Protein Science最新文献

{"title":"Understanding the stability landscape of LbCas12a by deep analysis of stabilizing mutations and mutation combinations.","authors":"Jiajun Dong, Shaojie Wang, Wenxue Xu, Jingyao Xin, Jia Liu","doi":"10.1002/pro.70280","DOIUrl":"https://doi.org/10.1002/pro.70280","url":null,"abstract":"<p><p>Cas12a is one of the most widely used Cas nucleases for genome editing and in vitro diagnosis. A number of engineered Cas12a mutants have been identified with improved activity and stability. However, it remains largely unaddressed how these mutations interact. In a previous study, we used a deep learning model to evolve the stability of Lachnospiraceae bacterium Cas12a (LbCas12a) and obtained about 90 mutants with improved stability. In the present study, we performed a deep analysis of these stabilizing mutations and mutation combinations to understand the stability landscape of LbCas12a. It was found that most of the stabilized mutants had shifted fitness, as characterized by higher trans-cleavage activity at high temperatures but lower activity at the \"fit\" temperature for the parent protein. These stabilizing mutations were found to have sophisticated epistatic effects. Stabilizing mutation S962K improved protein stability in the context of other stabilizing mutations but by itself exhibited minor improvements. Saturation mutagenesis of S962 had differential effects on the stability of wild-type (WT) LbCas12a and C10L/I976L/C1090D variant, despite similar melting temperatures (T_m) for WT (41.9°C) and C10L/I976L/C1090D (41.1°C). Interestingly, 12 out of 19 amino acid substitutions at S962 reduced the T_m in the context of WT LbCas12a, while 18 out of 19 mutations increased T_m in the C10L/I976L/C1090D variant. We also showed that stabilizing mutations could recover the stability and trans-activity of a destabilized LbCas12a variant. Our findings can facilitate the understanding of LbCas12a natural evolution and provide insights to developing novel engineering strategies for Cas nucleases.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70280"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12369400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966428","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":"DR and SPIT: Statistical approaches for identifying transient structure in intrinsically disordered proteins via NMR chemical shifts.","authors":"Dániel Kovács, Andrea Bodor","doi":"10.1002/pro.70250","DOIUrl":"10.1002/pro.70250","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs) play key roles in various biological processes; they are associated with liquid-liquid phase separation and are targets in disorder-based drug design. Efforts to identify their structural propensities-that can be linked to molecular recognition, malfunction, targeting-still lead to ambiguous results. Secondary structure is routinely assessed by NMR spectroscopy by calculating the secondary chemical shifts (SCSs). Focusing on a given environment in the polypeptide backbone, SCSs highlight the deviation from the \"random coil\" state. However, the analysis is dependent on which of the numerous random coil chemical shift (RCCS) predictors is applied in the calculations, resulting in an especially pronounced ambiguity for IDPs. To overcome this, we introduce two novel statistical tools that enable the sound identification of structural propensities. We propose the chemical shift discordance ratio (DR) for prefiltering RCCS predictors based on self-consistency. Further on, we introduce the Structural Propensity Identification by t-statistics (SPIT) approach for extracting maximum information from SCS data by using multiple RCCS predictors simultaneously. This way SCS patterns indicating structural propensities can be clearly distinguished from the \"noise\". The applicability of these methods is demonstrated for four proteins of varying degrees of disorder. Ubiquitin and α-synuclein are used as respective benchmarks for a globular and a disordered protein, while two proline-rich IDPs are included as especially challenging molecules in secondary structure analysis.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70250"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356139/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856115","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":"Probing the extent of importin-α targeting of the TAF8 NLS by eliminating its cationic net-charge.","authors":"Amirabbas Abdoli, Zhihan Yang, Abdullah Odeh-Ahmed, Olga Bednova, Bruno Lemieux, Leanne Dawe, Aymeric Ravel-Chapuis, Pierre Lavigne, Natalie Zeytuni, Jeffrey V Leyton","doi":"10.1002/pro.70272","DOIUrl":"https://doi.org/10.1002/pro.70272","url":null,"abstract":"<p><p>The nucleus, as the control center of the eukaryotic cell, is a prime target for therapeutic interventions due to its role in regulating genetic material. Importin-α is critical for successful nuclear import as it recognizes and binds to cargo proteins bearing a classical nuclear localization signal (NLS), which facilitates their transport from the cytoplasm into the nucleus. NLS tagging to 'actively' import therapeutics provides the most effective means of maximizing nuclear localization and therapeutic efficacy. However, traditional NLSs are highly cationic due to the recognition and binding requirements with importin-α. Because of their highly 'super-charged' nature, NLS-tagged therapeutics face significant challenges, including poor pharmacokinetics due to non-specific interactions. In this study, we engineered novel NLS tags with zero net charge to potentially overcome this limitation. Computational modeling and experimental validation revealed that these net-neutral NLSs bind to importin-α with similar modes and energies as their cationic counterpart. High-resolution structural determination and analysis by X-ray crystallography then confirmed their binding modes. Biophysical methods using circular dichroism, microscale thermophoresis, and cellular localization studies demonstrated that these NLSs maintain sufficiently stable complexes and acceptable binding to importin-α and are functional. Additionally, this study revealed that the minor NLS-binding site of importin-α, with its extensive cationic surface area, was particularly suited for interactions with the acidic residues of the net-neutral NLSs. This study provides a foundational understanding of NLS-importin interactions and presents net-neutral NLSs as viable candidates for next-generation NLS-therapeutic development and expands the scope of nuclear-targeting therapies.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70272"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966544","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":"Human IgE monoclonal antibodies define two unusual epitopes trapping dog allergen Can f 1 in different conformations.","authors":"Kriti Khatri, Alyssa Ball, Jill Glesner, Christina Linn, Lisa D Vailes, Sabina Wünschmann, Scott A Gabel, Jian Zhang, R Stokes Peebles, Tomasz Borowski, Geoffrey A Mueller, Martin D Chapman, Scott A Smith, Anna Pomés, Maksymilian Chruszcz","doi":"10.1002/pro.70269","DOIUrl":"10.1002/pro.70269","url":null,"abstract":"<p><p>Molecular analysis of interactions between IgE antibody and allergen allows the structural basis of IgE recognition to be defined. Human IgE (hIgE) epitopes of respiratory lipocalin allergens, including Can f 1, remain elusive due to a lack of IgE-allergen complexes. This study aims to map the structure of allergenic epitopes on Can f 1. The fragment antigen-binding (Fab) regions of Can f 1 specific human IgE monoclonal antibodies (hIgE mAb) were used to determine the structures of IgE epitopes. Epitope mutants were designed to target Can f 1 epitopes. Immunoassays and a human FcεRIα transgenic mouse model of passive anaphylaxis in vivo were used to assess the functional activity of epitope mutants. Crystal structures of natural or recombinant Can f 1 complexed with two hIgE mAb 1J11 and 12F3 Fabs, respectively, were determined. The hIgE mAb bound to two partially overlapping epitopes and recognized two different Can f 1 conformations. The hIgE mAb 12F3 showed an unusual mode of binding by protruding its heavy chain CDR3 inside the Can f 1 calyx. Epitope mutants generated based on the structural analyses displayed a 64%-89% reduction in IgE antibody binding and failed to induce passive anaphylaxis in a human FcεRIα transgenic mouse model. In summary, the structures of Can f 1-hIgE Fab complexes revealed two unique and partially overlapping epitopes on Can f 1. The modification of the identified IgE epitopes provides a pathway for the design of hypoallergens to treat dog allergies.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70269"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874901","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":"Chimerolectins: Classification, structural architecture, and functional perspectives.","authors":"Vanir Reis Pinto-Junior, Benildo Sousa Cavada, Kyria Santiago Nascimento","doi":"10.1002/pro.70261","DOIUrl":"10.1002/pro.70261","url":null,"abstract":"<p><p>Lectins are proteins or glycoproteins capable of binding specifically and reversibly to carbohydrates, a property that, in itself, gives them great functional versatility in organisms from all kingdoms of nature. A subclass of these proteins, called chimerolectins, is composed of proteins that have at least one lectin domain associated with another functional domain, such as enzymatic domains or modules involved in molecular signaling processes. The emergence of chimerolectins throughout evolution significantly expanded the functional repertoire of lectins, allowing their action to go beyond the interaction with carbohydrates and glycoconjugates. These proteins are involved in the regulation of the immune system in humans and animals, in the defense of plants against pathogens and predators, as well as in the mediation of responses to biotic and abiotic stresses. In addition, they can act as potent lethal toxins or as factors in the infection of several pathogens and are often associated with the manifestation of symptoms of diseases, which makes them therapeutic targets of great interest. Deepening the structural knowledge of these proteins has been essential for understanding their mechanisms of action, in addition to providing solid bases for biotechnological applications and for the rational development of artificial lectins with specific functions. This approach has enabled the creation of chimerolectins with potent antiviral activity, as well as the development of new therapeutic strategies aimed at inducing death in cells of different tumor lineages.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70261"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856112","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":"Crystal structures of Salmonella enterica FraB deglycase reveal a conformational heterodimer with remarkable structural plasticity at the active site.","authors":"Katerina Zakharova, Jamison D Law, Yuan Gao, Sravya Kovvali, Vicki H Wysocki, Venkat Gopalan, Charles E Bell","doi":"10.1002/pro.70260","DOIUrl":"10.1002/pro.70260","url":null,"abstract":"<p><p>The fra locus of Salmonella enterica encodes five genes for metabolism of fructose-asparagine, an Amadori product formed by condensation of asparagine with glucose. In the last step of this pathway, the FraB deglycase cleaves 6-phospho-fructose-aspartate into glucose-6-phosphate and aspartate. In homology models, FraB forms a homodimer with two equivalent active sites located at the dimer interface. E214 and H230, two invariant residues essential for catalysis, project into each active site cleft from opposing subunits of the dimer. Here, we have determined six crystal structures of FraB, three of a variant containing an N-terminal His₆ tag and two mutations needed for crystallization (hereafter referred to as WT'), two with additional mutations to active site residues (E214A and P232A), and one of a variant with C-terminal residues 313-325 deleted. Surprisingly, in the WT' FraB structure, the two catalytic residues, E214 (general base) and H230 (general acid), are positioned ~22 Å apart. In the E214A and C-terminus-truncated FraB variants, however, a conformational change in the E214-residing helix brings E214 and H230* to ~7 Å (* indicates residue from the second protomer that creates the inter-subunit catalytic center). The loop bearing H230 also exhibits significant variation, ranging from being completely disordered to adopting open or closed states, with the nearby P232* residue being either cis or trans. The C-terminal residues 313-325 form a flexible \"C-tail\" that can be fully disordered, bind in the active site to block access of substrate, or angle across the active site to wrap across the other subunit of the dimer and potentially close over substrate. Collectively, these structures reveal that FraB is a conformational heterodimer with two chemically identical subunits that are constrained to adopt different structures as they come together for catalysis. This plasticity likely involves correlated opening and closure of the two active sites for their respective binding and release of substrates and ligands.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70260"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12359202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874898","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":"Finding the dark matter: Large language model-based enzyme kinetic data extractor and its validation.","authors":"Galen Wei, Xinchun Ran, Runeem Ai-Abssi, Zhongyue Yang","doi":"10.1002/pro.70251","DOIUrl":"10.1002/pro.70251","url":null,"abstract":"<p><p>Despite the vast number of enzymatic kinetic measurements reported across decades of biochemical literature, the majority of relational enzyme kinetic data-linking amino acid sequence, substrate identity, kinetic parameters, and assay conditions-remains uncollected and inaccessible in structured form. This constitutes a significant portion of the \"dark matter\" of enzymology. Unlocking these hidden data through automated extraction offers an opportunity to expand enzyme dataset diversity and size, critical for building accurate, generalizable models that drive predictive enzyme engineering. To address this limitation, we built EnzyExtract, a large language model-powered pipeline that automates the extraction, verification, and structuring of enzyme kinetics data from scientific literature. By processing 137,892 full-text publications (PDF/XML), EnzyExtract collected more than 218,095 enzyme-substrate-kinetics entries, including 218,095 k_cat and 167,794 K_m values. These entries are mapped to enzymes spanning 3569 unique four-digit EC numbers, with a total of 84,464 entries assigned at least a first-digit EC number. EnzyExtract identified 89,544 unique kinetic entries (k_cat and K_m combined) absent from BRENDA, significantly expanding the known enzymology dataset. The newly curated dataset was compiled into a database named EnzyExtractDB. EnzyExtract demonstrates high accuracy when benchmarked against manually curated datasets and strong consistency with BRENDA-derived data. To create model-ready datasets, enzyme and substrate sequences were aligned to UniProt and PubChem, yielding 92,286 high-confidence, sequence-mapped kinetic entries. To assess the practical utility of our dataset, we retrained several state-of-the-art k_cat predictors (including MESI, DLKcat, and TurNuP) using EnzyExtractDB. Across held-out test sets, all models demonstrate improved predictive performance in terms of RMSE, MAE, and R², highlighting the value of high-quality, large-scale, literature-derived EnzyExtractDB for enhancing predictive modeling of enzyme kinetics. The EnzyExtract source code and the database are openly available at https://github.com/ChemBioHTP/EnzyExtract, and an interactive demo can be accessed via Google Colab at https://colab.research.google.com/drive/1MwKSEZzLPNOseksRshbzkkFoO_cgJhva.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70251"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856116","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":"Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson's disease.","authors":"Rajeev Jain, Sharavanakkumar Sk, Krishnananda Chattopadhyay","doi":"10.1002/pro.70253","DOIUrl":"10.1002/pro.70253","url":null,"abstract":"<p><p>The process of protein phase separation, particularly in the context of intrinsically disordered proteins, has been extensively studied for its implications in several neurodegenerative diseases. Although the mechanism of protein phase separation and the involved molecular grammar have been well explored under in vitro conditions, the focus is now shifting toward developing more complex models of phase separation in order to mimic the biological systems closely. Here, we studied the phase separation of alpha synuclein (α-syn), an intrinsically disordered protein whose aggregation is implicated in the pathology of Parkinson's disease inside yeast cells (Saccharomyces cerevisiae). Using a positively charged polymer, polyethylenimine (PEI), which binds presumably at the negatively charged C-terminal domain of α-syn, we find that the aggregation of α-syn inside yeast can be modulated by at least two pathways: one involving phase separation and the second one without phase separation. We find further that these two pathways lead to varying fibril characteristics and toxicities. We believe that this model can be used as a quick and convenient system to screen novel and repurposed small molecules against toxic protein droplets.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70253"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856117","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":"T-cell receptor insights: Determinants of Major Histocompatibility Complex class I versus class II recognition.","authors":"Marcus De Almeida Mendes, Leila Chihab, Jonas Birkelund Nilsson, Lonneke Scheffer, Morten Nielsen, Bjoern Peters","doi":"10.1002/pro.70262","DOIUrl":"10.1002/pro.70262","url":null,"abstract":"<p><p>In this study, we analyzed large-scale T-cell receptor (TCR) sequence data to determine whether TCRs preferentially bind to major histocompatibility complex (MHC) class I (CD8+) or class II (CD4+) epitopes. Using the International ImMunoGeneTics information system numbering scheme, we identified specific positions with distinct amino acid enrichment for each MHC class and developed machine learning models for classification. While our frequency-based approach effectively differentiated MHC-I from MHC-II TCRs in cross-validation, performance declined when only beta chain data were used from real-world peripheral blood mononuclear cell samples. However, incorporating the TCR alpha chain significantly improved accuracy, emphasizing its importance for MHC recognition. Overall, we found that V-region loops can signal MHC class bias, aiding in immunotherapy design and TCR repertoire analysis, while highlighting the need for larger, more diverse datasets for reliable predictions.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70262"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856188","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":"Unraveling ShuA detergent-induced colloidal behavior in solution: A comprehensive SEC-MALS, SAXS, and SANS study.","authors":"A Pozza, A Martel, M Moir, T A Darwish, K Wimalan, A Koutsioubas, S Combet, F Bonneté","doi":"10.1002/pro.70258","DOIUrl":"10.1002/pro.70258","url":null,"abstract":"<p><p>In this study, we investigate the detergent-induced behavior of the integral membrane protein ShuA in solution, focusing on its interactions with octyl polyoxyethylene (OPOE) and n-dodecyl-β-D-maltoside (DDM). Using a combination of size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS) and small-angle scattering techniques (SAXS and SANS), we provide a detailed characterization of the protein-detergent complex (PDC) behavior under varying conditions. Our results reveal that ShuA remains monomeric in 1% OPOE, whereas in 0.5 mM DDM, it undergoes a reversible monomer/dimer equilibrium that shifts towards a monodisperse, monomeric state with increasing DDM concentration to 7.5 mM, highlighting the significant influence of detergent type and concentration on protein colloidal stability. These findings have direct implications for membrane protein purification and structural studies, particularly in crystallization and cryo-EM sample preparation. The study emphasizes the necessity of optimizing detergent conditions to ensure monodispersity and structural integrity, preventing detergent-induced artifacts that could affect structural interpretations. Importantly, our results highlight the power of the SEC-MALS technique in determining oligomeric or association equilibrium states, detecting weak intermolecular interactions often overlooked in conventional SEC, and achieving this even in the particularly complex case of MPs. By integrating advanced scattering techniques, this work contributes valuable insights into MP colloidal behavior, refining strategies for structural characterization and providing a framework for optimizing detergent conditions in biochemical and biophysical studies.</p>","PeriodicalId":20761,"journal":{"name":"Protein Science","volume":"34 9","pages":"e70258"},"PeriodicalIF":5.2,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856192","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}