The Journal of Physical Chemistry B最新文献_第4页

Microscopic Origins of Flow Activation Energy in Biomolecular Condensates.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-05 DOI: 10.1021/acs.jpcb.4c05834

Sean Yang, Priya R Banerjee, Davit A Potoyan

{"title":"Microscopic Origins of Flow Activation Energy in Biomolecular Condensates.","authors":"Sean Yang, Priya R Banerjee, Davit A Potoyan","doi":"10.1021/acs.jpcb.4c05834","DOIUrl":"10.1021/acs.jpcb.4c05834","url":null,"abstract":"The material properties of biomolecular condensates govern their dynamics and functions by influencing the molecular diffusion rates and biochemical interactions. A recent report has identified a characteristic timescale of temperature-dependent viscosity in biomolecular condensates arising from an activated dissociation events collectively referred to as flow activation energy. The microscopic origin of this activation energy is a complex function of sequence, stoichiometry, and external conditions. In this study, we elucidate the microscopic origins of flow activation energy in single and multicomponent condensates formed from model peptide sequences with varying \"sticker\" and \"spacer\" motifs, incorporating RNA as a secondary component. We examined how condensate density, RNA stoichiometry, and peptide sequence patterning impact these properties through detailed sequence-resolved coarse-grained simulations. Our findings reveal that flow activation energy is closely tied to the lifetime of sticker-sticker interactions under specific conditions. However, the presence of multiple competing stickers may complicate this relationship leading to frustrated interactions in condensates and lowering of activation energy. The findings of this study should help to create predictive models of material properties of condensates, which in turn can facilitate a more profound understanding of functions and programmable design principles of biomolecular condensates.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12348-12357"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From Molecule to Aggregate: Understanding AIE through Multiscale Experimental and Computational Techniques.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-10 DOI: 10.1021/acs.jpcb.4c03744

Deeksha Rajput, Sanyam, Gaurav Rawat, Priyanshu Sorout, Sriram Kanvah, Anirban Mondal

{"title":"From Molecule to Aggregate: Understanding AIE through Multiscale Experimental and Computational Techniques.","authors":"Deeksha Rajput, Sanyam, Gaurav Rawat, Priyanshu Sorout, Sriram Kanvah, Anirban Mondal","doi":"10.1021/acs.jpcb.4c03744","DOIUrl":"10.1021/acs.jpcb.4c03744","url":null,"abstract":"Aggregation-induced emission (AIE) phenomena have garnered significant attention due to their applications in various fields, ranging from materials science to biomedicine. Despite substantial progress, the underlying mechanism governing the AIE activity of molecules remains elusive. This study employs a comprehensive and multiscale approach, combining experimental and theoretical methodologies, to discern the determinants of AIE activity. Our investigations involve synthesizing four organic molecules with D-π-A-D architecture, accompanied by quantum mechanics (QM) and molecular dynamics (MD) simulations, providing a deep understanding of the interactions within aggregates. The symmetry-adapted perturbation theory (SAPT) calculations further corroborate our findings, revealing a clear correlation between AIE activity and the type of aggregate formed. Specifically, we demonstrate that AIE-active molecules exhibit a distinctive J-type aggregation characterized by enhanced emission from the S1 state. In contrast, AIE-inactive molecules adopt an H-type aggregate configuration, where the emission from the S1 state is constrained. In addition, we investigated the subcellular localization of the molecules, revealing localization within the lipid droplets. Our findings contribute to the fundamental understanding of AIE phenomena and provide insights into the design principles for AIE-active materials with potential applications in advanced sensing and imaging technologies.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12559-12570"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the Bromoform Membrane Interactions Using Atomistic Simulations and Machine Learning: Implications for Climate Change Mitigation.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-06 DOI: 10.1021/acs.jpcb.4c04930

Kevin J Cheng, Jie Shi, Taras V Pogorelov, Sara Capponi

{"title":"Investigating the Bromoform Membrane Interactions Using Atomistic Simulations and Machine Learning: Implications for Climate Change Mitigation.","authors":"Kevin J Cheng, Jie Shi, Taras V Pogorelov, Sara Capponi","doi":"10.1021/acs.jpcb.4c04930","DOIUrl":"10.1021/acs.jpcb.4c04930","url":null,"abstract":"Methane emissions from livestock contribute to global warming. Seaweeds used as food additive offer a promising emission mitigation strategy because seaweeds are enriched in bromoform─a methanogenesis inhibitor. Therefore, understanding bromoform storage and production in seaweeds and particularly in a cell-like environment is crucial. As a first step toward this aim, we present an atomistic description of bromoform dynamics, diffusion, and aggregation in the presence of lipid membranes. Using all-atom molecular dynamics simulations with customized CHARMM-formatted bromoform force field files, we investigate the interactions of bromoform and lipid bilayer across various concentrations. Bromoform penetrates membranes and at high concentrations forms aggregates outside the membrane without affecting membrane thickness or lipid tail order. Aggregates outside the membrane influence the membrane curvature. Within the membrane, bromoform preferentially localizes in the membrane hydrophobic core and diffuses the slowest along the membrane normal. Employing general local-atomic descriptors and unsupervised machine learning, we demonstrate the similarity of bromoform local structures between the liquid and aggregated forms.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12493-12506"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mode-Specific Photoresponse of Retinal Protonated Schiff Base Isomers in the Reversible Photochromic Reactions of Microbial and Animal Rhodopsins.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-06 DOI: 10.1021/acs.jpcb.4c06832

Pavel A Kusochek, Olga A Smitienko, Anastasia V Bochenkova

{"title":"Mode-Specific Photoresponse of Retinal Protonated Schiff Base Isomers in the Reversible Photochromic Reactions of Microbial and Animal Rhodopsins.","authors":"Pavel A Kusochek, Olga A Smitienko, Anastasia V Bochenkova","doi":"10.1021/acs.jpcb.4c06832","DOIUrl":"10.1021/acs.jpcb.4c06832","url":null,"abstract":"The primary photoisomerization reactions of the all-trans to 13-cis and 11-cis to all-trans retinal protonated Schiff base (RPSB) in microbial and animal rhodopsins, respectively, occur on a subpicosecond time scale with high quantum yields. At the same time, the isolated RPSB exhibits slower excited-state decay, in particular, in its all-trans form, and hence the interaction with the protein environment is capable of changing the time scale as well as the specificity of the reaction. Here, by using the high-level QM/MM calculations, we provide a comparative study of the primary photoresponse of cis and trans RPSB isomers in both the initial forms and first photoproducts of microbial Krokinobacter eikastus rhodopsin 2 (KR2) and Halobacterium salinarum bacteriorhodopsin (BR), and animal Bos taurus visual rhodopsin (Rho). By simulating photoabsorption band shapes of RPSB inside the proteins, we show that its photoresponse is highly mode-specific for the forward reactions, resulting in excitation of those vibrational modes that facilitate particular double-bond isomerization. The reverse reaction shows specificity only for 13-cis isomers in microbial rhodopsins, whereas the specificity is lost for all-trans RPSB in visual rhodopsin. This indicates evolutionary highly tuned 11-cis chromophore-protein interactions in visual rhodopsin. We also highlight the differences in the photoresponse of RPSB in two microbial rhodopsins and discuss the implications to their excited-state dynamics.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12471-12482"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Solvatochromic Effects on the Absorption Spectrum of 2-Thiocytosine".

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-08 DOI: 10.1021/acs.jpcb.4c07835

Sebastian Mai, Brennan Ashwood, Philipp Marquetand, Carlos E Crespo-Hernández, Leticia González

引用次数: 0

Molecular Insights into the Penetration Enhancement Mechanism of Terpenes to Skin.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-09 DOI: 10.1021/acs.jpcb.4c05910

Xindong Yu, Shasha Liu, Ying Li, Shiling Yuan

{"title":"Molecular Insights into the Penetration Enhancement Mechanism of Terpenes to Skin.","authors":"Xindong Yu, Shasha Liu, Ying Li, Shiling Yuan","doi":"10.1021/acs.jpcb.4c05910","DOIUrl":"10.1021/acs.jpcb.4c05910","url":null,"abstract":"Terpenes are widely used in cosmetic formulations as chemical penetration enhancers (CPEs). However, the molecular mechanisms underlying the skin-penetration-enhancing effect have not been completely understood. In this work, molecular dynamics (MD) simulations were used to explore the influence of terpineol (TER), 1,8-cineole (CIN), and limonene (LIM) on the stratum corneum (SC) model. The results indicated that terpenes affected lipid membranes in a concentration-dependent manner and promoted skin permeation by disorganizing the cholesterol (CHOL) portion. The penetration of CPEs across the skin membrane also differed, with diffusion rates of limonene > 1,8-cineole > terpineol. The limonene molecules could penetrate the bilayer's center, forming a \"triple layer\" membrane structure. Furthermore, constrained simulations showed that the most favorable penetration pathway is via areas rich in CHOL. Terpineol could lower the energy barrier of the hydrophilic molecule (caffeic acid) across the cholesterol region. For the lipophilic molecule (osthole), limonene and 1,8-cineole could reduce the energy barrier across the cholesterol region. Each of the results provides novel insights into the mechanism of penetration of CPEs in the skin.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12507-12516"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Mechanistic Analysis of Liquid-Crystalline Polymers Composed of p-Hydroxybenzoic Acid I: Thermal Properties.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 DOI: 10.1021/acs.jpcb.4c06169

Kazushi Fujimoto, Hiroaki Ishikawa, Minoru Shimooka, Toshihiro Kaneko, Susumu Okazaki

{"title":"Molecular Mechanistic Analysis of Liquid-Crystalline Polymers Composed of p-Hydroxybenzoic Acid I: Thermal Properties.","authors":"Kazushi Fujimoto, Hiroaki Ishikawa, Minoru Shimooka, Toshihiro Kaneko, Susumu Okazaki","doi":"10.1021/acs.jpcb.4c06169","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06169","url":null,"abstract":"All-atom molecular dynamics (MD) calculations of the crystalline polymeric p-hydroxybenzoic acid (pHBA) were conducted at various temperatures to investigate its thermal response. The calculated structure factor equivalent to the X-ray diffraction pattern of pHBA clearly showed two phase transitions occurring at 600 and 650 K. The first transition at 600 K occurred from the orthorhombic phase to the pseudohexagonal phase, identified by the presence of the 211-peak. This peak disappeared during the second transition at 650 K, indicating that the phase at 650 K was hexagonal. The structure of the pseudohexagonal phase was anisotropic with respect to the ab plane but isotropic in the hexagonal phase. Discontinuous changes in the calculated unit cell volume and unit cell length were observed at 600 K, associated with the first phase transition. We also calculated the linear expansion coefficients in three directions. An anisotropic expansion was observed in three directions for the orthorhombic crystal. In particular, the linear expansion coefficient in the c-direction was negative. In contrast to this, an isotropic expansion was found in the a- and b-directions for the hexagonal crystal, while the expansion in the c-direction is still negative. This study provides valuable insights into the thermal behavior of polymeric pHBA, which is essential for understanding its structural transformations and designing crystalline polymers with tailored thermal properties.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Computational Approach to Modeling Excitation Energy Transfer and Quenching in Light-Harvesting Complexes.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 DOI: 10.1021/acs.jpcb.4c06617

Chris John, Laura Pedraza-González, Elena Betti, Lorenzo Cupellini, Benedetta Mennucci

{"title":"A Computational Approach to Modeling Excitation Energy Transfer and Quenching in Light-Harvesting Complexes.","authors":"Chris John, Laura Pedraza-González, Elena Betti, Lorenzo Cupellini, Benedetta Mennucci","doi":"10.1021/acs.jpcb.4c06617","DOIUrl":"https://doi.org/10.1021/acs.jpcb.4c06617","url":null,"abstract":"Light-harvesting complexes (LHCs) play a critical role in modulating energy flux within photosynthetic organisms in response to fluctuating light. Under high light conditions, they activate quenching mechanisms to mitigate photodamage. Despite their importance, the molecular mechanisms underlying these photoprotective processes remain incomplete. Herein, we present a computational protocol to model the energy pathways in the LHC, focusing specifically on the minor CP29 antenna complex of plants. We explore the factors that modulate the switch between the light-harvesting and quenched states. The protocol includes modeling the exciton Hamiltonian of the chlorophylls/lutein aggregate and calculating population dynamics using a kinetic model based on the Redfield-Förster approach. Our analysis reveals a highly tunable excited-state lifetime for the complex, that can switch between quenched and unquenched state depending on the excitation energy of the lutein, which acts as a final quencher, in accordance with recent experiments. Moreover, we observe that the s-trans lutein conformers are more likely to exhibit characteristics of the quencher.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Furopyridine Derivatives as Potent Inhibitors of the Wild Type, L858R/T790M, and L858R/T790M/C797S EGFR.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-05 DOI: 10.1021/acs.jpcb.4c06246

Duangjai Todsaporn, Alexander Zubenko, Victor G Kartsev, Panupong Mahalapbutr, Athina Geronikaki, Samvel N Sirakanyan, Lyudmila N Divaeva, Victoria Chekrisheva, Ilkay Yildiz, Kiattawee Choowongkomon, Thanyada Rungrotmongkol

{"title":"Furopyridine Derivatives as Potent Inhibitors of the Wild Type, L858R/T790M, and L858R/T790M/C797S EGFR.","authors":"Duangjai Todsaporn, Alexander Zubenko, Victor G Kartsev, Panupong Mahalapbutr, Athina Geronikaki, Samvel N Sirakanyan, Lyudmila N Divaeva, Victoria Chekrisheva, Ilkay Yildiz, Kiattawee Choowongkomon, Thanyada Rungrotmongkol","doi":"10.1021/acs.jpcb.4c06246","DOIUrl":"10.1021/acs.jpcb.4c06246","url":null,"abstract":"The treatment of patients with nonsmall cell lung cancer (NSCLC) using epidermal growth factor receptor (EGFR) inhibitors is complicated by drug-sensitive activating L858R/T790M and L858R/T790M/C797S mutations. To overcome drug resistance, a series of furopyridine (PD) compounds were virtually screened to identify potent EGFR inhibitors using molecular docking and molecular dynamics (MD) simulations based on the solvated interaction energy (SIE) method. Several PD compounds identified from virtual screening demonstrated the potential to suppress both wild-type and mutant forms of EGFR, with IC50 values in the nanomolar range. Among these, PD18 and PD56 exhibited highly potent inhibitory activity against both wild-type and mutant forms of EGFR, surpassing the efficacy of known drugs. Additionally, both PD compounds were cytotoxic to NSCLC cell lines (A549 and H1975) while being nontoxic to normal cell lines (Vero). The interaction mechanisms of both PD compounds complexed with wild-type and mutant forms of EGFR were elucidated through 500 ns molecular dynamics simulations. The predicted binding affinity from molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) correlated well with the experimental binding affinity derived from IC50 values. Furthermore, it was observed that van der Waals interactions, rather than electrostatic interactions, played a significant role in interacting with EGFR's active site. The strong inhibitory activity against EGFR was attributed to two key residues, M793 and S797, via hydrogen bonding, corresponding with lower solvent accessibility and a higher number of atomic contacts. Therefore, these potent compounds could be developed as promising drugs targeting both wild-type and mutant EGFR for the treatment of NSCLC.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12389-12402"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Probing the Conformational Ensemble of the Amyloid Beta 16-22 Fragment with Parallel-Bias Metadynamics.

IF 2.8 2区化学

The Journal of Physical Chemistry B Pub Date : 2024-12-19 Epub Date: 2024-12-05 DOI: 10.1021/acs.jpcb.4c04919

Timur Magsumov, Ilya Ibraev, Igor Sedov

{"title":"Probing the Conformational Ensemble of the Amyloid Beta 16-22 Fragment with Parallel-Bias Metadynamics.","authors":"Timur Magsumov, Ilya Ibraev, Igor Sedov","doi":"10.1021/acs.jpcb.4c04919","DOIUrl":"10.1021/acs.jpcb.4c04919","url":null,"abstract":"Aβ(16-22) is a segment of the Alzheimer's-related β-amyloid peptide that plays a crucial role in its aggregation. This study applies well-tempered parallel-bias metadynamics to investigate the impact of several denaturants and osmolytes on the conformational ensembles of both termini-capped and uncapped Aβ(16-22) monomers. Comparison of the different sets of collective variables in the metadynamics bias shows that using the set of backbone torsional angles results in better and faster convergence of simulations than employing more general structural characteristics of the short peptide. The equilibrium conformational ensembles of the peptides are characterized in pure water and in the presence of TMAO, urea, guanidinium chloride, and trifluoroethanol. In particular, trifluoroethanol and TMAO are found to increase the population of compact peptide conformations, whereas urea and guanidinium chloride favor extended structures. The analysis of the free energy surfaces in the presence of various substances with a comparison of the behavior of the capped and uncapped peptide forms reveals the role of different types of intrapeptide interactions such as salt bridges, hydrophobic contacts, and hydrogen bonds in stabilization of the compact or extended structures. As compounds reducing the abundance of the compact states of Aβ(16-22) and other disordered peptides are likely to suppress their amyloid fibril formation, simulations in the systems with this short peptide may be useful for the virtual screening of such compounds.","PeriodicalId":60,"journal":{"name":"The Journal of Physical Chemistry B","volume":" ","pages":"12333-12347"},"PeriodicalIF":2.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0