{"title":"Molecular mechanisms of Lobeline-mediated inhibition of lysozyme amyloidogenesis: A synergistic approach using biophysical and cheminformatics techniques","authors":"Vibeizonuo Rupreo , Ria Saha , Jhimli Bhattacharyya , Rajib Kumar Mitra","doi":"10.1016/j.bpc.2025.107502","DOIUrl":"10.1016/j.bpc.2025.107502","url":null,"abstract":"<div><div>Numerous pathological conditions, collectively termed amyloidosis, are associated with the aggregation of misfolded proteins under stressed physiochemical conditions. Natural compounds capable of modulating protein aggregation or disassembling preformed fibrils hold promise as potential therapeutic candidates for treating aggregation-related diseases. In this study, we aim to examine the binding interaction and effectiveness of Lobeline (Lob), a piperidine alkaloid, in preventing the formation of acid-denatured Lysozyme (Lyz) amyloid using various spectroscopic, cheminformatics and imaging techniques. Steady-state and time-resolved fluorescence measurements confirm a direct interaction between Lyz and Lob with a binding constant of ∼10<sup>6</sup> M<sup>−1</sup> with a 1:1 binding stoichiometry. The association has been found to be spontaneous and is driven by entropy involving non-electrostatic interactions. Molecular Docking shows that Lob stabilizes Lyz by hydrophobic and hydrophilic interactions. The anti-amyloid properties of Lob in Lyz amyloid fibrils are assessed through a range of in vitro techniques, including turbidity measurement, dynamic light scattering (DLS), Thioflavin T (ThT) fluorescence, Circular Dichroism studies and Field Emission Scanning Electron Microscopy (FESEM) imaging. These studies demonstrate that Lob halts the fibrillation of acid-treated Lyz at the nucleation stage by providing alternative pathways for hydrogen bonding and other weak interactions with key amino acid residues necessary for the formation of oligomers and fibrils.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"326 ","pages":"Article 107502"},"PeriodicalIF":2.2,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750822","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}
Huzaifa Yasir Khan , Yassir Hasan Khan , Md Nadir Hassan , Azeem Ahmad , Rizwan Hasan Khan , Farukh Arjmand
{"title":"Inhibition of nucleation and disruption of amyloid fibrillation in human lysozyme aggregation by a potent Cu(II) flufenamate chemotherapeutic drug candidate","authors":"Huzaifa Yasir Khan , Yassir Hasan Khan , Md Nadir Hassan , Azeem Ahmad , Rizwan Hasan Khan , Farukh Arjmand","doi":"10.1016/j.bpc.2025.107493","DOIUrl":"10.1016/j.bpc.2025.107493","url":null,"abstract":"<div><div>Amyloid fibrillation is a key feature in the pathogenesis of various protein misfolding diseases. This process is driven by both primary and secondary nucleation mechanisms. Many small molecules are known to modulate protein aggregation, with certain anticancer drugs demonstrating the ability to interfere with amyloid formation. In lieu of above rationale, with the aim to repurpose anticancer drugs for other therapeutic remedies, we investigated the potential of an ionic anticancer chemotherapeutic drug candidate, namely aquachlorobis(DACH)copper(II) flufenamate complex; [{Cu(DACH)<sub>2</sub>(H<sub>2</sub>O)Cl}.(fluf)] for the inhibition of amyloid formation in Human lysozyme protein. Utilizing various biophysical techniques, <em>viz.</em>, distinctive dye binding assays, confocal microscopy, and dynamic light scattering experiments, the potency of Cu(II) complex to inhibit human lysozyme fibrillation was studied. Our findings demonstrated that Cu(II) complex significantly disrupted amyloid fibrillation by targeting and inhibiting both primary and secondary nucleation pathways. The results indicated the high effectiveness of Cu(II) complex in preventing Human Lysozyme fibrillation, making it a promising candidate for addressing amyloidosis and paving a way for repurposing anticancer drug scaffolds as anti-AD agents.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"326 ","pages":"Article 107493"},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672260","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":"Molecular crowding effect on specific binding of Hg2+ to T–T mismatched base pair in duplex DNA","authors":"Hidetaka Torigoe, Sumire Nakayama","doi":"10.1016/j.bpc.2025.107492","DOIUrl":"10.1016/j.bpc.2025.107492","url":null,"abstract":"<div><div>Many biomolecules are crowded in vivo environments. Metal ion–nucleic acid interactions are important in vivo molecular crowding conditions for structure formation and biological activity of nucleic acids. Although metal ion–nucleic acid interactions have been investigated in detail under diluted conditions, studies examining the molecular crowding effect on metal ion–nucleic acid interactions are limited. Hg<sup>2+</sup> specifically binds to T–T mismatched duplex DNA to form T–Hg–T base pair under diluted conditions. Here, we examined the binding under molecular crowding conditions. To the best of our knowledge, no previous studies reported the metal-mediated base-pair formation under molecular crowding conditions. UV melting showed that the specific stabilization of only the T–T mismatched duplex by Hg<sup>2+</sup> addition was maintained under molecular crowding conditions. CD spectra showed that no significant structural change of the T–T mismatched duplex by Hg<sup>2+</sup> addition was preserved under molecular crowding conditions. Isothermal titration calorimetric analyses showed that the 1:1 M ratio for the specific binding of Hg<sup>2+</sup> to T<em>–</em>T was maintained under molecular crowding conditions. However, the magnitudes of the negative ∆<em>H</em> and the positive ∆<em>S</em> were significantly larger and smaller, respectively, than those under diluted conditions, which may lead to the smaller magnitudes of <em>K</em><sub>a</sub> and ∆<em>G</em>. Smaller number of released water molecules upon the binding under molecular crowding conditions may result in these results. The present findings may be useful for developing efficient metal-mediated base-pair formation, leading to progress in their efficient applications in various fields including nanotechnology.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"326 ","pages":"Article 107492"},"PeriodicalIF":3.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144623810","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}
Shreyada N. Save , Soumya S. Sahoo , Kalyani Ananthamohan , Saleem Yousf , Pratishtha Singh , Osama Aazmi , Jeetender Chugh , Shilpy Sharma
{"title":"Mapping the metabolic perturbations associated with palmitate-induced oxidative stress and development of insulin resistance in skeletal muscle cells","authors":"Shreyada N. Save , Soumya S. Sahoo , Kalyani Ananthamohan , Saleem Yousf , Pratishtha Singh , Osama Aazmi , Jeetender Chugh , Shilpy Sharma","doi":"10.1016/j.bpc.2025.107490","DOIUrl":"10.1016/j.bpc.2025.107490","url":null,"abstract":"<div><div>The development of insulin resistance (IR) in the skeletal muscle has been identified as one of the hallmarks of Type 2 diabetes mellitus (T2DM). Studies have shown that palmitic acid (PA), a saturated free fatty acid (FFA), can contribute to the development of IR in various insulin-responsive tissues via the induction of oxidative stress and mitochondrial dysfunction. The specific molecular mechanisms and metabolic changes that lead to IR development are not completely defined, and a better understanding of these mechanisms is needed. Our study aims to identify metabolites linked with the development of IR in skeletal muscles using PA and map the major metabolic pathways involved. Rat-derived L6 myotubes were exposed to PA to establish IR. Cellular and biochemical experiments were performed, and the metabolic perturbations associated with the induction of oxidative stress and IR were identified using <sup>1</sup>H NMR-based metabolomics. PA exposure was associated with a loss of cellular viability due to lipid accumulation in the myotubes. This was associated with an induction of oxidative stress, loss of function, and reduced mitochondrial membrane potential. The metabolic fingerprint linked with the development of oxidative stress and IR in skeletal muscles was identified, wherein significant perturbations in the levels of methanol, dimethylamine, serine, lysine, proline, glycerol, and alanine (<em>p</em> < 0.05) were observed. The dysregulated metabolites and pathways identified in this study can be proposed as biomarkers for detecting palmitate-induced oxidative stress and development of IR in the skeletal myotubes – phenotypes associated with T2DM and related metabolic disorders.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"326 ","pages":"Article 107490"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654622","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}
Michael Overduin , Gestél C. Kuyler , Mansoore Esmaili , Catharine A. Trieber , Claudia Acevedo-Morantes , Alexander P. Orazietti , Rustem Shaykhutdinov , Rakesh K. Bhat , Tomisin Omotoso , Sabiha Tajammul , Mohammad Rahim , Sophie Zinn-Justin , Russell E. Bishop , R. Scott Prosser , Holger Wille , Bert Klumperman
{"title":"Design of zwitterionic fluorescent polymers for membrane protein solubilization into native nanodiscs","authors":"Michael Overduin , Gestél C. Kuyler , Mansoore Esmaili , Catharine A. Trieber , Claudia Acevedo-Morantes , Alexander P. Orazietti , Rustem Shaykhutdinov , Rakesh K. Bhat , Tomisin Omotoso , Sabiha Tajammul , Mohammad Rahim , Sophie Zinn-Justin , Russell E. Bishop , R. Scott Prosser , Holger Wille , Bert Klumperman","doi":"10.1016/j.bpc.2025.107489","DOIUrl":"10.1016/j.bpc.2025.107489","url":null,"abstract":"<div><div>Copolymers formed by non-alternating distributions of styrene and maleic acid monomers directly solubilize intact membranes into ∼10 nm discs. However, these copolymers are inherently polydisperse in terms of polymer structure, difficult to detect, prone to precipitation with divalent cations, and have limited working pH ranges due to their charges. The exposed polar sidechain of nanodisc-forming amphipathic copolymers provides a handle for integrating critical chemical features for facile solubilization, purification, detection, and resolution of diverse membrane protein complexes, including 7-transmembrane G-Protein-Coupled Receptor (GPCR) and beta-barrel proteins directly from cellular material. Here, we report that when derivatized with amine oxide (AO) moieties, alternating and intrinsically fluorescent derivatives of poly(styrene-<em>alt</em>-maleic anhydride) (SMAnh) spontaneously convert biological membranes into nanodiscs with diameters of 15–30 nm that can be resolved by dynamic light scattering and electron microscopy. Compared to non-alternating poly(styrene-<em>co</em>-maleic acid) (SMA), their fluorescence signals allow monitoring under diverse solution conditions, whether free or lipid bilayer-bound. These copolymers are useful in a broad pH range, are tolerant of high levels of divalent cations (>200 mM CaCl<sub>2</sub>) and are designed to reduce undesirable nonspecific interactions. The resulting nanodiscs can accommodate the PagP palmitoyltransferase expressed in <em>Escherichia coli</em> outer membranes and the human adenosine A<sub>2A</sub> receptor expressed into <em>Pichia pastoris</em> membranes, resulting in readily purified proteins that are less likely to be perturbed by polymer charge or hydrophobicity.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107489"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144606028","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":"Diagnostic biomarkers for Sepsis and septic shock: A NMR based serum metabolomics study","authors":"Swarnima Pandey , Afzal Azim , Neeraj Sinha","doi":"10.1016/j.bpc.2025.107491","DOIUrl":"10.1016/j.bpc.2025.107491","url":null,"abstract":"<div><div>Despite the availability of advanced treatment, sepsis and septic shock have the highest mortality in the intensive care unit. Theories suggested that targeting hyper inflammation can aid treatment, but oxidative stress plays a major role in disease pathogenesis. The present study aimed to explore the nuclear magnetic resonance (NMR) – based serum biomarkers of sepsis and septic shock resultant of oxidative stress. The serum metabolic profile of <em>n</em> = 41 septic shock, <em>n</em> = 21 sepsis, and <em>n</em> = 16 disease control patients were collected and analyzed using a 1D <sup>1</sup>H Carr Purcell Meiboom Gill (CPMG) pulse program. NMR spectroscopy-based quantitative assessment of metabolites was performed to compare the activity of lactate dehydrogenase and phenylalanine hydroxylase between sepsis, septic shock, and disease control in sepsis and septic shock by comparing pyruvate/lactate (Pyr/Lac) and phenylalanine/tyrosine (Phe/Tyr) ratios. These ratios were evaluated for their discriminatory potential, statistical and clinical significance. We found out that Pyr/Lac ratio was lowest in septic shock followed by sepsis and disease control, Phe/Tyr ratio was highest in septic shock, followed by sepsis and disease control. Pyr/Lac ratio and Phe/Tyr were negatively and positively correlated with APACHE II. Both the ratios illustrated high discriminatory potential in AUROC evaluation. The results presented in the study demonstrate that lactate dehydrogenase activity is elevated and phenylalanine hydroxylase declines in septic shock. This could be used as an effective tool for diagnosis, prognosis, evaluation of disease activity, and treatment response.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"326 ","pages":"Article 107491"},"PeriodicalIF":3.3,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654621","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":"Local optical probing of proteins of various sizes and charges with FITC label","authors":"D.P. Surzhikova , E.V. Nemtseva , L.A. Sukovatyi , A.V. Borgoyakova , E.A. Slyusareva","doi":"10.1016/j.bpc.2025.107488","DOIUrl":"10.1016/j.bpc.2025.107488","url":null,"abstract":"<div><div>Fluorescein dyes are widely applied in fluorescence bioimaging to visualize a spatial distribution of substructures or to monitor a kinetics of certain processes in cells. However, optical properties of the dyes are sensitive to a number of physical and chemical parameters of the microenvironment and, when conjugated to a macromolecule, the dye can additionally serve as an indicator of these parameters in near-surface regions. The present study aims to reveal the relationships between the response of the fluorescein probe and the structure of the macromolecule to which it is attached. We conjugated fluorescein-5-isothiocyanate (FITC) to four proteins of different sizes and surface charges (hen egg-white lysozyme, bovine carbonic anhydrase II, bovine serum albumin, and luciferase from <em>Photobacterium leiognathi</em>) and analyzed the relationship of spectral, time-resolved, and polarization characteristics of the fluorescence probe with protein size and charge parameters. The study shows that ionic equilibrium of FITC and dielectric permittivity (ε) near the protein surface differ from those in the bulk phase at pH 6.50. For the first time, a strong negative correlation between local ε and the hydrophobic surface area of the protein and a strong positive correlation between net charge density of protein and the ratiometric fluorescence signal of FITC (I<sup>488</sup>/I<sup>435</sup>) were found. The combined effect of covalent and electrostatic binding of FITC to the protein was found to increase the rigidity of conjugation, allowing adequate estimation of protein size using the fluorescence depolarization technique.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"325 ","pages":"Article 107488"},"PeriodicalIF":3.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572788","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":"Revealing the underlying mechanism of ZnO nanoparticles-induced modulation of structural features and thermodynamic stability of myoglobin","authors":"Beeta Kumari, Shabnam Yadav, Manisha Yadav, 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 <sup>1</sup>H 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 , Ashish Mohanrao Kanhed , Mohammed Afzal Azam , 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 (IC<sub>50</sub>35.88 μg/ml). 150 ns MD studies revealed the stability of NJ3c (IC<sub>50</sub>48.06 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}