Proteins-Structure Function and Bioinformatics最新文献

{"title":"Investigating Local Sequence-Structural Attributes of Amyloidogenic Light Chain Variable Domains.","authors":"Puneet Rawat, R Prabakaran, Divya Sharma, Vasanth Mandala, Victor Greiff, Sandeep Kumar, M Michael Gromiha","doi":"10.1002/prot.26815","DOIUrl":"https://doi.org/10.1002/prot.26815","url":null,"abstract":"<p><p>Light chain amyloidosis is a medical condition characterized by the aggregation of misfolded antibody light chains into insoluble amyloid fibrils in the target organs, causing organ dysfunction, organ failure, and death. Despite extensive research to understand the factors contributing to amyloidogenesis, accurately predicting whether a given protein will form amyloids under specific conditions remains a formidable challenge. In this study, we have conducted a comprehensive analysis to understand the amyloidogenic tendencies within a dataset containing 1828 (348 amyloidogenic and 1480 non-amyloidogenic) antibody light chain variable region (V_L) sequences obtained from the AL-Base database. Physicochemical and structural features often associated with protein aggregation, such as net charge, isoelectric point (pI), and solvent-exposed hydrophobic regions did not reveal a consistent association with the aggregation capability of the antibody light chains. However, the solvent-exposed aggregation-prone regions (APRs) occur with higher frequencies among the amyloidogenic light chains when compared with the non-amyloidogenic ones, with the difference ranging from 2% to 15% at various relative solvent-accessible surface area (rASA) cutoffs. We have, for the first time, identified structural gatekeeping residues around the APRs and assessed their impact on the amyloidogenicity of the antibody light chains. The non-amyloidogenic light chains contain these structural gatekeeper residues vicinal to their APRs more often than the amyloidogenic ones. We observed that the rASA cutoff of 35% is optimal for identifying the surface-exposed APRs, and a 4 Å distance cutoff from the APR motif(s) is optimal for identifying the structural gatekeeper residues. Moreover, lambda light chains were found to contain solvent-exposed APRs more often and surrounded by fewer gatekeepers, rendering them more susceptible to aggregation. The insights gained from this report have significant implications for understanding the molecular origins of light-chain amyloidosis in humans and the design of aggregation-resistant therapeutic antibodies.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the Role of RING-Between-RING E3 Ligase of the Human Malaria Parasite.","authors":"Varsha Kumari, Seema Vidyarthi, Aradhya Tripathi, Nirupa Chaurasia, Niharika Rai, Richa Shukla, Shagufa Nisrat Noorie, Girdhar Bhati, Simmi Anjum, Mohammad Anas, Shakil Ahmed, Niti Kumar","doi":"10.1002/prot.26813","DOIUrl":"https://doi.org/10.1002/prot.26813","url":null,"abstract":"<p><p>E3 ligases constitute an important component of proteostasis machinery, which plays a critical role in the survival of malaria parasites through post-translational modifications of their protein substrates. In contrast to humans, parasite E3 ligases have not been extensively studied. Here, we characterize a unique Plasmodium E3 ligase that has both RING and HECT-like features with zinc-coordinating domains. Plasmodium encodes a single RING-between-RING (RBR) E3 ligase that has evolutionarily diverged from human and other intracellular parasites. This RBR-E3 ligase is expressed throughout the erythrocytic phase of the P. falciparum lifecycle. Immunoprecipitation experiments showed that Pf RBR-E3 ligase catalyzes K6, K11, K48, and K63 mediated polyubiquitination, hinting towards its probable biological roles (DNA repair, proteasomal degradation, mitochondrial quality control). We observed that Pf RBR-E3 ligase interacts with UBCH5 and UBC13 family of E2-conjugating enzymes. Through mutational analysis in Pf RBR-E3 ligase, we identified residues in RING1 and RING2 domains that are critical for ubiquitination activity and its protein stability. Pf RBR-E3 ligase exhibits differences in immunofluorescence profile upon exposure of the parasite to different genotoxic (MMS) and proteotoxic (MG132, FCCP and artemisinin derivative) stress. Our study opens up avenues for exploring the client substrates of Pf RBR-E3 ligase and using this knowledge to design substrate-specific protein degradation-based alternative intervention strategies for malaria.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Implications of HIV-1 Protease Subtype C Bound to Darunavir: A Molecular Dynamics Study.","authors":"Sankaran Venkatachalam, Sowmya Ramaswamy Krishnan, Ramesh Pandian, Yasien Sayed, M Michael Gromiha","doi":"10.1002/prot.26817","DOIUrl":"https://doi.org/10.1002/prot.26817","url":null,"abstract":"<p><p>In recent years, Human Immunodeficiency Virus (HIV) remains a significant global health challenge, with millions affected worldwide, particularly in Africa and sub-Saharan regions. Despite advances in antiretroviral therapies, the genetic variability of HIV, including different subtypes and drug-resistant strains, poses persistent obstacles in the development of universally effective treatments. This study focuses on the dynamics of HIV protease, a key enzyme in viral replication and maturation, particularly targeting subtype C and its double insertion (HL) variant L38HL, in the context of interaction with Darunavir (DRV), a second-generation nonpeptidic protease inhibitor approved by the FDA in 2006. Through molecular dynamics simulations, structural analyses, dynamic cross-correlation analyses, and binding energy calculations, we investigated differences in the binding of DRV to WT and L38HL HIV-1 protease. The findings highlight that the double insertion at the hinge induces variation in Φ and Ψ angles, leading to increased residue fluctuations, solvent-accessible surface area (SASA), and radius of gyration (R_g). This alters the overall structural compactness and the hydrophobic core crucial for drug binding. Subtle structural changes result in the loss of hydrogen bond interactions, reducing the binding energy of L38HL HIV-1 protease subtype C bound to DRV, leading to drug resistance.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards a Greener AlphaFold2 Protocol for Antibody-Antigen Modeling: Insights From CAPRI Round 55.","authors":"Büşra Savaş, İrem Yılmazbilek, Atakan Özsan, Ezgi Karaca","doi":"10.1002/prot.26820","DOIUrl":"https://doi.org/10.1002/prot.26820","url":null,"abstract":"<p><p>In the 55th round of CAPRI, we used enhanced AlphaFold2 (AF2) sampling and data-driven docking. Our AF2 protocol relies on Wallner's massive sampling approach, which combines different AF2 versions and sampling parameters to produce thousands of models per target. For T231 (an antibody-peptide complex) and T232 (PP2A:TIPRL complex), we employed a 50-fold reduced MinnieFold sampling and a custom ranking approach, leading to a top-ranking medium prediction in both cases. For T233 and T234 (two antibody bound MHC I complexes), we followed data-driven docking, which did not lead to an acceptable model. Our post-CAPRI55 analysis showed that if we had used our MinnieFold approach on T233 and T234, we could have submitted a medium-quality model for T233 as well. In the scoring challenge, we utilized the scoring function of FoldX, which was effective in selecting acceptable models for T231 and medium-quality models for T232. Our success, especially in predicting and ranking a medium-quality model for T231 and potentially for T233, underscores the feasibility of green and accurate enhanced AF2 sampling in antibody complex prediction.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Crystal Structure of the Domain of Unknown Function 1480 (DUF1480) From Klebsiella pneumoniae.","authors":"Dhruvin H Patel, Nobuhiko Watanabe, Alexei Savchenko, Cameron Semper","doi":"10.1002/prot.26752","DOIUrl":"10.1002/prot.26752","url":null,"abstract":"<p><p>Domains of unknown function (DUFs) continue to comprise a significant portion of bacterial proteomes, with more than 20% of bacterial proteins remaining annotated as DUFs. The characterization of their molecular structure can provide valuable insight that is not captured by the primary sequence analysis, thus providing a segue into the identification of the molecular function of DUF representatives. Here, we present the crystal structure of KPN_02352 from Klebsiella pneumoniae subsp. pneumoniae, a DUF1480 domain-containing protein, which was determined to be 1.75 Å resolution. Representatives of the DUF1480 family are found broadly across Enterobacterales and have been previously shown to contribute to the antibiotic response. Our structural analysis suggests that DUF1480 is comprised of a six-stranded split barrel fold featuring a small alpha helix that is positioned to cap one end of the split barrel. DUF1480 was found to be monomeric in solution, and harbors structural similarity to response regulators. The crystal structure of DUF1480 is the first experimental insight into the molecular structure of this conserved protein family, revealing several conserved features that may be functionally relevant.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"569-574"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LGS-PPIS: A Local-Global Structural Information Aggregation Framework for Predicting Protein-Protein Interaction Sites.","authors":"Zhengli Zhai, Shiya Xu, Wenjian Ma, Niuwangjie Niu, Chunyu Qu, Chao Zong","doi":"10.1002/prot.26763","DOIUrl":"10.1002/prot.26763","url":null,"abstract":"<p><p>Exploring protein-protein interaction sites (PPIS) is of significance to elucidating the intrinsic mechanisms of diverse biological processes. On this basis, recent studies have applied deep learning-based technologies to overcome the high cost of wet experiments for PPIS determination. However, the existing methods still suffer from two limitations that remain to be solved. Firstly, the process of feature aggregation in most methods only took into account node features, but ignored the complex edge features of the target residue to its neighbor residues, resulting in insufficient local feature extraction. Secondly, such feature aggregation was limited to aggregating spatially adjacent residues, and could not capture the \"remote\" residues that played a critical role in determining PPIS, which can be summed up as the lack of global feature at the residue level. To break the above limitations, a local-global structural information aggregation framework, LGS-PPIS, was proposed in this study, including two modules of edge-aware graph convolutional network (EA-GCN) and self-attention integrated with initial residual and identity mapping (SA-RIM), which achieved the aggregation of local and global information for PPIS prediction. Evaluation results of LGS-PPIS showed that the proposed method outperformed state-of-the-art deep learning methods on three widely used PPIS prediction benchmarks. Besides, the results of ablation experiments demonstrated that the local features from spatially adjacent residues and global features from \"remote\" residues separately captured by EA-GCN and SA-RIM could benefit the model performance. Among them, the former was shown to have a more significant role in the PPIS prediction.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"716-727"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L858R/L718Q and L858R/L792H Mutations of EGFR Inducing Resistance Against Osimertinib by Forming Additional Hydrogen Bonds.","authors":"Ibrahim A Imam, Shatha Al Adawi, Xiaoqi Liu, Sally Ellingson, Christine F Brainson, Hunter N B Moseley, Ralph Zinner, Shulin Zhang, Qing Shao","doi":"10.1002/prot.26761","DOIUrl":"10.1002/prot.26761","url":null,"abstract":"<p><p>Acquired resistance to first-line treatments in various cancers both promotes cancer recurrence as well as limits effective treatment. This is true for epidermal growth factor receptor (EGFR) mutations, for which secondary EGFR mutations are one of the principal mechanisms conferring resistance to the covalent inhibitor osimertinib. Thus, it is very important to develop a deeper understanding of the secondary mutational resistance mechanisms associated with EGFR mutations arising in tumors treated with osimertinib to expedite the development of innovative therapeutic drugs to overcome acquired resistance. This work uses all-atom molecular dynamics (MD) simulations to investigate the conformational variation of two reported EGFR mutants (L858R/L718Q and L858R/L792H) that resist osimertinib. The wild-type EGFR kinase domain and the L858R mutant are used as the reference. Our MD simulation results revealed that both the L718Q and L792H secondary mutations induce additional hydrogen bonds between the residues in the active pocket and the residues with the water molecules. These additional hydrogen bonds reduce the exposure area of C797, the covalent binding target of osimertinib. The additional hydrogen bonds also influence the binding affinity of the EGFR kinase domain by altering the secondary structure and flexibility of the amino acid residues in the domain. Our work highlights how the two reported mutations may alter both residue-residue and residue-solvent hydrogen bonds, affecting protein binding properties, which could be helpful for future drug discovery.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"673-683"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PIM-1L Kinase Binds to and Inactivates SRPK1: A Biochemical and Molecular Dynamics Study.","authors":"Nastazia Lesgidou, Anastasia Koukiali, Eleni Nikolakaki, Thomas Giannakouros, Metaxia Vlassi","doi":"10.1002/prot.26757","DOIUrl":"10.1002/prot.26757","url":null,"abstract":"<p><p>SR/RS dipeptide repeats vary in both length and position, and are phosphorylated by SR protein kinases (SRPKs). PIM-1L, the long isoform of PIM-1 kinase, the splicing of which has been implicated in acute myeloid leukemia, contains a domain that consists largely of repeating SR/RS and SH/HS dipeptides (SR/SH-rich). In order to extend our knowledge on the specificity and cellular functions of SRPK1, here we investigate whether PIM-1L could act as substrate of SRPK1 by a combination of biochemical and computational approaches. Our biochemical data showed that the SR/SH-rich domain of PIM-1L was able to associate with SRPK1, yet it could not act as a substrate but, instead, inactivated the kinase. In line with our biochemical data, molecular modeling followed by a microsecond-scale all-atom molecular dynamics (MD) simulation suggests that the SR/SH-rich domain acts as a pseudo-docking peptide that binds to the same acidic docking-groove used in other SRPK1 interactions and induces inactive SRPK1 conformations. Comparative community network analysis of the MD trajectories, unraveled the dynamic architecture of apo SRPK1 and notable alterations of allosteric communications upon PIM-1L peptide binding. This analysis also allowed us to identify key SRPK1 residues, including unique ones, with a pivotal role in mediating allosteric signal propagation within the kinase core. Interestingly, most of the identified amino acids correspond to cancer-associated amino acid changes, validating our results. In total, this work provides insights not only on the details of SRPK1 inhibition by the PIM-1L SR/SH-domain, but also contributes to an in-depth understanding of SRPK1 regulation.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"629-653"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Alignments on the Accuracy of Protein Subcellular Localization Predictions.","authors":"Maryam Gillani, Gianluca Pollastri","doi":"10.1002/prot.26767","DOIUrl":"10.1002/prot.26767","url":null,"abstract":"<p><p>Alignments in bioinformatics refer to the arrangement of sequences to identify regions of similarity that can indicate functional, structural, or evolutionary relationships. They are crucial for bioinformaticians as they enable accurate predictions and analyses in various applications, including protein subcellular localization. The predictive model used in this article is based on a deep - convolutional architecture. We tested configurations of Deep N-to-1 convolutional neural networks of various depths and widths during experimentation for the evaluation of better-performing values across a diverse set of eight classes. For without alignment assessment, sequences are encoded using one-hot encoding, converting each character into a numerical representation, which is straightforward for non-numerical data and useful for machine learning models. For with alignments assessment, multiple sequence alignments (MSAs) are created using PSI-BLAST, capturing evolutionary information by calculating frequencies of residues and gaps. The average difference in peak performance between models with alignments and without alignments is approximately 15.82%. The average difference in the highest accuracy achieved with alignments compared with without alignments is approximately 15.16%. Thus, extensive experimentation indicates that higher alignment accuracy implies a more reliable model and improved prediction accuracy, which can be trusted to deliver consistent performance across different layers and classes of subcellular localization predictions. This research provides valuable insights into prediction accuracies with and without alignments, offering bioinformaticians an effective tool for better understanding while potentially reducing the need for extensive experimental validations. The source code and datasets are available at http://distilldeep.ucd.ie/SCL8/.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"745-759"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11809130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of N-Terminal Domain Conformation and Domain Interactions on RfaH Fold Switching.","authors":"Bahman Seifi, Stefan Wallin","doi":"10.1002/prot.26755","DOIUrl":"10.1002/prot.26755","url":null,"abstract":"<p><p>RfaH is a two-domain metamorphic protein involved in transcription regulation and translation initiation. To carry out its dual functions, RfaH relies on two coupled structural changes: Domain dissociation and fold switching. In the free state, the C-terminal domain (CTD) of RfaH adopts an all-α fold and is tightly associated with the N-terminal domain (NTD). Upon binding to RNA polymerase (RNAP), the domains dissociate and the CTD transforms into an all-β fold while the NTD remains largely, but not entirely, unchanged. We test the idea that a change in the conformation of an extended β-hairpin (β3-β4) located on the NTD, helps trigger domain dissociation. To this end, we use homology modeling to construct a structure, H₁, which is similar to free RfaH but with a remodeled β3-β4 hairpin. We then use an all-atom physics-based model enhanced with a dual basin structure-based potential to simulate domain separation driven by the thermal unfolding of the CTD with NTD in a fixed, folded conformation. We apply our model to both free RfaH and H₁. For H₁ we find, in line with our hypothesis, that the CTD exhibits lower stability and the domains dissociate at a lower temperature T, as compared to free RfaH. We do not, however, observe complete refolding to the all-β state in these simulations, suggesting that a change in β3-β4 orientation aids in, but is not sufficient for, domain dissociation. In addition, we study the reverse fold switch in which RfaH returns from a domain-open all-β state to its domain-closed all-α state. We observe a T-dependent transition rate; fold switching is slow at low T, where the CTD tends to be kinetically trapped in its all-β state, and at high-T, where the all-α state becomes unstable. Consequently, our simulations suggest an optimal T at which fold switching is most rapid. At this T, the stabilities of both folds are reduced. Overall, our study suggests that both inter-domain interactions and conformational changes within NTD may be important for the proper functioning of RfaH.</p>","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"608-619"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}