Korean Journal of Physiology & Pharmacology最新文献

{"title":"Roles of metabotropic glutamate receptor 5 in low [Mg²⁺]_o-induced interictal epileptiform activity in rat hippocampal slices.","authors":"Ji Seon Yang, Hyun-Jong Jang, Ki-Wug Sung, Duck-Joo Rhie, Shin Hee Yoon","doi":"10.4196/kjpp.2024.28.5.413","DOIUrl":"10.4196/kjpp.2024.28.5.413","url":null,"abstract":"<p><p>Group I metabotropic glutamate receptors (mGluRs) modulate postsynaptic neuronal excitability and epileptogenesis. We investigated roles of group I mGluRs on low extracellular Mg²⁺ concentration ([Mg²⁺]_o)-induced epileptiform activity and neuronal cell death in the CA1 regions of isolated rat hippocampal slices without the entorhinal cortex using extracellular recording and propidium iodide staining. Exposure to Mg²⁺-free artificial cerebrospinal fluid can induce interictal epileptiform activity in the CA1 regions of rat hippocampal slices. MPEP, a mGluR 5 antagonist, significantly inhibited the spike firing of the low [Mg²⁺]_o-induced epileptiform activity, whereas LY367385, a mGluR1 antagonist, did not. DHPG, a group 1 mGluR agonist, significantly increased the spike firing of the epileptiform activity. U73122, a PLC inhibitor, inhibited the spike firing. Thapsigargin, an ER Ca²⁺-ATPase antagonist, significantly inhibited the spike firing and amplitude of the epileptiform activity. Both the IP₃ receptor antagonist 2-APB and the ryanodine receptor antagonist dantrolene significantly inhibited the spike firing. The PKC inhibitors such as chelerythrine and GF109203X, significantly increased the spike firing. Flufenamic acid, a relatively specific TRPC 1, 4, 5 channel antagonist, significantly inhibited the spike firing, whereas SKF96365, a relatively non-specific TRPC channel antagonist, did not. MPEP significantly decreased low [Mg²⁺]_o DMEM-induced neuronal cell death in the CA1 regions, but LY367385 did not. We suggest that mGluR 5 is involved in low [Mg²⁺]_oinduced interictal epileptiform activity in the CA1 regions of rat hippocampal slices through PLC, release of Ca²⁺ from intracellular stores and PKC and TRPC channels, which could be involved in neuronal cell death.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"413-422"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network pharmacology prediction to discover the potential pharmacological action mechanism of Rhizoma Dioscoreae for liver regeneration.","authors":"Wei Liu, Wenyu Wang, Chenglong Tian, Ming-Zhong Sun, Shuqing Liu, Qinlong Liu","doi":"10.4196/kjpp.2024.28.5.479","DOIUrl":"10.4196/kjpp.2024.28.5.479","url":null,"abstract":"<p><p>Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and <i>in vivo</i> experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"479-491"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Specific kinesin and dynein molecules participate in the unconventional protein secretion of transmembrane proteins.","authors":"Sung Ho Eun, Shin Hye Noh, Min Goo Lee","doi":"10.4196/kjpp.2024.28.5.435","DOIUrl":"10.4196/kjpp.2024.28.5.435","url":null,"abstract":"<p><p>Secretory proteins, including plasma membrane proteins, are generally known to be transported to the plasma membrane through the endoplasmic reticulum- to-Golgi pathway. However, recent studies have revealed that several plasma membrane proteins and cytosolic proteins lacking a signal peptide are released via an unconventional protein secretion (UcPS) route, bypassing the Golgi during their journey to the cell surface. For instance, transmembrane proteins such as the misfolded cystic fibrosis transmembrane conductance regulator (CFTR) protein and the Spike protein of coronaviruses have been observed to reach the cell surface through a UcPS pathway under cell stress conditions. Nevertheless, the precise mechanisms of the UcPS pathway, particularly the molecular machineries involving cytosolic motor proteins, remain largely unknown. In this study, we identified specific kinesins, namely KIF1A and KIF5A, along with cytoplasmic dynein, as critical players in the unconventional trafficking of CFTR and the SARS-CoV-2 Spike protein. Gene silencing results demonstrated that knockdown of KIF1A, KIF5A, and the KIF-associated adaptor protein SKIP, FYCO1 significantly reduced the UcPS of △F508-CFTR. Moreover, gene silencing of these motor proteins impeded the UcPS of the SARS-CoV-2 Spike protein. However, the same gene silencing did not affect the conventional Golgimediated cell surface trafficking of wild-type CFTR and Spike protein. These findings suggest that specific motor proteins, distinct from those involved in conventional trafficking, are implicated in the stress-induced UcPS of transmembrane proteins.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"435-447"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transformative impact of large language models on medical writing and publishing: current applications, challenges and future directions.","authors":"Sangzin Ahn","doi":"10.4196/kjpp.2024.28.5.393","DOIUrl":"10.4196/kjpp.2024.28.5.393","url":null,"abstract":"<p><p>Large language models (LLMs) are rapidly transforming medical writing and publishing. This review article focuses on experimental evidence to provide a comprehensive overview of the current applications, challenges, and future implications of LLMs in various stages of academic research and publishing process. Global surveys reveal a high prevalence of LLM usage in scientific writing, with both potential benefits and challenges associated with its adoption. LLMs have been successfully applied in literature search, research design, writing assistance, quality assessment, citation generation, and data analysis. LLMs have also been used in peer review and publication processes, including manuscript screening, generating review comments, and identifying potential biases. To ensure the integrity and quality of scholarly work in the era of LLM-assisted research, responsible artificial intelligence (AI) use is crucial. Researchers should prioritize verifying the accuracy and reliability of AI-generated content, maintain transparency in the use of LLMs, and develop collaborative human-AI workflows. Reviewers should focus on higher-order reviewing skills and be aware of the potential use of LLMs in manuscripts. Editorial offices should develop clear policies and guidelines on AI use and foster open dialogue within the academic community. Future directions include addressing the limitations and biases of current LLMs, exploring innovative applications, and continuously updating policies and practices in response to technological advancements. Collaborative efforts among stakeholders are necessary to harness the transformative potential of LLMs while maintaining the integrity of medical writing and publishing.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"393-401"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of a synthetic phage-displayed nanobody library.","authors":"Minju Kim, Xuelian Bai, Hyewon Im, Jisoo Yang, Youngju Kim, Minjoo Mj Kim, Yeonji Oh, Yuna Jeon, Hayoung Kwon, Seunghyun Lee, Chang-Han Lee","doi":"10.4196/kjpp.2024.28.5.457","DOIUrl":"10.4196/kjpp.2024.28.5.457","url":null,"abstract":"<p><p>Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"457-467"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Cornuside inhibits glucose-induced proliferation and inflammatory response of mesangial cells.","authors":"Xiaoxin Li, Lizhong Guo, Fei Huang, Wei Xu, Guiqing Peng","doi":"10.4196/kjpp.2024.28.5.493","DOIUrl":"10.4196/kjpp.2024.28.5.493","url":null,"abstract":"","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"493"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling flavivirus pathogenesis: from bulk to single-cell RNA-sequencing strategies.","authors":"Doyeong Kim, Seonghun Jeong, Sang-Min Park","doi":"10.4196/kjpp.2024.28.5.403","DOIUrl":"10.4196/kjpp.2024.28.5.403","url":null,"abstract":"<p><p>The global spread of flaviviruses has triggered major outbreaks worldwide, significantly impacting public health, society, and economies. This has intensified research efforts to understand how flaviviruses interact with their hosts and manipulate the immune system, underscoring the need for advanced research tools. RNA-sequencing (RNA-seq) technologies have revolutionized our understanding of flavivirus infections by offering transcriptome analysis to dissect the intricate dynamics of virus-host interactions. Bulk RNA-seq provides a macroscopic overview of gene expression changes in virus-infected cells, offering insights into infection mechanisms and host responses at the molecular level. Single-cell RNA sequencing (scRNAseq) provides unprecedented resolution by analyzing individual infected cells, revealing remarkable cellular heterogeneity within the host response. A particularly innovative advancement, virus-inclusive single-cell RNA sequencing (viscRNA-seq), addresses the challenges posed by non-polyadenylated flavivirus genomes, unveiling intricate details of virus-host interactions. In this review, we discuss the contributions of bulk RNA-seq, scRNA-seq, and viscRNA-seq to the field, exploring their implications in cell line experiments and studies on patients infected with various flavivirus species. Comprehensive transcriptome analyses from RNA-seq technologies are pivotal in accelerating the development of effective diagnostics and therapeutics, paving the way for innovative treatments and enhancing our preparedness for future outbreaks.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 5","pages":"403-411"},"PeriodicalIF":1.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11362000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vinpocetine, a phosphodiesterase 1 inhibitor, mitigates atopic dermatitis-like skin inflammation.","authors":"Yeon Jin Lee, Jin Yong Song, Su Hyun Lee, Yubin Lee, Kyu Teak Hwang, Ji-Yun Lee","doi":"10.4196/kjpp.2024.28.4.303","DOIUrl":"10.4196/kjpp.2024.28.4.303","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is the most common inflammatory pruritic skin disease worldwide, characterized by the infiltration of multiple pathogenic T lymphocytes and histological symptoms such as epidermal and dermal thickening. This study aims to investigate the effect of vinpocetine (Vinp; a phosphodiesterase 1 inhibitor) on a 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like model. DNCB (1%) was administered on day 1 in the AD model. Subsequently, from day 14 onward, mice in each group (Vinp-treated groups: 1 mg/kg and 2 mg/kg and dexamethasone- treated group: 2 mg/kg) were administered 100 µl of a specific drug daily, whereas 0.2% DNCB was administered every other day for 30 min over 14 days. The Vinp-treated groups showed improved Eczema Area and Severity Index scores and trans-epidermal water loss, indicating the efficacy of Vinp in improving AD and enhancing skin barrier function. Histological analysis further confirmed the reduction in hyperplasia of the epidermis and the infiltration of inflammatory cells, including macrophages, eosinophils, and mast cells, with Vinp treatment. Moreover, Vinp reduced serum concentrations of IgE, interleukin (IL)-6, IL-13, and monocyte chemotactic protein-1. The mRNA levels of IL-1β, IL-6, Thymic stromal lymphopoietin, and transforming growth factor-beta (TGF-β) were reduced by Vinp treatment. Reduction of TGF-β protein by Vinp in skin tissue was also observed. Collectively, our results underscore the effectiveness of Vinp in mitigating DNCB-induced AD by modulating the expression of various biomarkers. Consequently, Vinp is a promising therapeutic candidate for treating AD.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 4","pages":"303-312"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygonatum sibiricum component liquiritigenin restrains breast cancer cell invasion and migration by inhibiting HSP90 and chaperone-mediated autophagy.","authors":"Suli Xu, Zhao Ma, Lihua Xing, Weiqing Cheng","doi":"10.4196/kjpp.2024.28.4.379","DOIUrl":"10.4196/kjpp.2024.28.4.379","url":null,"abstract":"<p><p>Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 4","pages":"379-387"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Requirement of β subunit for the reduced voltage-gated Na⁺ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of <i>SCN5A</i>.","authors":"Na Kyeong Park, Seong Woo Choi, Soon-Jung Park, JooHan Woo, Hyun Jong Kim, Woo Kyung Kim, Sung-Hwan Moon, Hun-Jun Park, Sung Joon Kim","doi":"10.4196/kjpp.2024.28.4.313","DOIUrl":"10.4196/kjpp.2024.28.4.313","url":null,"abstract":"<p><p>Mutations within the <i>SCN5A</i> gene, which encodes the α-subunit 5 (Na_V1.5) of the voltage-gated Na⁺ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within <i>SCN5A</i> in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of <i>SCN5A</i> mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the Na_V1.5 current (I_Na) in HEK293 cells transfected with the wild-type and mutant <i>SCN5A</i> with or without <i>SCN1B</i> co-expression. The amplitude of I_Na was not altered in mutant <i>SCN5A</i> (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of <i>SCN1B</i> with p.A385T/R504T revealed significant reduction of I_Na and slower recovery from inactivation, consistent with the loss-of-function in Na⁺ channels. The <i>SCN1B</i> dependent reduction of I_Na was also observed in a single mutation p.R504T, but p.A385T co-expressed with <i>SCN1B</i> showed no reduction. In contrast, the slower recovery from inactivation with <i>SCN1B</i> was observed in A385T while not in R504T. The expression of <i>SCN1B</i> is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of Na_V1.5, respectively.</p>","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"28 4","pages":"313-322"},"PeriodicalIF":1.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141460718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}