Ilona Metayer, Catherine Forest-Nault, Julie Guimond, Simon Joubert, Olivier Henry, Yves Durocher, Gregory De Crescenzo, Jimmy Gaudreault
{"title":"A Surface Plasmon Resonance-Based Integrated Assay for Quantification and Glycosylation Characterization of Monoclonal Antibodies in Crude Heterogeneous Samples","authors":"Ilona Metayer, Catherine Forest-Nault, Julie Guimond, Simon Joubert, Olivier Henry, Yves Durocher, Gregory De Crescenzo, Jimmy Gaudreault","doi":"10.1002/bit.70016","DOIUrl":"10.1002/bit.70016","url":null,"abstract":"<p>The rise in cancer, autoimmune, inflammatory, and infectious diseases in recent decades has led to a surge in the development of monoclonal antibodies (mAbs) therapies, now the most widely used family of biologics. To meet the growing global demand, biopharmaceutical industries are intensifying their production processes. One approach to achieve more efficient production of effective mAbs is to develop tools for real-time quality monitoring. Specifically, the glycosylation profile of mAbs must be closely monitored, since it greatly impacts their therapeutic efficacy and innocuity, making it a critical quality attribute. In this study, we developed a surface plasmon resonance-based integrated assay allowing for the simultaneous quantification and glycosylation characterization of mAbs in crude samples, hence permitting the at-line analysis of bioreactor cell cultures. Thanks to the high specificity of the interaction between biosensor surface-bound protein A and the Fc region of mAbs, we quantified crude IgG samples under mass transport limitations. Next, by flowing running buffer on the surface, impurities contained in the mAbs samples were washed away from the biosensor surface, allowing subsequent recording of the kinetics between the captured mAbs and injected FcγRII receptors. Of interest, with this strategy, we were able to quantify terminal galactosylation and core fucosylation of IgG lots, two important glycan modifications for mAb efficacy.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2724-2738"},"PeriodicalIF":3.6,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144566608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shuwei Lu, Mohd A. Khan, Saini Setua, Quintin O'Boyle, Kiruphagaran Thangaraju, Pedro Cabrales, Delaney C. Swindle, David C. Irwin, Paul W. Buehler, Andre F. Palmer
{"title":"Transferrin Purification, Biophysical Characterization, and Lung Biodistribution in Sickle Cell Disease Mice","authors":"Shuwei Lu, Mohd A. Khan, Saini Setua, Quintin O'Boyle, Kiruphagaran Thangaraju, Pedro Cabrales, Delaney C. Swindle, David C. Irwin, Paul W. Buehler, Andre F. Palmer","doi":"10.1002/bit.70012","DOIUrl":"10.1002/bit.70012","url":null,"abstract":"<p>Plasma transferrin (Tf) is the transport protein central to the process of iron recycling and metabolism. Holo-Tf serves as the body's pool of ferric iron, facilitating transport from tissues such as the intestine, liver, spleen, and finally bone marrow, where iron is incorporated into erythropoiesis. In sickle cell disease (SCD), iron overload is primarily caused by chronic blood transfusions in patients at risk of stroke or frequent acute pain crisis. However, we have identified that pulmonary vascular iron accumulation, independent of transfusion, is a driver of pulmonary hypertension in SCD patients and murine models. Therefore, we hypothesize that intra-pulmonary administration of apo-Tf localizes the protein to sites of iron accumulation within the lung, where reactive iron-driven pathology develops. This approach to therapeutic development focuses on optimizing administration using aerosol drug delivery, which can increase clinical compliance compared to subcutaneous or intravenous administration. The goal of this study was to purify apo-Tf using a novel process, perform biochemical characterization on the material, and test the proof of concept that apo-Tf protein can be delivered to lung regions where iron accumulation occurs in SCD pulmonary hypertension. We conclude that apo-Tf can be isolated from plasma Cohn fraction IV paste using a simple process and that characterization of the material identified a high-purity apo-Tf product with functional iron binding properties. Further, this material was administered to SCD mice to target pulmonary anatomical regions where pathology occurs. This data suggests an intriguing approach to iron chelation applicable to a relevant clinical population.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2709-2723"},"PeriodicalIF":3.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
He Ren, Jianqi Nie, Zichuan Song, Yankun Yang, Zhonghu Bai
{"title":"Enhanced Adeno-Associated Virus Production in HEK293 Cells via Dual Inducible Control of Cap and Rep Proteins","authors":"He Ren, Jianqi Nie, Zichuan Song, Yankun Yang, Zhonghu Bai","doi":"10.1002/bit.70013","DOIUrl":"10.1002/bit.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>Adeno-associated viruses (AAVs) are promising vectors for gene therapy due to their safety, stability, and broad tissue tropism. However, current AAV production strategies face challenges related to low yield and poor quality, limiting their ability to meet clinical demands. In this study, we developed a novel Cap-Rep dual control system for AAV production that delays Cap expression via mifepristone-dependent promoter and suppresses Rep78 expression at late stage using a tetracycline-dependent promoter. By delaying Cap protein expression, synchronization between viral DNA replication and Cap expression was achieved, leading to increased viral yield. Additionally, suppressing Rep78 protein expression at late stage increased cell density and viability further boosting AAV production. This novel Cap-Rep dual control system increased AAV5 yields from 8.56 × 10<sup>10</sup> to 3.14 × 10<sup>11</sup> vg/mL (3.67-fold) and full-to-empty ratio by 1.54-fold. Furthermore, this system enhanced production of AAV1 (3.94-fold), AAV2 (4.71-fold), AAV6 (4.05-fold), and AAV9 (2.13-fold) production while transduction efficiency is maintained. Our findings demonstrate that this novel Cap-Rep dual control system significantly enhances AAV manufacturing efficiency, providing a promising solution to reduce the production cost of AAV vectors.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2862-2873"},"PeriodicalIF":3.6,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cast-Molded Channelized Hydrogel Scaffolds With Stereolithography-Printed Templates","authors":"Chi Wang, Yingge Zhou","doi":"10.1002/bit.70007","DOIUrl":"10.1002/bit.70007","url":null,"abstract":"<p>Creating internal vascular networks within hydrogel scaffolds is crucial for providing the encapsulated cells with the necessary nutrients, oxygen, and metabolic exchange. Current methods for hydrogel scaffold fabrication face significant hurdles, including the challenge of forming sufficient internal channels, achieving precise scaffold geometry, and maintaining high cell viability, often compromised by the fabrication process and properties of the polymer materials used. Stereolithography (SLA) emerges as a promising 3D printing technique due to its exceptional precision, efficiency, and resolution, allowing for the creation of complex geometries with fine detail. This paper explores the application of SLA as a novel strategy to fabricate hydrogel scaffolds with interconnected small diameter channels, surpassing the capabilities of fused deposition modeling method to create templates. The encapsulated fibroblasts grown in the hydrogel scaffold containing channels showed significantly elevated cell viability compared to the ones without any channels. The capability of this SLA-assisted strategy to create channel structures with encapsulated cells demonstrate significant potential for generating 3D artificial tissue composites with precisely controlled micron-scale channels.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2874-2887"},"PeriodicalIF":3.6,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/bit.70007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modular RNAi Pathway Engineering Enhances Plasmid Copy Number Control in Yeast Bioproduction System","authors":"Qianru Cai, Manman Wang, Jinmei Zhu, Bangce Ye, Xiaohe Chu, Jiequn Wu","doi":"10.1002/bit.70014","DOIUrl":"10.1002/bit.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Rational design of microbial cell factories requires precise coordination of gene dosage and expression dynamics to optimize metabolic flux while minimizing cellular burden. In this study, an unexpected plasmid copy number amplification was identified following the reconstruction of an orthogonal RNA interference (RNAi) system in <i>Saccharomyces cerevisiae</i>, and a synthetic biology chassis with dynamically programmable plasmid copy numbers was developed. By integrating heterologous RNAi pathway genes from <i>Saccharomyces castellii</i> and designing sequence-specific small interfering RNAs (siRNAs) targeting plasmid-encoded selection markers, we established a chemically inducible gene dosage control platform capable of achieving plasmid copy number amplification up to 7.13-fold. Application of this RNAi-mediated copy number modulation to the carotenoid biosynthetic pathway resulted in an 18.6-fold increase in lycopene titers compared to static plasmid systems. This study presents an innovative approach for dynamic plasmid copy number regulation in <i>S. cerevisiae</i> to enable high-efficiency gene dosage control, further enriching the toolkit for synthetic metabolic regulation. This strategy exhibits significant potential for enhancing the production performance of microbial cell factories and offers novel perspectives for metabolic engineering optimizations within the synthetic biology framework.</p>\u0000 </div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2888-2898"},"PeriodicalIF":3.6,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qian Pan, Hui Gao, Weixian Su, Yupeng Nie, Rixu Liu, Weiqiang Dong, Yongchang Yao
{"title":"Enhancement of Chondrogenesis by a Microcavitary Hydrogel Coculture System Synergizing With SDF-1α and TGF-Β3","authors":"Qian Pan, Hui Gao, Weixian Su, Yupeng Nie, Rixu Liu, Weiqiang Dong, Yongchang Yao","doi":"10.1002/bit.70008","DOIUrl":"10.1002/bit.70008","url":null,"abstract":"<div>\u0000 \u0000 <p>A favorable microenvironment is of great significance for the repair of cartilage injury. In our previous study, a coculture system was devised, integrating genetically modified chondrocytes expressing transforming growth factor (TGF)-β3 with ATDC5 cells, which demonstrated an augmented chondrogenesis effect. In this study, a delivery platform for the controlled release of stromal cell-derived factor (SDF)-1α was constructed based on our microcavitary hydrogel system. Subsequently, it was combined with the coculture system to explore the release patterns of SDF-1α and TGF-β3 and investigate their synergistic impact on chondrogenesis. The findings indicated that both SDF-1α and TGF-β3 could be continuously and efficiently released from the delivery system throughout the culture period. Moreover, the combined application of SDF-1α and TGF-β3 was able to enhance cell proliferative activity, as demonstrated by the Cell Counting Kit-8 data. Synergistically, it led to superior chondrogenesis, as evidenced by real-time PCR, Western blot analysis, and immunohistochemistry staining assays. This study offers the insight that this delivery system, integrating the coculture system and microcavitary hydrogels, holds substantial potential for cell recruitment and cartilage repair, and may be applicable in regenerative medicine for diverse tissues.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2899-2911"},"PeriodicalIF":3.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poornima Ramesh Iyer, Xian Wu, Hyeon Choe, Linh Nguyen T. Tran, Karla Mercedes Paz González, Bahareh Rezaei, Shahriar Mostufa, Ebrahim Azizi, Ioannis H. Karampelas, Kai Wu, Jeffrey Chalmers, Jenifer Gomez-Pastora
{"title":"Magnetic-Assisted Manipulation of Rare Blood Cells for Diagnosis: A Systematic Review","authors":"Poornima Ramesh Iyer, Xian Wu, Hyeon Choe, Linh Nguyen T. Tran, Karla Mercedes Paz González, Bahareh Rezaei, Shahriar Mostufa, Ebrahim Azizi, Ioannis H. Karampelas, Kai Wu, Jeffrey Chalmers, Jenifer Gomez-Pastora","doi":"10.1002/bit.70010","DOIUrl":"10.1002/bit.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>The precise isolation and analysis of rare cells from blood are crucial for biomedical research and clinical diagnostics. This review examines recent advancements in magnetic-based separation techniques, focusing on their efficiency in capturing rare cells such as circulating tumor cells (CTCs), circulating fetal cells, and diseased red blood cells (RBCs). These methods use magnetophoresis under external magnetic fields for highly specific isolation with minimal contamination, offering advantages over traditional techniques in speed, cost-effectiveness, and robustness. Magnetic separation is categorized into label-based methods, which use immunomagnetic nanoparticles (IMNs) to target specific cell markers, and label-free methods, which exploit differences in magnetic susceptibility. Both approaches have achieved up to 99% efficiency in isolating diseased RBCs and CTCs. However, challenges remain in improving purity, scalability, and clinical applicability. A key limitation of label-based methods is the need to detach cells from magnetic beads without compromising viability. Label-free technologies, such as magnetic levitation, enable ligand-free separation based on density and susceptibility. Future research should focus on optimizing paramagnetic media, integrating machine learning for enhanced accuracy, and developing high-gradient magnetic fields (~1000 T/m) to improve efficiency. Advancements in IMNs with stronger magnetic properties will further enhance separation performance, driving clinical translation.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2625-2665"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Monica A. Mixon, Elena E. Paskaleva, Sheila Luong, Marc P. Douaisi, Mauricio Mora-Pale, Sandra P. Sanchez-Rodriguez, Jonathan S. Dordick
{"title":"Identification of Lytic Enzymes With Activity Against Corynebacterium Species","authors":"Monica A. Mixon, Elena E. Paskaleva, Sheila Luong, Marc P. Douaisi, Mauricio Mora-Pale, Sandra P. Sanchez-Rodriguez, Jonathan S. Dordick","doi":"10.1002/bit.70009","DOIUrl":"10.1002/bit.70009","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Corynebacteriales</i> are normal constituents of the human skin microbiota, involved in the metabolism of sweat and sebaceous glands secretions. The resultant compounds are a source of human body malodor. Some species, such as <i>Corynebacterium jeikeium</i>, are also opportunistic pathogens, and can cause systemic infection from colonization of medical devices such as intravascular catheters. Cell lytic enzymes have become effective alternatives to antibiotics and chemical oxidants in eliminating undesirable pathogens. As a baseline for antibacterial enzymatic activity we selected the broadly specific antibacterial enzyme lysozyme. While lysozyme had minimal activity on its own, the activity was significantly potentiated by the addition of a disruptor of the surface lipid layer of the bacterial cell wall, such as the lipase LysB (originating from a mycobacterial bacteriophage) or ethyleneglycol tetraacetic acid. To identify cell lytic enzymes with specific anti-<i>Corynebacterial</i> activity, we used a whole enzyme sequence as a probe to interrogate a custom-built <i>in silico</i> cDNA database of target <i>Corynebacterial</i> species and their bacteriophages. We also used a consensus enzymatically active domain as a probe. We evaluated the antibacterial activity of the thus discovered enzymes under a panel of application-relevant conditions, and determined that the newly identified bacterial autolysin NCBI WP_003861765.1 showed activity comparable to that of lysozyme, and the phage endolysin NCBI SLN03091 showed substantially higher activity than lysozyme and was significantly potentiated in the presence of LysB. As a result, we identified a nonchemical, nonantibiotic route to controlling <i>Corynebacterial</i> viability.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2666-2674"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144488181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xia Sheng, Zhenxu Wu, Xinyu Li, Qingming Ji, Xue Wang
{"title":"3D-Printed Sulfonated Polyetheretherketone Porous Scaffold Modified by Bioactive Glass for Bone Repair","authors":"Xia Sheng, Zhenxu Wu, Xinyu Li, Qingming Ji, Xue Wang","doi":"10.1002/bit.70000","DOIUrl":"10.1002/bit.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>The bioinert characteristics of the polyetheretherketone (PEEK) matrix determine that the PEEK scaffolds cannot display bioactivity in bone regeneration. Scaffolds that combine the excellent mechanical strength of PEEK with the bioactivity of bioactive glass (BAG) are highly desirable for orthopedic applications. In this study, the porous structure of a PEEK scaffold was designed and fabricated via the fused deposition modeling (FDM) 3D printing method. The BAG was used as a coating material to cover the surface of sulfonated PEEK (SPEEK) via a novel chemical liquid deposition (CLD) method. The modified scaffold with a pore structure and rough surface promoted the mineralization on the scaffold. Additionally, the scaffold showed outstanding cytocompatibility and osteoactivity. Moreover, a bone defect repair study in rabbits revealed that the new bone tissues grew into the scaffold from the margin toward the center. The bone defect region was completely connected to the host bone end after 4 weeks of implantation. In summary, the SPEEK-BAG scaffold has promising potential for bone repair applications.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2912-2927"},"PeriodicalIF":3.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biotechnological Advances in L-DOPA Biosynthesis and Production","authors":"Hongmei Han, Yue Chen, Lingtian Wu, Yongsheng Wang, Yibo Zhu","doi":"10.1002/bit.70011","DOIUrl":"10.1002/bit.70011","url":null,"abstract":"<div>\u0000 \u0000 <p><span>l</span>-DOPA (3,4-dihydroxyphenyl-<span>l</span>-alanine) has been the primary medication for treating Parkinson's disease (PD), a degenerative brain disorder related to dopamine depletion, for the past six decades. As a result, biotechnological approaches utilizing metabolic engineering in microorganisms or enzymatic processes have been extensively explored as promising alternatives for <span>l</span>-DOPA production. These methods not only enhance conversion efficiency and enantioselectivity but are also cost-effective and environmentally sustainable. Metabolic engineering strategies have been employed to engineer <i>Escherichia coli</i> strains capable of accumulating <span>l</span>-DOPA from glucose by regulating carbon metabolism pathways. Additionally, microbial systems expressing tyrosinase, <i>p</i>-hydroxyphenylacetate 3-hydroxylase (PHAH), or tyrosine phenol-lyase (TPL) have been utilized for <span>l</span>-DOPA biosynthesis. In this review, we summarize current advancements in <span>l</span>-DOPA biosynthesis and biotechnological production strategies, providing a comparative analysis of their advantages and limitations. Moreover, we discuss the promise of biotech-driven <span>l</span>-DOPA production, emphasizing its industrial applications and large-scale production feasibility.</p>\u0000 </div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 10","pages":"2615-2624"},"PeriodicalIF":3.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}