Biotechnology and Bioengineering最新文献

{"title":"Electrochemical Catheter Hub Operated by a Wearable Micropotentiostat Prevents Acinetobacter baumannii Infection In Vitro","authors":"Majid Al-Qurahi,&nbsp;Derek Fleming,&nbsp;Won-Jun Kim,&nbsp;Ibrahim Bozyel,&nbsp;Robin Patel,&nbsp;Haluk Beyenal","doi":"10.1002/bit.28990","DOIUrl":"10.1002/bit.28990","url":null,"abstract":"<p>Intraluminal infection of central venous catheters, used for long-term treatment, can result in central line-associated bloodstream infection (CLABSI). These infections can be challenging to prevent and treat due to formation of biofilms within catheter lumens, which shield bacteria from the human immune response and conventional antimicrobial therapies. Preventing bacterial colonization of catheter hubs is a strategy to prevent CLABSI. To address this, we developed a nonantibiotic, animal-ready electrochemical catheter hub (e-catheter hub), operated by a wearable, battery-powered micropotentiostat (MP), that internally generates tunable hypochlorous acid (HOCl) for preventing intraluminal infection. The design evaluated three different electrode materials—titanium, platinum, and gold—for HOCl generation and biocidal activity, using working and counter electrodes of the same materials and a silver/silver chloride-plated wire as a quasi-reference electrode. e-catheter hubs operated by MPs at 1.5 V_Ag/AgCl for 3 h generated HOCl, reducing <i>Acinetobacter baumannii</i> ATCC-17978 below the detection limit (average reduction of 4.40 ± 0.05 log₁₀ CFU/mL). The efficacy of e-catheter hubs operated by MPs in generating HOCl and achieving biocidal activity is comparable to that of a commercial potentiostat. This study represents the first step in developing a localized, nonantibiotic strategy to mitigate CLABSI risk.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1828-1839"},"PeriodicalIF":3.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28990","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836911","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":"A New Aerosol-Based Photobioreactor for the Cultivation of Cyanobacteria on Luffa","authors":"Jonas Kollmen,&nbsp;Andreas Stiefelmaier,&nbsp;Ramtin Mofrad,&nbsp;Dorina Strieth","doi":"10.1002/bit.28992","DOIUrl":"10.1002/bit.28992","url":null,"abstract":"<p>Cyanobacteria are promising organisms for sustainable biotechnology due to their ability to grow photoautotrophically and their wide range of products. Many cyanobacteria grow in the form of biofilms, which is why the development of photobioreactors (PBR) for the cultivation of cyanobacteria in the form of biofilms is of great interest. However, these biofilm PBR are mostly based on artificial growth surfaces, whereas biodegradable growth surfaces would be favored in terms of sustainable production and application. Luffa sponges (the dried fruit of <i>Luffa cylindrica</i>) are excellent biodegradable growth surfaces for cyanobacteria. Therefore, a biofilm PBR for cultivation of cyanobacteria on Luffa was developed in this study. Since many cyanobacteria grow naturally as biofilms in an air-exposed form and this should be imitated to improve growth, an aerosol-based PBR (abPBR) should be used for cultivation. This involves supplying the cyanobacteria with a nutrient mist. The abPBR was comprehensively characterized by determining the distribution of light, humidity and temperature inside the reactor. In addition, the residence time distribution of the aerosol was determined both experimentally and simulatively. In final cultivation experiments, it was shown that the abPBR is ideal for cultivating cyanobacteria and at the same time the aerosol system enables a simple imitation of drought stress. With the cyanobacteria <i>Nostoc</i> spec. and <i>Desmonostoc muscorum</i>, maximum area-time-yields (ATY) in relation to the growth surface of 6.34 and 4.19 g m⁻² d⁻¹, respectively, were achieved. Compared to previously developed abPBR, the ATY has been increased by a factor of 2.3.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1669-1683"},"PeriodicalIF":3.5,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28992","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827145","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":"Flux Sampling Suggests Metabolic Signatures of High Antibody-Producing CHO Cells","authors":"Kate E. Meeson,&nbsp;Joanne Watson,&nbsp;Susan Rosser,&nbsp;Ellie Hawke,&nbsp;Andrew Pitt,&nbsp;Tessa Moses,&nbsp;Leon Pybus,&nbsp;Magnus Rattray,&nbsp;Alan J. Dickson,&nbsp;Jean-Marc Schwartz","doi":"10.1002/bit.28982","DOIUrl":"10.1002/bit.28982","url":null,"abstract":"<p>Chinese hamster ovary (CHO) cells remain the industry standard for producing numerous therapeutic proteins, particularly monoclonal antibodies (mAbs). However, achieving higher recombinant protein titers remains an ongoing challenge and a fundamental understanding of the cellular mechanism driving improved bioprocess performance remains elusive. To directly address these challenges and achieve substantial improvements, a more in-depth understanding of cellular function within a bioprocess environment may be required. Over the past decade, significant advancements have been made in the building of genome-scale metabolic models (GEMs) for CHO cells, bridging the gap between high information content 'omics data and the ability to perform <i>in silico</i> phenotypic predictions. Here, time-course transcriptomics has been employed to constrain culture phase-specific GEMs, representing the early exponential, late exponential, and stationary/death phases of CHO cell fed-batch bioreactor culture. Temporal bioprocess data, including metabolite uptake and secretion rates, as well as growth and productivity, has been used to validate flux sampling results. Additionally, high mAb-producing solutions have been identified and the metabolic signatures associated with improved mAb production have been hypothesized. Finally, constraint-based modeling has been utilized to infer specific amino acids, cysteine, histidine, leucine, isoleucine, asparagine, and serine, which could drive increased mAb production and guide optimal media and feed formulations.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1898-1913"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28982","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822886","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":"Generating Multispecific Antibodies Through Column-Based Redox Reactions: Part I","authors":"Michael King,&nbsp;Verzhiniya Aho,&nbsp;Kimberly Nguyen,&nbsp;Jackson Temple,&nbsp;Dawn Eriksen-Stapleton,&nbsp;Aaron D'Antona,&nbsp;Timothy Iskra,&nbsp;Arch D. Creasy,&nbsp;Ryan A. Jackobek","doi":"10.1002/bit.28981","DOIUrl":"10.1002/bit.28981","url":null,"abstract":"<div>\u0000 \u0000 <p>Multispecific antibodies are increasingly being explored in the pharmaceutical industry for unmet patient needs. This study focuses on generating these molecules through an electrostatic-steering strategy, where two separate parent homodimer antibodies are expressed and purified, then combined into the heterodimer multispecific through reduction and oxidation chemistry. Traditional manufacturing operations for electrostatic steering multispecifics can include complex processing steps. Therefore, a novel redox process to generate the multispecific has been explored. This process involves a column-based reduction reaction and a spike of oxidant in the elution pool to form the heterodimer. This new strategy can simplify the downstream purification process for electrostatic-steering based molecules. The method consists of simultaneously binding two separate parental homodimers to the protein A chromatography resin and applying a reductant wash to reduce the interchain disulfide bonds. The molecules are then eluted, neutralized, and oxidized to form the intact heterodimer. The mechanism and rates of reduction, heterodimerization, and oxidation have been characterized to maximize conversion and product quality. This strategy has been demonstrated successfully for five multispecifics with diverse specificity and IgG subclasses. Implementing this method for pharmaceutical bioprocesses in the production of multispecific molecules offers the potential for the reduction in manufacturing complexity while maintaining acceptable product quality and yield.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1793-1803"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819936","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":"Improving Multispecific Antibody Bioprocesses Through Coculture and Column-Based Redox Reactions: Part II","authors":"Dawn Eriksen-Stapleton,&nbsp;Michael King,&nbsp;Guogang Dong,&nbsp;Dhruv Srivastava,&nbsp;Timothy Iskra,&nbsp;Verzhiniya Aho,&nbsp;Kimberly Nguyen,&nbsp;Lia Ingaharro,&nbsp;John J. Scarcelli,&nbsp;Joshua Ochocki,&nbsp;Matt Gagnon,&nbsp;Robert Hartsough,&nbsp;Hongheng Keo,&nbsp;Courtney Hulme,&nbsp;John Coyne,&nbsp;Cassandra Neubauer,&nbsp;Arch Creasy","doi":"10.1002/bit.28975","DOIUrl":"10.1002/bit.28975","url":null,"abstract":"<div>\u0000 \u0000 <p>Multispecifics are increasingly being evaluated in the pharmaceutical industry due to their unique mechanisms of action, enabled by their multiple antigen-binding capabilities. The complexity of these molecules can make production challenging, prompting the development of various generation approaches. This study employs an electrostatic-steering generation method, where charge-based differences between two parental homodimer antibodies drive correct heterodimerization during a redox reaction of the partially purified parental homodimers. This strategy can achieve high conversion to the heterodimer with minimal product-related impurities. However, it also necessitates separate bioreactors for each parental homodimer, leading to complex manufacturing campaigns. This work introduces a novel bioprocess for electrostatic-steering-based multispecifics, combining two unique components. First, two separate cell lines are cocultured, leading to the simultaneous production of both parental homodimers in a single bioreactor. The second component involves a column-based redox reaction, where the homodimers are captured, and their disulfide bonds are reduced while bound to the protein A resin using a reductant wash. The column is then eluted and neutralized, allowing the reduced parental homodimers to heterodimerize. Finally, the addition of an oxidant enables the reformation of disulfide bonds, completing the formation of the multispecific. This new process is robust and efficient across both the lab bench and manufacturing scales, maintaining well-controlled impurity profiles. Homodimer harvest ratios were consistently within 10%–15% of the target across various cocultured cell lines. Conversions from homodimers to heterodimers exceeded 90%, and multispecific percentages in all tested drug substance pools were above 95%. This strategy aligns the new multispecific bioprocess with typical antibody-like processes, optimizing clinical and commercial manufacturing resources while producing complex multispecific molecules with minimal impurities.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1696-1709"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143820070","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":"Physiology and Robustness of Yeasts Exposed to Dynamic pH and Glucose Environments","authors":"Luca Torello Pianale,&nbsp;Luisa Blöbaum,&nbsp;Alexander Grünberger,&nbsp;Lisbeth Olsson","doi":"10.1002/bit.28984","DOIUrl":"10.1002/bit.28984","url":null,"abstract":"<p>Gradients negatively affect performance in large-scale bioreactors; however, they are difficult to predict at laboratory scale. Dynamic microfluidics single-cell cultivation (dMSCC) has emerged as an important tool for investigating cell behavior in rapidly changing environments. In the present study, dMSCC, biosensors of intracellular parameters, and robustness quantification were employed to investigate the physiological response of three <i>Saccharomyces cerevisiae</i> strains to substrate and pH changes every 0.75–48 min. All strains showed higher sensitivity to substrate than pH oscillations. Strain-specific intracellular responses included higher relative glycolytic flux and oxidative stress response for strains PE2 and CEN.PK113-7D, respectively. Instead, the Ethanol Red strain displayed the least heterogeneous populations and the highest robustness for multiple functions when exposed to substrate oscillations. This result could arise from a positive trade-off between ATP levels and ATP stability over time. The present study demonstrates the importance of coupling physiological responses to dynamic environments with simultaneous characterization of strains, conditions, individual regimes, and robustness analysis. All these tools are a suitable add-on to traditional evaluation and screening workflows at both laboratory and industrial scale, and can help bridge the gap between these two.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1656-1668"},"PeriodicalIF":3.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28984","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143823138","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":"Development of an HEK293 Suspension Cell Culture Medium, Transient Transfection Optimization Workflow, and Analytics for Batch rAAV Manufacturing","authors":"Erica A. Green,&nbsp;Qiang Fu,&nbsp;Nelson Ndahiro,&nbsp;Thomas M. Leibiger,&nbsp;Yongdan Wang,&nbsp;Yongsuk Lee,&nbsp;Kelvin H. Lee,&nbsp;Michael Betenbaugh,&nbsp;Seongkyu Yoon,&nbsp;David J. McNally","doi":"10.1002/bit.28980","DOIUrl":"10.1002/bit.28980","url":null,"abstract":"<p>Recombinant adeno associated virus (rAAV) vectors have become popular delivery vehicles for in vivo gene therapies, but demand for rAAVs continues to outpace supply. Platform processes for rAAV production are being developed by many manufacturers, and transient chemical transfection of human embryonic kidney 293 (HEK293) cells is currently the most popular approach. However, the cutting edge nature of rAAV process development encourages manufacturers to keep cell culture media formulations, plasmid sequences, and other details proprietary, which creates hurdles for small companies and academic labs seeking to innovate in this space. To address this problem, we leveraged the resources of an academic-industry consortium (Advanced Mammalian Biomanufacturing Innovation Center, AMBIC) to develop an rAAV production system based on transient transfection of suspension HEK293 cells adapted to an in-house, chemically defined medium. We found that balancing iron and calcium levels in the medium were crucial for maintaining transfection efficiency and minimizing cell aggregation, respectively. A design of experiments approach was used to optimize the transient transfection process for batch rAAV production, and PEI:DNA ratio and cell density at transfection were the parameters with the strongest effects on vector genome (VG) titer. When the optimized transient process was transferred between two university sites, VG titers were within a twofold range. Analytical characterization showed that purified rAAV from the AMBIC process had comparable viral protein molecular weights versus vector derived from commercial processes, but differences in transducing unit (TU) titer were observed between vector preps. The developed media formulation, transient transfection process, and analytics for VG titer, capsid identity, and TU titer constitute a set of workflows that can be adopted by others to study fundamental problems that could improve product yield and quality in the nascent field of rAAV manufacturing.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1640-1655"},"PeriodicalIF":3.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28980","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798355","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":"Small Intestine on a Chip Demonstrates Physiologic Mucus Secretion in the Presence of Lacticaseibacillus rhamnosus Biofilm","authors":"Sanat Kumar Dash,&nbsp;Cláudia N. H. Marques,&nbsp;Gretchen J. Mahler","doi":"10.1002/bit.28989","DOIUrl":"10.1002/bit.28989","url":null,"abstract":"<p>The small intestine is an area of the digestive system difficult to access using current medical procedures, which prevents studies on the interactions between food, drugs, the small intestinal epithelium, and resident microbiota. Therefore, there is a need to develop novel microfluidic models that mimic the intestinal biological and mechanical environments. These models can be used for drug discovery and disease modeling and have the potential to reduce reliance on animal models. The goal of this study was to develop a small intestine on a chip with both enterocyte (Caco-2) and goblet (HT29-MTX) cells cocultured with <i>Lacticaseibacillus rhamnosus</i> biofilms, which is of one of several genera present in the small intestinal microbiota. <i>L. rhamnosus</i> was introduced following the establishment of the epithelial barrier. The shear stress within the device was kept in the lower physiological range (0.3 mPa) to enable biofilm development over the in vitro epithelium. The epithelial barrier differentiated after 5 days of dynamic culture with cell polarity and permeability similar to the human small intestine. The presence of biofilms did not alter the barrier's permeability in dynamic conditions. Under fluid flow, the complete model remained viable and functional for more than 5 days, while the static model remained functional for only 1 day. The presence of biofilm increased the secretion of acidic and neutral mucins by the epithelial barrier. Furthermore, the small intestine on a chip also showed increased MUC2 production, which is a dominant gel-forming mucin in the small intestine. This model builds on previous publications as it establishes a stable environment that closely mimics in vivo conditions and can be used to study intestinal physiology, food-intestinal interactions, and drug development.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1816-1827"},"PeriodicalIF":3.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28989","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798353","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":"Directed Evolution of an (R)-Selective Transaminase Toward Higher Efficiency of Sitagliptin Analog Biosynthesis","authors":"Dong-Xu Jia,&nbsp;Lei Zang,&nbsp;Chi-De Ni,&nbsp;Jia-Le Wang,&nbsp;Hai Yu,&nbsp;Zhi-Qiang Liu,&nbsp;Yu-Guo Zheng","doi":"10.1002/bit.28988","DOIUrl":"10.1002/bit.28988","url":null,"abstract":"<div>\u0000 \u0000 <p>Transaminase (TA)-catalyzed asymmetric amination is considered as a green chemistry approach to synthesize pharmaceutical analogs, but their ability to accept substrate for catalyzing sterically hindered ketones remains a challenge. Sitagliptin is an antihyperglycemic drug to treat type II diabetes. Herein, we exploited an efficient (<i>R</i>)-selective TA to biosynthesize sitagliptin analog (<i>R</i>)-3-amino-1-morpholino-4-(2,4,5-trifluorophenyl)butan-1-one. Starting from a previously constructed (<i>R</i>)-ATA5, two rounds of directed evolution were performed through combining error-prone PCR, site-directed saturation and combinatorial mutagenesis. The resultant variant ATA5/F189H/S236T/M121H showed a 10.2-fold higher activity and a 4-fold improved half-life at 45°C. Crucially, the variant was able to either catalyze the amination of 700 mM substrate with a conversion up to 93.1% and product <i>e.e</i>.&gt; 99% in a cosolvent reaction system, or biotransform 200 mM substrate with a conversion of 97.6% and product <i>e.e</i>.&gt; 99% in a cosolvent-free system. Furthermore, the structural analysis gave insight into how the mutations affected enzymatic activity and thermostability. This study, which consists of constructing a robust (<i>R</i>)-selective TA and the new synthesis route with the highest conversion ever reported, provides a reference for industrial manufacturing sitagliptin analog.</p></div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 7","pages":"1735-1746"},"PeriodicalIF":3.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143798383","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":"Biotechnology and Bioengineering: Volume 122, Number 5, May 2025","authors":"","doi":"10.1002/bit.28745","DOIUrl":"10.1002/bit.28745","url":null,"abstract":"","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 5","pages":"1063-1066"},"PeriodicalIF":3.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28745","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789575","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}