Biotechnology and Bioengineering最新文献

A Modular Mechanistic In Silico Model for In Vitro Transcription Process Yield and Product Quality Prediction. 体外转录过程产率和产品质量预测的模块化机制硅模型。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-07 DOI: 10.1002/bit.70222

Keqi Wang, Keilung Choy, Eli Reiser, Jinxiang Pei, Hua Zheng, Aparajita Dasgupta, Fuqiang Cheng, Guogang Dong, Bhanu Chandra Mulukutla, Joshua Mannheimer, Carolyn Huang, Hooman Farsani, Wei Xie

{"title":"A Modular Mechanistic In Silico Model for In Vitro Transcription Process Yield and Product Quality Prediction.","authors":"Keqi Wang, Keilung Choy, Eli Reiser, Jinxiang Pei, Hua Zheng, Aparajita Dasgupta, Fuqiang Cheng, Guogang Dong, Bhanu Chandra Mulukutla, Joshua Mannheimer, Carolyn Huang, Hooman Farsani, Wei Xie","doi":"10.1002/bit.70222","DOIUrl":"https://doi.org/10.1002/bit.70222","url":null,"abstract":"In vitro transcription (IVT) plays a critical role in the manufacture of mRNA vaccines and therapeutics. Optimizing mRNA yield and ensuring product quality, such as capping efficiency and integrity, are essential but mechanistically complex. This study presents a modular mechanistic model of the IVT process to advance scientific understanding and improve predictive capability. The IVT reaction network is decomposed into interconnected modules describing (1) initiation and capping, (2) elongation and truncation, (3) termination and read-through, (4) mRNA degradation, (5) magnesium pyrophosphate precipitation, and (6) enzymatic degradation of pyrophosphate. Guided by biochemical principles and experimental data, kinetic models were developed for each module, accounting for mass balances, molecular complexation, and enzyme activity, and were subsequently assembled to capture coupled IVT dynamics. Multivariate residual analysis and Shapley value-based sensitivity analysis-guided by domain knowledge-were applied to iteratively improve model fidelity. These machine learning-driven analytics enabled the identification of key mechanisms, supported in silico experimentation, and facilitated root-cause analysis. Combined with Gaussian-process-based batch Bayesian optimization for efficient parameter estimation, this framework establishes a scalable hybrid (mechanistic + machine-learning) modeling platform that integrates heterogeneous data, accelerates model calibration, and supports rational design and optimization of mRNA manufacturing processes.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833499","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

One-Pot Synthesis of a Small Synthetic Ligand for Antibody Purification. 一锅法合成用于抗体纯化的小合成配体。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70226

Carolina Mota Natal, Catarina Domingos, André Nascimento, José Mendes, Afonso B Ruiz, Ana Margarida Gonçalves Carvalho Dias, Luisa M Ferreira, Cristina Peixoto, Ana Cecília Afonso Roque

{"title":"One-Pot Synthesis of a Small Synthetic Ligand for Antibody Purification.","authors":"Carolina Mota Natal, Catarina Domingos, André Nascimento, José Mendes, Afonso B Ruiz, Ana Margarida Gonçalves Carvalho Dias, Luisa M Ferreira, Cristina Peixoto, Ana Cecília Afonso Roque","doi":"10.1002/bit.70226","DOIUrl":"https://doi.org/10.1002/bit.70226","url":null,"abstract":"The development of synthetic affinity ligands offers a cost-effective alternative to traditional biological ligands used in affinity purification. Here, we report a rapid, one-pot liquid-phase chemical synthesis of a synthetic affinity ligand displaying affinity for antibody molecules. The resulting ligand, B1Al2A2, was immobilized onto two chromatographic supports at distinct ligand densities. The best performing adsorbent was selected for further proof-of-function. It exhibited robust performance in the capture of human IgG from plasma and IgY from crude samples, achieving antibody recoveries of 55% and 91%, respectively, with purity exceeding 86%. This streamlined workflow highlights the advantages of liquid-phase synthesis over solid-phase synthesis for ligand characterization and adsorbent optimization, enabling facile purification, controlled ligand density, and rigorous ligand characterization. The approach is broadly applicable to other small synthetic ligands, providing a versatile platform for advancing affinity purification technologies.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833576","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

Detergent Virus Inactivation in Chromatography Systems. 色谱系统中洗涤剂病毒的灭活。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70231

Kang Cai, Etienne Utiger, Chris Afdahl, Rayan Zamat, Jennifer Anderson, Yeldys De Armas, Gisela Ferreira

引用次数: 0

Glycerol-Assisted Thermal Strategy for Intensifying Bioconversion Performance of Gluconobacter oxydans. 甘油辅助热策略增强氧葡萄糖杆菌的生物转化性能。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70230

Wei Hu, Biying Guo, Yating Hu, Yong Xu, Xia Hua

{"title":"Glycerol-Assisted Thermal Strategy for Intensifying Bioconversion Performance of Gluconobacter oxydans.","authors":"Wei Hu, Biying Guo, Yating Hu, Yong Xu, Xia Hua","doi":"10.1002/bit.70230","DOIUrl":"https://doi.org/10.1002/bit.70230","url":null,"abstract":"Increasing the biotransformation temperature to balance the conditions of saccharification (50°C-60°C) is a crucial measure for intensifying bioprocess competitiveness. The study established a glycerol-assisted thermal strategy to mitigate the damage caused by high temperature on Gluconobacter oxydans. This approach successfully improved bioconversion performance by simultaneously overcoming limitations in catalytic efficiency and cell recovery. With 15 mmol/L glycerol assistance, the proportion of live cells remained at 75.9% after whole-cell catalysis at 37°C for 40 h. Moreover, 570.2 g xylonic acid was accumulated from pure xylose with the average volumetric productivity per round of 14.3 g/L/h, which was 14.5% and 19.6% higher than that of 30°C and 37°C without assistance. Additionally, to validate its practicality, this strategy was further applied to corncob hydrolysate, resulting 216.8 g xylonic acid from 1000 g corncob with the productivity of 4.1 g/h. This work presented an economically viable approach for lignocellulosic biorefinery and offers insights for its further development.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833610","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

Microphysiological Systems: Transforming Biomedical and Clinical Research. 微生理系统：转化生物医学和临床研究。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70229

Om Saswat Sahoo, Avisha Tyagi, Aparna K Sharma, Gurpreet Singh Gill, Ruby Dhar, Subhradip Karmakar

{"title":"Microphysiological Systems: Transforming Biomedical and Clinical Research.","authors":"Om Saswat Sahoo, Avisha Tyagi, Aparna K Sharma, Gurpreet Singh Gill, Ruby Dhar, Subhradip Karmakar","doi":"10.1002/bit.70229","DOIUrl":"https://doi.org/10.1002/bit.70229","url":null,"abstract":"The pharmaceutical industry continues to face a critical translational bottleneck, with the majority of drug candidates failing in clinical trials despite promising preclinical results, largely due to the limited predictive power of conventional in vitro systems and animal models. Microphysiological systems (MPS), including organ-on-chip and organoid-on-chip platforms, have emerged as transformative human-relevant technologies capable of recapitulating organ-level structure, function, and disease dynamics under precisely controlled microenvironments. By integrating advances in microfabrication, biomaterials, stem cell and organoid biology, microfluidics, and real-time sensing, MPS enables physiologically faithful modeling of tissue interfaces, mechanical forces, metabolic processes, and inter-organ communication. Recent progress has led to robust organ-specific platforms, interconnected multi-organ systems, and body-on-chip models that support systemic pharmacokinetic and pharmacodynamic studies. Concurrently, regulatory recognition through the FDA Modernization Acts and accelerating international standardization efforts have positioned MPS as a validated new approach for drug development and safety assessment. Despite these advances, challenges related to cell sourcing, tissue heterogeneity, scalability, statistical rigor, and protocol standardization remain. This review synthesizes the technological foundations, biological applications, regulatory landscape, and emerging challenges of MPS, emphasizing the need to quantify and harness biological heterogeneity rather than eliminate it.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833625","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

Systematic Engineering of Escherichia coli to Enhance 1,6-Hexamethylenediamine Biosynthesis and Mitigate Byproduct 1,5-Pentanediamine. 大肠杆菌促进1,6-己二胺生物合成和减少副产物1,5-戊二胺的系统工程。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70233

Zanwen Chen, Haoran Sun, Zichen Lin, Naiqiang Li

{"title":"Systematic Engineering of Escherichia coli to Enhance 1,6-Hexamethylenediamine Biosynthesis and Mitigate Byproduct 1,5-Pentanediamine.","authors":"Zanwen Chen, Haoran Sun, Zichen Lin, Naiqiang Li","doi":"10.1002/bit.70233","DOIUrl":"https://doi.org/10.1002/bit.70233","url":null,"abstract":"1,6-Hexamethylenediamine (HMD), a key nylon 6,6 intermediate, is traditionally derived from fossil feedstocks, demanding sustainable alternatives. Despite the great potential of the L-lysine-based carbon chain elongation system for biosynthetic HMD, its practical application is hampered by low catalytic efficiency. In this study, systematic engineering strategies were developed to overcome these limitations: site-saturation mutagenesis of 3-isopropylmalate dehydratase (LeuCD) yielded a dual-site mutant with a 2.13-fold higher HMD biosynthesis. Synergistic integration of NAD⁺ synthase overexpression, pyridoxal 5'-phosphate supplementation, optimized ammonia donors, and fed-batch fermentation markedly boosted HMD biosynthesis. Specifically, continuous feeding of glucose and L-lysine resulted in an HMD titer of 1835.35 ± 14.64 mg/L, with a productivity of 25.48 mg/L/h, representing over a 7.15-fold increase versus shake flask fermentation. Finally, a novel dual-cell module further enhanced the HMD titer, increased the molar yield of L-lysine to HMD to 24.78%, and reduced the byproduct 1,5-pentanediamine (PDA) to 22.22% of the original level. This work establishes a feasible, efficient, and sustainable HMD biomanufacturing process, addressing the critical issue of substrate competition in multi-step biosynthetic pathways.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833633","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

Optimizing Bispecific Antibody Expression via Multi-Omics Analysis and Vector Redesign. 通过多组学分析和载体重新设计优化双特异性抗体表达。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70228

Jeremy J Gam, Michelle M Chang, Dinghai Zheng, Jennitte Stevens, Alec A K Nielsen, Kevin D Smith

{"title":"Optimizing Bispecific Antibody Expression via Multi-Omics Analysis and Vector Redesign.","authors":"Jeremy J Gam, Michelle M Chang, Dinghai Zheng, Jennitte Stevens, Alec A K Nielsen, Kevin D Smith","doi":"10.1002/bit.70228","DOIUrl":"https://doi.org/10.1002/bit.70228","url":null,"abstract":"Bispecific antibodies are a growing class of therapeutics that simultaneously engage two targets. However, their complex molecular structures pose challenges for production in Chinese hamster ovary cells, the current industry standard for biologics manufacturing. Here we present a case study of three IgG-scFv format bsAbs expressed in CHO cells, in which one candidate exhibited markedly lower titers despite high sequence homology to the other two. Using multi-omics analysis (RNA sequencing, splicing prediction, codon optimization assessment, and motif screening) to investigate potential causes, we identified several likely mechanisms for poor expression, including aberrant splicing motifs, ribosome pausing sites, and suboptimal codon usage. Through targeted protein and DNA sequence engineering, we generated a revised variant with an 11-fold increase in stable expression titers. This work demonstrates that integrating sequence-level bioinformatic and synthetic biology diagnostics can directly improve manufacturability, providing a generalizable framework for resolving hidden expression liabilities in complex biologics.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833628","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

Beyond CO₂: Incorporating Bicarbonate, Dynamic Carbon Speciation, and Stoichiometric Plasticity Into Algal Growth Models. 超越二氧化碳：将碳酸氢盐，动态碳形态和化学计量塑性纳入藻类生长模型。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70182

Elizabeth Flanagan, Caye Drapcho, Mary Katherine Watson

{"title":"Beyond CO2: Incorporating Bicarbonate, Dynamic Carbon Speciation, and Stoichiometric Plasticity Into Algal Growth Models.","authors":"Elizabeth Flanagan, Caye Drapcho, Mary Katherine Watson","doi":"10.1002/bit.70182","DOIUrl":"https://doi.org/10.1002/bit.70182","url":null,"abstract":"The design of biological carbon capture systems to uptake carbon dioxide by photoautotrophic cultivation of algae has been proposed to mitigate atmospheric carbon emissions. Multiple models to predict algal growth as a function of nutrients have been proposed, but few have delved into the complex dynamic reactions of algal growth as influenced by individual inorganic carbon species. In this work, dynamic algal growth models based on inorganic carbon-limited specific growth rates that considered carbon dioxide (CO2), bicarbonate (HCO3 -) and carbonate (CO3 2-) as potential substrates in Monod model equations were investigated and compared to batch, closed reactor data. The model incorporates dynamic rates of inorganic carbon species conversion rather than equilibrium conditions and algal biomass stoichiometry that accounts for algal plasticity as a function of nutrient concentration. After analysis of 8 models, the model that included CO2 and HCO3 - as substitutable substrates is best supported by literature and provided the best estimates of total inorganic carbon concentrations, biomass, and pH for a set of experimental cultures. These results provide a grounded framework for predicting algal growth and carbon speciation, thereby informing the design and operation of algal cultivation systems for carbon abatement and bioproduct formation under carbon-limited, low-light, and high-pH conditions.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833591","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

Protein Engineering of a Genetically Encodable Biosensor for Wastewater Detection of Profen NSAIDs. 用于废水中非甾体抗炎药检测的基因可编码生物传感器的蛋白质工程。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70220

Zoë Davis, Hao Tian, Ian R Wheeldon, Sean R Cutler, Timothy A Whitehead

{"title":"Protein Engineering of a Genetically Encodable Biosensor for Wastewater Detection of Profen NSAIDs.","authors":"Zoë Davis, Hao Tian, Ian R Wheeldon, Sean R Cutler, Timothy A Whitehead","doi":"10.1002/bit.70220","DOIUrl":"https://doi.org/10.1002/bit.70220","url":null,"abstract":"Non-steroidal anti-inflammatory drugs (NSAIDs) are pervasive environmental contaminants due to their frequent and widespread use, multiple paths of release into surface and ground water supply, diversity of the chemical class, and toxicity to aquatic and other non-target species. In particular, the 2-arylpropionic acid (\"profen\") class of NSAIDs poses significant risks to aquatic ecosystems due to incomplete removal during wastewater treatment. Current monitoring precludes high-frequency testing at point sources. Here, we present the engineering and application of a genetically encodable, protein-based biosensor for the detection of the NSAIDs ketoprofen and pranoprofen in wastewater effluent. We repurposed the plant hormone receptor PYR1 to bind selectively to profens using computational protein design, deep mutational scanning, and yeast 2-hybrid and yeast surface display screening. The resulting sensor, PYR1NSAID, has a nanomolar limit of detection for ketoprofen and panoprofen, and µM sensitivity to the NSAIDs ibuprofen, fenoprofen, tolmetin and diclofenac. We also demonstrated dose-responsive activity of our sensor in simulated wastewater matrices containing the common wastewater contaminants sulfamethoxazole, caffeine, acetaminophen, and 2,4-dichlorophenol using a split Nanoluc luminescence assay. PYR1NSAID is the first step towards a scalable, cost-effective alternative for real-time monitoring of pharmaceutical pollution.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833601","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

Design Space Assessment of Virus Inactivation in Plasma-Derived Matrices Establishes a Single Detergent Alternative to TX-100-Containing Mixes. 血浆衍生基质中病毒灭活的设计空间评估建立了一种单一洗涤剂替代含有tx -100的混合物。

IF 3.6 2区生物学

Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70232

Johanna Kindermann, Cecilie Klausen, Michael Karbiener, Thomas R Kreil

{"title":"Design Space Assessment of Virus Inactivation in Plasma-Derived Matrices Establishes a Single Detergent Alternative to TX-100-Containing Mixes.","authors":"Johanna Kindermann, Cecilie Klausen, Michael Karbiener, Thomas R Kreil","doi":"10.1002/bit.70232","DOIUrl":"https://doi.org/10.1002/bit.70232","url":null,"abstract":"The detergent Triton X-100 (TX-100) is a typical component of solvent/detergent (S/D) mixes applied for virus inactivation steps of biomanufacturing processes, yet environmentally unfavorable properties have led to restrictions on its use. Deviron 13-S9 has recently been described as an eco-friendly TX-100 alternative, with powerful virus-inactivating properties determined in matrices representative of recombinant and some plasma-derived process intermediates such as cryo-poor plasma. The present study extends this knowledge via a side-by-side comparison of virus inactivation by Deviron 13-S9, applied as a single detergent, and a traditional TX-100-containing S/D mix, in four plasma-derived matrices, bracketing a broad range of protein concentrations and pH values. Across all conditions, three distinct model/target viruses were rapidly inactivated to below the respective assay detection limit, even at Deviron 13-S9 concentrations as low as 0.05% (v/v), that is, markedly below the lower limits of TX-100 concentrations in current GMP processes. In addition, Vaccinia virus, considered as the worst-case model with respect to detergent-mediated clearance, was inactivated by Deviron 13-S9 with similar kinetics as by a conventional, TX-100-containing S/D mix. Collectively, these results establish equivalent potency for virus inactivation, at a favorable use of only one detergent versus traditional S/D mixes from a biotechnological efficiency perspective.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833612","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