Frontiers in Chemical Biology最新文献

{"title":"Impact of different spacers on the conjugation between Anderson-Evans polyoxometalates and peptides","authors":"Haihong Yu, C. Honisch, Mattia Frigo, Nicola Balice, Valeria Tagliavini, Xue Zhao, Elisabetta Stramiglio, Ambra Campofelice, Simona Serratì, Amalia Azzariti, L. Porcelli, Laura Zanetti Polzi, Stefano Corni, Paolo Ruzza, Mauro Carraro","doi":"10.3389/fchbi.2024.1377357","DOIUrl":"https://doi.org/10.3389/fchbi.2024.1377357","url":null,"abstract":"The Anderson-Evans polyoxometalates (POM) display a promising anticancer activity. The conjugation with the GRP-receptor antagonist peptide Demobesin (fQWAVGHL-NHEt) was exploited to impart cell targeting capabilities and improve the selectivity of such polyanions. However, the POM interacts with the grafted peptides, inducing chains folding and self-assembly of the resulting hybrids, thus decreasing their recognition ability. Within this context, a tailored spacer, including two domains, i.e., a hydrophilic one (1,13-diamino-4,7,10-trioxatridecan-succinamic acid, Ttds) and a tetra-anionic one (Glu-Glu-Glu-Glu-βAla, EEEE-βA) was previously utilized to mitigate such interaction. In this work, hybrid POMs containing only Ttds or EEEE-βA were prepared and the contribution of the two spacers was separately studied by using 2D NMR, fluorimetry and circular dichroism (CD). Transmission electron microscopy (TEM) was also used to observe the impact of the different spacers on self-assembly. Owing to the relevant effects observed for EEEE-βA, MD calculations were finally performed to elucidate its behavior when incorporated in the hybrid POM. Our results show that, despite the stronger impact of EEEE-βA spacer, only when both spacer are present together it is possible to observe a significant effect on the retention of peptide's secondary structure and recognition capability.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":" 896","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140383123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Conjugation of an anti-metabolite nucleobase analogue with a mitochondriotropic agent via palladium(II) against breast cancer cells","authors":"C. Banti, A. J. Tasiopoulos, S. Hadjikakou","doi":"10.3389/fchbi.2024.1338630","DOIUrl":"https://doi.org/10.3389/fchbi.2024.1338630","url":null,"abstract":"The conjugation of the uracil (a nucleobase) analogue, 6-methyl-thiouracil (MTUC), with the mitochondriotropic agent of Tri-o-Tolyl-Phosphine (TOTP) through palladium(II) leads to the formation of the metallodrug of formula [PdCl(TOTP)(MTUC)] (1). The metallodrug was characterized in solid state using Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray diffraction crystallography (XRD), while its behavior in solution was examined through Ultra Violet (UV) and 1H NMR spectroscopies. The in vitro cytotoxicity of 1 was assessed against human breast adenocarcinoma cell lines: MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)), as well as fetal lung fibroblast (MRC-5) cells. The MCF-7 cell morphology suggests apoptotic pathway, and this was confirmed by Acridine Orange/Ethidium Bromide (AO/EB) Staining, and the loss of the permeabilization of the mitochondrial membrane. The binding affinity of 1 toward the calf thymus (CT) DNA was clarified.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"27 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140420144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Mn coordination compounds be good candidates for medical applications?","authors":"Sandra Kozieł, Daria Wojtala, Magdalena Szmitka, Jacek Sawka, U. K. Komarnicka","doi":"10.3389/fchbi.2024.1337372","DOIUrl":"https://doi.org/10.3389/fchbi.2024.1337372","url":null,"abstract":"Metal centres provide unique foci for varied biological modes of action that often but not exclusively involve redox or metal-ligand reactions. Metal complexes offer alternative and flexible coordination geometries, electron and proton transfer sites, inner and outer sphere reactivities, sites for redox-active, hemi-labile, and non-innocent ligands, and a variety of potentially controllable properties for exploitation in a therapeutic or biological context. The discovery of the first anticancer, the metal-based compound cisplatin in 1965 by Barnett Rosenberg was a historical outstanding breakthrough and led to a new area of metal-drug discovery. Some metal-based compounds have FDA approval for clinical use, while some undergo clinical trials for various medical therapies. This mini-review focuses on recent progress on Mn-based complexes with potential anticancer, antibacterial, and antifungal activities.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"211 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140475044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Facing diseases caused by trypanosomatid parasites: rational design of multifunctional oxidovanadium(IV) complexes with bioactive ligands","authors":"Gonzalo Scalese, Ignacio Machado, Fabiana Salazar, E. L. Coitiño, Isabel Correia, J. Pessoa, Leticia Pérez-Díaz, D. Gambino","doi":"10.3389/fchbi.2023.1304571","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1304571","url":null,"abstract":"Searching for new prospective drugs against Chagas disease (American trypanosomiasis) and Leishmaniasis, a series of five heteroleptic vanadium compounds, [VIVO(L-H)(mpo)], where L are 8-hydroxyquinoline derivatives and mpo is 2-mercaptopyridine N-oxide, are synthesized and characterized. Comprehensive characterizations are conducted in solid state and in solution. The compounds are evaluated on epimastigotes and trypomastigotes of Trypanosoma cruzi and in promastigotes of Leishmania infantum, alongside on VERO cells, as a mammalian cell model. The compounds exhibit activity against both forms of T. cruzi and promastigotes of L. infantum, with the trypomastigote infective stage of T. cruzi displaying the highest sensitivity. The most selective vanadium compound [VIVO(L2-H)(mpo)], with L2 = 5-chloro-7-iodo-8-hydroxyquinoline, globally shows adequate selectivity towards the parasite and was selected to carry out further in-depth biological studies. [VIVO(L2-H)(mpo)] significantly impacted the infection potential of cell-derived trypomastigotes and hindered the replication of the T. cruzi amastigote form. Low total vanadium uptake by T. cruzi parasites and preferential accumulation in the soluble proteins fraction, with negligible localization in the DNA fraction, are determined. A trypanocide effect is observed across various concentrations of the compound. The generation of oxidative stress and the induction of mitochondria-dependent apoptosis are proposed as the main mechanisms of the parasite’s death by the VIVO compounds. Both theoretical predictions and experimental data support the hypothesis that inhibiting the parasite-specific enzyme NADH-fumarate reductase activity plays a crucial role in the trypanocidal action of these complexes. Globally, [VIVO(L-H)(mpo)] complexes could be considered interesting anti-T. cruzi agents that deserve further research.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":" 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139619756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative proteomics and applications in covalent ligand discovery","authors":"Ananya A. Basu, Xiaoyu Zhang","doi":"10.3389/fchbi.2024.1352676","DOIUrl":"https://doi.org/10.3389/fchbi.2024.1352676","url":null,"abstract":"The development of multiplexing technologies for proteomics has enabled the quantification of proteins on a global scale across samples with high confidence. In the covalent ligand discovery pipeline, quantitative proteomics can be used to establish selectivity profiles and provide critical mechanistic insight into the action of lead compounds. Current multiplexing systems allow for the analysis of up to eighteen samples in a single run, allowing proteomic analyses to match the pace of high-throughput covalent ligand discovery workflows. This review discusses several quantitative proteomic techniques and their applications in the field of covalent ligand discovery.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":" 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139618202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A natural product noraucupatin against multidrug-resistant Enterococcus faecium: an inhibition mechanism study","authors":"Fan Yu, Xiao-Le Han, Jiahua Zhu, Le Dai, Shuzhi Liu, Qingwei Liu, Jian Yang, Yue Sun, Lanping Guo, Xiao-Long Yang","doi":"10.3389/fchbi.2023.1181137","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1181137","url":null,"abstract":"Background: This work elucidates the antimicrobial activity and mechanism of action of the natural product noraucupatin against MDR Enterococcus faecium. E. faecium has become a major opportunistic pathogen with the worldwide spread of multidrug-resistant (MDR) isolates, especially vancomycin-resistant enterococci (VRE), belongs to “ESKAPE” organisms causing significant problems widely. Hence, there is a pressing need to discover new promising drugs or alternative therapies. Fortunately, we found a natural product noraucupatin (C13H12O3, a biphenyl compound) with “extremely encouraging” anti-clinical drug-resistant bacterial activity isolated from yeast-induced Rowan suspension cells. A comprehensive and in-depth exploration of antimicrobial mechanisms will bring fresh insights for researchers to develop novel antimicrobial strategies against MDR bacteria. Methods: The antibacterial effect of noraucupatin against MDR E. faecium is investigated from a microbial metabolism perspective using microcalorimetry. The antibacterial effect is determined based on the thermodynamic parameters. Based on spectroscopic techniques, microscopy techniques and confocal scanning laser microscopy with membrane probes, the antibacterial mechanism is elucidated definitely. Results: Comparing with the IC 50 of noraucupatin against MDR Enterococcus faecalis, MRSA, CRPA, the IC 50 of noraucupatin against MDR E. faecium was just 67.54 μM. The growth rate of MDR E. faecium decreases with the increase of concentration of noraucupatin. The bacterial intracellular structure entirely collapses and the slurries flow out under the influence of high levels of noraucupatin by TEM. The changes of membrane potential, permeability and evidences of nucleic acid leakage was obtained by CSLM and UV, the mechanism of noraucupatin against MDR E. faecium we explored. Conclusion: The present study highlights the excellent antibacterial activity of noraucupatin against MDR E. faecium by altering the permeability of the membrane and disrupting the membrane potential leading to electrolyte permeation. In addition, noraucupatin has excellent biocompatibility through its haemolytic activity in rabbit erythrocyte. These findings suggest that noraucupatin could be used in infectious diseases caused by MDR E. faecium.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"50 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131706347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Grand challenges in bioinorganic chemistry","authors":"I. Correia, S. Draper","doi":"10.3389/fchbi.2023.1165773","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1165773","url":null,"abstract":"In this combined grand challenge article, the specialty co-chief editors have attempted to pull-out the promising and burgeoning areas of bioinorganic chemistry both from a general and a personal perspective. Emphasising how these are dependent on inorganic syntheses, they seek to highlight the strengths and opportunities of these research directions and to suggest where aspects of these fields might be heading and why.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115590898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polyoxidovanadates [MoVIVV 9O28]5- and [H2PtIVVV 9O28]5- interact with CHO cell plasma membrane lipids causing aggregation and activation of a G protein-coupled receptor","authors":"Kateryna Kostenkova, Duaa Althumairy, A. Rajan, U. Kortz, B. Barisas, D. Roess, D. Crans","doi":"10.3389/fchbi.2023.1126975","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1126975","url":null,"abstract":"Mono substituted heteropolyoxidovanadates, when compared to effects of a corresponding isopolyoxidovanadate (POV), were found to be more effective initiators of signal transduction by a G protein-coupled receptor (GPCR), specifically the luteinizing hormone receptor (LHR). Here we report that LHRs signal productively when CHO cells expressing the receptor are treated with two heteropolyoxidovanadates PtIV in monoplatino(IV)nonavanadate(V) ([H2PtVIVV 9O28]5-, V9Pt), and MoIV in monomolybdo(VI)nonavanadate(V) (Mo[VIVV 9O28]5-, V9Mo). Both substituted decavanadate derivatives were more effective than decavanadate which is more charged, has greater stability and forms the [V10O28]6- anion (V10) in cell culture medium at pH 7.4. For viable CHO cells expressing 10 k or 32 k LHR/cell and treated with 11 μM V9Pt and 13 μM V9Mo, mono substituted heteropolyoxidovanadates significantly decreased the packing of plasma membrane lipids for about 1 h. This brief change in membrane structure was accompanied by increased aggregation of LHR and cell signaling as indicated by increased intracellular levels of cAMP. More pronounced changes in lipid packing and LHR signaling were associated with short acting heteropolyoxidovanadates than with the more stable V10. When LHR was overexpressed, V9Pt and V9Mo had little or no effect on membrane lipid packing or receptor aggregation and the LHR was constitutively activated as indicated by elevated intracellular cAMP levels. Speciation of V9Pt and V9Mo in H2O and cell medium was monitored using 51V NMR spectroscopy and confirmed that V9Pt and V9Mo had greater effects on CHO cells despite decomposing more rapidly in the cell growth medium. Thus, under conditions that promote CHO cell growth, V9Pt and V9Mo, despite their smaller molecular charge and their reduced stability, favor LHR signaling over that induced by V10. Importantly, under the same experimental conditions, CHO cells treated with V9Pt and V9Mo do not exhibit as strong toxic effects observed for cells treated with the longer lived V10. In summary, unlike the longer lived V10 which is more growth inhibitory to cells, monosubstituted heteropolyoxidovanadates are more effective in transiently initiating signaling by a G protein-coupled receptor but, because of rapid hydrolysis, inhibit cell growth less.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126071747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Specialty grand challenge: Structure, spectroscopy, and imaging","authors":"Ana Maria da Costa Ferreira","doi":"10.3389/fchbi.2023.1146814","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1146814","url":null,"abstract":"In the interdisciplinary field of chemical biology, different scientists, generally chemists and biologists, undertake their best efforts to develop advanced methodologies and innovative approaches to address important scientific goals and societal demands. Furthermore, confronting the complexity of problems to be solved and sophisticated systems to be discerned, the partnership of diverse other specialists is demanded, including physicists, spectroscopists, pharmacologists, and physicians. Collectively, their complemented work brings together several areas of research, experimental as well as theoretical, to accomplish higher levels of knowledge about the structural and functional characterization of biological systems. A profound understanding of life and its wide-ranging processes are their final aims. Recently, AlphaFold, a revolutionary artificial intelligence (AI) network, predicted the structures of more than 200 million proteins in a universe of 1 million species, reaching to determine the protein structures of nearly every organism with known protein sequence data. It made it possible to understand the relationships between protein functions and its 3D structures, and the results are now available to scientists in a database (Callaway, 2022). These data can certainly encourage numerous types of studies in the future. A significant example of the structural feature’s importance in basic and applied investigations is the development of messenger RNA (mRNA)-based therapeutics (Dammes and Peer, 2020). Since its discovery in the 1960s, improvements in its engineering to express therapeutic proteins or manipulate specific genes’ expression have enabled a broad range of applications in intractable diseases, such as severe infections, varied forms of cancer, and genetic diseases, besides new vaccines, and accelerate its clinical translation (Kim, 2022; Qin, Tang, Chen et al., 2022). Because of the unfavorable characteristics of mRNA’s, such as large size, instability, immunogenicity, sensitivity to enzymatic degradation by RNases, and limited cellular uptake, many pivotal issues had to be solved during the development of mRNA-based therapeutics. Additionally, a variety of delivery strategies, including nanolipids, exosomes, or polymeric micelles as carriers, was crucial for their wide applicability (Uchida et al., 2020). Moreover, investigations in this chemico–biological field frequently lead to the conception, design, and provision of new molecules capable of interacting efficiently with selected biomolecules, and consequently causing remarkable modifications in their functional behavior. Results can establish new parameters and lead to new drugs that are more efficient, safe, and selective in facing illnesses and syndromes. Significant examples are found in the literature, illustrating important and innovative chemical–biological studies. They include small peptides and large protein effects in Alzheimer’s disease (Picone et al., 2022), emerg","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132384112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the catalytic mechanism of the chlorothalonil dehalogenase from Pseudomonas sp. CTN-3","authors":"Xinhang Yang, Karla Diviesti, Callie Miller, B. Bennett, R. Holz","doi":"10.3389/fchbi.2023.1105607","DOIUrl":"https://doi.org/10.3389/fchbi.2023.1105607","url":null,"abstract":"The catalytically competent Co(II)-loaded form of the chlorothalonil dehalogenase from Pseudomonas sp. CTN-3 (Chd, EC 3.8.1.2) was characterized by kinetic and spectroscopic methods. Maximum chlorothalonil (TPN; 2,4,5,6-tetrachloroisophtalonitrile) dehalogenase activity was observed in the presence of one Co(II) ion per monomer with k cat and K m values of 12 ± 3 s−1 and 130 ± 10 μM, respectively, providing a catalytic efficiency (k cat/K m) of ∼9.2 × 104 M−1s−1. The dissociation constant (K d) for Co(II) was determined to be 0.29 µM, and UV-Vis spectroscopy indicated the active site Co(II) ion resides in a penta-coordinate environment. EPR spectra of Co1-Chd contain at least three distinct signals, an M S = ± 1/2 signal with a ∼94 G 59Co hyperfine pattern centered at g 1’ ≅ 6.7, a broader M S = ± 1/2 signal with g 1’ ≅ 5.7, an M S = ± 3/2 signal with tentatively estimated parameters of g 1’ ≅ 10.5 (g z = 2.75), A 1(59Co) ≅ 110 G, and a high-field broad resonance at g 3’ ≅ 1.8. Four substrate-analog inhibitors with IC50 values ranging from 110 μM to 19 mM were also identified and characterized. Upon the addition of each of the substrate-like inhibitors to Co1-Chd, changes in the EPR spectrum were observed that, in all cases, were simpler than that of Co1-Chd in the absence of inhibitors and could be simulated as either a single species or a mixture of two. Simulation of these data indicate that the corresponding EPR signals are each due to a ground state M S = 1/2 Kramers’ doublet and are consistent with pentacoordinate Co(II) with a relatively constrained coordination sphere. These data suggest that the nitrile moiety of TPN may not directly coordinate to the active site metal ion, providing new insight into the catalytic mechanism for Chd.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123868371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}