Current medicinal chemistry最新文献

{"title":"Liposomal Nanoformulation-encapsulated Paclitaxel for Reducing Chemotherapy Side Effects in Lung Cancer Treatments: Recent Advances and Future Outlooks.","authors":"Kave Mohammad-Jafari, Seyed Morteza Naghib, M R Mozafari","doi":"10.2174/0109298673308951240921121345","DOIUrl":"https://doi.org/10.2174/0109298673308951240921121345","url":null,"abstract":"<p><p>Paclitaxel is one notable chemotherapy drug that is used to treat a number of cancers, including lung cancer. Nevertheless, it has drawbacks such as toxicity, low solubility in water, and the emergence of multidrug resistance (MDR). This article reviews the use of liposomal formulations to improve paclitaxel administration and efficacy for lung cancer therapy. Paclitaxel's pharmacological characteristics can be improved by liposomes through increased solubility, extended circulation, passive tumor targeting through leaky vasculature, and decreased side effects. Recent developments in paclitaxel liposomal formulations, including as cationic liposomes, conventional liposomes, targeted liposomes with particular ligands, and liposome-loaded microorganisms, are outlined in this article. In comparison to free paclitaxel, these nanoformulations exhibit enhanced cytotoxicity, cellular uptake, apoptosis, tumor growth suppression, and anticancer effects in lung cancer cell lines and animal models. One efficient way to get around the drawbacks of paclitaxel is to alter its size, makeup, and surface characteristics. This will let the medication accumulate and penetrate tumors more easily, avoid multidrug resistance, and cause less systemic toxicity. The article explores clinical studies showcasing the safety and therapeutic efficacy of liposomal paclitaxel for individuals afflicted with lung cancer. In its entirety, the document provides an in-depth examination of the potential enhancement in paclitaxel's dispersion and anti-tumor impacts through the utilization of liposomal technology when addressing diverse manifestations of lung cancer.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, Synthesis, Docking Studies, and Biological Activity of Novel Analogs of Cyclophosphamide as Potential Anticancer Agents.","authors":"Khodayar Gholivand, Soobieh Alemi Rostami, Marzie Sabaghian, Sanam Sadeghi-Mohammadi, Azam Babaei, Rahime Eshaghi Malekshah, Hossein Naderi-Manesh","doi":"10.2174/0109298673332921240920065129","DOIUrl":"https://doi.org/10.2174/0109298673332921240920065129","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to present the synthesis and characterization of four novel analogs of cyclophosphamide (2, 3, 4, 7) and their related precursors (1, 5, 6) and assess their anticancer activity against breast cancerous (MCF-7) and normal (HUVEC) cells.</p><p><strong>Method: </strong>Notably, 2-(bis(2-chloroethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((2)) and 2-(bis(2-hydroxyethyl)amino)-1,3,2-diazaphospholidine 2-oxide ((7)) exhibited concentration- dependent cytotoxicity against the MCF-7 cell line, with IC50 values of 8.98 and 28.74 μM, respectively.</p><p><strong>Result: </strong>Annexin V/PI staining and ROS assays demonstrated reduced cell viability and mitochondrial dysfunction. in silico studies involving DFT-D optimization and Molegro virtual docking against B-DNA dodecamer and STAT3 receptors revealed enhanced interactions for certain compounds compared to cyclophosphamide.</p><p><strong>Conclusion: </strong>Importantly, the in silico and in vitro results corroborated each other, supporting the potential anticancer efficacy of these novel analogs.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quassinoids as Promising Anti-cancer Agents.","authors":"Tripti Mishra, Saima, Bimal Krishna Banik","doi":"10.2174/0109298673313760240911160930","DOIUrl":"https://doi.org/10.2174/0109298673313760240911160930","url":null,"abstract":"<p><p>The use of current anticancer drugs is hampered by significant side effects and high costs. In the pursuit of safer, more effective, and affordable options, researchers have turned to nature as a valuable source of potential anticancer compounds. Quassinoids, a class of natural terpenoids, have garnered attention for their anticancer properties. This comprehensive review aims to shed light on natural quassinoids and their anticancer effects, offering valuable insights for researchers dedicated to the development of novel anticancer therapeutics.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Exploration of Pyranocoumarin Derivatives as Synergistic Inhibitors of Dual-target for Mpro and PLpro Proteins of SARS-CoV-2 through Molecular Docking, ADMET Analysis, and Molecular Dynamics Simulation.","authors":"Imane Yamari, Lamiae El Bouamri, Oussama Abchir, Mohammed Bouachrine, Mhammed El Kouali, Abdelouahid Samadi, Samir Chtita","doi":"10.2174/0109298673331781240829094334","DOIUrl":"https://doi.org/10.2174/0109298673331781240829094334","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to explore the potential of natural anticoagulant compounds as synergistic inhibitors of the main protease (Mpro) and papain-like protease (PLpro) of SARS-CoV-2 and find effective therapies against SARS-CoV-2 by investigating the inhibitory effects of natural anticoagulant compounds on key viral proteases.</p><p><strong>Objective: </strong>The objectives of this study were to conduct rigorous virtual screening and molecular docking analyses to evaluate the binding affinities and interactions of selected anticoagulant compounds with Mpro and PLpro, to assess the pharmacokinetic and pharmacodynamic profiles of the compounds to determine their viability for therapeutic use, and to employ molecular dynamics simulations to understand the stability of the identified compounds over time.</p><p><strong>Methods: </strong>In this study, a curated collection of natural anticoagulant compounds was conducted. Virtual screening and molecular docking analyses were performed to assess binding affinities and interactions with Mpro and PLpro. Furthermore, pharmacokinetic and pharmacodynamic analyses were carried out to evaluate absorption, distribution, metabolism, and excretion profiles. Molecular dynamics simulations were performed to elucidate compound stability.</p><p><strong>Results: </strong>Natural compounds exhibiting significant inhibitory activity against Mpro and PLpro were identified. A dual-target approach was established as a promising strategy for attenuating viral replication and addressing coagulopathic complications associated with SARS-CoV-2 infection.</p><p><strong>Conclusion: </strong>The study lays a solid foundation for experimental validation and optimization of identified compounds, potentially leading to the development of precise treatments for SARS-CoV-2.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Single-cell RNA-seq and Bulk RNA-seq Identify Diagnostic Biomarkers for Postmenopausal Osteoporosis.","authors":"Hanyu Wang, Chong Peng, Guangbing Hu, Wenhao Chen, Yong Hu, Honglin Pi","doi":"10.2174/0109298673343344240930054414","DOIUrl":"https://doi.org/10.2174/0109298673343344240930054414","url":null,"abstract":"<p><strong>Aim: </strong>We aimed to explore diagnostic biomarkers of postmenopausal osteoporosis (PMOP).</p><p><strong>Background: </strong>PMOP brings enormous physical and economic burden to elderly women.</p><p><strong>Objectives: </strong>This study aims to screen new biomarkers for osteoporosis, providing insights for early diagnosis and therapeutic targets of osteoporosis.</p><p><strong>Methods: </strong>Weighted gene co-expression network analysis (WGCNA) was applied to identify osteoporosis-related hub genes. Single-cell transcriptomic atlas of osteoporosis was depicted and the heterogeneity of monocytes was analyzed, based on which the biomarkers for osteoporosis were screened. Gene set enrichment analysis (GSEA) was conducted on the biomarkers. The diagnostic model (nomogram) was established and evaluated based on the expression levels of biomarkers. Additionally, the transcription factor (TF) regulatory network was constructed to predict the potential TF and targeted miRNA of biomarkers. The drugs with significant correlation with biomarkers were identified by Spearman correlation analysis.</p><p><strong>Results: </strong>We obtained 30 osteoporosis-associated hub genes. 9 cell types were identified, and the monocytes were subdivided to 4 subtypes. Three biomarkers, DHX29, LSM5, and UBE2V2, were screened. DHX29 and UBE2V2 were highly expressed in non-classical monocytes, while LSM5 exhibited the highest expression in other monocytes, followed by non-classical monocytes. GSEA indicated that osteoporosis may be correlated with vascular calcification and the biomarkers may be involved in the formation of immune cells. Then, nomogram was constructed and exhibited good robustness. In addition, MYC and SETDB1 were the shared IF in three biomarkers, which may play critical regulatory roles in the progression of osteoporosis. Moreover, 41, 49, and 68 drugs appeared significant correlations with DHX29, LSM5, and UBE2V2, respectively.</p><p><strong>Conclusion: </strong>This study provided a basis for early diagnosis and targeted treatment of osteoporosis.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Punicalagin Compound Mitigates Bronchial Epithelial Cell Senescence Induced by Cigarette Smoke Extract through the PAR2/mTOR Pathway.","authors":"Jianguo Xu, Xin Li, Xiaoli Zeng, Hairong Bao, Xiaoju Liu","doi":"10.2174/0109298673346794241001110826","DOIUrl":"https://doi.org/10.2174/0109298673346794241001110826","url":null,"abstract":"<p><strong>Background: </strong>Tobacco smoke is an important inducer of airway epithelial cell aging. Punicalagin(PCG) is a natural anti-aging compound. The effect of PCG on tobacco smoke-induced airway epithelial cell senescence is unknown.</p><p><strong>Objective: </strong>Our study investigated whether PCG can treat the human bronchial epithelial cell line (BEAS-2B) aging by inhibiting the protease-activated receptor 2 (PAR2)/m- TOR pathway.</p><p><strong>Methods: </strong>Bioinformatics techniques were used to analyze the potential biological functions of PAR2. Molecular dynamics evaluated the binding ability of PCG and PAR2. The CCK8 assay was used to detect the cytotoxicity of CSE and PCG. The activity of the PAR2/mTOR pathway and the expression of the characteristic aging markers p16, p21, and SIRT1 are detected by qRT-PCR and Western blotting. Cell senescence was observed by Senescence-associated β-galactosidase (SA-β-gal) staining. The senescence-associated secretory phenotype (SASP): concentrations of interleukin IL-6, IL-8, and TNF- α were detected by ELISA.</p><p><strong>Results: </strong>The GSE57148 bioinformatics analysis dataset showed that PAR2 regulates lung senescence through the mTOR signaling pathway. Molecular dynamics results found that PCG and PAR2 had a strong and stable binding force. CSE induces BEAS-2B cell senescence and activates the PAR2/mTOR pathway. Inhibition of PAR2 mitigated the senescence changes. In addition, PCG's pretreatment can significantly alleviate CSE-induced BEAS-2B cell senescence while inhibiting the PAR2/mTOR pathway.</p><p><strong>Conclusion: </strong>PCG has a therapeutic effect on the senescence of airway epithelial cells.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design and Synthesis of Benzimidazole Carboxamide Cysteine Protease Inhibitors as Promising Anti-leishmanial Agents.","authors":"Gowsia Akhter, Hinna Hamid, Mirza A Beg, Mushtaq A Tantray, Bharti Dhawan, Mohammad Sarwar Alam, Angamuthu Selvapandiyan, Sayeed Ur Rehman, Sharma Kalicharan","doi":"10.2174/0109298673310232240910062647","DOIUrl":"https://doi.org/10.2174/0109298673310232240910062647","url":null,"abstract":"<p><strong>Introduction: </strong>More than 20 protozoan species of Leishmania are responsible for causing Leishmaniasis, an infection spread by blood-feeding phlebotomine sandflies. A narrow pool of drugs is currently available rendering the current drug stratagem to treat this infection . Development of novel, less toxic, and more effective regimens is thus a need of the hour. Design and synthesis of benzo[d]imidazole carboxamides as agents to combat Leishmaniasis are also required.</p><p><strong>Methods: </strong>14 benzo[d]imidazole carboxamides were synthesized and gauged against L. donovani promastigotes and intramacrophage amastigote forms. All of the tested compounds exhibited significant anti-promastigote properties with IC50 well below 10 uM. Compounds 4a, 4b, and 4d, showing the highest anti-parasitic activity against promastigote forms (IC50 0.91- 1.33 μM), were also found to be associated with better anti-leishmanial potential (IC50 0.78- 1.67 μM) against the intramacrophage amastigotes comparable to Amphotericin-B (0.13 μM), a drug used for Leishmaniasis. Compound (4a), namely N-(2-(trifluoromethyl)-1Hbenzo[ d]imidazol-5-yl)benzo[d][1,3]-5-carboxamide-dioxole, was found to be most potent against L. donovani amastigotes among all the tested compounds, and demonstrated better antileishmanial properties (IC50 0.78 μM) when compared to the standard. Compound 4a was also assessed for its toxicity profile against THP-1 human monocytic cells. To establish the molecular target(s) in silico, molecular docking studies were performed against cysteine protease, a putative virulence factor of Leishmania parasites, and nucleoside diphosphate kinase, an enzyme with a critical role in nucleotide recycling, also associated with resistance in Leishmania strains. Compound 4a showed better binding affinity than the standard to these targets; furthermore, the molecular dynamic simulation studies further affirmed the stability of compound 4a, within the active site of the targets. In vitro, cysteine protease inhibitory activity (IC50 8.53 μM) using Bz-Arg-AMC hydrochloride fluorogenic peptide substrate established the promising potential of 4a as a cysteine protease inhibitor.</p><p><strong>Result: </strong>Computational ADMET analysis indicated appropriate pharmacokinetic profile and physicochemical characteristics for all members of the synthesized library.</p><p><strong>Conclusion: </strong>Both in vitro and in silico studies indicate that the synthesized imidazole carboxamides can act as potent hits and that N-(2-(trifluoromethyl)-1H-benzo[d]imidazol-5- yl)benzo[d][1,3]-5-carboxamide-dioxole 4a can be an effective hit molecule which can be further developed into potent lead molecule (s) to fight Leishmania donovani.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Risk Model Developed based on Homologous Recombination Deficiency Genes for Evaluating the Drug Sensitivity and Prognostic Prediction of Lung Adenocarcinoma.","authors":"Lingling Hong, Jiashun Li, Weiwei Shao","doi":"10.2174/0109298673333745240927074414","DOIUrl":"https://doi.org/10.2174/0109298673333745240927074414","url":null,"abstract":"<p><strong>Aim: </strong>This study was designed to construct a risk model based on homologous recombination deficiency (HRD) to evaluate the prognosis and drug sensitivity for patients with lung adenocarcinoma (LUAD).</p><p><strong>Background: </strong>LUAD is a subtype of lung cancer with unfavorable overall survival (OS) and prognosis. HRD has been widely studied in various tumors, but its role in LUAD has not been fully understood.</p><p><strong>Objective: </strong>We aimed to construct an HRD-related risk model for predicting the prognosis and drug sensitivity of patients with LUAD.</p><p><strong>Methods: </strong>Gene expression data of the LUAD samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. We extracted HRD genes from previous literature and performed univariate COX analysis to select those closely associated with LUAD prognosis. ConsensusClusterPlus was employed to stratify the samples in the TCGA-LUAD cohort into different subtypes. A RiskScore model was established applying random forest method. Furthermore, immunotherapy response and drug sensitivity were predicted using Tumor Immune Dysfunction and Exclusion (TIDE) software and pRRophytic R package, respectively. Finally, the clinical features between High- and Low- RiskScore groups were compared.</p><p><strong>Results: </strong>A total of 16 HRD genes relevant to LUAD prognosis were selected and used to classify 3 LUAD clusters (C1, C2, and C3). Specifically, C1, with a lower TIDE score displayed higher immune infiltration and immunotherapy benefit and the optimal OS, while C2 was closely correlated with tumor-relevant pathways and had the worst OS. Finally, 4 HRD genes (RAD51AP1, BRCA1, H2AFX, and FANCL) were determined to develop a RiskScore signature. It was found that a higher RiskScore was related to more advanced stages, worse OS, and tumor development pathways. Additionally, the High-RiskScore group with a higher TIDE score was sensitive to 44 traditional chemotherapy drugs. A nomogram combined with RiskScore exhibited an accurate survival prediction ability.</p><p><strong>Conclusion: </strong>The HRD-based RiskScore played a crucial role in LUAD development, showing a strong potential to serve as a prognostic indicator for LUAD. Our findings contributed to the diagnosis of LUAD and its treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancerous Inhibitor of Phosphatase 2A (CIP2A): A Sensitive Diagnostic Marker and Therapeutic Agent in Oral Cancer.","authors":"Thangavel Lakshmipriya","doi":"10.2174/0109298673333274240925044553","DOIUrl":"https://doi.org/10.2174/0109298673333274240925044553","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point-of-Care Testing for Cardiovascular Disease: A Narrative Review.","authors":"Xiaolong Liu, Mengxiao He, Rongbo Hu, Sihang Huang, Zhencheng Chen","doi":"10.2174/0109298673320582240920061613","DOIUrl":"https://doi.org/10.2174/0109298673320582240920061613","url":null,"abstract":"<p><p>Cardiovascular disease is a major global public health challenge. Point-of-- care testing (POCT) technologies are crucial for the prevention, early diagnosis, and treatment of cardiovascular conditions. Numerous POCT technologies for cardiovascular disease are currently available, which include but are not limited to conventional methods, paper-based microfluidic technology, microfluidic chip technology, electrochemical detection technology, ultrasonic detection technology, and smartphone-based detection technology. Each method has a broad range of applications and performs differently across various detection scenarios. This article offers a comprehensive analysis of current POCT technologies for cardiovascular disease, assessing their effectiveness, limitations, and future development directions. The aim is to provide insights and theoretical references for innovative research and clinical applications in POCT methods for cardiovascular disease.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}