Biotechnology Journal最新文献

{"title":"The Role of Exosomes in Bone Metastasis and Bone Tissue Engineering: Molecular Mechanisms and Therapeutic Opportunities","authors":"Asrin Emami,&nbsp;Iman Menbari Oskouie","doi":"10.1002/biot.70257","DOIUrl":"10.1002/biot.70257","url":null,"abstract":"<div>\u0000 \u0000 <p>Exosomes, nanoscale extracellular vesicles secreted by almost all cell types, have emerged as pivotal mediators of intercellular communication within both pathological and regenerative microenvironments. In bone metastasis, tumor-derived exosomes (TDEs) play a crucial role in the establishment of pre-metastatic niches, modulation of osteoclast–osteoblast balance, and promotion of tumor cell colonization through the transfer of bioactive molecules such as proteins, lipids, and non-coding RNAs. Conversely, in bone tissue engineering, stem cell-derived exosomes have demonstrated remarkable potential to promote osteogenesis, angiogenesis, and tissue regeneration by activating signaling pathways that regulate bone remodeling. This dual role of exosomes—as drivers of disease progression and as therapeutic agents—highlights their significance as both diagnostic biomarkers and next-generation biologics. This review provides a comprehensive overview of the molecular mechanisms underlying exosome-mediated communication in bone metastasis and bone regeneration, summarizes recent advances in exosome-engineered biomaterials, and discusses the translational challenges that must be addressed to enable clinical applications. Understanding the multifaceted functions of exosomes will pave the way for the development of novel exosome-based strategies for the diagnosis and treatment of bone-related diseases.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systems-Level Metabolic Regulation Strategies of Xylose Metabolism in Saccharomyces cerevisiae","authors":"Song Gao,&nbsp;Zhi-Hua Liu,&nbsp;Hao-Ran Zhang,&nbsp;Guang-Rong Zhao,&nbsp;Jian Zha,&nbsp;Ying-Jin Yuan","doi":"10.1002/biot.70258","DOIUrl":"10.1002/biot.70258","url":null,"abstract":"<div>\u0000 \u0000 <p>As the second most abundant sugar in lignocellulosic hydrolysates, efficient xylose utilization is critical for achieving high carbon efficiency and economic viability of lignocellulosic fermentation. While heterologous pathway engineering has enabled xylose metabolism in <i>Saccharomyces cerevisiae</i>, xylose fermentation efficiency remains far inferior to glucose, due to imbalanced carbon flux, redox cofactor mismatch, carbon catabolite repression, and signaling pathway‑mediated stress dysregulation, which cannot be resolved by traditional single‑pathway engineering. This review focuses on the conceptual shift from single-pathway construction to system-level metabolic regulation of xylose metabolism in <i>S. cerevisiae</i>. We summarize advances in the optimization of heterologous xylose-assimilation pathways and endogenous metabolic network reprogramming. We then elaborate on non-rational engineering strategies such as adaptive laboratory evolution and synthetic chromosome rearrangement, which uncover hidden regulatory layers and drive the paradigm shift toward system-level design. We further dissect the core global regulatory mechanisms, and their role in coordinating cellular growth, metabolism, and stress tolerance via hierarchical coupling to metabolic networks. By integrating these strategies within a unified regulatory framework, this review provides a systems-level perspective for building efficient and robust xylose-fermenting <i>S. cerevisiae</i>, and offers guiding principles for future lignocellulosic biorefineries targeting multi-substrate utilization.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Xylt2 Knockout Eliminates O-Xylosylation and Enhances Bone Morphogenetic Protein 2 Production in Chinese Hamster Ovary Cells","authors":"Lin Han,&nbsp;Nana Wu,&nbsp;Quanxue Li,&nbsp;Ying Li,&nbsp;Yu Zhang,&nbsp;Xiaoyue Chen,&nbsp;Hang Zhou,&nbsp;Fei Chen,&nbsp;Tao Sun","doi":"10.1002/biot.70256","DOIUrl":"10.1002/biot.70256","url":null,"abstract":"<div>\u0000 \u0000 <p>O-xylosylation of glycine–serine (GS) linkers in multispecific antibodies or fusion proteins introduces product heterogeneity, posing critical challenges for biomanufacturing quality control and elevating potential immunogenicity risks. This post-translational modification is primarily catalyzed by xylosyltransferase 2 (<i>Xylt2</i>) in chinese hamster ovary (CHO) cells. To address this, we generated <i>Xylt2</i>-deficient CHO cells via both clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) and zinc finger nuclease (ZFN)-mediated gene knockout, which resulted in the complete elimination of O-xylosylation as verified by mass spectrometry in a GS linker-containing bispecific antibody. Furthermore, because heparan sulfate proteoglycans (HSPGs), key cell-surface receptors for ligand binding and internalization, rely on O-xylosylation for their proper biosynthesis and function, the <i>Xylt2</i> knockout also enhanced the titer of human bone morphogenetic protein 2 (hBMP2), which undergoes HSPG-dependent cellular uptake, with up to a 2.5-fold increase from 9.62 to 34.09 µg/mL in engineered cells compared to wild-type CHO controls. Collectively, our results demonstrate that <i>Xylt2</i>-deficient cell lines provide a genetic approach to produce recombinant proteins without O-xylosylation, as well as for enhancing the titer of hBMP2.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlled Feeding Facilitates the Development of a Robust Production Process for Terpolymeric Polyhydroxyalkanoates","authors":"Birk Achenbach,&nbsp;Pravesh Tamang,&nbsp;Steven Leonhardt,&nbsp;Günter E. M. Tovar,&nbsp;Susanne Zibek","doi":"10.1002/biot.70252","DOIUrl":"10.1002/biot.70252","url":null,"abstract":"<p>Polyhydroxyalkanoates (PHAs) are a promising class of biodegradable and sustainable biopolymers. However, the current use of PHA is limited by its restricted availability, which is deplorable, as novel PHA variants such as copolymers or terpolymers could offer improved material properties. In this study, we report the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxyvalerate) (PHBVV) terpolymer with high 3-hydroxyvalerate (3HV) content using <i>Cupriavidus necator</i>. A fully controlled feeding strategy, based on the pH- and pO₂-signal, was successfully implemented and validated in 7.5 and 42-L bioreactors, enabling controlled delivery of the growth-inhibiting substrate levulinic acid. A maximum biomass of 40.2 ± 0.9 g L⁻¹ with 75% CDW PHA was obtained, corresponding to a yield of 0.32 ± 0.02 g_PHA g_LA⁻¹. Importantly, the process enabled the production of PHBVV with a high 3HV content of 38%–46% and a 4HV content of 1%–2% at both production scales. Beyond demonstrating scalable PHBVV production in stirred tank bioreactors, this work provides a comprehensive comparative dataset, including specific growth rates, substrate uptake rates, yield coefficients, and respiratory activity. The findings presented here constitute both a methodological framework for scaling and process automation of PHBVV production and a valuable reference for the future optimization of PHA bioprocesses.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/biot.70252","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142175","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":"Synbiotic Supplementation With Heyndrickxia coagulans TBC169 Improves Chronic Constipation in Middle-Aged and Elderly","authors":"Xiaoni Zhou,&nbsp;Canhui Guo,&nbsp;Gang Hu,&nbsp;Leiping Ding,&nbsp;Tingting Zou,&nbsp;Mei Wang,&nbsp;Wenjie Xiong,&nbsp;Wen Deng,&nbsp;Jing Wei,&nbsp;Jiangqing Yu,&nbsp;Chunbo Zhang,&nbsp;Huaijun Tu,&nbsp;Tingtao Chen","doi":"10.1002/biot.70250","DOIUrl":"10.1002/biot.70250","url":null,"abstract":"<div>\u0000 \u0000 <p><b>Background</b>: Chronic constipation is prevalent in middle-aged and elderly individuals and can markedly impair quality of life and increase comorbidity risk. However, safe and effective therapies for this population remain limited because of age-related physiological changes, polypharmacy, and concerns about long-term medication use.</p>\u0000 <p>Methods: We conducted a randomized, double-blind, controlled clinical trial enrolling 140 participants aged ≥45 years with chronic constipation to evaluate a synbiotic containing <i>Heyndrickxia coagulans</i> (<i>H. coagulans</i>) TBC169 plus dietary fibers as an adjunct intervention.</p>\u0000 <p><b>Results</b>: Compared with dietary fiber alone, the TBC169-based synbiotic significantly improved constipation outcomes, including increased weekly bowel movements (WBMs), higher Bristol stool scale (BSS) scores, and reduced Wexner and Patient Assessment of Constipation Quality of Life (PAC-QOL) scores. Post-intervention gut microbiota profiling showed higher Shannon and Faith_PD diversity indices and distinct community composition in the synbiotic group compared with the dietary-fiber control group, along with higher relative abundance of <i>Blautia</i>, <i>Akkermansia</i>, <i>Faecalibacterium</i>, and <i>Bacillus</i> and lower relative abundance of <i>Collinsella</i>. Because baseline faecal samples were not collected, these microbiota findings should be interpreted as exploratory between-group associations. Ecological analyses suggested enhanced microbial stability and metabolic potential, and correlations linked key taxa with clinical improvement. The intervention was well-tolerated, with only mild, transient adverse events.</p>\u0000 <p><b>Conclusions</b>: The synbiotic formulation containing <i>H. coagulans</i> TBC169 and dietary fiber-related components was well-tolerated and may improve constipation-related outcomes in middle-aged and elderly adults. Because the formulation contained both probiotic and fiber components, the observed effects should be attributed to the combined synbiotic product rather than to <i>H. coagulans</i> TBC169 alone.</p>\u0000 <p><b>Trial Registration</b>: Chinese Clinical Trial Registry (ChiCTR2400085844, http://www.chictr.org.cn/), registered on June 19, 2024.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Copper-Inducible Regulatory System for Dynamic Enhancement of Gene Editing Efficiency in Yarrowia lipolytica","authors":"Jiacan Cao,&nbsp;Qing Hong,&nbsp;Jiaxin Sun,&nbsp;Jiaxin Fu,&nbsp;Zhenmin Liu,&nbsp;Baixi Zhang","doi":"10.1002/biot.70251","DOIUrl":"10.1002/biot.70251","url":null,"abstract":"<div>\u0000 \u0000 <p>To circumvent the potential irreversible risks to cells posed by permanent genetic modifications, this study developed a copper-inducible system for dynamically regulating gene editing efficiency of <i>Yarrowia lipolytica</i>. By combining promoters <i>pMT2</i> or enhanced <i>pUAS16MT2</i> with genes <i>scRAD52</i>, <i>scRAD59</i>, and <i>ylRAD52</i>, homologous recombination efficiency was raised from 21.4% to 56.4%, while maintaining a transformation efficiency of 75 ± 5 CFU/OD₆₀₀. Employing a homology-mediated end joining strategy further improved DNA fragment integration efficiency from 15% to approximately 60%. Subsequently, the engineered chassis was subsequently applied to investigate stable conjugated linolenic acid (CLNA) production. Transcriptomic analysis and combinatorial gene knockouts identified <i>POX2</i>, <i>POX3</i>, and <i>POX5</i> as key acyl-CoA oxidases involved in β-oxidation of long-chain fatty acids. A triple knockout strain increased extracellular lipid content by 64.19%, with <i>POX5</i> playing a critical role in lipid-rich environments. Consequently, the CLNA degradation rate reduced from 92.9% to 19.2%, and final CLNA yield of muti-copy strains reached to 5.2 g/L. In summary, this study establishes a tunable gene editing system for <i>Y. lipolytica</i> and provides an effective engineering strategy for high-value lipid production.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Enzyme Cascade Reaction of Crude Enzyme Strategy for the Economical and Efficient Bioconversion of Rebaudioside A to Rebaudioside M.","authors":"Yuanyuan Huang, Yuxia Ge, Min Zhang, Wei Zhou","doi":"10.1002/biot.70270","DOIUrl":"10.1002/biot.70270","url":null,"abstract":"<p><p>Rebaudioside M (Reb M) is a natural sweetener with high sweetness, low caloric content, and an excellent sensory profile. However, it's extremely low natural abundance in Stevia rebaudiana leaves renders conventional extraction processes costly, inefficient, and unsustainable, limiting its industrial utilization. In this study, we developed a one-pot, stepwise enzyme addition cascade strategy for the efficient biosynthesis of Reb M. In the first step, a glycosyltransferase mutant YojK_M0 from Bacillus subtilis 168 catalyzed the conversion of rebaudioside A (Reb A) to rebaudioside D (Reb D). In the second step, a glycosyltransferase mutant UGT76G1_M3 from Stevia rebaudiana converted Reb D to Reb M. Simultaneously, sucrose synthase from Glycine max enabled continuous in situ regeneration of UDP-glucose from sucrose and UDP throughout both reaction steps. Following systematic optimization of reaction conditions, a scaled-up 3 L bioconversion using crude enzymes obtained from high-cell-density fermentation in Escherichia coli successfully converted 30 mmol Reb A into 24.1 mmol Reb M, achieving an overall yield of 80.34%. This work demonstrates a highly efficient, scalable, and cost-effective enzymatic biomanufacturing platform for Reb M, providing a promising route for sustainable industrial production of next-generation natural sweeteners.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":"e70270"},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315048","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":"Enabling Clinical Translation of Oral Probiotics Through Formulation Engineering and Scalable Manufacturing","authors":"Junyu Liu,&nbsp;Yuqi Zhang,&nbsp;Yuqing Huang,&nbsp;Xiaobin Li,&nbsp;Xiangxuan Huang,&nbsp;Xin-Hui Xing,&nbsp;Can Yang Zhang","doi":"10.1002/biot.70253","DOIUrl":"10.1002/biot.70253","url":null,"abstract":"<div>\u0000 \u0000 <p>Oral probiotics, as living therapeutics, hold considerable promise for modulating host health and preventing diseases, with substantial potential for industrial and clinical applications. However, their efficacy is substantially limited by gastrointestinal degradation and inadequate colonization, and the oversimplified linear correlation between strain survival and therapeutic efficacy, further hinder their clinical translation. This review first provides a systematic overview of current formulation approaches in oral probiotics, encompassing advanced coating techniques based on electrostatic, covalent, coordinate, bio-recognitive interactions, and synthetic biology-driven strain engineering. We emphasize the functional output of probiotic formulations as the core therapeutic driver, rather than merely structural protection. Then, the scalable manufacturing platforms including high-density fermentation and microfluidic encapsulation are summarized. The advantages and limitations of these approaches are critically assessed with regard to viability protection, targeting efficacy, industrial feasibility, and functional output for diverse diseases including colorectal cancer (CRC), inflammatory bowel disease (IBD), metabolic disorders, and neuroinflammatory conditions. Looking ahead, the convergence of multiple technological platforms is expected to drive the development of next-generation probiotic formulations. We believe that intelligently engineered oral probiotics are poised to become a safe, effective and personalized therapeutics, paving the way for their clinical adoption in precision medicine.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic and Synthetic Biology Strategies for Enhancing Single-Cell Protein Production in Saccharomyces cerevisiae.","authors":"Xiaoyu Wang, Huayou Chen, Huiqing Chen, Hongwei Yu, Lidan Ye, Zhongjian Guo","doi":"10.1002/biot.70273","DOIUrl":"10.1002/biot.70273","url":null,"abstract":"<p><p>Single cell protein (SCP), distinguished by its high production efficiency, flexible substrate utilization, and excellent nutritional value, has broad application prospects in both feed and food sectors. With the advancement of synthetic biology and metabolic engineering, SCP is poised to become a mainstream protein source, providing key solutions for global food security and carbon neutrality goals. This review focuses on Saccharomyces cerevisiae as an SCP chassis and summarizes recent metabolic and synthetic biology strategies aimed at enhancing cellular protein content and cell biomass, thereby improving its potential for sustainable large-scale protein production.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":"e70273"},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13383604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148314985","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":"Validation of an Automated Fluorescence- and Image-Based Viable Cell Counting Method for Fecal Microbiota Transplantation Drug Products.","authors":"Timon Lang, Fedja Farowski, Jozef Al-Gousous, Peter Langguth, Maria J G T Vehreschild","doi":"10.1002/biot.70269","DOIUrl":"10.1002/biot.70269","url":null,"abstract":"<p><p>Fecal microbiota transplantation (FMT) is an established treatment for recurrent Clostridioides difficile infection. As a drug product, FMT is subject to pharmaceutical quality standards, including accurate quantification of viable bacteria to ensure product consistency. We developed and validated an automated fluorescence- and image-based viable-cell counting method for FMT products; total-cell enumeration was examined secondarily. The QUANTOM Tx system (Logos Biosystems) was validated according to ICH Q2(R2) using Escherichia coli and Bacillus subtilis as reference strains. The Viable Cell Staining Kit was validated with Escherichia coli, whereas the Total Cell Staining Kit was examined in selected experiments using both strains. Applicability to complex FMT matrices was confirmed using authentic fecal samples. Viable-cell counting showed strong linearity across a range of 9.4 × 10⁶-1.2 × 10⁸ cells/mL, with adequate accuracy and precision. Specificity was ensured by particle-size gating, unaffected by nonviable cells or diluent. Robustness was confirmed across operators and time points. Fecal samples showed linear quantifiability and acceptable precision; total-cell enumeration fulfilled linearity and precision requirements. The validated method enables rapid, reproducible viable-cell quantification suitable for Quality Control of FMT drug products, supporting formulation development, and dosing verification. Viable-cell quantification remains the analytical focus, despite limitations in spore detection. Total-cell enumeration provides complementary process information.</p>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 6","pages":"e70269"},"PeriodicalIF":3.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13273919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148262477","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}