATP binding cassette (ABC) protein family homolog that lacks membrane transport activity but is essential for K<sub>ATP</sub> expression and function. For more than four decades, understanding the structure-function relationship of Kir6 and SUR has remained a central objective of clinical significance. Here, we review progress in correlating the wealth of functional data in the literature with recent K<sub>ATP</sub> cryoEM structures.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140137551","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2023-12-06DOI: 10.1080/19336950.2023.2289256
Mohammad-Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Philip R Effraim, Sulayman D Dib-Hajj, Stephen G Waxman
{"title":"Sodium currents in naïve mouse dorsal root ganglion neurons: No major differences between sexes.","authors":"Mohammad-Reza Ghovanloo, Sidharth Tyagi, Peng Zhao, Philip R Effraim, Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1080/19336950.2023.2289256","DOIUrl":"10.1080/19336950.2023.2289256","url":null,"abstract":"<p><p>Sexual dimorphism has been reported in multiple pre-clinical and clinical studies on pain. Previous investigations have suggested that in at least some states, rodent dorsal root ganglion (DRG) neurons display differential sex-dependent regulation and expression patterns of various proteins involved in the pain pathway. Our goal in this study was to determine whether sexual dimorphism in the biophysical properties of voltage-gated sodium (Nav) currents contributes to these observations in rodents. We recently developed a novel method that enables high-throughput, unbiased, and automated functional analysis of native rodent sensory neurons from naïve WT mice profiled simultaneously under uniform experimental conditions. In our previous study, we performed all experiments in neurons that were obtained from mixed populations of adult males or females, which were combined into single (combined male/female) data sets. Here, we have re-analyzed the same previously published data and segregated the cells based on sex. Although the number of cells in our previously published data sets were uneven for some comparisons, our results do not show sex-dependent differences in the biophysical properties of Nav currents in these native DRG neurons.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138500362","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}
Channels (Austin, Tex.)Pub Date : 2024-12-01Epub Date: 2024-09-20DOI: 10.1080/19336950.2024.2398565
Kangjun Li, Vaishali Satpute Janve, Jerod Denton
{"title":"Characterization of four structurally diverse inhibitors of SUR2-containing K<sub>ATP</sub> channels.","authors":"Kangjun Li, Vaishali Satpute Janve, Jerod Denton","doi":"10.1080/19336950.2024.2398565","DOIUrl":"10.1080/19336950.2024.2398565","url":null,"abstract":"<p><p>Vascular smooth muscle ATP-sensitive potassium (K<sub>ATP</sub>) channels play critical roles in modulating vascular tone and thus represent important drug targets for diverse cardiovascular pathologies. Despite extensive research efforts spanning several decades, the search for selective inhibitors that can discriminate between vascular K<sub>ATP</sub> (i.e. Kir6.1/SUR2B) and pancreatic and brain K<sub>ATP</sub> (i.e. Kir6.2/SUR1) channels has, until recently, been unsuccessful. Our group therefore carried out a high-throughput screen of chemically diverse compounds with the goal of discovering specific Kir6.1/SUR2B inhibitors. This screen identified several novel classes of Kir6.1/SUR2B inhibitors, including the first potent (IC<sub>50</sub> ~100 nM) and selective inhibitor published to date, termed VU0542270. Here, we expand on this work by disclosing the identity and pharmacological properties of four additional Kir6.1/SUR2B inhibitors that are structurally unrelated to Kir to VU0542270. These inhibitors, named VU0212387, VU0543336, VU0605768, and VU0544086, inhibit Kir6.1/SUR2B with IC<sub>50</sub> values ranging from approximately 100 nM to 1 µM and exhibit no apparent inhibitory activity toward Kir6.2/SUR1. Functional analysis of heterologously expressed subunit combinations of Kir6.1, Kir6.2, SUR1, SUR2A, and SUR2B and demonstrated that all four inhibitors act on SUR2 to induce channel inhibition. Interestingly, VU0543336 and VU0212387 exhibit paradoxical stimulatory effects on Kir6.2/SUR1 at higher doses. This study broadens our understanding of K<sub>ATP</sub> channel pharmacology, generally, and reveals novel chemical matter for the development of Kir6.1/SUR2-selective drugs, specifically.</p>","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142302304","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}