Biotechnology Progress最新文献

{"title":"Continuous concentration and diafiltration tangential flow filtration with scalable dual membrane technology.","authors":"Alexander Helling, Ehsan Espah Borujeni, Martin Leuthold, Stuart Tindal, Lara Fernandez-Cerezo, Mark Brower","doi":"10.1002/btpr.88501","DOIUrl":"https://doi.org/10.1002/btpr.88501","url":null,"abstract":"<p><p>Intensified, integrated, and continuous bioprocessing are key trends in current biologics biomanufacturing. They model more efficient and economical production in upstream and downstream processes. Continuous or single-pass (SP) tangential flow filtration (TFF) and particularly diafiltration (buffer exchange) are key applications needed in downstream processing. This work presents a novel flat sheet membrane cassette for TFF diafiltration with optional simultaneous ultrafiltration (concentration). It enables effective buffer exchange of feed streams in a single-pass, without dilution and with reduced shear stress to the valuable product. Contaminants such as salts, media components, or any small molecules smaller than the respective membrane cut-off are continuously removed while the needed buffer volume is comparable to conventional diafiltration processes with recirculation. The flat-sheet membrane cassette design resembles classic TFF cassettes and can therefore be scaled up and down and handled analogously. In addition, the design allows for a closed configuration, suitable for aseptic or bioburden-controlled conditions. To introduce the buffer, only one additional external connection port is required. This allows continuous diafiltration without significant increase in operator or process control complexity. This work presents ultrafiltration and diafiltration application data using bovine serum albumin (BSA) as a model protein and real antibodies processed with an automated lab-scale process system for reproducible data collection. The process performance was evaluated based on buffer exchange efficiency, transmembrane pressure (TMP) and permeate flux rates under varying process parameters, namely feed protein concentration, feed flow rate and diafiltration volumes. Buffer consumptions similar to conventional recirculation diafiltration have been observed with even reduced buffer consumptions at diafiltration volumes below 3. Buffer exchange values ranged over a broad range depending on the process parameters while relevant settings achieved a ~97 to >99% buffer exchange at, for example, 3, 5 or 7 diafiltration volumes at relatively low TMP between 50 and 350 mbar using both BSA and mAb. Typical permeability values and feed flow rates ranged from 10 to 60 L/(m²h) and 1 to 7 L/(m²h), respectively, using BSA and mAb protein concentrations from ~3 to 80 g/L and were significantly depending on the set process parameters. The data demonstrates how this new SPTFF concept can contribute to intensified and continuous biomanufacturing.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":" ","pages":"e88501"},"PeriodicalIF":2.5,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148148313","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":"Effect of cell retention techniques in Komagataella phaffii lab-scale continuous processes","authors":"Marina Y. Linova,&nbsp;Satish K. Kodiripaka,&nbsp;Edite Martins,&nbsp;Sobhana A. Sripada,&nbsp;Stefano Menegatti,&nbsp;John M. Woodley","doi":"10.1002/btpr.70092","DOIUrl":"10.1002/btpr.70092","url":null,"abstract":"<p>Perfusion technologies play a growing role in the implementation of continuous processes for biotherapeutics production in mammalian-based manufacturing. However, their application to alternative production hosts is limited. Cell retention systems are of key importance for the efficiency of perfusion bioreactors. In this study, we investigate two cell retention technologies for the development of lab-scale <i>Komagataella phaffii</i> continuous processes. An acoustic-based process (AP) and a membrane-based process (MP) were developed using an acoustic cell separator (ACS) and a vibrating membrane filtration (VMF) device, respectively. Both systems allowed for continuous cell recycle and production of scFv13R4 antibody fragment for 8 days (AP) and 9 days (MP), without loss in productivity, while maintaining high viability (greater than 90%). Higher volumetric and specific productivities were achieved during the AP process, namely 50.63 ± 1.63 mg L⁻¹ day⁻¹ and 1.09 ± 0.07 mg g⁻¹ day⁻¹, against the 32.29 ± 1.21 mg L⁻¹ day⁻¹ and 0.44 ± 0.02 mg g⁻¹ day⁻¹ afforded by the MP process. The VMF device provided 100% separation efficiency with biomass accumulating up to concentrations of 74.1 ± 0.1 g L⁻¹ dry cell weight (DCW), whereas the acoustic device reached 55.1 ± 0.47 g L⁻¹ DCW at 98% separation efficiency. The acoustic device showed selectivity towards larger and more complex cells in the yeast population, which might be linked to the observed higher productivities for the AP process. This study discusses the advantages and drawbacks of both cell retention technologies and provides an outlook towards their future investigation in <i>K. phaffii</i> perfusion processes.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548047","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":"Unveiling microbial and microalgal chassis for therapeutic and diagnostic protein expression","authors":"Lakshika Bhandari,&nbsp;Samir Kulkarni,&nbsp;Gunjan Prakash","doi":"10.1002/btpr.70098","DOIUrl":"10.1002/btpr.70098","url":null,"abstract":"<p>Biopharmaceuticals are becoming one of the most successful clinical therapeutic products for treating various disorders and are gradually being utilized across nearly all areas of medicine. They have revolutionized the treatment of numerous diseases and continue to represent a significant area of research and development. Presently, host cell systems like bacteria, yeast, insects, and mammalian cells dominate the production of both therapeutic and diagnostic proteins. This review explores the strengths and limitations of these existing host systems for recombinant protein production, emphasizing the promising potential of microalgal systems for expressing therapeutic and diagnostic proteins. It accentuates the advantages of microalgae, such as their rapid growth rates, scalability, and sustainability. We delve into the intricacies of glycosylation patterns in microalgae, comparing them with those in other expression systems. This review highlights recent advancements in algal-based protein expression systems for diagnostic and therapeutic applications. It also outlines a strategic roadmap for future developments in biopharmaceutical production, emphasizing how each expression system's unique characteristics can help meet modern medicine's growing demands.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146008787","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":"Augmenting therapeutic protein production in CHO cells: A proline-based selection strategy for enhanced productivity and product quality","authors":"Bin Zhao,&nbsp;Boya Zhang,&nbsp;Yanshen Kang,&nbsp;Shenghai Liu,&nbsp;Zhangying Jia,&nbsp;Chenlin Lu,&nbsp;Yajing Cao,&nbsp;April Xu,&nbsp;Kyu-Sung Lee,&nbsp;Zheng Zhang,&nbsp;Jing Song","doi":"10.1002/btpr.70091","DOIUrl":"10.1002/btpr.70091","url":null,"abstract":"<p>Chinese hamster ovary (CHO) cells have emerged as the predominant mammalian host for the production of therapeutic recombinant proteins, including monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), and fusion proteins. To meet the growing demand for biologics and reduce manufacturing costs, the exploitation of efficient cell line development platforms is essential. Over the past decades, various selection markers, such as dihydrofolate reductase (DHFR), glutamine synthetase (GS), and antibiotic resistance genes, have been widely utilized in the development of production cell lines. In this study, we introduce the proline selection system, an alternative metabolic selection strategy, as an efficient approach to optimize our CHO cell line development platform. By employing yeast <i>PRO1</i> and <i>PRO2</i> genes as selection markers, proline selection effectively complements GS selection to establish high-producing cell lines for both mAbs and bsAbs. In particular, the integration of <i>PRO1</i> and <i>PRO2</i> genes into a single plasmid, in conjunction with the GS gene, significantly enhances productivity for asymmetric molecules. Optimized chain configuration across proline and GS selection plasmids can further boost protein yield. Additionally, the overexpression of regulator proteins can be leveraged with proline selection to enhance antibody production or fine-tune product quality. Taken together, the incorporation of proline selection into CHO cell line development, particularly when combined with GS selection, provides a consistent and streamlined strategy to meet the growing demand for high-quality biologics in the pharmaceutical industry.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538977","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":"In silico mediated development of orthogonally selective mAb downstream processes for the removal of process-related impurities","authors":"Dongyoun Jang,&nbsp;Mario A. Gutierrez-Diaz,&nbsp;Scott H. Altern,&nbsp;Hendri Tjandra,&nbsp;Steven M. Cramer","doi":"10.1002/btpr.70097","DOIUrl":"10.1002/btpr.70097","url":null,"abstract":"<p>Continued advancements in recombinant CHO expression of therapeutic mAbs have led to improved productivity but have also increased the HCP burden on the downstream purification process. In this work, we developed an in silico mediated workflow to facilitate the rapid development of non-protein A three-step processes for the effective removal of HCPs from a CHO-derived mAb therapeutic. Null CCF and pure mAb retention patterns were generated using linear gradient screens on a set of strategically selected resins, membrane adsorbers, and novel adsorbents. HCP characterization of key fractions was then carried out using RPLC “HCP fingerprinting” and the resulting retention database was processed using an in silico tool to generate a list of all possible three-step sequences subject to design constraints. Top-ranked processes generated by the tool were then evaluated and refined at the bench scale to produce several successful processes consisting of bind-elute capture followed by either a bind-elute and flowthrough step (91.4 ppm HCP with a cumulative product yield of 78.7%) or two flowthrough steps with no salt (96.1 ppm HCP with a cumulative yield of 81.4%).</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761963","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":"Artificial intelligence and machine learning-assisted digital applications for biopharmaceutical manufacturing","authors":"Shyam Panjwani,&nbsp;Hao Wei,&nbsp;John Mason","doi":"10.1002/btpr.70089","DOIUrl":"10.1002/btpr.70089","url":null,"abstract":"<p>Artificial intelligence and automation are no longer just buzzwords in the biopharmaceutical industry. The manufacturing of a class of biologics, comprising monoclonal antibodies, cell therapies, and gene therapies, is far more complex than that of traditional small molecule drugs. Therefore, applications based on artificial intelligence are essential for successfully manufacturing this new class of biologics more quickly and more economically. Some biologics manufacturers, academic researchers, and young entrepreneurs have already begun implementing artificial intelligence-based applications to increase operational efficiency, enhance process understanding, improve process monitoring, and achieve better regulatory compliance. Regulatory guidance from health agencies on the use of artificial intelligence and machine learning is acting as a catalyst in the adoption process of these new technologies by the biopharmaceutical industry. Research in artificial intelligence and machine learning has also advanced significantly in the last decade. At the same time, new cloud technologies have made the development and deployment of machine learning applications much easier. Several examples of artificial intelligence and machine learning applications in monoclonal antibodies manufacturing already exist. Cell and gene therapy, which present the future of medicine, will also benefit from this new technology. Overall, advancements in this domain will essentially help better serve patients' needs.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480580","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":"Enhancing CHO cell recombinant protein production using a perfusion-directed host evolution approach","authors":"Peter Amaya,&nbsp;Rajesh K. Mistry,&nbsp;Susie Sou,&nbsp;Sonja Hess,&nbsp;Bijay Khanal,&nbsp;Zayla Schaeffer,&nbsp;Jie Zhu,&nbsp;Lina Chakrabarti","doi":"10.1002/btpr.70093","DOIUrl":"10.1002/btpr.70093","url":null,"abstract":"<p>Clonally derived cell lines generated from Chinese hamster ovary (CHO) cells encounter numerous stressors when cultured in high-intensity perfusion bioreactors leading to poor process performance. To circumvent this, the ability of CHO cells to adapt to different culture environments was exploited. Here host cells were selected in the presence of physical and chemical stressors associated with a perfusion environment by culturing at a high cell density in a perfusion bioreactor for 30 days. Following recovery and expansion, the performance of the resulting perfusion-evolved host was evaluated using stable transfectant pools and clones expressing biotherapeutics of different formats. Cell lines generated from the perfusion host outperformed the parental host at several fundamental stages of the clone selection process. Perfusion host-derived pools showed elevations in productivity, cell-specific productivity, end-of-run viability, and reduced lactate production in fed-batch culture. Use of the perfusion host for cell line generation resulted in an increased frequency of high-producing clones. Moreover, the perfusion host-derived clones demonstrated 30% higher productivity and improved mannose profile in the perfusion environment compared to the clones from the parental host. Furthermore, a comparative proteomic analysis between the two host types revealed unique regulatory networks that allowed us to gain insights into the underlying molecular processes influencing production performance. Taken together, the results suggest that the perfusion host may not only increase the efficiency of the cell line development process but may also serve as an efficient tool for improvement in production capability in the perfusion platform.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628444","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":"A case study showing the role of hydrophobicity variants and other enriched mAb proteoforms on filterability through a virus filter with productivity improvement measures","authors":"Solomon Isu,&nbsp;Derek Silva,&nbsp;Melissa Holstein,&nbsp;Angela Lewandowski,&nbsp;Kristina Cunningham,&nbsp;Adam Sokolnicki,&nbsp;Bala Raghunath","doi":"10.1002/btpr.70101","DOIUrl":"10.1002/btpr.70101","url":null,"abstract":"<p>A rapid assessment of manufacturability for drug candidates is crucial for advancing a prospective biotherapeutic from a candidate to a bulk drug substance. A lot-to-lot approach to manufacturability is adopted where each biologic batch is assessed for manufacturability as a bulk, unfractionated pool. Manufacturers may explore a more granular approach, independently enriching and evaluating the filterability of antibody variants within each lot, especially within the confines of relative hydrophobicity and surface charge. This study examined the use of bind-and-elute chromatography to alter the proportions of monoclonal antibody (mAb) proteoforms in eluate sub-pools from a mixed-mode chromatography resin-packed column. Filterability of each sub-pool through a virus-retaining filter was subsequently examined. Circular dichroism and Fourier transform infrared spectroscopy were performed for each sub-pool to probe for higher-order structure differences between mAb variants enriched therein. Bioanalytical techniques were also used to assess colloidal stability, surface hydrophobicity, surface charge, and size differences. Results showed that basic charge variants, high-mannose glycovariants, high relative hydrophobicity proteoforms, and high-molecular-weight species were enriched in the last-eluting (terminal) sub-pools. The first sub-pool and the final sub-pool showed the most fouling propensity on VPro virus filters. Circular dichroism showed that enriched proteoforms in the last sub-pool possessed a higher percentage of bends. Most secondary structures did not vary significantly between sub-pools. Diffusion interaction parameter was highly negative across all sub-pools and the bulk unfractionated pool. These results provide a design space for identifying and depleting problematic mAb variants before the crucial virus filtration step.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997225","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":"Development of a co-culture of Ureibacillus thermosphaericus and Cupriavidus taiwanensis for inhibitors removal from hemicellulose prehydrolysate","authors":"Mariem Theiri,&nbsp;Mariya Marinova,&nbsp;Hassan Chadjaa,&nbsp;Mario Jolicoeur","doi":"10.1002/btpr.70107","DOIUrl":"10.1002/btpr.70107","url":null,"abstract":"<p>For biofuels production, hemicellulose pre-hydrolysate is considered an attractive feedstock rich in fermentable sugars. The lignocellulosic biomass comprises, along with sugars, several inhibitors that can hamper its efficient conversion. In this work, mixed cultures of <i>Ureibacillus thermosphaericus</i> and <i>Cupriavidus taiwanensis</i> were used for the first time to detoxify the pre-hydrolysate. The nutrient source was first optimized in synthetic media with mono-cultures to detoxify phenolic compounds, and a medium containing inorganic salts was selected. Afterwards, the efficiency of phenolic degradation was compared in a single-compound solution and in a mixture. The simultaneous co-culture showed the highest degradation efficiency (90% at 2.8 g/L of phenolic compounds). Finally, the detoxification of a raw pre-hydrolysate was conducted, and a maximum degradation of 14% of the phenolics was obtained using sequential inoculation of <i>Ureibacillus thermosphaericus</i> followed by <i>Cupriavidus taiwanensis</i> addition.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13055127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997216","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":"A size-exclusion chromatography fingerprinting workflow for the development of flow-through polishing operations for mAbs derived from continuous precipitation processes","authors":"Mario A. Gutierrez-Diaz,&nbsp;Scott H. Altern,&nbsp;Todd M. Przybycien,&nbsp;Steven M. Cramer","doi":"10.1002/btpr.70104","DOIUrl":"10.1002/btpr.70104","url":null,"abstract":"<p>In this work we present a workflow for developing two-step, flow-through polishing processes for monoclonal antibodies (mAbs). The approach is demonstrated using redissolved precipitates from three CHO-derived mAbs generated by a continuous, PEG/ZnCl₂-mediated precipitation capture process. Size Exclusion Chromatography (SEC) fingerprinting and a percent SEC clearance (PSC) metric are developed to enable simultaneous quantification of monomer yield and impurity removal during high-throughput screening and scale-down column studies. Batch slurry plate screens are used to evaluate multimodal anion exchange (MMA) resins and an activated carbon composite adsorber under varying pH and ionic strengths, assessing partition coefficients and PSC values against both low-molecular-weight (LMW) and high-molecular-weight (HMW) impurities. Top candidates were then assessed in single-column, higher-loading flow-through experiments using the redissolved precipitates as feeds. Activated carbon emerged as a highly effective first polishing step for LMW impurity removal under acidic, low-conductivity conditions, while MMA resins provided complementary LMW and HMW clearances in a subsequent flow-through step. The two-step processes achieved overall mAb recoveries of 80%–87%, reduced HMW species from &gt;1.7% down to 1.1%, and decreased host-cell protein levels from &gt;10,000 to &lt;40 ppm for all three mAbs. SEC fingerprints showed the ability to identify orthogonal impurity removal opportunities between the two polishing materials, validating the screening methodology for a process devoid of bind-elute processing steps. This work demonstrates that SEC-based impurity profiling and PSC metrics can guide the development of flow-through polishing processes and offer a useful intensification strategy to alleviate DSP bottlenecks and reduce reliance on affinity capture.</p>","PeriodicalId":8856,"journal":{"name":"Biotechnology Progress","volume":"42 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997255","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}