Biophysical chemistry最新文献

{"title":"Molecular dynamics of SARS-CoV-2 omicron variants from Philippine isolates against hesperidin as spike protein inhibitor","authors":"June Alexis A. Santos ,&nbsp;Searle S. Duay","doi":"10.1016/j.bpc.2024.107387","DOIUrl":"10.1016/j.bpc.2024.107387","url":null,"abstract":"<div><div>SARS-CoV-2 remains a global threat with new sublineages posing challenges, particularly in the Philippines. Hesperidin (HD) is being studied as a potential prophylactic for COVID-19. However, the virus's rapid evolution could alter how HD binds to it, affecting its effectiveness. Here, we study the mutation-induced variabilities of HD dynamics and their effects on molecular energetics in SARS-CoV-2 spike receptor complex systems. We considered eight different point mutations present in the Omicron variant. Root-mean-square deviation and binding energy analysis showed that S477N and Omicron did not eject HD throughout the simulation. Hydrogen bond distribution analysis highlighted the involvement of hydrogen bonding in mutant-HD stabilization, especially for S477N and Omicron. Root-mean-square fluctuation analysis revealed evidence of Y505H destabilization on complex systems, while distal-end loop mutations increased loop flexibility for all models bearing the three mutations. Per-residue energy decomposition demonstrated that Q493R substitution increased HD interaction. Free energy landscape and essential dynamics through principal component analysis provided insights into the conformational subspace distribution of mutant model molecular dynamics trajectories. In conclusion, significant mutations contributed to the HD interaction in different ways. S477N has shown significant binding contributions through favorable ligand interaction, while other mutations contribute via conformational modifications, increased affinity due to sidechain mutations, and increased loop flexibility.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107387"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macromolecular interaction mechanism of the bacteriocin EntDD14 with the receptor binding domain (RBD) for the inhibition of SARS-CoV-2 and the JN.1 variant: Biomedical study based on elastic networks, stochastic Markov models, and macromolecular volumetric analysis","authors":"Luis Moncayo Molina ,&nbsp;María Erlinda Aguaiza Pichazaca ,&nbsp;José Isidro Yamasqui Padilla ,&nbsp;María Eufemia Pinos Calle ,&nbsp;Karla Maribel Yamasqui Pinos ,&nbsp;Arlene Cardozo Urdaneta ,&nbsp;Carla Lossada ,&nbsp;Yovani Marrero-Ponce ,&nbsp;Felix Martinez-Rios ,&nbsp;Ysaías J. Alvarado ,&nbsp;Aleivi Pérez ,&nbsp;Lenin González-Paz","doi":"10.1016/j.bpc.2024.107388","DOIUrl":"10.1016/j.bpc.2024.107388","url":null,"abstract":"<div><div>Bacteriocins, a class of molecules produced by bacteria, exhibit potent antimicrobial properties, including antiviral activities. The urgent need for treatments against SARS-CoV-2 has proposed bacteriocins such as enterocin DD14 (EntDD14) as potential therapeutic agents. However, the mechanism of macromolecular interaction of EntDD14 for the inhibition of SARS-CoV-2 is not yet fully understood, and its efficacy against variants like JN.1 has not been completely established. To address these knowledge gaps, biocomputational analyses were employed using a diverse set of tools, including Markov state models and volumetric analyses. This analysis revealed a favorable interaction between EntDD14 and the receptor-binding domain (RBD) of SARS-CoV-2. Furthermore, it was found that EntDD14 induces changes in the flexibility of the RBD and alters the distribution and size of its internal cavities, particularly in the JN.1 variant. These findings align with experimental observations and support the inhibitory mechanism of EntDD14 against SARS-CoV-2. Additionally, they suggest that EntDD14 may possess a broader spectrum of action, encompassing the JN.1 variant. This study paves the way for future investigations and therapeutic applications, encouraging further exploration of the antiviral activity of bacteriocins like EntDD14 against variants of concern like JN.1. However, additional experimental demonstrations are warranted to substantiate these findings.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107388"},"PeriodicalIF":3.3,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of serotonin-receptor interactions, stability and signal transduction pathways via molecular dynamics simulations","authors":"Arunima Verma ,&nbsp;Padmabati Mondal","doi":"10.1016/j.bpc.2024.107386","DOIUrl":"10.1016/j.bpc.2024.107386","url":null,"abstract":"<div><div>Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT_1<em>B</em> receptor (5HT_1<em>B</em>R) via electrostatic interactions. Key residues for electrostatic interactions were identified via bond distance analysis and frustration analysis methods. An end-point free energy calculation method determines the stability of the 5-HT_1<em>B</em>R due to serotonin binding. The single-point mutation of the polar/charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the quantitative contribution of these residues to the stability of the serotonin-receptor complex. The principal component analysis reflects that the serotonin-bound 5-HT_1<em>B</em>R is more stabilized than the apo-receptor regarding dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembranes and mini-G_<em>o</em>, which indicates that the signal transduction happens between mini-G_<em>o</em> and the receptor. Allosteric pathway analysis reveals the key nodes and key pathways for signal transduction in 5-HT_1<em>B</em>R. These results provide useful insights into the study of signal transduction pathways and mutagenesis to regulate the binding and functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107386"},"PeriodicalIF":3.3,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cationic liposomes as carriers of natural compounds from plant extract","authors":"Claudia Bonechi ,&nbsp;Gabriella Tamasi ,&nbsp;Alessandro Donati ,&nbsp;Flavia Bisozzi ,&nbsp;Michele Baglioni ,&nbsp;Marco Andreassi ,&nbsp;Francesca Ietta ,&nbsp;Gemma Leone ,&nbsp;Agnese Magnani ,&nbsp;Claudio Rossi","doi":"10.1016/j.bpc.2024.107381","DOIUrl":"10.1016/j.bpc.2024.107381","url":null,"abstract":"<div><div>Lipid-based nanocarriers provide versatile platforms for the encapsulation and delivery of many different bioactive compounds to improve the solubility, stability and therapeutic efficacy of bioactive phyto-compounds. In this study, liposomes were used to load leaf extract of <em>Coffea Arabica</em>, which is known to be rich beneficial substances such as alkaloids, flavonoids, etc. The aim of this work is to optimize the valorization of agricultural wastes containing natural antioxidants. The physico-chemical properties of the liposomes loaded with chlorogenic acid or <em>Coffea arabica</em> leaf extract were evaluated. The average size of empty and loaded liposomes was found to range of 120–150 nm, which is consistent with the fact that the addition of chlorogenic acid or <em>Coffea arabica</em> leaf extract can change the average size of the vesicles without affecting the physicochemical properties of the lipid bilayer, which remain stable systems. A structural and morphological characterization as well as an evaluation of biological properties such as viability in normal human dermal fibroblasts, is also been carried out. The cationic liposomes show a good average size and low polydispersity index values, indicating that the liposomes tend to be monodisperse and therefore stable. In particular, DOPC/DOTAP liposomes generally have better properties than DOPC/DDAB liposomes for use as encapsulation systems for natural plant extracts.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107381"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and structural characterization of CB1 receptor antagonists: A comprehensive virtual screening and molecular dynamics study of arachidin-2","authors":"Ana C. Murrieta,&nbsp;Paola Mendoza-Espinosa,&nbsp;José Luis Velasco-Bolom,&nbsp;Flavio F. Contreras-Torres","doi":"10.1016/j.bpc.2024.107385","DOIUrl":"10.1016/j.bpc.2024.107385","url":null,"abstract":"<div><div>The cannabinoid receptor 1 (CB1) is an essential component of the endocannabinoid system, responsible for regulating various physiological processes such as pain, mood, and appetite. Despite increasing interest in the therapeutic potential of CB1 modulators, the precise mechanisms by which small molecules modulate receptor activity—particularly without fully transitioning between active and inactive states—remain partially understood. In this study, the complexity of CB1–ligand interactions was evaluated for the inactive CB1 state. A comprehensive pipeline, integrating ligand-based similarity search, 2D fingerprint-based reverse virtual screening and molecular dynamics (MD) simulations, identified compounds with core scaffolds commonly found in bioactive natural products, such as stilbenoids and polyphenolic compounds. Arachidin-2 (AR2) and a polyphenolic derivative were subjected to extended MD simulations, revealing their ability to stabilize the inactive CB1 state across key helices. The distinct stability differences observed in the helices HI, HIV, and HVI of the active CB1 state further highlighted ligand-specific conformational dynamics. A comparative analysis with co-crystallized synthetic ligands AM6538 and AM841 demonstrated the distinct binding behaviors of natural and synthetic ligands. AR2 showed more favorable binding to the inactive form (−22.0 kcal/mol) than to the active state. Similarly, the polyphenolic compound exhibited a greater binding difference (∼6 kcal/mol) between the inactive and active states. Notably, AM6538 and AM841 demonstrated the strongest binding (∼30 kcal/mol) to the inactive and active state, respectively. Key residues stabilizing the identified compounds in CB1-inactive state included PHE102, GLY166, PHE170, VAL196, LEU359, SER383, and CIS386. These findings underscore the utility of computational methods in the discovery and development of novel CB1 modulators for potential biomedical applications.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107385"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations","authors":"Prateek Kumar,&nbsp;Kumar Udit Saumya,&nbsp;Taniya Bhardwaj,&nbsp;Rajanish Giri","doi":"10.1016/j.bpc.2024.107384","DOIUrl":"10.1016/j.bpc.2024.107384","url":null,"abstract":"<div><div>Despite being mostly neglected in structural biology, the C-terminal Regions (CTRs) are studied to be multifunctional in humans as well as in viruses. Previously, SARS-CoV-2 Spike and NSP1 proteins' CTRs are observed to be disordered, and experimental evidence showed a gain of structure properties in different physiological environments. In this line, we have investigated the structural dynamics of CTR (residues 38–61) of SARS-CoV-2 ORF6 protein, disrupting bidirectional transport between the nucleus and cytoplasm. ORF6-CTR is disordered in nature but doesn't gain any structure in most conditions. As per studies, residue such as Methionine at 58th position in ORF6 is critical for interaction with Rae1-Nup98. Therefore, along with M58, we have identified a few other mutations from the literature and performed extensive structure modelling and dynamics studies using computational simulations. The exciting revelations in CTR models provide evidence of its structural flexibility and possible capabilities to perform multifunctionality inside the host.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107384"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating the pH-activity profile of the glucose isomerase from Thermotoga marimita by introducing positively and negatively charged residues","authors":"Weihuan Feng ,&nbsp;Qing Kong ,&nbsp;Xihui Wang ,&nbsp;Ke Zhao ,&nbsp;Chao Lv ,&nbsp;Zengyu Yu","doi":"10.1016/j.bpc.2024.107382","DOIUrl":"10.1016/j.bpc.2024.107382","url":null,"abstract":"<div><div>Glucose isomerase is generally used in the industrial production of high-fructose corn syrup, and a heat- and acid-resistant glucose isomerase is preferred. However, most glucose isomerases exhibit low activity or inactivation at low pH. In this study, we demonstrated that two combination mutants formed by introducing positive and negative charges near the active site and on the surface of the enzyme demonstrated a successful reduction in the optimal pH and increase in the specific activity of glucose isomerase from <em>Thermotoga maritima</em> (TMGI). Thirteen residues, eight surface amino acids and five near the vicinity of active sites, were selected by introducing positively charged residues near the active site (mutant E237R/N298K/N337R) and negatively charged residues at the enzyme surface (mutant R112E/K220E) and were site-mutated on the basis of computational analysis. In mutants E237R/N298K/N337R and R112E/K220E, there was a decrease in the optimal pH of the glucose isomerase from 7.0 to 6.0 and 5.5, respectively, and an increase in the optimal temperature of E237R/N298K/N337R from 95 °C to 100 °C. At pH 5.5 and pH 6.0, the specific activities of R112E/K220E and E237R/N298K/N337R were 2.81 and 1.79 times greater than that of the wild-type enzyme, respectively, and their thermostabilities were greater than that of TMGI. Therefore, these two mutants (E237R/N298K/N337R and R112E/K220E) have great potential for use in the industrial production of high-fructose corn syrup. Moreover, glucose isomerase was expressed in <em>Pichia pastoris</em>, which demonstrated that the high expression and secretion capacity of <em>Pichia pastoris</em> could be used to reduce the production cost of high-fructose corn syrup.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107382"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the therapeutic potential of novel TIGIT/PVR interaction blockers based advanced computational techniques and experimental validation","authors":"Xudong Lü ,&nbsp;Xiyu Wei ,&nbsp;Chenyu Wang ,&nbsp;Mengjia Tang ,&nbsp;Yuanyuan Jin ,&nbsp;Shuai Fan ,&nbsp;Zhaoyong Yang","doi":"10.1016/j.bpc.2024.107383","DOIUrl":"10.1016/j.bpc.2024.107383","url":null,"abstract":"<div><div>The inhibition of the TIGIT/PVR interaction demonstrates considerable anticancer properties by enhancing the cytotoxic activity of natural killer (NK) and CD8+ T cells. However, the development of small molecule inhibitors that target TIGIT is currently limited. In this study, small molecules with the capacity to bind TIGIT and block the TIGIT/PVR interaction were screened through an advanced computational process, subsequently confirmed by blocking assays. Combined machine learning model XGBOOST and centroid-based molecular docking were employed to expeditiously exclude negative molecules, thereby reducing the chemical space. Subsequently, a blockade assay targeting the TIGIT/PVR interaction was conducted on 14 candidate molecules along with positive control, wherein compound MCULE-5547257859 exhibited the most potent inhibitory effect. Molecular dynamics simulations and binding free energy analyses revealed that compound MCULE-5547257859 possesses a thermodynamically stable conformation, indicative of a stronger binding affinity to TIGIT. In conclusion, our investigation has delineated that compound MCULE-5547257859 effectively impedes the TIGIT/PVR interaction, thereby offering a novel therapeutic modality for oncology.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107383"},"PeriodicalIF":3.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural dynamics of a designed peptide pore under an external electric field","authors":"Ai Niitsu ,&nbsp;Jaewoon Jung ,&nbsp;Yuji Sugita","doi":"10.1016/j.bpc.2024.107380","DOIUrl":"10.1016/j.bpc.2024.107380","url":null,"abstract":"<div><div>Membrane potential is essential in biological signaling and homeostasis maintained by voltage-sensitive membrane proteins. Molecular dynamics (MD) simulations incorporating membrane potentials have been extensively used to study the structures and functions of ion channels and protein pores. They can also be beneficial in designing and characterizing artificial ion channels and pores, which will guide further amino acid sequence optimization through comparison between the predicted models and experimental data. In this study, we implemented a uniform external electric field function in the GENESIS MD simulation package to investigate the conformational dynamics of de novo-designed peptide pores. Our simulations and single-channel current recording experiments demonstrate that both charged amino acid residues in the N-terminal sequence of the peptide and the membrane potential are crucial for the structural stability and dynamics of the peptide pores. This suggests that MD simulations with an external electric field enable more accurate screening of designed proteins functioning under membrane potentials, which will ultimately contribute to a deeper understanding of voltage-sensitive membrane proteins from a bottom-up synthetic biology perspective.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107380"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B prevents the amyloid transformation of A53T mutant of α-synuclein","authors":"Almas Akhtar,&nbsp;Payal Singh,&nbsp;Nikita Admane,&nbsp;Abhinav Grover","doi":"10.1016/j.bpc.2024.107379","DOIUrl":"10.1016/j.bpc.2024.107379","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder involving the progressive loss of dopaminergic neurons in the substantia nigra pars compacta triggered by the accumulation of amyloid aggregates of α-synuclein protein. This study investigates the potential of Salvianolic Acid B (Sal<img>B), a water-soluble polyphenol derived from <em>Salvia miltiorrhiza Bunge</em>, in modulating the aggregation of the A53T mutant of α-synuclein (A53T Syn). This mutation is associated with rapid aggregation and a higher rate of protofibril formation in early-onset familial PD. Computational and experimental approaches demonstrated Sal-B effectively prevents the amyloid fibrillation of A53T Syn by interacting with the N-terminal region and NAC domain. Sal-B particularly associates with the KTKEGV motif and NACore segment of A53T Syn by hydrophobic and hydrogen bonding interactions. Replica exchange molecular dynamics (REMD) simulations indicated that Sal-B reduces intramolecular hydrogen bonding and structural transitions into β-sheet rich conformations, thereby lowering the aggregation propensity of A53T Syn. Systematic analysis conducted using biophysical techniques and high-end microscopy has demonstrated significant inhibition in the amyloid transformation of A53T Syn corroborated by a 92 % decrease in ThT maxima at 100 μM Sal-B concentration and microscopic techniques validated the absence of mature fibrillar amyloids. DLS data revealed heterogeneous particle sizes, supporting the formation of smaller unstructured aggregates. These findings underscore Sal-B as a promising therapeutic candidate for PD and related synucleinopathies, warranting further investigation in cellular and animal models to advance potential treatments and early intervention strategies.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107379"},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}