Protein Science最新文献

{"title":"A robust fluorogenic substrate for chikungunya virus protease (nsP2) activity.","authors":"Sparsh Makhaik, Wioletta Rut, Shruti Choudhary, Tulsi Upadhyay, Chenzhou Hao, Michael Westberg, Cedric Bobst, Euna Yoo, Jasna Fejzo, Michael Z Lin, Matthew Bogyo, Paul Thompson, Marcin Drag, Jeanne A Hardy","doi":"10.1002/pro.70069","DOIUrl":"10.1002/pro.70069","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is an emerging pathogen with pandemic potential. CHIKV infection in humans is transmitted by mosquitoes and induces common symptoms of high fever, arthralgia and myalgia. Because no specific antiviral drugs for treatment of CHIKV infection are available, drug development remains a central goal. The chikungunya virus protease from nsP2 (CHIKVP) has emerged as a key drug target due to its indispensable role in viral replication via cleavage of the viral polyprotein. To date, effective tools for screening for CHIKVP inhibitors that reflect the most critical polyprotein cleavage sites have been lacking, hampering drug-development efforts. We found that the recognition ability of CHIKVP is sensitive to the length of peptide substrates. In this study, we report a robust fluorogenic substrate comprising a 15-mer peptide derived from the nsP3/4 junction from the CHIKV polyprotein. This peptide is flanked by an ACC-Lys(dnp) donor-quencher pair. Our new substrate acc-CHIK₁₅-dnp shows a 30-fold improved signal-to-noise ratio as compared to the previously reported edab₈ substrate, which is also based on the nsP3/4 junction. We found acc-CHIK₁₅-dnp is recognized only by CHIKVP but not by other alphavirus proteases. This is surprising due to the high level of sequence conservation in the alpha virus polyprotein junctions and indicates that the P-side residues are more important than the P'-side sequence for effective CHIKVP cleavage. The robust signal-to-noise ratio obtained using acc-CHIK₁₅-dnp derived from the nsP3/4 cleavage site enabled much improved small molecule HTS on CHIKV relative to other fluorogenic reporters.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70069"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of a protein by a single halogen-based aromatic amplifier.","authors":"Krystel El Hage, Balamurugan Dhayalan, Yen-Shan Chen, Nelson B Phillips, Jonathan Whittaker, Kelley Carr, Linda Whittaker, Manijeh H Phillips, Faramarz Ismail-Beigi, Markus Meuwly, Michael A Weiss","doi":"10.1002/pro.70064","DOIUrl":"10.1002/pro.70064","url":null,"abstract":"<p><p>The utility of halogenation in protein design is investigated by a combination of quantitative atomistic simulations and experiment. Application to insulin is of complementary basic and translational interest. In a singly halogenated aromatic ring, regiospecific inductive effects were predicted to modulate multiple surrounding electrostatic (weakly polar) interactions, thereby amplifying changes in thermodynamic stability. In accordance with the simulations, we demonstrated stabilization of insulin by single halogen atoms at the ortho position of an invariant phenylalanine (2-F-Phe^B24, 2-Cl-Phe^B24, and 2-Br-Phe^B24; ΔΔG_u = -0.5 to -1.0 kcal/mol) located at the edge of a protein crevice; corresponding meta and para substitutions had negligible effects. Although receptor-binding affinities were generally decreased (in accordance with packing of the native Phe at the hormone-receptor interface), the ortho-analogs retained biological activity in mammalian cells and in a rat model of diabetes mellitus. Further, the ortho-modified analogs exhibited enhanced resistance to fibrillation above room temperature in two distinct assays of physical stability. Regiospecific halo-aromatic stabilization may thus augment the shelf life of pharmaceutical insulin formulations under real-world conditions. This approach, extending principles of medicinal chemistry, promises to apply to a broad range of therapeutic proteins and vaccines whose biophysical stabilization would enhance accessibility in the developing world.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70064"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docking guidance with experimental ligand structural density improves docking pose prediction and virtual screening performance.","authors":"Althea T Hansel-Harris, Andreas F Tillack, Diogo Santos-Martins, Matthew Holcomb, Stefano Forli","doi":"10.1002/pro.70082","DOIUrl":"10.1002/pro.70082","url":null,"abstract":"<p><p>Recent advances in structural biology have led to the publication of a wealth of high-resolution x-ray crystallography (XRC) and cryo-EM macromolecule structures, including many complexes with small molecules of interest for drug design. While it is common to incorporate information from the atomic coordinates of these complexes into docking (e.g., pharmacophore models or scaffold hopping), there are limited methods to directly leverage the underlying density information. This is desirable because it does not rely on the determination of relevant coordinates, which may require expert intervention, but instead interprets all density as indicative of regions to which a ligand may be bound. To do so, we have developed CryoXKit, a tool to incorporate experimental densities from either cryo-EM or XRC as a biasing potential on heavy atoms during docking. Using this structural density guidance with AutoDock-GPU, we found significant improvements in re-docking and cross-docking, important pose prediction tasks, compared with the unmodified AutoDock4 force field. Failures in cross-docking tasks are additionally reflective of changes in the positioning of pharmacophores in the site, suggesting it is a fundamental limitation of transferring information between complexes. We additionally found, against a set of targets selected from the LIT-PCBA dataset, that rescoring of these improved poses leads to better discriminatory power in virtual screenings for selected targets. Overall, CryoXKit provides a user-friendly method for improving docking performance with experimental data while requiring no a priori pharmacophore definition and at virtually no computational expense. Map-modification code available at: https://github.com/forlilab/CryoXKit.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70082"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11854350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An improved variant of tobacco etch virus (TEV) protease that does not need reducing agents.","authors":"Stella M Davis, Bryn L Romig, Alyssa A Abe, Nikolaus M Loening","doi":"10.1002/pro.70049","DOIUrl":"10.1002/pro.70049","url":null,"abstract":"<p><p>Here we show that a combination of previously suggested mutations for tobacco etch virus (TEV) protease results in a TEV protease mutant that maintains the same catalytic efficiency as previously described mutants but has enhanced stability and solubility. Another advantage of this new variant of TEV protease is that it does not need the inclusion of a reducing agent to maintain its effectiveness, making it easier to generate, store, and use in cleavage reactions compared to previous TEV protease mutants and, in particular, makes it a good choice for cleaving proteins that contain disulfide bonds that would otherwise be altered by the inclusion of a reducing agent. We also provide a straightforward purification protocol for generating this new version of TEV protease.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70049"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ExploreTurns: A web tool for the exploration, analysis, and classification of beta turns and structured loops in proteins; application to beta-bulge and Schellman loops, Asx helix caps, beta hairpins, and other hydrogen-bonded motifs.","authors":"Nicholas E Newell","doi":"10.1002/pro.70046","DOIUrl":"10.1002/pro.70046","url":null,"abstract":"<p><p>The most common type of protein secondary structure after the alpha helix and beta sheet is the four-residue beta turn, which plays many key structural and functional roles. Existing tools for the study of beta turns operate in backbone dihedral-angle (Ramachandran) space, which presents challenges for the visualization, comparison and analysis of the wide range of turn conformations. In this work, a new turn-local coordinate system and structural alignment, together with a set of geometric descriptors for turn backbone shape, are incorporated into ExploreTurns, a web facility for the exploration, analysis, geometric tuning and retrieval of beta turns and their contexts which combines the advantages of Ramachandran- and Euclidean-space representations. Due to the prevalence of beta turns in proteins, this facility, supported by its interpreter for a new general nomenclature which classifies H-bonded loop motifs and beta hairpins, serves as an exploratory browser and analysis tool for most loop structure. The tool is applied to the detection of new H-bonded loops, including short and \"double\" Schellman loops, a large family of beta-bulge loops with a range of geometries and H-bond topologies, and other motifs. Other applications presented here include the mapping of sequence preferences in Asx helix N-caps and an investigation of the depth dependence of beta-turn geometry. ExploreTurns, available at www.betaturn.com, should prove useful in research, education, and applications such as protein design, in which an enhanced Euclidean-space picture of turn and motif structure and the ability to identify and tune structures suited to particular requirements may improve performance.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70046"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 local unfolding fluctuations on the evolution of regional sequence preferences in proteins.","authors":"Keila Voortman-Sheetz, James O Wrabl, Vincent J Hilser","doi":"10.1002/pro.70015","DOIUrl":"10.1002/pro.70015","url":null,"abstract":"<p><p>The number of distinct structural environments in the proteome (as observed in the Protein Data Bank) may belie an organizing framework, whereby evolution conserves the relative stability of different sequence segments, regardless of the specific structural details present in the final fold. If true, the question arises as to whether the energetic consequences of amino acid substitutions, and thus the frequencies of amino acids within each of these so-called thermodynamic environments, could depend less on what local structure that sequence segment may adopt in the final fold, and more on the local stability of that final structure relative to the unfolded state. To address this question, a previously described ensemble-based approach (the COREX algorithm) was used to define proteins in terms of thermodynamic environments, and the naturally occurring frequencies of amino acids within these environments were used to generate statistical energies (a type of knowledge-based potential). By comparing compatibility scores from the statistical energies with energies calculated using the Rosetta all-atom energy function, we assessed the information overlap between the two approaches. Results revealed a substantial correlation between the statistical scores and those obtained using Rosetta, directly demonstrating that a small number of thermodynamic environments are sufficient to capture the perceived multiplicity of different structural environments in proteins. More importantly, the agreement suggests that regional amino acid distributions within each protein in any proteome have been substantially driven by the evolutionary conservation of the regional differences in stabilities within protein families.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70015"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein Data Bank Japan: Improved tools for sequence-oriented analysis of protein structures.","authors":"Gert-Jan Bekker, Chioko Nagao, Matsuyuki Shirota, Tsukasa Nakamura, Toshiaki Katayama, Daisuke Kihara, Kengo Kinoshita, Genji Kurisu","doi":"10.1002/pro.70052","DOIUrl":"10.1002/pro.70052","url":null,"abstract":"<p><p>Protein Data Bank Japan (PDBj) is the Asian hub of three-dimensional macromolecular structure data, and a founding member of the worldwide Protein Data Bank. We have accepted, processed, and distributed experimentally determined biological macromolecular structures for over two decades. Although we collaborate with RCSB PDB and BMRB in the United States, PDBe and EMDB in Europe and recently PDBc in China for our data-in activities, we have developed our own unique services and tools for searching, exploring, visualizing and analyzing protein structures. We have recently introduced a new UniProt-integrated portal to provide users with a quick overview of their target protein and shows a recommended structure with integrated data from various internal and external resources. The portal page helps users identify known genomic variations of their protein of interest and provide insights into how these modifications might impact the structure, stability and dynamics of the protein. Furthermore, the portal page also helps users to select the optimal structure to use for further analysis. We have also introduced another service to explore proteins using experimental and computational approaches, which enables experimental structural biologists to increase their insight to help them to more efficiently design their experimental studies. With these new additions, we have enhanced our service portfolio to benefit both experimental and computational structural biologists in their search to interpret protein structures, their dynamics and function.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70052"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FASTIA: A rapid and accessible platform for protein variant interaction analysis demonstrated with a single-domain antibody.","authors":"Ryo Matsunaga, Kouhei Tsumoto","doi":"10.1002/pro.70065","DOIUrl":"10.1002/pro.70065","url":null,"abstract":"<p><p>Antibodies are critical tools in medicine and research, and their affinity for their target antigens is a key determinant of their efficacy. Traditional antibody affinity maturation and interaction analyses are often hampered by time-consuming steps such as cloning, expression, purification, and interaction assays. To address this, we have developed FASTIA (Fast Affinity Screening Technology for Interaction Analysis), a novel platform that integrates rapid gene fragment preparation, cell-free protein synthesis, and bio-layer interferometry with non-regenerative analysis. Using this approach, we can analyze the intermolecular interactions of over 20 variants over 2 days, requiring only the parent protein expression plasmid and basic equipment. We have demonstrated the ability of FASTIA to discriminate between single-domain antibody variants with different binding affinities using the anti-HEL VHH antibody D2-L29, and mapped the results to the crystal structure to identify key interaction sites. FASTIA provides results comparable to those obtained using traditional methods. Our system bypasses the need for genetic engineering facilities and can be easily adopted by laboratories, accelerating the protein engineering and optimization processes. In addition, FASTIA is applicable to other protein-protein interactions, making it a versatile tool for studying molecular recognition. FASTIA facilitates efficient affinity maturation, protein engineering, and analysis of protein-protein interactions. This provides a rapid and accessible route for improving antibodies and a broader understanding of protein interactions.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70065"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taming interleukin-12: Engineering of bispecific antibody-based IL-12 mimetics with biased agonism capacities.","authors":"Britta Lipinski, Laura Unmuth, Paul Arras, Ron Endruszeit, Stefan Becker, Jonathan Mathias Rödel, Jürgen Scheller, Silke Pudewell, Doreen M Floss, Simon Krah, Julia Harwardt, Achim Doerner, Laura Helming, Chunxiao Xu, Andreas Menrad, Andreas Evers, Harald Kolmar, Desislava Elter, Lukas Pekar, Stefan Zielonka","doi":"10.1002/pro.70072","DOIUrl":"10.1002/pro.70072","url":null,"abstract":"<p><p>In this work, we have generated bispecific interleukin (IL)-12 surrogate agonists based on camelid-derived single-domain antibodies (sdAbs) targeting the IL-12 receptor (IL-12R) subunits IL-12Rβ1 and IL-12Rβ2. Following immunization and antibody display-based paratope isolation, respective sdAbs were combinatorially reformatted into a monovalent bispecific architecture by grafting resulting paratopes onto the hinge region of a heterodimeric Fc region. Functional characterization using NK-92 cells enabled the identification of multiple different sdAb-based bispecifics displaying divergent IL-12R agonism capacities as analyzed by STAT4 phosphorylation. Further investigations by harnessing peripheral blood mononuclear cells (PBMCs) from healthy donors revealed attenuated pSTAT4 activation compared to recombinant human (rh) wild-type IL-12 regarding both natural killer (NK)-cell and T-cell activation but robust IL-12R agonism on stimulated T cells. While several sdAb-based IL-12 mimetics were nearly inactive on NK cells as well as T cells obtained from PBMCs, they elicited significant STAT4 phosphorylation and interferon (IFN)-γ release on stimulated T cells as well as an IL-12-like transcriptional signature. Furthermore, we demonstrate that the activity of receptor agonism of generated bispecific IL-12 mimetics can also be biased towards stimulated T cells by changing the spatial orientation of the individual sdAbs within the molecular design architecture. Taken together, we present an alternative strategy to generate IL-12-like biologics with tailor-made characteristics.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70072"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nitro-fatty acids-mediated nitroalkylation modulates fine-tuning catalase antioxidant function during salinity stress in plants.","authors":"Mounira Chaki, Lorena Aranda-Caño, Juan C Begara-Morales, Beatriz Sánchez-Calvo, Francisco Javier López-Jaramillo, María N Padilla, Raquel Valderrama, José Rafael Pedrajas, Juan B Barroso","doi":"10.1002/pro.70076","DOIUrl":"10.1002/pro.70076","url":null,"abstract":"<p><p>Nitro-fatty acids (NO₂-FAs) are novel molecules resulting from the interaction of unsaturated fatty acids and nitric oxide (NO) or NO-related molecules. In plants, it has recently been described that NO₂-FAs trigger a powerful antioxidant and defense response against stressful situations, the induction of the heat-shock response (HSR), and they exert their signaling function mainly through a reversible post-translational modification called nitroalkylation. Catalase (CAT) is a key antioxidant enzyme for the control of the hydrogen peroxide (H₂O₂) levels generated by environmental oxidative stress. The data presented in this study provide novel information on the role of NO₂-FAs in modulating the antioxidant activity of catalase 2 (CAT2) during salinity stress in Arabidopsis thaliana. Initially, in vitro treatment with nitro-linolenic acid (NO₂-Ln) down-regulated Arabidopsis CAT2 activity, as a consequence of the nitroalkylation of His 156 and His 248, evolutionarily conserved residues with key functional implications for the quaternary structure and hence CAT2 activity. Any effect of NO₂-Ln on the heme group or S-nitrosylation of CAT2 was excluded. To further our knowledge of the regulatory mechanism of this antioxidant enzyme by nitroalkylation, the functional modulation of CAT by NO₂-FAs was analyzed in 5-day-old Arabidopsis cell suspension cultures subjected to salinity stress. In this situation, the oxidative stress generated caused the nitroalkylation of these residues to disappear through the cleavage of NO₂-Ln binding to CAT2, thus restoring CAT2 catalytic activity. Thus, during salinity stress, CAT2 enzymatic activity increased without changes in protein levels. These results highlight the amino acid targets that are susceptible to nitroalkylation and the modulatory effect of this post-translational modification on CAT2 enzymatic activity in vitro and in vivo. These findings underline the regulatory role of nitroalkylation in CAT2 functionality, which is strongly influenced by the redox state thus becoming a new key control mechanism of this antioxidant enzyme in abiotic stress cell response processes.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 3","pages":"e70076"},"PeriodicalIF":4.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11862108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}