Current topics in medicinal chemistry最新文献

{"title":"Roles of C/EBPβ/AEP in Neurodegenerative Diseases.","authors":"Jing Guo, Xin-Yi Liu, Sha-Sha Yang, Qiang Li, Yang Duan, Shan-Shan Zhu, Ke Zhou, Yi-Zhi Yan, Peng Zeng","doi":"10.2174/0115680266357822250119172351","DOIUrl":"https://doi.org/10.2174/0115680266357822250119172351","url":null,"abstract":"<p><p>In recent years, an increasing number of studies have shown that increased activation of aspartic endopeptidases (AEPs) is a common symptom in neurodegenerative diseases (NDDs). AEP cleaves amyloid precursor protein (APP), tau (microtubule-associated protein tau), α- synuclein (α-syn), SET (a 39-KDa phosphoprotein widely expressed in various tissues and localizes predominantly in the nucleus), and TAR DNA-binding protein 43 (TDP-43), and promotes their aggregation, contributing to Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) pathogenesis. Abundant evidence supports the notion that CCAAT/enhancer-binding protein β (C/EBPβ)/AEP may play an important role in NDDs. Developing its small molecule inhibitors is a promising treatment of NDDs. However, current research suggests that the pathophysiological mechanism of the C/EBPβ/AEP pathway is very complex in NDDs. This review summarizes the structure of C/EBPβ and AEP, their major physiological functions, potential pathogenesis, their small molecule inhibitors, and how C/EBPβ/AEP offers a novel pathway for the treatment of NDDs.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051973","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":"Synthesis and Evaluation of Coumarin Clubbed Sulfanilamide and 2-Aminobenzothiazole Hybrids for Antibacterial Applications.","authors":"Suman Lata, Gagandeep Mehmi, Hardeep Kaur, Anuradha Sharma, Amit Pandit, Vikrant Abbot","doi":"10.2174/0115680266362029250111172921","DOIUrl":"https://doi.org/10.2174/0115680266362029250111172921","url":null,"abstract":"<p><strong>Background: </strong>The increasing prevalence of drug-resistant bacterial infections poses a significant challenge to global healthcare, necessitating the development of novel antibacterial agents. Coumarin-based derivatives are well-recognized for their diverse biological activities, and hybridization with other pharmacophores offers a promising strategy for enhancing therapeutic efficacy and overcoming resistance.</p><p><strong>Objective: </strong>This study aimed to synthesize and evaluate a novel series of coumarin hybrids by integrating the coumarin scaffold with sulfanilamide (9a-e) and 2-aminobenzothiazole (10a-e), targeting bacterial pathogens through a dual pharmacophoric approach.</p><p><strong>Methods: </strong>The synthesized hybrids were characterized using mass spectrometry, FTIR, and NMR (1H and 13C) to confirm their structural integrity. Antibacterial activity was assessed in vitro against Escherichia coli and Staphylococcus aureus at concentrations of 100, 250, and 500 μg/ml, with ciprofloxacin as the standard. The molecular binding mechanism was explored using molecular docking and pharmacophore-based analysis.</p><p><strong>Results: </strong>Among the synthesized derivatives, compounds 9e and 10e exhibited the highest antibacterial activity, with inhibition zones of 22 mm and 21 mm against E. coli and 25 mm and 22 mm against S. aureus at 500 μg/ml, demonstrating comparable efficacy to ciprofloxacin. Molecular docking studies revealed strong interactions of these compounds with bacterial enzymes, supporting the in vitro results and highlighting their potential as protein-inhibitor candidates.</p><p><strong>Conclusion: </strong>The novel hybrid derivatives demonstrated significant antibacterial activities, suggesting their potential as promising therapeutic agents. Their effectiveness against various bacterial strains indicated that these compounds could serve as a foundation for the development of new antibacterial drugs. Further research and optimization are needed to enhance their potency and ensure their safety, paving the way for future clinical applications.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001816","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":"Osseointegration Process Improving via Functionalization of Titanium Dioxide Nanotubes: A Bibliometric Analysis and Systematic Review.","authors":"Sergio Murilo da Silva Braga Martins Junior, Jose Manuel Noguera Bazan, Lucas Dos Santos Silva, Luis Claudio Nascimento da Silva","doi":"10.2174/0115680266334190241213101547","DOIUrl":"https://doi.org/10.2174/0115680266334190241213101547","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>Failures of osseointegrated implants pose a significant challenge in the medical field, often attributed to prolonged osseointegration periods and bacterial infections. Functionalization of Titanium Dioxide Nanotubes (TNTs) has emerged as a promising strategy to improve osseointegration and mitigate infections. This study aims to conduct a bibliometric analysis and systematic review to identify trends, gaps, and advancements in research on the functionalization of TNTs for osseointegration improvement.</p><p><strong>Methods: </strong>Articles were retrieved from the Web of Science database using the keywords \"osseointegration,\" \"titanium dioxide nanotubes,\" and \"functionalization.\" The inclusion criteria were studies published between 2014 and 2023, written in English, and focusing on the use of TNTs in implant surface modifications. A total of 126 articles were included after screening. Data extraction and analysis were performed using VOS Viewer, Microsoft Excel, and GraphPad Prism.</p><p><strong>Results: </strong>The review revealed a growing number of publications on TNT functionalization, with China, the United States, and Brazil leading in contributions. Key findings include the effectiveness of TNTs loaded with bioactive agents (e.g., silver, strontium, hydroxyapatite) in promoting osseointegration and antibacterial activity. Collaborative networks among institutions and authors were mapped, highlighting the Sao Paulo State University and Yong Huang as the most prolific contributors.</p><p><strong>Conclusion: </strong>The findings underscore the potential of TNT functionalization to enhance implant performance. However, a gap remains in translating preclinical findings into clinical trials. Future research should focus on clinical validation to bridge this gap and translate laboratory advancements into therapeutic solutions.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022627","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":"SRT1720 Treatments Hepatic Ischemia Reperfusion Injury by Regulation of NF-κB Signaling Pathways and Reduce Cell Apoptosis: From Network Pharmacology to Experimental Validation.","authors":"Zhongzhe Li, Wenting Geng, Beilei Yu, Bin Wang, Shuxuan Sun, Lu Zhou","doi":"10.2174/0115680266322450241212070042","DOIUrl":"https://doi.org/10.2174/0115680266322450241212070042","url":null,"abstract":"<p><strong>Background and objective: </strong>Hepatic ischemia reperfusion injury (HIRI) is a common complication closely related to the prognosis of liver surgery, and effective treatment methods are still unavailable. SRT1720 has the characteristics of multifunction and multitarget which may cope with the multidirectional complex pathological process caused by HIRI. The present study aimed to explore the potential mechanism of SRT1720 in HIRI through a combination of network pharmacology, in vitro experiments and in vivo models.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were identified based on the GSE15480 and Genecards database. Enrichment analyses were then conducted. SRT1720-targeted genes were obtained through databases such as Chembl, TTD, GtoPdb, and so on. All target genes were standardized by the Uniprot database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified by STRING. Shared KEGG pathways were identified using a Venn diagram among SRT1720-targeted pathways and HIRI. Furthermore, experimental techniques such as cell apoptosis assay and western blotting were used to confirm the most significant biological processes and the key pathway between SRT1720-targeted and HIRI.</p><p><strong>Results: </strong>This study identified 118 HIRI-related DEGs, 69 shared KEGG pathways of SRT1720 and HIRI. In addition, the findings revealed that SRT1720 significantly reduced liver ischemiareperfusion (I/R) injury. NF-κB signaling pathway and the expression of promoting apoptosis factors such as Bax and Caspase3 were inhibited, while antiapoptotic protein Bcl-2 was promoted in the SRT1720 group compared with the I/R group.</p><p><strong>Conclusion: </strong>The findings indicate that SRT1720 may inhibit the development of HIRI by inhibiting the NF-κB signaling pathway and reducing cell apoptosis, acting as a treatment for HIRI.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022635","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":"Advances in the Study of Halogenated Natural Products.","authors":"Lijing Zhang, Bing Liu, Ting Zhu, Xue Tian, Ning Chen, Yuxin Wang","doi":"10.2174/0115680266344796241211214414","DOIUrl":"https://doi.org/10.2174/0115680266344796241211214414","url":null,"abstract":"<p><p>Halogenated natural products are an important class of secondary metabolites that are widely distributed in nature. The presence of halogen atoms usually enhances the pharmacological activity of the compounds. As a result, halogenated natural products have shown promising pharmacological activities in antibacterial, antitumour, anti-inflammatory and antiplasmodial properties, providing a rich resource for the development of new drugs. To date, more than 62% of halogenated compounds are produced by marine organisms, mainly including marine sponges, algae, corals, fungi and other organisms. In addition, terrestrial microorganisms, including bacteria and fungi, also produce halogenated metabolites, which are equally important sources of halogenated natural products. The biosynthesis of halogenated natural products involves the synergistic action of multiple enzymes that efficiently and selectively bind halogen atoms to organic molecules, a process that enhances the biological activity of the compounds. Halogenated natural products have a wide range of uses as important raw materials in the agricultural, pharmaceutical and chemical industries. This paper reviews the progress of research on halogenated compounds and their biosynthesis in recent years, laying the foundation for further utilisation and development of halogenated compounds.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022625","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 Advances in the Development of Greener Methodologies for the Synthesis of Benzothiazoles.","authors":"Nirjhar Saha, Asim Kumar, Bibhuti Bhusan Debnath, Anirban Sarkar, Asit K Chakraborti","doi":"10.2174/0115680266347975241217112119","DOIUrl":"https://doi.org/10.2174/0115680266347975241217112119","url":null,"abstract":"<p><p>The benzothiazole ring system has been recognised with crucial pharmacophoric features being present among various approved drugs and clinical and pre-clinical candidates. The medicinal importance of this privileged scaffold stimulated the interest of synthetic medicinal/ organic chemists for the synthesis of its derivatives due to their diverse biological applications. In most of the reports in the literature, benzothiazoles were synthesized by cyclocondensation of 2- aminothiophenol with either carboxylic acid and its derivatives or aldehydes. However, many of these procedures involve reaction conditions that are not in conformity with sustainable chemistry development. The negative impact of chemicals and their manufacturing processes on the environment, human health, and biodiversity raises safety concerns. On the other hand, the utilization of non-renewable energy sources, use of rare earth metals as catalysts, involvement of costly chemicals, prolonged reaction time at high temperatures, and considerable waste generation diminish the greener impact of these reaction methodologies and make them non-sustainable. In order to avoid such drawbacks of the non-sustainable practices in the synthesis of benzothiazoles, there have been continuous efforts to develop greener methodologies for the construction of this bioactive scaffold. This review aims to delve into the literature reports on the recent advancements in the development of greener methodologies for the synthesis of bioactive benzothiazoles.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022632","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":"PAV-05 Naphthoquinone Potently Inhibit Zika Virus Replication in Infected Cells.","authors":"Claudio Cesar Cirne-Santos, Daniel Tadeu Gomes Gonzaga, Gabriel Oliveira de Resende, Mariana de Castro Gonçalves, Aymee da Silva Andrade, Paulo Anastácio Furtado Pacheco, Alexandre Dos Santos-Rodrigues, Vitor Won-Held Rabelo, Paula Alvarez Abreu, Robson Xavier Faria, David Rodrigues da Rocha, Fernando de Carvalho da Silva, Vitor Francisco Ferreira, Caroline de Souza Barros, Izabel Christina Nunes de Palmer Paixão","doi":"10.2174/0115680266323907241212062715","DOIUrl":"https://doi.org/10.2174/0115680266323907241212062715","url":null,"abstract":"<p><strong>Background: </strong>Zika (ZIKV) is a virus transmitted by mosquitoes that can cause Guillain- Barré syndrome and congenital malformations like microcephaly. Given its explosive resurgence and the resulting epidemics in 2016, the search for effective antiviral drugs has become absolutely necessary.</p><p><strong>Methods: </strong>In this study, we examined the potential of naphthoquinone derivatives that have a sulfonamide or sulfonate group to inhibit ZIKV replication in primary cultured neurons and in Vero cells.</p><p><strong>Results: </strong>In our in vitro studies, we found that PAV05 had low cytotoxicity with a CC50 of 329 μM ±3.6 for Vero cells and 290 μM ±3.5 for neurons. Additionally, we observed a strong inhibitory activity on viral replication with an EC50 value of EC50 of 0.92 μM ±0.15 in Vero cells, resulting in a Selectivity Index (SI) of 357. Even when added 16 hours post-infection, PAV05 maintained its inhibitory effect. When PAV05 was evaluated in sub-optimal concentrations together with Ribavirin, we observed a strong synergistic effect, with an inhibition greater than 90% even at doses of 0.5 μM. In silico tests suggested that PAV05 may have effects on ZIKV NS2B-NS3.</p><p><strong>Conclusion: </strong>The ZIKV inhibitor described in this study shows promise as a compound for the development of therapies against ZIKV. It may also be considered for inclusion in the portfolio of broad-spectrum antiflavivirus inhibitors.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022630","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":"Synthesis, X-Ray Structure, Characterization, Antifungal Activity, DFT, and Molecular Simulation of a Novel Pyrazole Carboxylic Acid.","authors":"Said Tighadouini, Imane Yamari, Othmane Roby, Abdullah Y A Alzahrani, Oussama Abchir, Imane Nait Irahal, Rafik Saddik, Marilena Ferbinteanu, Samir Chtita","doi":"10.2174/0115680266348692241211111312","DOIUrl":"https://doi.org/10.2174/0115680266348692241211111312","url":null,"abstract":"<p><strong>Background: </strong>The search for new antifungal agents is critical due to the rising resistance of fungal pathogens to existing treatments. This study focuses on the synthesis and evaluation of a novel compound, 1-benzyl-5-methyl-1H-pyrazole-3-carboxylic acid (compound L1), as a potential antifungal agent.</p><p><strong>Methods: </strong>Compound L1 was synthesized and characterized using a range of analytical techniques, including 1H^1H1H NMR, 13C^{13}C13C NMR, FT-IR, GC-MS, and X-ray single crystal diffraction (XRD). The antifungal activity of the compound was assessed in vitro, and its molecular structure was studied using Density Functional Theory (DFT). Molecular docking and dynamics simulations were conducted to evaluate the interaction of the compound with sterol 14-alpha demethylase (CYP51) from Candida albicans. ADME/Tox evaluations were also performed to assess the drug-like properties of compound L1.</p><p><strong>Results: </strong>Compound L1 exhibited moderate antifungal activity with an IC50 value of 34.25 μg/mL. DFT studies confirmed the highly stable molecular structure of the compound. Molecular docking and dynamics simulations demonstrated that compound L1 had a higher affinity and stability when forming complexes with the crystal structure of CYP51, particularly in interaction with the tetrazole- based antifungal drug candidate VT1161 (PDB ID: 5TZ1). ADME/Tox evaluations indicated favorable drug-like properties for compound L1.</p><p><strong>Conclusion: </strong>The results suggest that compound L1 is a promising antifungal candidate, showing greater potential than fluconazole in the conducted evaluations. Further studies are warranted to explore its full therapeutic potential.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022637","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":"Exploring the Therapeutic Potential of Natural Flavonoids in Inflammatory Bowel Disease: Insights into Intestinal Mucosal Barrier Regulation.","authors":"Min Wang, Yanqing Zhang, Yaxin Li, Mengyu Zhang, Jinrui Liu, Yuxin Cao, Junbo Xie, Shuo Wang","doi":"10.2174/0115680266337430241127112031","DOIUrl":"https://doi.org/10.2174/0115680266337430241127112031","url":null,"abstract":"<p><p>Inflammatory Bowel Disease (IBD) is a chronic non-specific disease that affects the gastrointestinal tract, and Intestinal Mucosal Barrier (IMB) damage is closely related to its pathogenesis. The management of IBD often involves repairing the mechanical, chemical, immune, or biological barriers of the intestinal mucosa to alleviate symptoms. Currently, the treatment of IBD patients requires continuous medication or surgical interventions, which can cause irreversible damage to the patient's body over time. Natural flavonoids, commonly found in human diets, offer a safe, effective, and non-toxic alternative, presenting significant potential for promoting intestinal health and disease prevention. This article aimed to explore current research concerning the role of natural flavonoids in modulating the IMB in IBD, offering a new perspective for the prevention and management of IBD and highlighting new opportunities for the development and application of natural flavonoids.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001813","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":"Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.","authors":"Shruti Shukla, Shikha Kushwah, Ashutosh Mani","doi":"10.2174/0115680266348099250108065838","DOIUrl":"https://doi.org/10.2174/0115680266348099250108065838","url":null,"abstract":"<p><p>The global rise of drug-resistant malaria parasites is becoming an increasing threat to public health, emphasizing the urgent need for the development of new therapeutic strategies. Artimisinin- based therapies, once the backbone of malaria treatment, are now at risk due to the resistance developed in parasites. The lack of a universally accessible malaria vaccine exacerbates this crisis, underscoring the need to explore new antimalarial drugs. A more comprehensive understanding of the parasites's life cycle has revealed several promising targets, including enzymes, transport proteins, and essential metabolic pathways that the parasite relies on for its survival and proliferation. This review provides an in-depth analysis of the vulnerabilities displayed by Plasmodium and recent advances that highlight potential drug targets and candidate molecules.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982603","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}