Biotechnology and Bioengineering最新文献_第6页

Immobilization of Alginate Microbeads With Whole-Cells Expressing Nitrilase for Continuous Nicotinic Acid Production in Chip Millireactor. 用全细胞表达硝化酶固定化海藻酸盐微球在片式微反应器中连续生产烟酸。

IF 3.9 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-30 DOI: 10.1002/bit.70391

Jonathan Bassut, Emina Mehić, Luana Cuvillier, Carine Vergne-Vaxelaire, Jean-Louis Petit, Maïté Michaud, Zoé Anxionnaz-Minvielle, Anne Zaparucha, Guillaume Nonglaton

{"title":"Immobilization of Alginate Microbeads With Whole-Cells Expressing Nitrilase for Continuous Nicotinic Acid Production in Chip Millireactor.","authors":"Jonathan Bassut, Emina Mehić, Luana Cuvillier, Carine Vergne-Vaxelaire, Jean-Louis Petit, Maïté Michaud, Zoé Anxionnaz-Minvielle, Anne Zaparucha, Guillaume Nonglaton","doi":"10.1002/bit.70391","DOIUrl":"https://doi.org/10.1002/bit.70391","url":null,"abstract":"The biocatalytic production of nicotinic acid using nitrilases has emerged as a promising alternative to conventional chemical synthesis, offering improved selectivity and environmental sustainability. In this study, we developed a continuous-flow millireactor system employing Escherichia coli cells expressing a nitrilase from Paraburkholderia phymatum (NitPhym) for the continuous production of nicotinic acid. To enhance catalytic efficiency and stability, whole cells were immobilized using two different strategies: covalent attachment to the reactor walls and encapsulation in alginate microbeads. The performance of these immobilization techniques was evaluated in millireactors with two different geometries: pillar and zigzag configurations. Encapsulation of NitPhym-expressing E. coli cells in alginate microbeads was achieved through a centrifuge-assisted microencapsulation method, yielding beads with diameters of up to 350 µm. Continuous-flow reactions demonstrated that the microencapsulated cells maintained their activity over at least 7 days, achieving stable conversion rates of approximately 30% in both pillar and zigzag millireactors. Compared to direct covalent immobilization, microencapsulation significantly reduced cell leaching and contamination of the reaction product. These findings highlight the potential of whole-cell microencapsulation for enhancing the stability and efficiency of biocatalytic processes in continuous-flow millireactors.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149079810","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}

引用次数: 0

Loop-Centric Engineering of Terminal Deoxynucleotidyl Transferase for Enhanced Catalysis of 3'-Modified Nucleotides. 末端脱氧核苷酸转移酶的环中心工程增强3'-修饰核苷酸的催化作用。

IF 3.9 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-30 DOI: 10.1002/bit.70397

Kun Shi, An-Na Li, Jian-He Xu, Hui-Lei Yu

引用次数: 0

Implementing an Intensified Dynamic Perfusion Process for Biologics Manufacturing at Scale and Continued Development. 实施强化动态灌注工艺的生物制剂生产规模和持续发展。

IF 3.9 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-27 DOI: 10.1002/bit.70389

Jennifer Nguyen, Alaina Anand, Meghan Sullivan, Wenge Wang, Spencer Barr, José Gomes, Alessandra Molinaro, Greg Porter, Matthew Gagnon, Aravindan Rajendran

{"title":"Implementing an Intensified Dynamic Perfusion Process for Biologics Manufacturing at Scale and Continued Development.","authors":"Jennifer Nguyen, Alaina Anand, Meghan Sullivan, Wenge Wang, Spencer Barr, José Gomes, Alessandra Molinaro, Greg Porter, Matthew Gagnon, Aravindan Rajendran","doi":"10.1002/bit.70389","DOIUrl":"https://doi.org/10.1002/bit.70389","url":null,"abstract":"Perfusion cell culture is increasingly adopted to improve productivity, reduce footprint, and enable integrated continuous bioprocessing. The high-intensity, low-volume perfusion (HILVOP) process for antibody production was implemented at both 100 L pilot and 500 L manufacturing scales for early clinical supply, and development work was completed in tandem to create a next-generation HILVOP platform. The HILVOP process employs a dynamic two‑stage strategy, using cell‑controlled perfusion during the growth phase followed by product removal during the intensified production phase via tangential flow filtration (TFF). Scale‑up performance was evaluated across multiple CHO cell lines with a focus on membrane robustness, product recovery, and space‑time yield. Early manufacturing runs identified membrane fouling as a key risk, particularly with challenging cell lines. Systematic optimization of TFF operating conditions (reduced membrane wall shear rate, larger pore size, alternative filter membrane, and refinement of perfusion rate profiles) improved membrane performance, delayed transmembrane pressure (TMP) rise, and increased cumulative product recovery while reducing media consumption. Additional productivity gains were achieved through high‑density seeding and extension of the productive perfusion phase, resulting in increased permeate space‑time yield. These results demonstrate the robustness and scalability of the HILVOP platform and highlight key design considerations enabling reliable manufacturing‑scale perfusion operation.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069160","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}

引用次数: 0

Remodeling the Active Site of Sucrose Phosphorylase for Effective Resveratrol Glycosylation. 蔗糖磷酸化酶活性位点的重塑促进白藜芦醇有效糖基化。

IF 3.9 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-27 DOI: 10.1002/bit.70383

Changxin Lu, Xin Wang, Shuaibin Du, Jiajia He, Hanchi Chen, Linjiang Zhu, Xiaolong Chen

引用次数: 0

Transcriptomics-Driven Identification and Engineering of a Novel Lactone Esterase (SrLE) for Efficient Sophorolipid Lactonization in the Yeast Starmerella riodocensis. 一种新型内酯酯酶（SrLE）的转录组学鉴定和工程技术，用于酵母中苦参脂的高效内酯化。

IF 3.9 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-25 DOI: 10.1002/bit.70381

Sirawich Sapsirisuk, Jungho Lee, Inge Noëlle Adrienne Van Bogaert, Nitnipa Soontorngun

{"title":"Transcriptomics-Driven Identification and Engineering of a Novel Lactone Esterase (SrLE) for Efficient Sophorolipid Lactonization in the Yeast Starmerella riodocensis.","authors":"Sirawich Sapsirisuk, Jungho Lee, Inge Noëlle Adrienne Van Bogaert, Nitnipa Soontorngun","doi":"10.1002/bit.70381","DOIUrl":"https://doi.org/10.1002/bit.70381","url":null,"abstract":"Lactonic sophorolipids (LSLs) are high-value glycolipid biosurfactants with superior bioactivities, yet their industrial application is hampered by the low lactonization efficiency of wild-type strains. In this study, we employed a transcriptomics-driven approach to decode the regulatory landscape of the underexplored yeast Starmerella riodocensis GT-SL1R and engineer it for high-titer LSL production. Comparative transcriptome analysis under nitrogen limitation revealed a massive metabolic reprogramming, identifying 497 upregulated genes, including the core SL biosynthetic cluster (CYP52M1, ugta1, ugtb1, at, and mdr1). Crucially, we identified a novel lactone esterase (SrLE) with only 49% similarity to the well-known SbLE from Starmrella bombicola. While growth-related pathways (ribosome biogenesis and DNA replication) were repressed, nitrogen recycling mechanisms were activated to fuel SL biosynthesis. Directed metabolic engineering of the lactonization pathway through SrLE or SbLE overexpression, coupled with fed-batch fermentation in a 5-L bioreactor, achieved exceptional LSL titers of 189.33 g·L-1 and 191.45 g·L-1, respectively. Conversely, SrLE knockout resulted in the exclusive production of acidic SLs, confirming its pivotal role in lactonization. These results provide deep mechanistic insights into SL biosynthesis and demonstrate the power of targeted enzyme engineering in creating robust microbial cell factories for specialized glycolipid production.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036326","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}

引用次数: 0

Enhanced Performance of H 2 ‐Mediated Acetate‐Producing Microbial Electrosynthesis at a Mildly Alkaline pH of 7.5 在pH为7.5的轻度碱性条件下，h2介导的产醋酸微生物电合成性能的增强

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-25 DOI: 10.1002/bit.70394

Jia‐Yao Gao, Yu‐Xiao Zhang, Meng‐Meng Wang, Shun‐Jiang Wang, Shuo Zhang, Wan‐Song Liu, Tian Zhao, Yun‐Hai Wang, Wen‐Fang Cai, Kun Guo

{"title":"Enhanced Performance of H 2 ‐Mediated Acetate‐Producing Microbial Electrosynthesis at a Mildly Alkaline pH of 7.5","authors":"Jia‐Yao Gao, Yu‐Xiao Zhang, Meng‐Meng Wang, Shun‐Jiang Wang, Shuo Zhang, Wan‐Song Liu, Tian Zhao, Yun‐Hai Wang, Wen‐Fang Cai, Kun Guo","doi":"10.1002/bit.70394","DOIUrl":"https://doi.org/10.1002/bit.70394","url":null,"abstract":"Optimizing catholyte pH is pivotal for intensifying H 2 ‐mediated microbial electrosynthesis (MES) of acetate from CO 2 because pH co‐governs gas–liquid transfer, cathodic overpotential, and acetogen's activity, yet their coupled effects on reactor performance remain poorly resolved. Here, we systematically investigated acetate production from CO 2 across pH 7.0–9.0 by integrating H 2 transfer, cell voltage, productivity, and microbial community shifts. Increasing pH enhanced H 2 availability through higher mass‐transfer rates, but also increased cathodic overpotential and cell voltage, establishing a trade‐off between substrate supply and electrical energy demand. The optimum pH of 7.5 delivered the shortest lag phase (2.2 ± 0.3 d), the highest acetate titer (18.43 ± 0.92 g·L −1 ), near‐complete H 2 uptake, and peak coulombic efficiency up to 79%, yielding minimal electricity intensity (~26.95 kWh·kg −1 ). Further pH elevation to 8.5–9.0 disrupted this balance, leading to reduced productivity and sharply increased energy consumption (136.77–236.96 kWh·kg −1 ). Notably, the specific NaOH addition for pH control at pH 7.5 remained comparable to that at pH 7.0 due to greater productivity. Microbial community analysis revealed acetogen enrichment near pH 7.5 and diversification at pH 9.0. These results define a pH‐centered design strategy that aligns H 2 transfer with microbial kinetics while minimizing energy and base usage, offering guidance for process intensification and scale‐up.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"32 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048725","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}

引用次数: 0

Weaving Life Into Regolith: Synthetic Autotrophic–Heterotrophic Consortia for Autonomous Biofabrication From Granular Feedstocks 将生命编织到风化层：合成自养-异养联合体，用于颗粒原料的自主生物制造

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-25 DOI: 10.1002/bit.70392

Nisha Rokaya, Erin C. Carr, Kumar Shrestha, Richard A. Wilson, Yong Huang, Congrui Jin

{"title":"Weaving Life Into Regolith: Synthetic Autotrophic–Heterotrophic Consortia for Autonomous Biofabrication From Granular Feedstocks","authors":"Nisha Rokaya, Erin C. Carr, Kumar Shrestha, Richard A. Wilson, Yong Huang, Congrui Jin","doi":"10.1002/bit.70392","DOIUrl":"https://doi.org/10.1002/bit.70392","url":null,"abstract":"Long‐duration human missions to Mars will require autonomous systems capable of converting in situ resources into structural materials, tools, and functional components. More broadly, such systems represent a class of resource‐limited bioprocesses relevant to extreme‐environment manufacturing. Here, we investigate synthetic autotrophic–heterotrophic consortia, inspired by lichen biology, as a platform for autonomous biofabrication from granular feedstocks. We experimentally screened filamentous fungi and paired them with diazotrophic cyanobacteria to identify mutually supportive consortia capable of sustained growth and biomineral production in the presence of Martian regolith simulant as the primary inorganic substrate, without external organic carbon or nitrogen inputs. Selected co‐cultures exhibited evidence of metabolic coupling, and untargeted metabolomic analysis revealed coordinated reprogramming consistent with integrated carbon and nitrogen metabolism within the consortia. These systems facilitated mineral consolidation of regolith particles, demonstrating the feasibility of near–closed‐loop biomineral production under resource‐limited conditions. While integration with additive manufacturing remains conceptual, this study establishes a framework for engineering self‐sustaining microbial consortia for biomaterials production and highlights opportunities for coupling metabolism with material synthesis in both extraterrestrial and terrestrial environments.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"1 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048724","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}

引用次数: 0

Identification of Putative Cellulose Synthase Gene xcsA2 Required for c‐di‐GMP‐Induced Biofilm Formation and Cell Aggregation in Synechococcus elongatus PCC 7942 c - di - GMP诱导长聚球菌PCC 7942生物膜形成和细胞聚集所需纤维素合酶基因xcsA2的鉴定

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-25 DOI: 10.1002/bit.70396

Chihiro C. Yamaguchi, Jiro F. Mori, Shinsuke Kutsuna, Robert A. Kanaly

{"title":"Identification of Putative Cellulose Synthase Gene xcsA2 Required for c‐di‐GMP‐Induced Biofilm Formation and Cell Aggregation in Synechococcus elongatus PCC 7942","authors":"Chihiro C. Yamaguchi, Jiro F. Mori, Shinsuke Kutsuna, Robert A. Kanaly","doi":"10.1002/bit.70396","DOIUrl":"https://doi.org/10.1002/bit.70396","url":null,"abstract":"Synechococcus elongatus PCC 7942 is a widely used model cyanobacterium for diverse research fields and for bioproduction applications owing to its ease of cultivation, genetic modification, and ability to fix CO 2 . We found that a laboratory strain of S. elongatus PCC 7942 expressing the ydeH gene from E. coli exhibited pronounced biofilm formation and cell aggregation upon ydeH induction, despite the species rarely showing these phenotypes under standard laboratory conditions. Our findings demonstrate that this strain harbors latent potential for biofilm formation and aggregation through c‐di‐GMP synthesis, suggesting possible applications in biomass recovery. Further, we identified that xcsA2 (Synpcc7942_2151), a putative cellulose synthase gene containing a PilZ domain that binds c‐di‐GMP is an indispensable gene in this biofilm‐producing phenotype and experimentally confirmed ydeH ‐induced cellulose‐like β−1,4‐linked glucans production. Notably, xcsA2 represents the first putative functional cellulose synthase gene involved in biofilm/aggregate formation in S. elongatus and suggests that this organism may serve as a useful platform for bacterial cellulose bioproduction. Overall, discovery of xcsA2 provides a new genetic basis for exploring cellulose synthase evolution in cyanobacteria and specifically opens possibilities for engineering cellulose bioproduction utilizing S. elongatus .","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"6 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149048723","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}

引用次数: 0

Process Analytical Technology (PAT) for Continuous Purification of mRNA via Precipitation and Tangential Flow Filtration 通过沉淀和切向流过滤连续纯化mRNA的过程分析技术（PAT）

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-23 DOI: 10.1002/bit.70372

Rajan R. Bhawnani, Maria del Carme Pons Royo, Rohan Kadambi, Andrew Hatas, Steve Burcat, Tyler Arnold, Hasan Al‐Mahayni, Richard D. Braatz, Allan S. Myerson

{"title":"Process Analytical Technology (PAT) for Continuous Purification of mRNA via Precipitation and Tangential Flow Filtration","authors":"Rajan R. Bhawnani, Maria del Carme Pons Royo, Rohan Kadambi, Andrew Hatas, Steve Burcat, Tyler Arnold, Hasan Al‐Mahayni, Richard D. Braatz, Allan S. Myerson","doi":"10.1002/bit.70372","DOIUrl":"https://doi.org/10.1002/bit.70372","url":null,"abstract":"Continuous downstream processing of messenger ribonucleic acid (mRNA) therapeutics requires purification strategies that are scalable, robust, and capable of removing product‐ and process‐related impurities from in vitro transcription mixtures. Precipitation‐based purification coupled with tangential flow filtration (TFF) has recently been demonstrated as a chromatography‐free route for continuous mRNA purification. However, implementation of this approach requires real‐time monitoring strategies that can distinguish the product‐rich precipitated phase from the impurity‐rich liquid phase, as well as phase‐dependent transport behavior across the integrated process. In this work, we develop a phase‐resolved process analytical technology (PAT) and residence time distribution (RTD) framework for continuous mRNA purification by PEG/NaCl precipitation and sequential TFF. Inline UV–Vis spectroscopy and LED‐based optical density measurements were used concurrently to separate nucleic‐acid absorbance from turbidity‐driven responses associated with suspended mRNA precipitates. RTD experiments with dissolved and precipitated tracers revealed phase‐dependent transport behavior in both the tubular precipitator and TFF module, which was quantified using axial dispersion and tanks‐in‐series models. During integrated operation, inline PAT captured startup, steady‐state, and washout behavior, while stable TMP indicated operation without observable membrane fouling. This work demonstrates that precipitation‐based continuous mRNA purification can be strengthened through phase‐resolved monitoring and RTD‐based process understanding, providing a framework for robust development of continuous downstream processes for nucleic acid therapeutics.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"395 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149021321","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}

引用次数: 0

Scale‐Down Platforms for Process‐Oriented Enzyme Screening Using Microfluidics 微流体技术在酶筛选过程中的应用

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-09-21 DOI: 10.1002/bit.70387

Maria I. Rodriguez‐Torres, Elif Erdem, Junhyeong Wang, Ulrich Krühne, Michael Daniele, John M. Woodley

{"title":"Scale‐Down Platforms for Process‐Oriented Enzyme Screening Using Microfluidics","authors":"Maria I. Rodriguez‐Torres, Elif Erdem, Junhyeong Wang, Ulrich Krühne, Michael Daniele, John M. Woodley","doi":"10.1002/bit.70387","DOIUrl":"https://doi.org/10.1002/bit.70387","url":null,"abstract":"Enzyme screening platforms are typically evaluated based on their throughput and analytical performance rather than their ability to mimic the conditions encountered at large scale. In bioreactors, enzymes experience gradients in substrate concentration, oxygen availability, pH, temperature, and interfacial exposure, caused by imperfect mixing and multiphase operation. These gradients affect both enzyme activity and stability, yet they are rarely incorporated into the assays used to select biocatalysts. Traditionally, a variant is chosen based on its performance under static, well‐mixed laboratory conditions, yet those conditions do not necessarily represent the process conditions it must eventually perform under. Microfluidic devices can in principle recreate process‐relevant conditions at a small scale since these devices offer precise control over the flow, residence time, and multiphase contact. Yet most current platforms are not built to mimic the scale‐down process‐derived conditions. Here, we assess current microfluidic tools against this process‐relevant conditions and outline how modular designs can be combined into sequential screening platforms that generate the conditions in a bioreactor, for early‐stage biocatalyst selection.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"472 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149009789","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}

引用次数: 0