Current medicinal chemistry最新文献

{"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":" ","pages":""},"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":"Pre-Stage Oral Cancer Biomarker Analysis in Non-invasive Salivary Samples: A Way to Go.","authors":"Periasamy Anbu, Subash C B Gopinath","doi":"10.2174/0109298673337297240923062829","DOIUrl":"https://doi.org/10.2174/0109298673337297240923062829","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361305","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":" ","pages":""},"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}

{"title":"Recent Advancements in the Delivery of Therapeutic Agents Targeting RNA-dependent RNA Polymerase of SARS-CoV-2.","authors":"Kalpesh Mahajan, Dipika Pawar, Sankha Bhattacharya","doi":"10.2174/0109298673312897240919111317","DOIUrl":"https://doi.org/10.2174/0109298673312897240919111317","url":null,"abstract":"<p><p>This study aimed to undertake a complete evaluation and analysis of all known data on RNA-dependent RNA polymerase (RdRp) inhibitors, concentrating on their safety, efficacy, and current improvements in the delivery of therapeutic drugs targeting RdRp of SARS-CoV-2. The work has attempted to emphasise the necessity for future research into the development of nanocarrier-based targeted drug delivery methods for RdRp inhibitors in the treatment of COVID-19. In December 2019, a novel SARS-- CoV-2 strain was discovered in Wuhan, China. SARS-CoV-2 is transferable among humans and has caused a global pandemic. The rapid global outbreak of SARS-CoV-2 and numerous deaths caused because of coronavirus disease (COVID-19) prompted the World Health Organization to announce a pandemic on March 12, 2020. COVID-19 is becoming a key concern that has a significant impact on an individual's life status. RdRp inhibitors are major pharmaceutical agents used in the treatment of COVID-19, which have various undesirable side effects, a greater risk of recurrence, lower bioavailability, as well as a lack of targeted therapy. Hence, the present article has provided a review on all known data on RdRp inhibitors, safety, and efficacy, and recent advances in the delivery of therapeutic agents targeting RdRp of SARS-CoV-2. An analysis has been done using a scientific data search engine, such as the National Center for Biotechnology Information (NCBI/PubMed), Science Direct, Google Scholar, WIPO, Lens, etc. The information has emphasized the need for more research into the safety, efficacy, and development of nanocarrier-based targeted drug delivery systems for RdRp inhibitors in the treatment of COVID-19.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343332","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":"Neuroimmune Interactions in Stress and Depression: Exploring the Molecular and Cellular Mechanisms within the Neuroinflammation-depression Nexus.","authors":"Alexey Sarapultsev, Evgenii Gusev, Valeriy Chereshnev, Maria Komelkova, Desheng Hu","doi":"10.2174/0109298673320710240920055041","DOIUrl":"https://doi.org/10.2174/0109298673320710240920055041","url":null,"abstract":"<p><strong>Background: </strong>The escalating global burden of stress and depression underscores an urgent need to unravel their complex interrelationships and underlying mechanisms. This investigation delves into the intricate dynamics between stress and depression, spotlighting the Neuroimmunoinflammatory Stress Model (NIIS), which elucidates the pivotal role of cellular and molecular pathways in mediating these conditions.</p><p><strong>Methods: </strong>Through an exhaustive review of literature spanning epidemiology, neurobiology, and psychoneuroimmunology, this study synthesizes the current understanding of stress and depression. It accentuates the definitional scopes, interplay, and intricacies of the NIIS model, which integrates neuroimmune-inflammatory responses into the conceptual framework of the stress-depression interaction.</p><p><strong>Results: </strong>By identifying stress as a multifactorial reaction to perceived adversities and depression as a manifestation of prolonged stress exposure, our analysis foregrounds the NIIS model. This paradigmatic model reveals the transition from normal stress responses to pathological neuroinflammatory pathways, highlighting neurotransmitter imbalances, disruptions in neuronal and glial homeostasis, and ensuing low-grade neuroinflammation as key factors in the pathogenesis of depression under chronic stress conditions. The NIIS model identifies prolonged cellular pro-inflammatory stress of neurons and microglia as a fundamental pathological subsystem of many neuropsychiatric disorders. In turn, neuroinflammation and associated neurodegenerative processes are complications of chronic psychoemotional stress, which can clinically manifest as depression.</p><p><strong>Conclusions: </strong>The NIIS model views depression as the terminal stage of chronic stress, pathogenetically linked to latent neuroinflammation. This insight not only advances our understanding of their etiopathogenesis but also paves the way for developing precise therapeutic interventions.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343330","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":"Phenolic Glycoside Monomer from Reed Rhizome Inhibits Melanin Production via PI3K-Akt and Ras-Raf-MEK-ERK Pathways.","authors":"Meijun Pang, Hong Yao, Kechen Bao, Ruitian Xu, Rongjiao Xi, Rui Peng, Hui Zhi, Kuo Zhang, Runnan He, Yunfei Du, Yanfang Su, Xiuyun Liu, Dong Ming","doi":"10.2174/0109298673341645240919072455","DOIUrl":"https://doi.org/10.2174/0109298673341645240919072455","url":null,"abstract":"<p><strong>Introduction: </strong>Melanogenesis, the process responsible for melanin production, is a critical determinant of skin pigmentation. Dysregulation of this process can lead to hyperpigmentation disorders.</p><p><strong>Method: </strong>In this study, we identified a novel <i>Reed Rhizome</i> extract, (1'S, 2'S)-syringyl glycerol 3'-O-β-D-glucopyranoside (compound 5), and evaluated its anti-melanogenic potential in zebrafish models and <i>in vitro</i> assays. Compound 5 inhibited melanin synthesis by 36.66% ± 14.00% and tyrosinase <i>in vivo</i> by 48.26% ± 6.94%, surpassing the inhibitory effects of arbutin. Network pharmacological analysis revealed key targets, including HSP90AA1, HRAS, and PIK3R1, potentially involved in the anti-melanogenic effects of compound 5.</p><p><strong>Results: </strong>Molecular docking studies supported the interactions between compound 5 and these targets. Further, gene expression analysis in zebrafish indicated that compound 5 up-regulates <i>hsp90aa1.1, hrasa,</i> and <i>pik3r1,</i> and subsequently down-regulating <i>mitfa,</i> tyr, and tyrp1, critical genes in melanogenesis.</p><p><strong>Conclusion: </strong>These findings suggest that compound 5 inhibits melanin production <i>via</i> PI3K-Akt and Ras-Raf-MEK-ERK signaling pathways, positioning it as a promising candidate for the treatment of hyperpigmentation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343331","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}