In silico pharmacology最新文献

{"title":"Elucidating the structural basis for the enhanced antifungal activity of amide derivative against <i>Candida albicans</i>: a comprehensive computational investigation.","authors":"Eban L Kechi, Chioma B Ubah, Musa Runde, Aniekan E Owen, Obinna C Godfrey, Daniel C Agurokpon, Michael O Odey, Uwem O Edet, Bassey O Ekpong, Solomon O Iyam, Innocent Benjamin, Gopinath Sampathkumar","doi":"10.1007/s40203-024-00222-3","DOIUrl":"10.1007/s40203-024-00222-3","url":null,"abstract":"<p><p>The continuous search for more effective options against well-known pathogens such as <i>Candida albicans</i> remains the rationale for the search for novel lead compounds from various sources. This study aims to investigate the chemical structure, chemical properties, of 5-(2-((5-(((1S,3R) -3-(5-acetamido-1,3,4-thiadiazolidin-2-yl) cyclopentyl) methyl)-1,3,4-thiadiazolidin-2-yl)amino)-2-oxoethyl)-2-methyl-2,3-dihydro-1H-pyrazol-3-ide designated ATCTP using DFT method ωB97XD/-311 +  + g(2d, 2p) and the biological potential of compound ATCTP against <i>Candida albicans</i> using molecular docking and ADMET studies. Geometry optimization was carried out in DMSO, ethanol. gas and water revealing minute discrepancies in bond length and wider differences in bond angles. Frontier molecular orbital investigations reveal HOMO-LUMO energy gap magnitude in decreasing order of ATCTP_Gas > ATCTP_Water > ATCTP_ethanol > ATCTP_DMSO inferring that water influences chemical stability of the compound the most compared to ethanol and DMSO. Density of state investigations have revealed electron density contributions at corresponding energy peaks. In silico pharmacokinetic predicts ATCTP not to be cytotoxic, hepatotoxic, immunotoxic or mutagenic but probable mutagen. Molecular docking investigation of ATCTP against aspartic proteinase of <i>Candida albicans</i> (ID: 2QZX) in comparison with standard drug Fluconazole. Compound ATCTP had higher binding affinity (- 8.1 kcal/mol) compared to that of the standard drug fluconazole (- 5.6 kcal/mol) which records 4 conventional hydrogen interactions compared to 2 formed in the interaction of ATCTP + 2QZX. ATCTP also reports binding affinity of - 7.2 kcal/mol which reportedly surpassed that of 2QZX interaction with fluconazole (- 5.7 kcal/mol). ATCTP binds with lanosterol14-α-demethylase (5v5z) with binding affinity of - 9.7 kcal/mol binding to active site amino acid residues of the protein compared to fluconazole + 5v5z (- 8.0 kcal/mol). ATCTP is therefore recommended to be a lead compound for the possible design of a new and more effective anti-candida therapeutic compound.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"48"},"PeriodicalIF":0.0,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201634","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 docking of curcumin and curcuminoids as human Zn⁺ dependent histone deacetylase (HDAC) enzyme inhibitors.","authors":"Annuja Anandaradje, Bikashita Kalita, Mohane S Coumar, Sandhiya Selvarajan","doi":"10.1007/s40203-024-00221-4","DOIUrl":"10.1007/s40203-024-00221-4","url":null,"abstract":"<p><p>Chemotherapy is one of the most well-established and effective cancer treatments available. However, non-tumor-associated damage restrict the treatment's effectiveness and safety. Our growing understanding of cancer epigenetics has resulted in new therapeutic options and the potential of better patient outcomes in recent decades. In cancer, epigenetic changes are widespread, particularly increased expression and activity of histone deacetylases (HDACs). Epi-drugs are chemical agents that modify the structure of DNA and chromatin facilitating disruption of transcriptional and post-transcriptional changes. First generation epi-drugs include HDAC inhibitors (HDACi) (approved to treat hematological malignancies) harbor various adverse effects demanding the discovery and development of potential natural HDACi that might benefit cancer treatment especially in hematological malignancies. Curcumin (diferuloylmethane), a polyphenolic, component of <i>Curcuma longa</i>, is a well-known anti-inflammatory, anti-oxidative, and anti-lipidemic agent and has recently been shown to be a pan HDACi. Yet the potential of other curcuminoids in <i>Curcuma longa</i> as pan HDACi remains unexplored. (i) To virtually screen curcumin and curcuminoids (Desmethoxycurcumin [DMC] & Bisdemethoxycurcumin [BDMC]) against human Histone deacetylase (HDAC) class I, II and IV enzymes in comparison to their pan HDAC inhibition activity with FDA approved human HDACis available in market and also (ii) to predict the drug likeness property and ADME/ toxicity of curcumin, curcuminoids and approved HDACis via computational approach. Homology modelling followed by docking was performed for human HDAC class I, II and IV enzymes with curcumin, Desmethoxycurcumin, Bisdemethoxycurcumin and with 5 reference HDACi compounds Vorinostat (SAHA), Trichostatin A (TSA), Chidamide, Romidepsin, and Panobinostat to understand the protein -ligand interactions and binding efficiencies. Further, the study ligands with low binding energy were predicted for pharmacokinetic properties and Lipinski's rule of 5. Our study revealed that BDMC followed by DMC and curcumin had high inhibitory effect by interacting at the active site of Zn⁺ HDACs similar to that of the standard HDACi (curcumin, DMC, BDMC, Belinostat, Chidamide, Romidepsin, Panobinostat, Trichostatin A and Vorinostat). Likewise, all of the chosen ligand molecules, with the exception of Romidepsin (refractive index > 130 m³mol^-1), adhered to Lipinski's rule of five and none of the natural compounds (curcumin, DMC, BDMC) did report any toxicity and mutagenic property also, the lethal doses (LD50) of all the natural compounds were higher when compared to chemical drugs. BDMC could be a potential pan HDACi than curcumin and DMC owing to high binding affinity among human Zn⁺ HDACs. The results of our present study can be useful for the design and development of novel compounds having better HDAC inhibitory ","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11133269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141181736","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 pharmacokinetic and therapeutic evaluation of Musa acuminata peels against aluminium chloride-induced hepatotoxicity in adult BALB/c mice","authors":"H. Onohuean, Eseohe Fanny Onohuean, S. Igbinoba, Saidi Odoma, I. Usman, J. Ifie, A. Alagbonsi, Afodun Adam Moyosore, Godswill J. Udom, P. Agu, P. M. Aja, J. Ezeonwumelu, H. Al-kuraishy, G. Batiha, A. Osuntoki","doi":"10.1007/s40203-024-00216-1","DOIUrl":"https://doi.org/10.1007/s40203-024-00216-1","url":null,"abstract":"","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"78 1","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141105805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems biology approach: identification of hub genes, signaling pathways, and molecular docking of COL1A1 gene in cervical insufficiency.","authors":"Sushma Shah, Pooja Trivedi, Mohammadfesal Ghanchi, Gaurang Sindhav, Haresh Doshi, Ramtej J Verma","doi":"10.1007/s40203-024-00218-z","DOIUrl":"https://doi.org/10.1007/s40203-024-00218-z","url":null,"abstract":"<p><p>The collagen type I alpha 1 <b>(</b>COL1A1, OMIM #120,150) gene, encoding the alpha-1 chain of type I collagen (UniProt #P02452), plays a key role in life-homeostasis due to its remarkable involvement in collagen synthesis. It is a promising candidate gene implicated in the pathogenesis of cervical insufficiency (CI). This study aimed to identify genetic variations within the COL1A1 gene that contribute to the development of CI. Polymerase chain reaction (PCR) and amplicon sequencing were implemented for single nucleotide polymorphisms (SNPs) detection (+ 1245G/T, SP1 rs1800012), which revealed wild-type sequence for targeted SNPs in enrolled proband indicated negative results regarding COL1A1 gene involvement for current form of CI. It allows further investigation of other closely connected genes probed in this study. Computational approaches viz. Protein-protein interaction (PPI), gene ontology (GO), and pathway participation were used to identify the crucial hub genes and signaling pathways for COL1A1 and CI. Using the Yet Another Scientific Artificial Reality Application (YASARA) software, molecular docking, and molecular dynamic (MD) simulation with the oxytocin (CID 439,302), estradiol (CID 129,728,744), progesterone (CID 5994) and hydroxyprogesterone (CID 150,788) were done. Interactive bioinformatics analysis demonstrated that the COL1A1 and more than 10 collagen sister genes had a strong connection with CI. In sum, the findings of this study provide insights into a modus operandi that can be utilized to illuminate the path toward studying sister genes and smooth diagnosis of CI. These findings have implications for understanding the foundational process of the condition and potentially developing screening, diagnostic, and therapeutic interventions.</p><p><strong>Graphical abstract: </strong></p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"45"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959707","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":"Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of squalene against inflammation","authors":"S. S. Luke, M. N. Raj, Suraj Ramesh, N. P. Bhatt","doi":"10.1007/s40203-024-00217-0","DOIUrl":"https://doi.org/10.1007/s40203-024-00217-0","url":null,"abstract":"","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"33 10","pages":"1-18"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140981153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems biology approach: identification of hub genes, signaling pathways, and molecular docking of COL1A1 gene in cervical insufficiency","authors":"Sushma Shah, Pooja Trivedi, Mohammadfesal Ghanchi, Gaurang M. Sindhav, Haresh Doshi, Ramtej J. Verma","doi":"10.1007/s40203-024-00218-z","DOIUrl":"https://doi.org/10.1007/s40203-024-00218-z","url":null,"abstract":"","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 3","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140980602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-diabetic, anti-pancreatic lipase, and anti-protein glycation potential of <i>Irvingia gabonensis</i> stem bark extracts: in vitro and in silico studies.","authors":"Akhere A Omonkhua, Catherine Otitolaiye, Bobby Aguebor-Ogie, Olusola Elekofehinti, Edward Okello, Iyere Onoagbe, Friday Okonofua","doi":"10.1007/s40203-024-00219-y","DOIUrl":"10.1007/s40203-024-00219-y","url":null,"abstract":"<p><p>Diabetes mellitus is a chronic metabolic disorder that affects glucose, lipid, and protein metabolism. Targeting these metabolic derangements can optimize the therapeutic strategies for this disease. Utilizing in vitro and in silico models, this study investigated the ability of aqueous and ethanol extracts of <i>Irvingia gabonensis</i> to inhibit α-amylase, α-glucosidase, pancreatic lipase, and protein glycation. High-performance liquid chromatography (HPLC) was used to identify the compounds found in the stem bark of <i>I. gabonensis</i>. In silico analysis determined the binding mode and mechanism of interactions between the enzymes and phytochemicals. With an IC₅₀ value of 11.47 µg/ml, the aqueous extract demonstrated higher inhibitory efficacy against α-amylase compared to the ethanol extract (IC₅₀ 19.88 µg/ml). However, the ethanol extract had stronger inhibitory activities against α-glucosidase, pancreatic lipase, and protein glycation compared to the aqueous extract (IC₅₀ values of 3.05, 32.85, 0.0014 versus 25.72, 332.42, 0.018 µg/ml respectively). Quercetin ranked highest in binding energy with α-amylase (-6.6 kcal/mol), α-glucosidase (-6.6 kcal/mol), and pancreatic lipase (-5.6 kcal/mol). This was followed by rhamnetin (6.5, 6.5, and 6.1 kcal/mol respectively). Hydrogen bonding, hydrophobic interactions, and pi-pi stacking are forces responsible for the binding of quercetin and rhamnetin to these enzymes. Molecular dynamics simulation showed that the lead phytochemicals formed stable and energetically stabilized complexes with the target proteins. This study showed that the extracts of <i>I. gabonensis</i> stem bark had significant in vitro anti-diabetic, anti-pancreatic lipase, and anti-protein glycation activities. The strong binding affinities of some of the identified compounds could be responsible for the inhibitory potential of the extracts. <i>I. gabonensis</i> stem bark could be further explored as a natural remedy for the treatment of diabetes mellitus and its complications.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"43"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140946739","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":"Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of squalene against inflammation.","authors":"Shana Sara Luke, M Naveen Raj, Suraj Ramesh, N Prasanth Bhatt","doi":"10.1007/s40203-024-00217-0","DOIUrl":"https://doi.org/10.1007/s40203-024-00217-0","url":null,"abstract":"<p><p>Squalene (SQ) has been documented in the past for its ability to reduce inflammation, but its mechanism needs more information. In this study, we investigated squalene as an anti-inflammatory drug candidate and the framework involved in treating inflammation (INF) using the network pharmacology concept. The molecular targets of SQ and INF that are available in databases and the overlaps between these targets were demonstrated using InteractiVenn. The protein-protein networks were generated that in turn revealed several key targets and were further processed with Cytoscape. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) studies were performed. We also performed molecular docking tests that validated the binding affinity of molecular targets and drugs. A total of 100 SQ targets and 11,417 INF-related targets yielded 93 overlapping targets. Seven core targets, CRHR1, EGFR, ERBB2, HIF1A, SLC6A3, MAP2K1, and F2R were found to be relevant with respective to SQ's anti-inflammatory activity. The underlying mechanism of SQ with regard to INF was interpreted by analyzing various enrichment analyses along with the KEGG pathway. In conclusion, SQ played a vital role in the management of INF by regulating CRHR1, EGFR, ERBB2, HIF1A, SLC6A3, MAP2K1, and F2R. The research outcomes are crucial as they offer significant insights into the use of SQ for combating inflammation.</p><p><strong>Graphical abstract: </strong></p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00217-0.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"44"},"PeriodicalIF":0.0,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11093945/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959617","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 immunoinformatic approach for developing a multi-epitope subunit vaccine against Monkeypox virus.","authors":"Ashmad Kumar Nayak, Aritra Chakraborty, Sakshi Shukla, Nikhil Kumar, Sunanda Samanta","doi":"10.1007/s40203-024-00220-5","DOIUrl":"10.1007/s40203-024-00220-5","url":null,"abstract":"<p><p>An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00220-5.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"42"},"PeriodicalIF":0.0,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11089034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140924170","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 potential marine bioactive compounds from brown seaweeds towards BACE1 inhibitors: molecular docking and molecular dynamics simulations approach.","authors":"Anantha Krishnan Dhanabalan, Saranya Vasudevan, Devadasan Velmurugan, Mohd Shahnawaz Khan","doi":"10.1007/s40203-024-00210-7","DOIUrl":"10.1007/s40203-024-00210-7","url":null,"abstract":"<p><p>The drug target protein β-secretase 1 (BACE1) is one of the promising targets in the design of the drugs to control Alzheimer's disease (AD). Patients with neurodegenerative diseases are increasing in number globally due to the increase in the average lifetime. Neuro modulation is the only remedy for overcoming these age related diseases. In recent times, marine bioactive compounds are reported from Phaeophyceae (Brown Algae), Rhodophyta (Red Algae) and Chlorophyta (Green Algae) for neuro-modulation. Hence, an important attempt is made to understand the binding and stability of the identified bioactive compounds from the above marine algae using BACE1 as the molecular target. The docking study shows that the bioactive compound Fucotriphlorethol A ( - 17.27 kcal/mol) has good binding affinity and energy compared to other compounds such as Dieckol ( - 16.77 kcal/mol), Tetraphlorethol C ( - 15.12 kcal/mol), 2-phloroeckol ( - 14.98 kcal/mol), Phlorofucofuroeckol ( - 13.46 kcal/mol) and the co-crystal ( - 8.59 kcal/mol). Further, molecular dynamics simulations studies had been carried out for β-secretase 1 complex with Fucotriphlorethol A and Phlorofucofuroeckol for 100 ns each. Results are compared with that of the co-crystal inhibitor. Molecular dynamics simulations studies also support the stability and flexibility of the two bioactive compounds Fucotriphlorethol A and Phlorofucofuroeckol with BACE1.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s40203-024-00210-7.</p>","PeriodicalId":94038,"journal":{"name":"In silico pharmacology","volume":"12 1","pages":"40"},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11074097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140893070","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}