Journal of Biological Engineering最新文献

{"title":"Insect cell expression system: advances in applications, engineering strategies, and bioprocess development.","authors":"Nongyu Huang, Yuquan Wei, Jiong Li","doi":"10.1186/s13036-025-00562-4","DOIUrl":"https://doi.org/10.1186/s13036-025-00562-4","url":null,"abstract":"<p><p>As technology and regulatory guidelines continue improve, insect cell expression system has gained increasing attention as promising and versatile platforms for production of biopharmaceuticals. This review provides a comprehensive overview of recent advances in this platform, with a focus on their applications in human and veterinary vaccines, therapeutic proteins, and structurally complex proteins for biomedical research. Special emphasis is placed on emerging strategies such as larval expression systems, baculovirus-mediated antigen displaying technologies, and the development of gene therapy vectors. Despite their growing utility, insect cell systems face critical technical bottlenecks that limit scalability, productivity, and regulatory compliance. We discuss recent innovations aimed at addressing these challenges, including improvements in baculovirus infection dynamics, the genome engineering, and bioprocess optimization at both upstream and downstream levels. By synthesizing current knowledge and technological trends, this review outlines future directions for unlocking the full potential of insect cell platforms in next generation biomanufacturing.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"88"},"PeriodicalIF":6.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238790","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":"Sustainable valorization of fish head wastes into nitrogen-based nutrients: a comparative life cycle assessment.","authors":"Somyong Lee, Soeon Ahn, Jin Ho Zong, Chulhong Oh, Sangwon Suh, Dong Soo Hwang","doi":"10.1186/s13036-025-00560-6","DOIUrl":"https://doi.org/10.1186/s13036-025-00560-6","url":null,"abstract":"","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"87"},"PeriodicalIF":6.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238767","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":"Bioengineered injectable HAMA/GelMA hydrogel encapsulating exosomes loaded lycopene mitigates deoxynivalenol-induced testicular injury via apoptotic pathway modulation.","authors":"Feng Ru, Ramaiyan Velmurugan, Chunfeng Li, Ying Mu, Haiyan Tian, Lina Zhou, Xiaoming Cao","doi":"10.1186/s13036-025-00555-3","DOIUrl":"10.1186/s13036-025-00555-3","url":null,"abstract":"<p><p>Deoxynivalenol (Dex), a widespread mycotoxin found in contaminated cereals, induces testicular dysfunction primarily through oxidative stress, inflammation, and activation of apoptotic pathways. Lycopene (Lyc), a natural antioxidant, offers cytoprotective potential but is limited by poor aqueous solubility and instability. To address these limitations, we developed a bioengineered injectable hydrogel system composed of hyaluronic acid and gelatin methacrylate, both natural biopolymers, to encapsulate exosomes preloaded with lycopene (HAMA-GelMA@Exo-Lyc) for controlled, localized delivery. Comprehensive characterization demonstrated successful integration of HAMA-GelMA@Exo-Lyc hydrogel, evidenced by a shifted amide I band at 1643.67 cm⁻¹ and a uniform porous network of 50-150 μm. The modified hydrogel exhibited improved mechanical strength (21.8 ± 1.6 kPa), faster gelation (95 ± 8 s), and enhanced water retention (85.7 ± 3.1%) compared to the unmodified HAMA/GelMA system. In vitro, GC-1 spg cells treated with HAMA-GelMA@Exo-Lyc hydrogel exhibited enhanced viability, maintaining over 79.0 ± 0.30% cell survival at 150 µg/mL after 24 h, alongside reduced ROS levels and improved proliferative capacity compared to free Lyc. In a Dex-induced testicular injury model, HAMA/GelMA@Exo-Lyc treatment restored serum testosterone levels, improved spermatogenic architecture, and significantly reduced oxidative stress markers. Elevated levels of GSH and CAT indicated an enhanced antioxidant defense, whereas reductions were noted in inflammatory mediators TNF-α and IL-1β, as well as in mitochondrial apoptosis-associated proteins, such as Cyt-c, Bax, and Caspase-3. Meanwhile, Bcl-2 expression rose, suggesting anti-apoptotic effects. These results suggest that HAMA-GelMA@Exo-Lyc represents a promising bioengineered platform for mitigating Dex-induced testicular damage by suppressing oxidative stress and modulating the apoptosis pathway.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"86"},"PeriodicalIF":6.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206556","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":"Systemic versus local delivery of mesenchymal stem cells to improve the early stages of fracture healing in a polytrauma model.","authors":"Augustine Mark Saiz, Maryam Rahmati, Soren David Johnson, Aneesh Satish Bhat, Tony Daniel Baldini, Øystein Øvrebø, Liebert Parreiras Nogueira, Thaqif El Khassawna, Sabine Stötzel, Fernando A Fierro, Mark A Lee, J Kent Leach, Håvard Jostein Haugen","doi":"10.1186/s13036-025-00554-4","DOIUrl":"10.1186/s13036-025-00554-4","url":null,"abstract":"<p><p>Fracture healing complications, including nonunion, are common in polytrauma patients partly due to systemic inflammatory dysregulation. Although mesenchymal stem cells (MSCs) have been widely explored for their regenerative properties, their therapeutic potential in polytrauma patients remains uncertain. Given the clinical interest in both systemic and localized stem cell therapies, understanding how delivery route influences MSCs biodistribution, inflammatory modulation, and therapeutic efficacy is critical for optimizing treatment strategies in polytrauma. Hence, we compared systemic versus local MSCs delivery in a polytrauma model. We evaluated inflammatory responses and bone formation in a C57BL/6J murine model across four groups: (1) isolated fracture, (2) polytrauma (femur fracture + chest trauma), (3) polytrauma + systemic MSC delivery, and (4) polytrauma + local MSC delivery in hyaluronic acid-based hydrogels at the fracture site. Polytrauma induced a prolonged inflammatory response characterized by elevated interleukin 1 alpha and beta (IL-1α & β), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and monocyte chemoattractant protein-1 and - 5 (MCP-1 & MCP-5). Both delivery methods significantly reduced inflammation and proinflammatory cytokines, though local delivery yielded more consistent effects. IVIS imaging confirmed MSC retention at the fracture site in the local delivery group, while systemic administration of MSCs resulted in pulmonary entrapment. Although systemic MSCs failed to enhance fracture healing significantly, local MSC delivery promoted bone formation evidenced by CT and histological characterizations. These findings demonstrate that local MSC delivery in a hydrogel scaffold represents a superior strategy for improving fracture healing in polytrauma patients compared to systemic delivery.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"82"},"PeriodicalIF":6.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199465","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":"Cinnamaldehyde/cinnamon essential oil loaded poly-L-lactic acid/ hydroxyapatite fibrous scaffolds as osteogenic differentiation enhancing system for bone tissue engineering applications.","authors":"Fateme Darchin Tabrizi, Mehdi Doosti-Telgerd, Narges Forouzideh, Fatemeh Naghshnejad, Ehsan Seyedjafari, Hamid Akbari Javar, Fatemeh Saadat Mahdavi, Mina Habibizadeh, Mahdi Tavakolizadeh","doi":"10.1186/s13036-025-00547-3","DOIUrl":"10.1186/s13036-025-00547-3","url":null,"abstract":"","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"84"},"PeriodicalIF":6.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199484","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":"Combinatorial engineering pinpoints shikimate pathway bottlenecks in para-aminobenzoic acid production in Pseudomonas putida.","authors":"Marco A Campos-Magaña, Sara Moreno-Paz, Maria Martin-Pascual, Vitor Ap Martins Dos Santos, Luis Garcia-Morales, Maria Suarez-Diez","doi":"10.1186/s13036-025-00553-5","DOIUrl":"10.1186/s13036-025-00553-5","url":null,"abstract":"<p><p>Combinatorial expression libraries to optimize multigene pathways can improve product titers, but the large number of potential genetic variants makes exhaustive testing impractical. Statistical Design of Experiments (DoE) offers a powerful alternative to enable efficient exploration of gene expression landscapes with a limited number of measurements. Here, we applied this approach to modulate expression levels across all genes in the shikimate and para-aminobenzoic acid (pABA) biosynthesis pathways in Pseudomonas putida. From a theoretical library of 512 strain variants, we trained a regression model using a statistically structured sample comprising 2.7% of the total library, as defined by our DoE approach, and used the model to predict new genotypes with improved pABA titers. This strategy enabled us to achieve product titers ranging from 2 to 186.2 mg/L in the initial screen and subsequently guide a second round of strain engineering, culminating in a maximum titer of 232.1 mg/L. Our analysis indicated that aroB, encoding 3-dehydroquinate synthase, is a critical bottleneck in pABA biosynthesis. This study highlights the utility of combining DoE with linear regression modeling to systematically optimize complex metabolic pathways, paving the way for more efficient microbial production.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"81"},"PeriodicalIF":6.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199467","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":"CRISPR/Cas9-mediated mutation of GhCAD decreases the gossypol content of cottonseed.","authors":"Lili Zhou, Yali Wang, Jiamin Wang, Peilin Wang, Guoqing Lu, Xiaofeng Su, Mahideen Afridi, Huiming Guo, Hongmei Cheng","doi":"10.1186/s13036-025-00556-2","DOIUrl":"10.1186/s13036-025-00556-2","url":null,"abstract":"<p><p>Cottonseed is the most important byproduct of cotton production. However, high free gossypol contents limit the application of cottonseed in the food or feed industry. In this study, CRISPR/Cas9 technology was used to knock out the (+)-δ-cadinene synthase gene (GhCAD) to decrease the gossypol content. Gossypol levels decreased approximately 64% in cottonseeds and leaves following the targeted mutation of GhCAD. If only GhCAD1-A was edited, the seed gossypol content decreased by approximately 46%, but there were no major changes in the leaf gossypol content. In addition, the protein and fatty acid (C16:0, C18:1, and C18:2) profiles of the transgenic cotton seeds were similar to those of the control cotton seeds. Furthermore, transcriptome analysis revealed that the jasmonic acid signal transduction pathway was significantly enriched among the DEGs, and GhMYC2-D09 expression was down-regulated. Silencing of GhMYC2-D09 via virus-induced gene silencing decreased the expression of gossypol biosynthesis-related genes, ultimately restricting the accumulation of gossypol in cotton leaves. In contrast, the overexpression of GhMYC2-D09 in hairy roots had the opposite effect. Dual-luciferase assays revealed that GhMYC2-D09 can activate the expression of GhCAD1-A and GhCAD1-C, but Y1H assays revealed that GhMYC2-D09 cannot bind directly to GhCAD promoters. In conclusion, we used CRISPR/Cas9 technology to silence GhCAD expression and developed new genetic resources for generating low-gossypol cotton materials. Furthermore, we characterized GhMYC2-D09 as a transcription factor that increases gossypol biosynthesis. These findings may provide new insights to further elucidate the regulatory network of gossypol biosynthesis.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"83"},"PeriodicalIF":6.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12486840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199527","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":"Streamlined purification of ADDomer nanoparticles for scalable biomanufacturing.","authors":"Raquel Arinto-Garcia, Cláudia S Paiva, Emerson Bryan Dilla, Dirk E Martens, Justin Sargunas, Michael Betenbaugh, Dora Buzas, Georgia Balchin, Mafalda Moleirinho, Rute Castro, Cristina Peixoto, Imre Berger, Christiane Schaffitzel, Paula M Alves, António Roldão","doi":"10.1186/s13036-025-00558-0","DOIUrl":"10.1186/s13036-025-00558-0","url":null,"abstract":"<p><p>Current lab-scale purification methods for ADDomer are labour-intensive, time-consuming and poorly scalable. The intracellular nature of ADDomer production further complicates downstream processing, requiring robust, scalable solutions for cell lysis and clarification. In the present work we focus on developing a scalable, GMP-compliant process for ADDomer purification. The workflow combines tangential microfiltration (TMF) using a 0.4 μm hollow fiber for cell retention, chemical lysis with 0.06 % Deviron^® C16, and in-line Benzonase^® treatment for DNA removal. Several capture approaches were explored, including anion and cation exchange, hydrophobic interaction and multimodal chromatography. Among these, the Sartobind^® Q anion exchange membrane demonstrated superior performance, achieving ADDomer purity of ~ 83 % and recovery yields > 85 %. Ultrafiltration membranes of different chemistries (regenerated cellulose, RC, and polyethersulfone, PES) and cut-off (300 kDa, 500 kDa, 1 MDa) were evaluated for polishing and buffer exchange. The 1 MDa RC membrane enabled a recovery of ~ 87 % and purity > 97%. Final sterile filtration with a PES membrane preserved particle integrity, purity and achieved > 80 % recovery. Overall, the purification process herein established yielded ~ 47 mg of ADDomer particles per L of culture volume while removing > 97 % and > 99 % of total protein and dsDNA, respectively. In summary, this study showcases the implementation of a scalable and GMP-compliant purification platform for ADDomer, paving the way for the development of next-generation ADDomer-based vaccines and antivenoms.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"85"},"PeriodicalIF":6.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199470","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":"Enhanced osteogenicity of adipose tissue-derived stem cells induced by phytochemically synthesized Fe₃O₄/Lanthanum/SiO₂ nanocomposite using ulmus minor Mll. extract.","authors":"Kosar Rahbari Badri, Saeed Jafarirad, Hadi Sadeghzadeh, Nasrin Valizadeh, Roya Salehi","doi":"10.1186/s13036-025-00540-w","DOIUrl":"10.1186/s13036-025-00540-w","url":null,"abstract":"<p><p>In this study, nanofibrous scaffolds composed of Polycaprolactone/Collagen (PCL/COL) infused with Fe₃O₄/Lanthanum/SiO₂ nanocomposite were developed. Fe₃O₄ and La-doped Fe₃O₄ nanoparticles were synthesized using a straightforward co-precipitation method. Silica extracted from Ulmus leaves via green synthesis was used to coat the Fe₃O₄-La nanocomposite. Then, PCL/COL nanocomposite scaffolds entrapping nanocomposites were created by electrospinning and characterized through FT-IR, VSM, EDX, DLS, TEM, FE-SEM, XRD, tensile strength, and contact angle techniques. The study comprehensively assessed their impacts on physical, mechanical, chemical, and biological attributes to evaluate their suitability for bone regeneration applications. The results revealed that the Fe₃O₄-La and Fe₃O₄-La@SiO₂ magnetic nanoparticles were synthesized at the nanoscale (64.3 and 83.6 nm), exhibiting superparamagnetic properties and a spherical morphology. The addition of MNPs enhanced the hydrophilicity and mechanical characteristics of the PCL/COL nanofibers. ADSCs were cultured onto nanocomposite scaffolds and the ALP activity, calcium mineralization, and the expression of bone-related proteins (such as Runx2, OCN, ON, and BMP2) were significantly increased in cells cultured on PCL/COL-MNPs nanofibers compared to PCL/COL scaffold and control groups. Nanocomposite scaffolds significantly enhanced cell viability (Day 5, p value < 0.0001), ALP elevation (p value < 0.0001), calcium deposition (Days 14 & 21) versus control, demonstrating high osteoinductivity (p value < 0.0001). PCL/COL/Fe₃O₄-La@SiO₂ showed the most intense mineralization at 21 days (22-fold). Fe₃O₄-La@SiO₂ synergizes all osteogenic phases (BMP2/Runx2/Osteocalcin), positioning it as the optimal bone-regeneration scaffold. These results endorse the incorporation of natural extracellular matrix (ECM) materials with magnetic particles to create composite scaffolds, thereby maximizing their therapeutic efficacy in bone tissue engineering applications.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"80"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955255","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":"Efficient site-specific recombination by self-activating split-Dre recombinase in mammalian cells and E. coli.","authors":"Chichu Xie, Jinfeng Gan, Yuanhao Zhang, Wentao Yu, Ruirui Li, Dan Yu, Yu Liu, Song Guo Zheng, Guangying Qi","doi":"10.1186/s13036-025-00551-7","DOIUrl":"10.1186/s13036-025-00551-7","url":null,"abstract":"<p><strong>Background: </strong>Site-specific recombination (SSR) systems are essential tools for conditional genetic manipulation and are valued for their efficacy and user friendliness. However, the development of novel SSR strategies is urgently needed. This study aimed to identify a split Dre protein configuration that can self-activate.</p><p><strong>Results: </strong>By exploiting the homology between Dre and Cre, we designed a strategy to split the Dre protein at specific amino acid residues and systematically pair the resulting peptide fragments. Among these combinations, the N191/192C pair exhibited detectable recombinase activity when mediating recombination between episomal rox sites in 293T cells, whereas the other pairs presented minimal recombinase activity. Subsequent experiments revealed that the N191/192C combination efficiently mediated site-specific recombination at the integrated rox sites, without the need for auxiliary protein fusions, and demonstrated recombinase activity that is at least equivalent to that of the intact Dre protein. Interestingly, while fusion with the intein peptide increased the activity of N60/61C pair, it had a deleterious effect on the N191/192C pair. The N191/192C combination also displayed robust recombinase activity in both the murine 4T1 cell line and E. coli bacteria. Finally, our experiments demonstrated that there was no detectable cross-complementation between the split Dre and split Cre proteins.</p><p><strong>Conclusions: </strong>The N191/192C split Dre protein and the intein-fused N60/61C split Dre protein can effectively mediate recombination of the integrated rox sites without the need for external signals such as light or chemical compounds. Split Dre and Cre proteins can be used together in the same cell without interfering with each other. These findings introduce new tools and strategies for gene editing and the generation of transgenic animals.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"79"},"PeriodicalIF":6.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955246","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}