生物设计研究(英文)最新文献

{"title":"Dual distal insertions drive pimarane-to-miltiradiene rearrangement with enhanced enzymatic activity.","authors":"Jianing Liu, Jian Wang, Guanghong Cui, Haiyan Zhang, Mei Tian, Ying Zheng, Baolong Jin, Luqi Huang","doi":"10.1016/j.bidere.2025.100028","DOIUrl":"10.1016/j.bidere.2025.100028","url":null,"abstract":"<p><p>Miltiradiene, the major biosynthetic precursor of abietane diterpenoid natural products, has downstream metabolic derivatives with a significant potential for pharmacologically development. The formation of the characteristic abietane skeleton is attained through the rearrangement of the C13 methyl group in the pimarane intermediate, but the key enzyme mechanism responsible for this rearrangement remains elusive. Previous studies have shown that IrKSL3a in <i>Isodon rubescens</i> generates the pimarane diterpene isopimaradiene, and the insertion of two amino acids in the flexible region distal to the enzyme active center can change the enzyme's function to produce the abietane diterpene miltiradiene. In this paper, mutation studies were conducted on another isopimaradiene synthase IrKSL6 in <i>Isodon rubescens</i> and the miltiradiene synthase SmKSL1 in <i>Salvia miltiorrhiza</i> at these two sites. It was found that the insertion at these two sites is conservative in changing the enzyme function, and it can also affect the solubility of SmKSL1 and its affinity for the substrate. The titer of miltiradiene in the mutant SmKSL1: E550 + KR engineered bacteria increased by approximately 44 ​% compared to the wild type, the solubility of the protein increased by 24 ​%, and the catalytic efficiency (<i>Kcat/Km</i>) increased by 26 ​%. This paper conducted a preliminary study on the influence of the distal flexible region of the protein on the physicochemical properties of the enzyme, establishing critical molecular targets for the rational design of abietane diterpene synthases, while the high-performance mutants obtained provide superior enzymatic components for constructing biosynthesis platforms of pharmacologically relevant metabolites.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100028"},"PeriodicalIF":4.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme promiscuity in the field of synthetic biology applied to white biotechnology: Opportunities and weaknesses.","authors":"Thibault Malfoy, Ceren Alkim, Jean Marie François","doi":"10.1016/j.bidere.2025.100026","DOIUrl":"10.1016/j.bidere.2025.100026","url":null,"abstract":"<p><p>White biotechnology stands as a major sustainable alternative to address pressing environmental issues arising from our heavy dependence on petrochemical synthesis. However, reaching this goal, both technologically and economically, will take time, resources and money. A major reason is within the biological system itself, as it has evolved into a bow-tie structure in which carbon and energy are converted, via highly regulated, complex and interconnected metabolic networks, into cellular components for growth and homeostasis. This objective is fundamentally at odds with that of biotechnology, which aims to convert carbon and energy into bioproducts. Engineering of microorganism using systems and synthetic biological systems tools has been developed to provide a compromise between these two objectives. However, these genetic and metabolic interventions have revealed often unexpected physiological behaviors, in part due to the fact that a large proportion of metabolic enzymes are catalyzing other reactions than those for which they were evolved. While this promiscuity is the source of an underground metabolism that can prove very advantageous in building high-performance production routes, it is also responsible for loss of yield and production due to metabolic disturbances, negative cross-talks between natural and heterologous pathways as well as it is at the onset of metabolic damages. Identifying these promiscuous enzymes and thus anticipating their opportunities or weaknesses in engineering microbial cell factories for bioproduction is a major challenge in order to improve their performance. It is foreseen that machine learning tools operating on databases continuously fed by genetic, metabolic, enzymatic and fermentation processes data can help to overcome these challenges and provide a better understanding of the physiological functioning of the microbial system.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 3","pages":"100026"},"PeriodicalIF":4.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient synthesis of clascoterone <i>via</i> lipase-catalyzed solvent-free alcoholysis.","authors":"Qian Li, Mingpeng Li, Ling Wang, Xiaojuan Yu, Yuling Zhou, Chenghua Gao, Aitao Li","doi":"10.1016/j.bidere.2025.100025","DOIUrl":"10.1016/j.bidere.2025.100025","url":null,"abstract":"<p><p>Clascoterone (cortexolone 17α-propionate), a novel therapeutic agent for acne, provides enhanced safety and efficacy over conventional therapies. However, the traditional synthesis of clascoterone, especially the final step, suffers from the use of hazardous and excessive organic solvents, along with suboptimal yields due to side reactions and incomplete conversion, which poses environmental and economic challenges. In this study, we developed a regioselective solvent-free alcoholysis method with the commercially available immobilized lipase Novozyme 435 as a catalyst and isopropanol (IPA) as an alcohol donor, achieving a conversion rate of over 98.0 ​% with 20 ​g/L substrate. Furthermore, we implemented a continuous flow microreactor process that increased the conversion rate to 100 ​% with 4 ​g/L substrate, demonstrating scalability for industrial manufacturing.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100025"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing thermophilic, synthetic microbial communities for consolidated bioprocessing.","authors":"Hansen Tjo, Kelly Blundin, Jonathan M Conway","doi":"10.1016/j.bidere.2025.100024","DOIUrl":"10.1016/j.bidere.2025.100024","url":null,"abstract":"<p><p>Lignocellulose-derived fuels and chemicals are vital to breaking the world's dependence on fossil fuels. Though plant biomass is notoriously resistant to deconstruction, lignocellulolytic thermophiles are especially adept at degrading its constituent polysaccharides into mono- and oligo-saccharides for catabolism. And many thermophiles, whether lignocellulolytic or not, can be engineered to ferment lignocellulose-derived sugars into valuable fuels and chemicals as part of consolidated bioprocesses. Although the past twenty years have seen major advances in the genetic and metabolic engineering of individual thermophiles, the strategy of co-culturing thermophilic strains as part of synthetic communities has not been well established. Synthetic communities unlock synergistic interactions that outperform monocultures, thereby enhancing product titers, rates, and yields. While limited genetic tools once hindered the development of synthetic thermophilic communities, recent advances now offer robust systems for engineering these industrially relevant organisms. Here, we propose that this expanded genetic malleability enables engineering of 1) transport specialization to reduce substrate competition between strains and 2) division of labor strategies whereby one strain focuses on lignocellulose deconstruction while another strain dedicates metabolic burden for product synthesis. We draw on examples of engineered thermophiles like <i>Clostridium thermocellum, Thermoanaerobacter saccharolyticum,</i> and <i>Anaerocellum bescii</i> to illustrate how these mechanisms have been applied in thermophilic co-cultures. In brief, this perspective outlines design principles to construct effective thermophilic communities for lignocellulose bioprocessing.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100024"},"PeriodicalIF":7.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced vitamin A production by engineering transporters, ATP and precursor supply.","authors":"Yijun Zhang, Qiongyue Hu, Hongwei Yu, Lidan Ye","doi":"10.1016/j.bidere.2025.100023","DOIUrl":"10.1016/j.bidere.2025.100023","url":null,"abstract":"<p><p>Vitamin A (retinoids) is essential for human metabolism and has extensive applications in medicine, health, and cosmetics. Microbial cell factories have been developed for retinoid biosynthesis, coupled with two-phase fermentation for <i>in situ</i> extraction. Given that notable portions of retinoids remained in the cells, promotion of retinoid secretion is expected for further production improvements. This study investigates the potential of yeast endogenous PDR family proteins to enhance retinoid efflux by overexpressing them in retinoid-producing <i>Saccharomyces cerevisiae</i> strains. Among the PDR proteins tested, the transcriptional factor Pdr3p and the transporters Pdr10p and Snq2p significantly enhanced retinol and retinal secretion and production, while the transcriptional factor Pdr8p and the transporters Pdr11p, Pdr12p, Pdr18p, and Aus1p markedly increased retinoic acid production. <i>PDR3</i>/<i>PDR10</i> co-overexpression improved retinal production to a record 638.12 ​mg/L, while <i>PDR8</i> overexpression led to 106.75 ​mg/L retinoic acid production in shake flasks. For retinol, synergistic overexpression of <i>PDR3</i> and <i>PDR10</i> elevated the extracellular proportion to 96.7 ​%. Given the ATP requirement of PDR protein-mediated transportation, ATP supply was strengthened by overexpressing the mitochondrial fusion-related gene <i>MGM1</i> and introducing hemoglobin Vgb, both enhancing retinol secretion and production. Further precursor supply enhancement resulted in 727.30 ​mg/L retinol from 20 ​g/L glucose in shake flasks, with a carbon conversion rate of 7.62 ​%. These results confirm the combination of transport engineering, energy regulation and precursor supply enhancement as a pivotal strategy for augmenting vitamin A production.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100023"},"PeriodicalIF":4.7,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>De novo</i> biosynthesis of cannabinoids and their analogs in <i>Yarrowia lipolytica</i>.","authors":"Yuxiang Hong, Yang Gu, Dewei Lin, Zizhao Wu, Wenhao Chen, Tianjian Lu, Pornpatsorn Lertphadungkit, Jingbo Ma, Haili Wang, Bo Zhou, Gil Bar-Sela, Idan Cohen, Peng Xu","doi":"10.1016/j.bidere.2025.100021","DOIUrl":"10.1016/j.bidere.2025.100021","url":null,"abstract":"<p><p><i>Cannabis sativa</i> has long been a cornerstone of both medicinal and cultural practices, with its therapeutic use spanning over 2700 years. Central to its therapeutic effects are cannabinoids, which interact with the endocannabinoid system to influence various physiological processes such as anxiety, pain, and inflammation. Despite its benefits, cannabinoid production faces challenges and scarcity from plant extraction. This work leverages <i>Yarrowia lipolytica</i> as a platform for cannabinoid biosynthesis. By optimizing the precursor supply, engineering biomolecular condensate-like dual prenyltransferase expression and expanding endogenous metabolism with a noncanonical polyketide synthase, we achieved the <i>de novo</i> biosynthesis of various cannabinoids and their analogs. Our engineered <i>Y. lipolytica</i> produced ∼3.5 ​mg/L cannabigerolic acid, 18.8 ​mg/L orsellinic acid, and 0.5 mg/L cannabigerorcinic acid. Additionally, the CBGA titer reached 15.7 ​mg/L with olivetolic acid supplementation. This work demonstrates the versatility of <i>Y. lipolytica</i> as a promising host for the production of cannabinoids and their analogs, which opens avenues for further research and medicinal applications.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100021"},"PeriodicalIF":4.7,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolution-assisted engineering of <i>E</i>. <i>coli</i> improved succinic acid production from glycerol.","authors":"Jing Peng, Junru Sun, Yuanchan Luo, Hui Wu","doi":"10.1016/j.bidere.2025.100022","DOIUrl":"10.1016/j.bidere.2025.100022","url":null,"abstract":"<p><p>Glycerol, a major byproduct of biodiesel production, serves as a promising and versatile feedstock for synthesizing high-value chemicals. In this study, the NZN111, a potential succinic acid (SA) producer, was subjected to adaptive laboratory evolution (ALE) under selective pressure imposed by sodium acetate (NaAC) pressure. By analyzing the differences in the transcript levels of genes related to substrate utilization and product generation in the evolved strains, it was found that NaAC metabolism in <i>Escherichia coli</i> involves a series of enzymatic reactions that are apparently benefit for glycerol metabolism and SA biosynthesis. To further enhance the strain's performance, a metabolic engineering strategy was implemented, including introduction of exogenous carboxykinases and HCO₃ ^- transporter proteins. The engineered strain produced 84.27 ​g/L SA in an anaerobic fermentation medium containing 100 ​g/L glycerol with a yield of 1.25 ​g/g glycerol, which was 1.38 and 1.16 times higher than those of the original strain, respectively. These findings highlight the potential of combining ALE with targeted metabolic engineering to develop robust microbial platforms for the efficient conversion of glycerol into high-value chemicals, contributing to the sustainable utilization of biodiesel byproducts.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100022"},"PeriodicalIF":4.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioproduction of 3,4-methylenedioxymethamphetamine and derivatives.","authors":"Natali Ozber, Jing Li, Peter J Facchini","doi":"10.1016/j.bidere.2025.100011","DOIUrl":"10.1016/j.bidere.2025.100011","url":null,"abstract":"<p><p>3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a recreational drug under clinical investigation for the treatment of central nervous system disorders, including post-traumatic stress disorder. Chemical synthesis of MDMA mainly relies on the use of safrole and piperonal as starting materials. We report a novel strategy integrating bioconversion and biocatalysis in the bioproduction of MDMA and other methamphetamine derivatives. For the initial step, a yeast-based bioconversion system was used to produce phenylacetylcarbinol (PAC) derivatives from ring-substituted benzaldehyde precursors, including piperonal, using variants of pyruvate decarboxylase (PDC). Among seven wildtype enzymes tested, <i>Candida tropicalis</i> PDC (CtPDC) showed the highest yield from piperonal, and a CtPDC1-I479A mutant further improved the titer. Five of sixteen ring-substituted benzaldehyde analogs (i.e., piperonal, 6-chloropiperonal, 4-acetylbenzaldehyde, 2-fluoro-4-methoxybenzaldehyde, and 2-fluoro-4-propoxybenzaldehyde) yielded corresponding PAC derivatives with yields between 20 and 70 ​%, which allowed the purification of multiple milligram quantities of each product. Three stereoselective ω-transaminases were evaluated for their ability to catalyze the transamination of PAC derivatives, with the (<i>R</i>)-selective enzyme ATA-117-Rd11 able to convert all five isolated PAC derivatives. Isolated transamination products were subsequently <i>N</i>-methylated using human phenylethanolamine <i>N</i>-methyltransferase. Chemical reduction facilitated the final production of MDMA and its analog 6-chloro-MDMA. Our work represents the first reported bioproduction method leading to MDMA and other methamphetamine derivatives, suitable for future pathway and strain optimization.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100011"},"PeriodicalIF":4.7,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing plant synthetic biology to accelerate plant-microbe interactions research.","authors":"Xiaohan Yang, Joanna Tannous, Tomás A Rush, Ilenne Del Valle, Shunyuan Xiao, Bal Maharjan, Yang Liu, David J Weston, Kuntal De, Timothy J Tschaplinski, Jun Hyung Lee, Mallory Morgan, Daniel Jacobson, Md Torikul Islam, Feng Chen, Paul E Abraham, Gerald A Tuskan, Mitchel J Doktycz, Jin-Gui Chen","doi":"10.1016/j.bidere.2025.100007","DOIUrl":"10.1016/j.bidere.2025.100007","url":null,"abstract":"<p><p>Plant-microbe interactions are critical to ecosystem resilience and substantially influence crop production. From the perspective of plant science, two important focus areas concerning plant-microbe interactions include: 1) understanding plant molecular mechanisms involved in plant-microbe interfaces and 2) engineering plants for increasing plant disease resistance or enhancing beneficial interactions with microbes to increase their resilience to biotic and abiotic stress conditions. Molecular biology and genetics approaches have been used to investigate the molecular mechanisms underlying plant responses to various beneficial and pathogenic microbes. While these approaches are valuable for elucidating the functions of individual genes and pathways, they fall short of unraveling the complex cross-talk across pathways or systems that plants employ to respond and adapt to environmental stresses. Also, genetic engineering of plants to increase disease resistance or enhance symbiosis with microbes has mainly been attempted or conducted through targeted manipulation of single genes/pathways of plants. Recent advancements in synthetic biology tool development are paving the way for multi-gene characterization and engineering in plants in relation to plant-microbe interactions. Here, we briefly summarize the current understanding of plant molecular pathways involved in plant interactions with beneficial and pathogenic microorganisms. Then, we highlight the progress in applying plant synthetic biology to elucidate the molecular basis of plant responses to microbes, enhance plant disease resistance, engineer synthetic symbiosis, and conduct <i>in situ</i> microbiome engineering. Lastly, we discuss the challenges, opportunities, and future directions for advancing plant-microbe interactions research using the capabilities of plant synthetic biology.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 2","pages":"100007"},"PeriodicalIF":4.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TropiCODB: A multi-omics resource for supporting biodesign in tropical crops.","authors":"Wenbao Dai, Shuang He, Yunqing Luo, Chengjun Zhao, Zhijuan Yang, Junyu Zhang, Qibin Wu, Wenquan Wang, Fei Chen","doi":"10.1016/j.bidere.2025.100003","DOIUrl":"10.1016/j.bidere.2025.100003","url":null,"abstract":"<p><p>Tropical crops play a pivotal role in ensuring global food security and driving sustainable agricultural development, particularly in regions with limited resources. However, the complexity of tropical crop genomes and the lack of integrated omics data pose significant challenges to genetic improvement and biodesign research. TropiCODB is a comprehensive multi-omics database designed to address these challenges by integrating high-quality genomic, variome, transcriptomic, metabolomic, and phenotypic datasets for eight economically significant tropical crops, including cassava, sugarcane, and oil palm. Advanced tools such as gene family analysis, miRNA profiling, and precision guideRNA design are seamlessly incorporated, offering unprecedented support for functional genomics and molecular breeding. TropiCODB's user-friendly interface and dynamic visualization capabilities enable researchers to efficiently explore key genetic mechanisms and design targeted breeding strategies. By leveraging innovative technologies and curated datasets, TropiCODB provides a robust foundation for advancing tropical agriculture through precision biodesign.</p>","PeriodicalId":56832,"journal":{"name":"生物设计研究(英文)","volume":"7 1","pages":"100003"},"PeriodicalIF":4.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}