Biophysical chemistry最新文献

{"title":"Revealing the underlying mechanism of ZnO nanoparticles-induced modulation of structural features and thermodynamic stability of myoglobin","authors":"Beeta Kumari,&nbsp;Shabnam Yadav,&nbsp;Manisha Yadav,&nbsp;Rajesh Kumar","doi":"10.1016/j.bpc.2025.107487","DOIUrl":"10.1016/j.bpc.2025.107487","url":null,"abstract":"<div><div>Characterization by various surface morphological and compositional analysis techniques showed that ZnO NPs have a cylindrical crystalline structure with a size of ≤50 nm. The analysis of ZnO NPs effects on UV–visible, CD, fluorescence, and ¹H NMR spectra of horse myoglobin (h-MB) in aqueous and denaturant media at pH 7.4 revealed that ZnO NPs reinforce the urea impact by weakening the heme-globin interaction and protein structures in the denaturant medium. Analysis of ZnO NPs effects on urea- and heat-induced denaturation profiles of h-MB revealed that ZnO NPs reduce the local (heme-globin interaction) thermal stability of h-MB in an aqueous medium, but they decrease both local and structural thermodynamic stability in denaturant medium. Analysis of ZnO NPs effects on entropy-enthalpy plot, protein stability curve, and average fluorescence lifetime of h-MB revealed that the attractive enthalpic electrostatic interactions between the ZnO NPs and h-MB contribute to the decrease in thermodynamic stability of h-MB by ZnO NPs.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107487"},"PeriodicalIF":3.3,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549550","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":"Computational insights, synthesis and cytotoxicity evaluation of phenothiazine derivatives as a dual inhibitors targeting MAO-B and AChE","authors":"Neeru Dugar ,&nbsp;Ashish Mohanrao Kanhed ,&nbsp;Mohammed Afzal Azam ,&nbsp;Srikanth Jupudi","doi":"10.1016/j.bpc.2025.107486","DOIUrl":"10.1016/j.bpc.2025.107486","url":null,"abstract":"<div><div>Alzheimer's disease is a paragon of neurodegenerative diseases with prominent vagueness of cognitive impairment due to dysregulation of cholinergic and monoaminergic systems. This research employed molecular mechanics and quantum Mechanics to evaluate the plausible role of designed phenothiazine-derivatives as dual MAO-B and Acetylcholinesterase inhibitors. Synthesis and Cytotoxicity studies were performed for the eloquent molecules. <em>In-silico</em> studies revealed that halogens may enhance the binding affinity of compounds towards the target. NJ3b-d exhibited moderate inhibition in the SH-SY5Y cell lines compared with memantine (IC₅₀35.88 μg/ml). 150 ns MD studies revealed the stability of NJ3c (IC₅₀48.06 μg/ml) in the catalytic pockets of enzymes. DFT, pKa, BDE, Fukui-function, Epik-state, and membrane-permeability studies were performed to analyze the chemical stability and permeability. The results of QM displayed the compound NJ3c as BBB-permeable and it has thermal and kinetic stability. Our findings suggested that NJ3c can be considered a potential candidate for dual targeting MAO-B and Acetylcholinesterase.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107486"},"PeriodicalIF":3.3,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144517652","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":"The Boltzmann principle in the theory of enzymatic catalysis and conformational mobility of biomolecules","authors":"A.I. Osetsky","doi":"10.1016/j.bpc.2025.107485","DOIUrl":"10.1016/j.bpc.2025.107485","url":null,"abstract":"<div><div>The fluctuation microdeformations of biomolecules have been analyzed on the basis of Boltzmann principle taking into account their internal thermal dynamics. The “active biomolecule - passive medium” model, which is fundamentally different from the Brownian activation models, is considered. In the frame of that model, the exponential dependence of the reaction-rate constant of non-diffusion-controlled biochemical reactions on the dynamic viscosity of the medium has been obtained. The obtained dependencies are used to explain the experimentally observed deviations of the temperature behavior of the reaction-rate constant of enzymatic reactions from the Arrhenius equation and the influence of the medium viscosity on the conformational mobility of biomolecules.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107485"},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144490236","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":"From Markovian to Non-Markovian: Advancing ion channel rate process theory","authors":"Yuval Ben-Abu","doi":"10.1016/j.bpc.2025.107484","DOIUrl":"10.1016/j.bpc.2025.107484","url":null,"abstract":"<div><div>Ion channels are essential membrane proteins that control ionic flow and cellular electrical activity. While traditional Markovian models have provided insights into channel gating, they fail to capture the memory-dependent dynamics of real ion channel behavior. This manuscript presents a novel semi non-Markovian framework for understanding ion channel gating processes. Using continuous time and discrete state space models for two and three-state systems, we derive Volterra convolution-type integral equations governing channel dynamics. Through Laplace transform analysis, we reveal asymptotic behaviors and previously hidden asymmetries between opening and closing rates. Our approach successfully predicts asymmetrical gating kinetics, characterizes infinite-state processes, and elucidates dynamic state creation—capabilities beyond conventional Markovian models. This breakthrough moves from phenomenological descriptions toward understanding the fundamental physics of ion channel gating, with significant implications for drug discovery and therapeutic development targeting ion channel dysfunction. This work establishes a new paradigm in ion channel research, providing the mathematical framework needed to unlock the full complexity of these critical cellular processes.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107484"},"PeriodicalIF":3.3,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366883","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":"Next-generation antibacterial cryogels: Berberine-infused smart membranes with molecular docking-guided targeting of MRSA and MDR E. coli","authors":"Metin Yildirim ,&nbsp;Mehmet Cimentepe ,&nbsp;Kemal Dogan ,&nbsp;Adem Necip ,&nbsp;Madina Amangeldinova","doi":"10.1016/j.bpc.2025.107481","DOIUrl":"10.1016/j.bpc.2025.107481","url":null,"abstract":"<div><div>Multidrug-resistant (MDR) bacteria have become a significant global concern in recent years, necessitating the development of innovative strategies to combat these pathogens. Berberine, a bioactive alkaloid found in <em>Berberis vulgaris</em>, <em>Berberis aquifolium</em>, <em>Coptis chinensis</em>, <em>Coptis japonica</em>, and <em>Hydrastis canadensis</em>, exhibits a broad spectrum of biological activities, including antibacterial effects. However, its low aqueous solubility limits its bioavailability, restricting its therapeutic potential. Poly(2-hydroxyethyl methacrylate) (pHEMA)-based cryogel membranes, known for their biocompatibility and ease of synthesis, have been widely utilized in biomedical applications, particularly in wound healing. In this study, berberine was successfully incorporated into pHEMA cryogel membranes and characterized using FT-IR spectroscopy. Biocompatibility assessments were conducted using L929 fibroblast cells, and MTT assay results confirmed that cell viability remained above 88 %, indicating good biocompatibility. The antibacterial properties of the prepared membranes against MDR <em>E. coli</em> and MRSA were evaluated using the disk diffusion and time-kill methods. According to the time-kill assay, high-dose berberine-loaded cryogel membranes (BM2) exhibited inhibition rates of 87.2 % against MRSA and 96.8 % against MDR <em>E. coli</em>. The antibacterial and antibiofilm effects of the membranes were further validated by SEM imaging, which revealed that berberine effectively disrupted bacterial biofilms. To gain insight into the molecular mechanisms underlying antibacterial activity, molecular docking studies were performed on key bacterial proteins involved in essential physiological processes, including the OmpA transmembrane domain (PDB ID: <span><span>1BXW</span><svg><path></path></svg></span>), <em>E. coli</em> DNA gyrase B (PDB IDs: <span><span>4WUB</span><svg><path></path></svg></span>, <span><span>6KZX</span><svg><path></path></svg></span>, <span><span>6KZV</span><svg><path></path></svg></span>), <em>E. coli</em> hydrogenase (PDB ID: <span><span>5LMM</span><svg><path></path></svg></span>), penicillin-binding protein 3 (PBP3; PDB ID: <span><span>3VSL</span><svg><path></path></svg></span>), and PBP2a from MRSA (PDB IDs: <span><span>1MWT</span><svg><path></path></svg></span>, <span><span>4CJN</span><svg><path></path></svg></span>, <span><span>5M18</span><svg><path></path></svg></span>, <span><span>6Q9N</span><svg><path></path></svg></span>). The strongest interaction was observed between berberine and 6KZX, with a docking score of −7.898 kcal/mol, whereas the weakest interaction was noted with 4CJN, with a docking score of −3.743 kcal/mol. These findings highlight the potential of berberine-loaded pHEMA cryogel membranes as a promising antibacterial platform for combating MDR bacterial infections, particularly for wound healing applications.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107481"},"PeriodicalIF":3.3,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306232","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":"Raman spectroscopic signatures of amyloid fibrils: Insights into structural and biochemical changes in human tissues","authors":"N.S. Mohd Nor Ihsan ,&nbsp;S.F. Abdul Sani ,&nbsp;L.M. Looi ,&nbsp;Dharini Pathmanathan ,&nbsp;P.L. Cheah ,&nbsp;S.F. Chiew ,&nbsp;D.A. Bradley","doi":"10.1016/j.bpc.2025.107480","DOIUrl":"10.1016/j.bpc.2025.107480","url":null,"abstract":"<div><div>Amyloid fibrils, characterized by β-sheet-rich protein aggregates, are closely associated with various diseases. Understanding the structural and biochemical changes in amyloid formation requires detailed characterization of their Raman spectroscopic signatures. This study evaluated the application of Raman spectroscopy, utilizing a 532-nm laser excitation source, for differentiating amyloid from normal tissues. Raman spectroscopy effectively identifies protein secondary structures and distinguishes normal tissues from amyloid-containing tissues, offering potential for real-time diagnosis. A total of 13 amyloid tissue samples (heart, kidney, and thyroid) and 9 normal controls were analyzed. Key spectral differences were observed in the amide I (∼1660 cm⁻¹) and amide III (∼1300 cm⁻¹) regions, characteristic of β-sheet structures in amyloid fibrils. Spatially resolved Raman spectra revealed molecular heterogeneity between amide and lipid components in amyloid deposits. Ratiometric analysis further supported this, demonstrating significant differences in the amide-to-lipid ratio (with attributed significant peak intensities at 1660 cm⁻¹ for amide I and 1440 cm⁻¹ for lipids) between amyloid and control tissues. Statistical analysis (Mann-Whitney <em>U</em> test, <em>p</em> = 0.006) confirmed significant differences in amide group intensities between amyloid and control tissues. These findings highlight Raman spectroscopy as a promising tool for real-time identification and characterization of amyloid deposits, with potential clinical applications in diagnosing amyloid-related diseases.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107480"},"PeriodicalIF":3.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144254174","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":"Concentration-dependent structural transition of huntingtin protein in Huntington's disease","authors":"Ji-Na Yoo ,&nbsp;Ha-Neul Kim ,&nbsp;Su-Yeon Choi ,&nbsp;Yuxi Lin ,&nbsp;Young-Ho Lee ,&nbsp;Min-Duk Seo","doi":"10.1016/j.bpc.2025.107473","DOIUrl":"10.1016/j.bpc.2025.107473","url":null,"abstract":"<div><div>Huntington's disease (HD) is a genetic neurodegenerative disorder caused by the abnormal expansion of the polyglutamine (polyQ) tract (&gt; 35Q) in the first exon of the huntingtin (Htt), HttEx1. This N-terminal fragment tends to form fibrillar inclusions, which constitute a key pathological hallmark of HD. Although polyQ expansion is commonly understood to be a primary cause of HttEx1 pathology, the molecular mechanism of aggregations of non-pathogenic polyQ tract with the N-terminally flanking region of N17 in HttEx1 (HttEx1-17Q) remains largely unknown. In this study, we exclusively investigated the effect of the protein concentration on the structural transition of HttEx1-17Q and its relation to the amyloid fibril formation by employing biophysical techniques including nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy, transmission electron microscopy (TEM), atomic force microscopy (AFM), and thioflavin T (ThT) fluorescence. Complementary analyses showed that monomeric HttEx1-17Q undergoes a multiple structural transition from largely unfolded structures to β structures <em>via</em> helical structures in a concentration-dependent manner in the early stages of aggregation. This structural rearrangement accelerates kinetically the formation of short amyloid fibrils of HttEx1-17Q by facilitating nucleation. Our findings provide new insights into the amyloid formation of HttEx1 by highlighting the critical role of a structural conversion into an amyloidogenic structure, of which mechanism is helpful to understand amyloidogenesis of other amyloid-forming molecules.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107473"},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230942","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":"Redox-dependent structural and thermal stability of HMGB1: A thermodynamic analysis","authors":"Weronika Malicka ,&nbsp;Marten Kagelmacher ,&nbsp;Michel W. Jaworek ,&nbsp;Roland Winter ,&nbsp;Leïla Bechtella ,&nbsp;Kevin Pagel ,&nbsp;Beate Koksch ,&nbsp;Andreas Herrmann ,&nbsp;Jens Dernedde ,&nbsp;Thomas Risse ,&nbsp;Matthias Ballauff ,&nbsp;Marina Pigaleva","doi":"10.1016/j.bpc.2025.107472","DOIUrl":"10.1016/j.bpc.2025.107472","url":null,"abstract":"<div><div>HMGB1 is a highly conserved nuclear protein with functions that depend on its biological environment, which are linked to structural differences in the protein. Inside the cell, HMGB1 adopts a reduced form, regulating DNA transcription. In contrast, in the extracellular environment, it exists in a form with a closed disulfide bridge within the A-box motif playing a role in inflammation. We analyzed the stability of HMGB1 in these two redox states using differential scanning fluorimetry (nanoDSF), which enables high-precision thermal unfolding measurements with minimal protein quantities — something not previously feasible for HMGB1. The A-box domain was found to unfold reversibly in both redox forms, unlike the B-box. Surprisingly, the reduced form showed lower thermal stability but higher enthalpy of unfolding, indicating that it is enthalpically favorable and suggesting a significant difference in entropy contributions. For full-length HMGB1, both redox variants displayed similar thermal stability. However, only the reduced form was able to refold after unfolding; the disulfide form could not return to its native structure. Additionally, the reduced full-length variant exhibited a decrease in unfolding enthalpy, likely due to the destabilizing effect of its negatively charged C-terminal tail. Overall, the redox state has a strong influence on HMGB1's thermodynamic behavior. These thermodynamic differences can be linked to the protein's dual functionality: enhanced flexibility is beneficial for DNA transcription inside the nucleus. At the same time, increased conformational stability is advantageous for extracellular protein-protein recognition pathways.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107472"},"PeriodicalIF":3.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312702","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":"Effect of pyrimethanil on aβ42 aggregation mechanisms revealed at single entity level and molecular dynamic simulations","authors":"Nathan Meyer ,&nbsp;Nicolas Arroyo ,&nbsp;Lois Roustan ,&nbsp;Jean-Marc Janot ,&nbsp;Véronique Perrier ,&nbsp;Joan Torrent ,&nbsp;Fabien Picaud ,&nbsp;Sebastien Balme","doi":"10.1016/j.bpc.2025.107471","DOIUrl":"10.1016/j.bpc.2025.107471","url":null,"abstract":"<div><div>This study investigated the impact of pyrimethanil, a fungicide, on the aggregation of amyloid-β 42 (aβ42) peptides in vitro. The findings demonstrated that pyrimethanil accelerated aβ42 aggregation kinetics, as evidenced by thioflavin T (ThT) fluorescence assays in both tube and microplate experiments. A combination of single molecule techniques and molecular dynamics simulations is used to elucidate the complex effects of pyrimethanil on aβ42 aggregation mechanism. Nanopore experiments indicated that pyrimethanil promoted the formation of small oligomers (6-13.5 nm) during the lag phase, which were not detected under control conditions. Confocal fluorescence spectroscopy revealed that pyrimethanil induced the formation of larger β-sheet structured aggregates. In the presence of preformed seeds, pyrimethanil exhibited a dual role by fragmenting existing fibrils into smaller species and enhancing aggregation, likely through combined effects with the newly formed smaller seeds. Molecular dynamics simulations confirmed that pyrimethanil has a higher affinity for fibrils than monomers and weakens monomer-fibril interactions. Overall, this study elucidates the complex effects of pyrimethanil on aβ42 aggregation, involving promotion of primary nucleation, fibril fragmentation, and modulation of monomer-fibril interactions. These findings provide important mechanistic insights into how environmental factors like pesticides may influence amyloid aggregation processes relevant to Alzheimer's disease.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107471"},"PeriodicalIF":3.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212245","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":"Influence of local ordering in the permeation of Temozolomide through the brain plasmatic membrane","authors":"Yanhong Ge ,&nbsp;Huixia Lu ,&nbsp;Jordi Martí","doi":"10.1016/j.bpc.2025.107457","DOIUrl":"10.1016/j.bpc.2025.107457","url":null,"abstract":"<div><div>Temozolomide, a small-molecule drug, is primarily used to treat glioblastoma, a tumor that attacks both the spinal cord and brain. Understanding how Temozolomide interacts with different lipids within the brain cell membrane at the atomic level can help elucidate its ability to permeate through cell membranes. In this study, we constructed a simplified brain plasma membrane model to explore the microscopic structure and dynamics of Temozolomide using all-atom microsecond-scale molecular dynamics simulations. Temozolomide is typically found in the solvent-aqueous fluid surrounding the brain membrane, but it can access the membrane interface regularly and eventually bind to lipids of the choline and cerebroside classes. To investigate the free energy barriers of Temozolomide related to its crossing of brain-like plasma membranes, we employed adaptive biasing force methods. These simulations revealed that the free energy barriers ranged between 28 and 50 kcal/mol at temperatures between 310 K and 323 K. Our findings suggest that Temozolomide cannot cross the membrane by pure diffusion at normal human body temperature, but that rising the temperature significantly increases the probability of barrier crossing. This is primarily due to the crucial role played by cholesterol and lipids of the cerebroside class. These results can be used to optimise the molecular design of Temozolomide and develop new analogs with improved pharmacokinetic properties.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"324 ","pages":"Article 107457"},"PeriodicalIF":3.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169142","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}