Current Research in Structural Biology最新文献

{"title":"The structural basis of the G protein–coupled receptor and ion channel axis","authors":"Yulin Luo ,&nbsp;Liping Sun ,&nbsp;Yao Peng","doi":"10.1016/j.crstbi.2025.100165","DOIUrl":"10.1016/j.crstbi.2025.100165","url":null,"abstract":"<div><div>Sensory neurons play an essential role in recognizing and responding to detrimental, irritating, and inflammatory stimuli from our surroundings, such as pain, itch, cough, and neurogenic inflammation. The transduction of these physiological signals is chiefly mediated by G protein-coupled receptors (GPCRs) and ion channels. The binding of ligands to GPCRs triggers a signaling cascade, recruiting G proteins or β-arrestins, which subsequently interact with ion channels (e.g., GIRK and TRP channels). This interaction leads to the sensitization and activation of these channels, initiating the neuron's protective mechanisms. This review delves into the complex interplay between GPCRs and ion channels that underpin these physiological processes, with a particular focus on the role of structural biology in enhancing our comprehension. Through unraveling the intricacies of the GPCR-ion channel axis, we aim to shed light on the sophisticated intermolecular dynamics within these pivotal membrane protein families, ultimately guiding the development of precise therapeutic interventions.</div></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"9 ","pages":"Article 100165"},"PeriodicalIF":2.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471490","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":"AI-based quality assessment methods for protein structure models from cryo-EM","authors":"Han Zhu ,&nbsp;Genki Terashi ,&nbsp;Farhanaz Farheen ,&nbsp;Tsukasa Nakamura ,&nbsp;Daisuke Kihara","doi":"10.1016/j.crstbi.2025.100164","DOIUrl":"10.1016/j.crstbi.2025.100164","url":null,"abstract":"<div><div>Cryogenic electron microscopy (cryo-EM) has revolutionized structural biology, with an increasing number of structures being determined by cryo-EM each year, many at higher resolutions. However, challenges remain in accurately interpreting cryo-EM maps. Inaccuracies can arise in regions of locally low resolution, where manual model building is more prone to errors. Validation scores for structure models have been developed to assess both the compatibility between map density and the structure, as well as the geometric and stereochemical properties of protein models. Recent advancements have introduced artificial intelligence (AI) into this field. These emerging AI-driven tools offer unique capabilities in the validation and refinement of cryo-EM-derived protein atomic models, potentially leading to more accurate protein structures and deeper insights into complex biological systems.</div></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"9 ","pages":"Article 100164"},"PeriodicalIF":2.7,"publicationDate":"2025-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143193904","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":"An easy-to-use three-dimensional protein-structure-prediction online platform \"DPL3D\" based on deep learning algorithms","authors":"Yunlong Gao ,&nbsp;He Wang ,&nbsp;Jiapeng Zhou ,&nbsp;Yan Yang","doi":"10.1016/j.crstbi.2024.100163","DOIUrl":"10.1016/j.crstbi.2024.100163","url":null,"abstract":"<div><div>The change in the three-dimensional (3D) structure of a protein can affect its own function or interaction with other protein(s), which may lead to disease(s). Gene mutations, especially missense mutations, are the main cause of changes in protein structure. Due to the lack of protein crystal structure data, about three-quarters of human mutant proteins cannot be predicted or accurately predicted, and the pathogenicity of missense mutations can only be indirectly evaluated by evolutionary conservation. Recently, many computational methods have been developed to predict protein 3D structures with accuracy comparable to experiments. This progress enables the information of structural biology to be further utilized by clinicians. Thus, we developed a user-friendly platform named DPL3D (<span><span>http://nsbio.tech:3000</span><svg><path></path></svg></span>) which can predict and visualize the 3D structure of mutant proteins. The crystal structure and other information of proteins were downloaded together with the software including AlphaFold 2, RoseTTAFold, RoseTTAFold All-Atom, and trRosettaX-Single. We implemented a query module for 210,180 molecular structures, including 52,248 human proteins. Visualization of protein two-dimensional (2D) and 3D structure prediction can be generated via LiteMol automatically or manually and interactively. This platform will allow users to easily and quickly retrieve large-scale structural information for biological discovery.</div></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"9 ","pages":"Article 100163"},"PeriodicalIF":2.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045823","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":"In silico approaches for developing sesquiterpene derivatives as antagonists of human nicotinic acetylcholine receptors (nAChRs) for nicotine addiction treatment","authors":"Taufik Muhammad Fakih ,&nbsp;Aden Dhana Rizkita ,&nbsp;Sintia Ayu Dewi ,&nbsp;Muchtaridi Muchtaridi","doi":"10.1016/j.crstbi.2024.100162","DOIUrl":"10.1016/j.crstbi.2024.100162","url":null,"abstract":"<div><div>Cinnamomum, a genus within the Lauraceae family, has gained global recognition due to its wide-ranging utility. Extensive research has been dedicated to exploring its phytochemical composition and pharmacological effects. Notably, the uniqueness of Cinnamomum lies in its terpenoid content, characterized by distinctive structures and significant biological implications. An intriguing discovery is that sesquiterpene compounds originating from Cinnamomum possess the capacity to function as antagonists for human nicotinic acetylcholine receptors (nAChRs), specifically the nAChRÿ3 subtype, rendering them potential candidates for nicotine replacement therapy (NRT) to aid active smokers. This investigation employed molecular docking and molecular dynamics simulations to assess the inhibitory effects of these compounds on nAChRÿ3. Among the 55 compounds examined, Dihydroxyeudesmene, Gibberodione, and Germacrene-E exhibited the highest binding affinities. These compounds demonstrated robust interactions with the nAChRÿ3 receptor, as evidenced by elevated molecular mechanics general surface area (MM/GBSA) values (ΔG Bind = Dihydroxyeudesmene: −36.45 kcal/mol, Gibberodione: −36.51 kcal/mol, and Germacrene-E: −36.51 kcal/mol). Molecular dynamics simulations further confirmed the stability of these three compounds, indicating their potential to effectively compete with native ligands. However, comprehensive in vitro, in vivo, and clinical investigations are imperative to ascertain the efficacy of these promising therapeutic candidates.</div></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"9 ","pages":"Article 100162"},"PeriodicalIF":2.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045827","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 structural modeling and physical characteristics of anti-breast cancer drugs via some novel topological descriptors and regression models","authors":"Summeira Meharban ,&nbsp;Asad Ullah ,&nbsp;Shahid Zaman ,&nbsp;Anila Hamraz ,&nbsp;Abdul Razaq","doi":"10.1016/j.crstbi.2024.100134","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100134","url":null,"abstract":"<div><p>Research is continuously being pursued to treat cancer patients and prevent the disease by developing new medicines. However, experimental drug design and development is a costly, time-consuming, and challenging process. Alternatively, computational and mathematical techniques play an important role in optimally achieving this goal. Among these mathematical techniques, topological indices (TIs) have many applications in the drugs used for the treatment of breast cancer. TIs can be utilized to forecast the effectiveness of drugs by providing molecular structure information and related properties of the drugs. In addition, these can assist in the design and discovery of new drugs by providing insights into the structure-property/structure-activity relationships. In this article, a Quantitative Structure Property Relationship (QSPR) analysis is carried out using some novel degree-based molecular descriptors and regression models to predict various properties (such as boiling point, melting point, enthalpy, flashpoint, molar refraction, molar volume, and polarizability) of 14 drugs used for the breast cancer treatment. The molecular structures of these drugs are topologically modeled through vertex and edge partitioning techniques of graph theory, and then linear regression models are developed to correlate the computed values with the experimental properties of the drugs to investigate the performance of TIs in predicting these properties. The results confirmed the potential of the considered topological indices as a tool for drug discovery and design in the field of breast cancer treatment.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100134"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000114/pdfft?md5=4e0b564e56e1dd72c10d1bc8f75eba85&pid=1-s2.0-S2665928X24000114-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140135141","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":"Computational insights into the circular permutation roles on ConA binding and structural stability","authors":"Vinicius J.S. Osterne ,&nbsp;Vanir R. Pinto-Junior ,&nbsp;Messias V. Oliveira ,&nbsp;Kyria S. Nascimento ,&nbsp;Els J.M. Van Damme ,&nbsp;Benildo S. Cavada","doi":"10.1016/j.crstbi.2024.100140","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100140","url":null,"abstract":"<div><p>The mechanisms behind Concanavalin A (ConA) circular permutation have been under investigation since 1985. Although a vast amount of information is available about this lectin and its applications, the exact purpose of its processing remains unclear. To shed light on this, this study employed computer simulations to compare the unprocessed ProConA with the mature ConA. This approach aimed to reveal the importance of the post-translational modifications, especially how they affect the lectin stability and carbohydrate-binding properties. To achieve these goals, we conducted 200 ns molecular dynamics simulations and trajectory analyses on the monomeric forms of ProConA and ConA (both unbound and in complex with D-mannose and the GlcNAc2Man9 N-glycan), as well as on their oligomeric forms. Our findings reveal significant stability differences between ProConA and ConA at both the monomeric and tetrameric levels, with ProConA exhibiting consistently lower stability parameters compared to ConA. In terms of carbohydrate binding properties, however, both lectins showed remarkable similarities in their interaction profiles, contact numbers, and binding free energies with D-mannose and the high-mannose <em>N</em>-glycan. Overall, our results suggest that the processing of ProConA significantly enhances the stability of the mature lectin, especially in maintaining the tetrameric oligomer, without substantially affecting its carbohydrate-binding properties.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100140"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000175/pdfft?md5=b06094ed529fd6dbc276a5c6062ee665&pid=1-s2.0-S2665928X24000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290612","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":"Specific binding of G-quadruplex in SARS-CoV-2 RNA by RHAU peptide","authors":"Le Tuan Anh Nguyen ,&nbsp;Thao Thu Thi Nguyen ,&nbsp;Dung Thanh Dang","doi":"10.1016/j.crstbi.2024.100126","DOIUrl":"10.1016/j.crstbi.2024.100126","url":null,"abstract":"<div><p>G-quadruplexes (G4s) are reported to present on the SARS-CoV-2 RNA genome and control various viral activities. Specific ligands targeting those viral nucleic acid structures could be investigated as promising detection methods or antiviral reagents to suppress this menacing virus. Herein, we demonstrate the binding between a G4 structure in the RNA of SARS-CoV-2 and a fluorescent probe created by fusing a parallel-G4 specific RHAU53 and a cyan fluorescent protein. The specific binding of G4 in SARS-CoV-2 by RHAU peptide was easily detected under the fluorescence spectrometer. The drawbacks of this approach and potential solutions are also discussed.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100126"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000035/pdfft?md5=36e9958a61277baeaf9b9c540a395f47&pid=1-s2.0-S2665928X24000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139393094","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 EGFR allosteric site with marine-natural products of Clathria Sp.: A computational approach","authors":"Nurisyah ,&nbsp;Dwi Syah Fitra Ramadhan ,&nbsp;Ratnasari Dewi ,&nbsp;Asyhari asikin ,&nbsp;Dwi Rachmawaty Daswi ,&nbsp;Adriyani adam ,&nbsp;Chaerunnimah ,&nbsp;Sunarto ,&nbsp;Rafika ,&nbsp;Artati ,&nbsp;Taufik Muhammad Fakih","doi":"10.1016/j.crstbi.2024.100125","DOIUrl":"10.1016/j.crstbi.2024.100125","url":null,"abstract":"<div><p>The EGFR-C797S resistance mutation to third-generation drugs has been overcome by fourth-generation inhibitors, allosteric inhibitors, namely EAI045 and has reached phase 3 clinical trials, so the Allosteric Site is currently an attractive target for development. In this study, researchers are interested in knowing the activity of metabolite compounds from marine natural ingredients Clathria Sp. against the Allosteric Site of EGFR computationally. The methods used include molecular docking using Autodock4 software and Molecular Dynamics simulation performed using GROMACS software. The research began with the preparation of metabolite samples from Clathria Sp. through the KnapSack database site and the preparation of EGFR receptors that have been complexed with allosteric inhibitors, namely proteins with PDB code 5D41. Each compound was docked to the Allosteric Site of the natural ligand and then molecular dynamics simulations were performed on the compound with the best docking energy compared to the natural ligand. From the docking results, the Clathrin_A compound showed the lowest binding energy compared to other metabolites, and the value was close to the natural ligand. Then from the molecular dynamics results, the clathrin_A compound shows good stability and resembles the natural ligand, which is analyzed through RMSD, RMSF, SASA, Rg, and PCA, and shows the binding free energy from MMPBSA analysis which is close to the natural ligand. It can be concluded, Clathrin_A compound has potential as an allosteric inhibitor.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100125"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000023/pdfft?md5=768e67815f45351208f3bea606293ab9&pid=1-s2.0-S2665928X24000023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139394087","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":"Identification of cholinesterases inhibitors from flavonoids derivatives for possible treatment of Alzheimer's disease: In silico and in vitro approaches","authors":"Morteza Sadeghi ,&nbsp;Seyedehmasoumeh Seyedebrahimi ,&nbsp;Mustafa Ghanadian ,&nbsp;Mehran Miroliaei","doi":"10.1016/j.crstbi.2024.100146","DOIUrl":"10.1016/j.crstbi.2024.100146","url":null,"abstract":"<div><p>Nowadays, one of the methods to prevent the progress of Alzheimer's disease (AD) is to prescribe compounds that inhibit the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Researchers are actively pursuing compounds, particularly of natural origin, that exhibit enhanced efficacy and reduced side effects. The inhibition of AChE and BChE using natural flavonoids represents a promising avenue for regulating AD. This study aims to identify alternative flavonoids capable of modulating AD by down-regulating AChE and BChE activity through a molecular docking approach. Molecular docking analysis identified Ginkgetin and Kolaflavanone as potent inhibitors of AChE and BChE, respectively, among the selected flavonoids. Asn87 and Ala127 involved in the interactions of AChE-Ginkgetin complex through conventional hydrogen bonds. While in the BChE-Kolaflavanone complex, Asn83, Ser79, Gln 47, and Ser287 are involved. <em>In vitro</em> analysis further corroborated the inhibitory potential, with Ginkgetin exhibiting an IC₅₀ of 3.2 mM against AChE, and Kolaflavanone displaying an IC₅₀ of 3.6 mM against BChE. These findings underscore the potential of Ginkgetin and Kolaflavanone as candidate inhibitors for the treatment of AD through the inhibition of AChE and BChE enzymes. Nevertheless, additional <em>in vitro</em> and <em>in vivo</em> studies are imperative to validate the efficacy of these compounds.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100146"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000230/pdfft?md5=a30048b2fd3abff7ea6d265df8fdded8&pid=1-s2.0-S2665928X24000230-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781258","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":"Evaluating therapeutic potential of AYUSH-64 constituents against omicron variant of SARS-CoV-2 using ensemble docking and simulations","authors":"Vinod Jani ,&nbsp;Shruti Koulgi ,&nbsp;Mallikarjunachari V.N. Uppuladinne ,&nbsp;Saket Ram Thrigulla ,&nbsp;Manohar Gundeti ,&nbsp;Goli Penchala Prasad ,&nbsp;Sanjaya Kumar ,&nbsp;Srikanth Narayanam ,&nbsp;Uddhavesh Sonavane ,&nbsp;Rajendra Joshi","doi":"10.1016/j.crstbi.2024.100151","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100151","url":null,"abstract":"<div><p>The COVID-19 pandemic in the later phase showed the presence of the B.1.1.529 variant of the SARS-CoV-2 designated as Omicron. AYUSH-64 a poly herbal drug developed by Central Council for Research in Ayurvedic Sciences (CCRAS) has been recommended by Ministry of Ayush in asymptomatic, mild to moderate COVID-19 patients. One of the earlier, <em>in-silico</em> study has shown the binding of the constituents of AYUSH-64 to the main protease (M^pro) of the SARS-CoV-2. This study enlisted four phytochemicals of AYUSH-64, which were found to have significant binding with the M^pro. In continuation to the same, the current study proposes to understand the binding of these four phytochemicals to main protease (M^pro) and receptor binding domain (RBD) of spike protein of the Omicron variant. An enhanced molecular docking methodology, namely, ensemble docking has been used to find the most efficiently binding phytochemical. Using molecular dynamics (MD) simulations and clustering approach it was observed that the M^pro and RBD Spike of Omicron variant of SARS-CoV-2 in complex with human ACE2 tends to attain 4 and 8 conformational respectively. Based on the docking studies, the best binding phytochemical of the AYUSH-64, akummicine N-oxide was selected for MD simulations. MD simulations of akummicine N-oxide bound to omicron variant of M^pro and RBD Spike-ACE complex was performed. The conformational, interaction and binding energy analysis suggested that the akummicine N-oxide binds well with M^pro and RBD Spike-ACE2 complex. The interaction between RBD Spike and ACE2 was observed to weaken in the presence of akummicine N-oxide. Hence, it can be inferred that, these phytochemicals from AYUSH-64 formulation may have the potential to act against the Omicron variant of SARS-CoV-2.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"7 ","pages":"Article 100151"},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X2400028X/pdfft?md5=836de7f1d95a5e52325b80b7e6600418&pid=1-s2.0-S2665928X2400028X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141244089","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}