{"title":"Sustainable production of natural sweeteners through synthetic biology.","authors":"Dong Li, Jinxin Fan, Jianfei Zong, Bingzhi Li, Guosheng Xin, Zhiwen Wang","doi":"10.1016/j.jbiosc.2026.04.001","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.04.001","url":null,"abstract":"<p><p>With the upgrading of global health demands and safety controversies surrounding artificial sweeteners, natural sweeteners have emerged as a research hotspot thanks to their low-calorie content, high safety, and potential physiological activities. Traditional plant extraction methods are limited by bottlenecks such as long growth cycles and geographical dependence, while synthetic biology has provided an innovative pathway for the efficient and sustainable production of natural sweeteners through metabolic engineering and enzyme engineering, by constructing microbial cell factories. This review systematically summarizes the metabolic pathways and microbial synthesis methods of 12 representative natural sweeteners (including sweet proteins, terpenoid glycosides, flavonoids, polyols, and monosaccharides). By analyzing the advantages and disadvantages of different synthetic schemes as well as the core technical bottlenecks in current production processes, and integrating the latest research progress, this review provides theoretical support and technical references for the future industrial optimization and production of natural sweeteners.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhanced tRNA array method version 2 for simultaneous in vitro synthesis of 21 tRNAs.","authors":"Ryota Miyachi, Anna Irie, Norikazu Ichihashi","doi":"10.1016/j.jbiosc.2026.03.014","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.03.014","url":null,"abstract":"<p><p>Transfer RNAs (tRNAs) play an essential role in translation, and their simultaneous in vitro synthesis remains a key challenge in bottom-up synthetic biology. We previously developed the tRNA array method that enables the simultaneous in vitro synthesis of 21 tRNAs from a single DNA template; however, the translational activity was substantially lower than that achieved using individually prepared 21 tRNAs for some proteins. Here, we identify the tRNA groups (PIEN group) that limit translation in the tRNA array method and improve the translational activities through sequence modification and incorporation of a leader sequence into the array construct. The resulting tRNA array method version 2 produces a tRNA set that allows translation at levels similar to those achieved with individually prepared tRNAs for multiple reporter proteins under both translation-coupled and uncoupled conditions. This tRNA synthesis scheme provides an improved platform for constructing self-reproducible gene expression systems.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Employing synthetic biology to modulate metabolic flux: Current strategies and applications.","authors":"Divya Ojha, Ram Kulkarni, Ambadas B Rode","doi":"10.1016/j.jbiosc.2026.03.012","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.03.012","url":null,"abstract":"<p><p>The world's increasing demand for petrochemical, pharmaceutical, and nutraceutical products necessitates the development of new strategies for producing these high-value chemicals. The depletion of the natural fossil reserves and environmental pollution associated with their procurement further compel us to find sustainable, greener, and cost-effective alternatives. In light of this, a shift has been witnessed in deriving these products from fossil-based sources or chemical synthesis to biomanufacturing (production using living systems). However, to fully utilize the potential of biomanufacturing, novel tools and strategies that can function in bacteria, archaea, and eukaryotes, regulate multi-enzyme pathways, offer precise and conditional gene regulation, and possess versatility are highly required. This review presents a comprehensive summary of the latest gene modulation tools and strategies used by metabolic engineers, along with a mechanistic overview and their applications. In addition, we presented the tools that have the potential to be used for pathway optimization but are still less explored. Within this context, we categorized these tools based on their molecular level of gene regulation, i.e., at and beyond the central dogma. We believe that a deeper understanding of the design, development, and application of these tools would be beneficial for metabolic engineers to reprogram biosynthetic pathways by adopting system-specific approaches, as a single strategy cannot be applied to all systems. Lastly, we discussed the challenges and future prospects of developing these gene regulatory tools to further advance the biomanufacturing field.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell-free screening of peptide tags for droplet-like assembly formation of glucose dehydrogenase.","authors":"Sayoko Ito-Harashima, Koharu Alicia Senda, Ako Kagawa, Seiji Kobayashi, Yuki Muroshige, Tomoaki Matsuura, Natsuko Miura, Michihiko Kataoka","doi":"10.1016/j.jbiosc.2026.03.008","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.03.008","url":null,"abstract":"<p><p>Glucose dehydrogenases (GDHs) are oxidoreductases that catalyze the oxidation of d-glucose to glucono-δ-lactone and are widely used in industrial applications such as biosensors, bioelectrodes, and biocatalytic cofactor regeneration. In particular, NAD(P)<sup>+</sup>-dependent GDHs are frequently employed as NAD(P)H-regenerating enzymes, with extensive efforts devoted to improving their robustness. BmGDH<sub>M6</sub>, an engineered variant of the Bacillus megaterium GDH with enhanced chemical and organic solvent tolerance, was developed as a potent cofactor-regeneration enzyme. In parallel, enzyme condensation via liquid-liquid phase separation has attracted increasing attention as a potential mechanism for organizing enzyme-catalyzed reactions, and short peptides capable of promoting condensate formation. However, efficient screening and evaluation of such peptide tags using conventional cell-based expression systems have remained challenging. This study established a peptide tag screening strategy using the PURE system, a reconstituted cell-free protein synthesis platform, and applied it to BmGDH<sub>M6</sub> as a model enzyme. A small library of metabolic enzymes transiently assembling (META) body-forming signal (METAfos) tags and intrinsically disordered region (IDR)-derived peptide tags was evaluated with respect to expression, solubility, and assembly behavior within a defined in vitro environment. From this library, a short peptide tag, K7G3, 10-amino-acids-long, was identified that conferred droplet-like assembly-forming properties on BmGDH<sub>M6</sub> under specified crowding conditions. These results demonstrated that the PURE system provided a rapid and controllable platform for screening peptide tags and down-selection of candidates that modulate enzyme assembly behavior in vitro.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147772535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficient hybridoma screening using extracellular vesicles for conformation-specific antibodies to transmembrane proteins.","authors":"Rina Sakamaki, Takao Matsuba, Yasuyuki Kurihara","doi":"10.1016/j.jbiosc.2026.03.011","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.03.011","url":null,"abstract":"<p><p>Here, we report a simple and rapid extracellular vesicle (EV)-based membrane-type immunoglobulin-directed hybridoma screening (MIHS) platform that enables efficient isolation of monoclonal antibodies (mAbs) recognizing three-dimensional conformations of transmembrane proteins. Transmembrane proteins are essential membrane components involved in signal transduction, transport, and energy conversion. As they function in native conformations, isolating mAbs that recognize conformational epitopes is critical for both research and therapeutic use. However, traditional methods, such as the enzyme-linked immunosorbent assay (ELISA), can disrupt the antigen structure, making it challenging to screen for such mAbs. To overcome this limitation, we developed a screening strategy combining MIHS with EVs as antigen-presenting tools. EVs, which are naturally bounded by lipid bilayers, display transmembrane proteins in native conformations and can be easily isolated. As a model, we engineered cells co-expressing alkaline phosphatase (ALP) and green fluorescent protein, generating fluorescent EVs displaying ALP. Hybridomas were screened by MIHS using these EVs, followed by ELISA without direct antigen immobilization. All isolated mAbs recognized conformational ALP epitopes, demonstrating the structural selectivity of this method. These results demonstrate that the EV-based MIHS approach provides a convenient and structurally faithful strategy for isolating conformation-specific mAbs, offering broad utility in basic biology and antibody development.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147716577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of the CYR1<sup>G2066A</sup> mutation in ethanol tolerance of sake yeast Kyokai no. 11.","authors":"Kazuya Morinaka, Yoshihiro Isida, Mamoru Watanabe, Daisuke Watanabe, Tetsuya Goshima, Takeshi Akao, Miwa Yamada, Hitoshi Shimoi","doi":"10.1016/j.jbiosc.2026.03.010","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.03.010","url":null,"abstract":"<p><p>Sake yeast Kyokai no. 11 (K11) is an ethanol-tolerant mutant of Kyokai no. 7 (K7) and produces a higher ethanol concentration in the sake mash than K7. A previous study revealed that stress-induced genes under the control of STRE elements were upregulated in K11. To elucidate the causal mutation responsible for ethanol tolerance, we compared the genome sequences of the ethanol-tolerant mutants (K11 and K7AT2, a newly isolated ethanol-tolerant mutant of K7) with that of their parental strain, K7. We identified a shared loss of heterozygosity region in the left arm of chromosome X in both mutants. We focused on CYR1 in this region, as it encodes adenylate cyclase, which negatively regulates expression of STRE-regulated genes through the upregulation of protein kinase A. Nucleotide 2066 of CYR1 was changed from G/A (amino acids Arg/His) in K7 to A/A (amino acids His/His) in K11 and K7AT2. When the plasmid containing CYR1<sup>2066G</sup> was introduced into K11 or K7AT2, the stress tolerance of the transformants decreased to the level of K7, whereas the introduction of CYR1<sup>2066A</sup> had a minimal effect. Consistently, disruption of the CYR1<sup>2066G</sup> allele in K7 increased stress tolerance, whereas disruption of CYR1<sup>2066A</sup> decreased stress tolerance. Furthermore, when CYR1 in a laboratory haploid strain was disrupted and either the CYR1<sup>2042A</sup> or CYR1<sup>2042G</sup> allele of S288C (corresponding to K7CYR1<sup>2066</sup>) was introduced into the disruptant, the transformants with CYR1<sup>2042A</sup> showed higher stress tolerance than those with CYR1<sup>2042G</sup>. We concluded that the CYR1<sup>G2066A</sup> mutation was responsible for ethanol tolerance in K11.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lian Chen, Awn Abbas, Nanxin Li, Xiaoyang Ai, Dongmei Dai, Yixing Chen, Sameera Naseer, Hualin Fu
{"title":"Biofilm-microenvironment responsive hybrid micelle based on novel betaine derivative for enhanced delivery of honokiol against stubborn bacterial biofilms.","authors":"Lian Chen, Awn Abbas, Nanxin Li, Xiaoyang Ai, Dongmei Dai, Yixing Chen, Sameera Naseer, Hualin Fu","doi":"10.1016/j.jbiosc.2026.02.011","DOIUrl":"https://doi.org/10.1016/j.jbiosc.2026.02.011","url":null,"abstract":"<p><p>The development of conventional antibiotics is being severely challenged by the rise of bacterial resistance and the obstacle of biofilm-associated infections. Given their enhanced permeability, nano micelles have emerged as a widely utilized platform for the delivery of hydrophobic drugs. In this study, a novel material named BS-12-PEG-OH (PB<sub>12</sub>) was synthesized, and an intelligent nanoplatform was successfully developed through thin film dispersion method by co assembling vitamin E polyethylene glycol succinate (TPGS) with PB<sub>12</sub> into hybrid micelles via thin film dispersion method, thereby enabling the encapsulation of Honokiol (designated as HK@PB<sub>12</sub>/TPGS Ms). The hybrid micelle can effectively penetrate the extracellular polymeric substance barrier of the biofilm. Upon reaching the acidic microenvironment, it responsively releases dodecyl dimethyl betaine (BS-12) and honokiol (HK), thus eliminating the biofilm structure and killing the embedded bacteria. Under acidic conditions, HK@PB<sub>12</sub>/TPGS Ms achieved a substantial bacterial reduction of 9.60 log<sub>10</sub> CFU/ml. Furthermore, under the acidic condition of the biofilm microenvironment, they effectively cleared 83.32 % of the biofilm and reduced the embedded S. aureus by 3.75 log<sub>10</sub> CFU/ml. The results indicate that the HK@PB<sub>12</sub>/TPGS Ms could effectively penetrate Staphylococcus aureus biofilms, disrupt their structure, and eliminate the bacteria inside the biofilm, hence preventing new infections and providing a novel therapeutic strategy for combating stubborn biofilm-associated infections.</p>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment of a simple and novel method for contact-dependent intercellular interaction analysis using extracellular vesicles","authors":"Rina Sakamaki , Takao Matsuba , Yasuyuki Kurihara","doi":"10.1016/j.jbiosc.2025.11.009","DOIUrl":"10.1016/j.jbiosc.2025.11.009","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are membrane-bound vesicles secreted by cells. They play essential roles in intercellular communications and are involved in numerous physiological processes. Given their functional importance, EVs have emerged as promising tools for diagnosing and treating various diseases. In this study, we focused on the utility of EVs and explored their application in the analysis of contact-dependent cell–cell interactions, which are essential for the control of cell differentiation and induction of immune responses. Although several methods have been developed to evaluate these interactions, they often require complex procedures and advanced optimization, limiting their broad applicability. To overcome these limitations, we developed a novel method utilizing EVs to present membrane proteins in their native conformations. Our strategy involved producing fluorescently labeled EVs with target antigens and quantitatively assessing their binding to target cells via flow cytometry. Using fluorescently labeled EVs presenting with either an N-terminal pro-brain natriuretic peptide or interleukin-2 receptor, we successfully detected specific interactions with corresponding hybridoma B cell receptors. This simpler method requires no advanced optimization and effectively analyzes cell–cell interactions under physiological conditions in a high-throughput and quantitative manner. Our findings highlight the potential of this EV-based system as a valuable tool for studying membrane protein-mediated cell–cell interactions in bioscience research.</div></div>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":"141 3","pages":"Pages 194-202"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Zein/Fucoidan microcarriers promote myogenic differentiation via topographical cues and hydrodynamic modulation","authors":"Wanli Xiong, Chengxin Ge, Botao Zhang, Ziying Chen, Yuzhe Guo, Qiaohui Lu, Wen-song Tan, Yan Zhou","doi":"10.1016/j.jbiosc.2025.11.003","DOIUrl":"10.1016/j.jbiosc.2025.11.003","url":null,"abstract":"<div><div>Microcarrier surface topography and fluid shear stress (FSS) critically regulate cellular behavior. An edible zein/fucoidan microcarrier with 200 μm grooves was designed for this study. Computational fluid dynamics (CFD) simulations and experiments were combined to analyze surface microfluidic characteristics during dynamic culture and their cellular effects. The research demonstrates controlled myogenic differentiation through groove topography and FSS modulation for scalable cultured meat production. The results demonstrated that the grooved microcarriers exhibited excellent cell attachment and proliferation capacity in spinner flask dynamic culture, achieving a maximum cell density of 1.16 × 10<sup>6</sup> cells/mL, comparable to commercial Cultispher-S microcarriers. The groove structure promoted cell alignment through contact guidance, significantly enhancing the gene expression of myogenic differentiation markers (myogenic differentiation 1, MyoD1; α-actinin; myosin heavy chain, MHC) and cell fusion (myomaker, MYMK). CFD simulations revealed that the grooves created a low-shear microenvironment (minimum average FSS: 3.93 × 10<sup>−2</sup> Pa, maximum: 1.18 × 10<sup>−1</sup> Pa), which effectively avoided high FSS-induced damage while maintaining mechanical stimulation. This optimal mechanical microenvironment further activated the expression of key genes involved in early-stage (MyoD1; myogenin, MyoG; myocyte enhancer factor 2C, MEF2C) and late-stage (α-actinin; myosin heavy chain 2, Myh2) myogenic differentiation. Flat and spherical microcarriers showed lower myogenic differentiation efficiency. This study elucidates the synergistic mechanism between groove structures and the low FSS microenvironment within grooves, providing a novel scaffold design rationale that combines biomimetic topology with fluid dynamics compatibility for large-scale cultured meat production.</div></div>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":"141 3","pages":"Pages 172-184"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145687478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masashi Tsuda , Yuki Nakatani , Satoshi Baba , Kumi Yoshida , Kazuhiko Someya , Yoshikuni Onodera , Koichi Nonaka , Yasunori Chiba
{"title":"Production and characterization of norovirus virus-like particles vaccine candidates in a genetically modified Ogataea minuta system","authors":"Masashi Tsuda , Yuki Nakatani , Satoshi Baba , Kumi Yoshida , Kazuhiko Someya , Yoshikuni Onodera , Koichi Nonaka , Yasunori Chiba","doi":"10.1016/j.jbiosc.2025.11.008","DOIUrl":"10.1016/j.jbiosc.2025.11.008","url":null,"abstract":"<div><div>The development of an effective vaccine against noroviruses remains a major public health priority. Norovirus GII.4 capsid protein VP1 as a promising vaccine candidate was produced by the methylotrophic yeast <em>Ogataea minuta</em> production system. It was intracellularly expressed and subsequently purified by immobilized metal affinity chromatography and anion exchange chromatography, yielding 13.4 mg of highly purified VP1 protein from 50 mL of culture supernatant. The formation of VP1-based virus-like particles (VLPs) that retained their structure even after freeze-thawing was confirmed by transmission electron microscopy. The VP1 protein purified in the form of VLPs displayed strong antigenicity and specific, dose-dependent binding to histo-blood group antigens, as determined by the enzyme-linked immunosorbent assay (ELISA). Immunogenicity studies in BALB/c mice demonstrated that intramuscular administration induced robust serum IgG responses across all tested doses, with no significant dose-dependent differences. Furthermore, mucosal administration intranasally or sublingually induced systemic IgG, systemic IgA, and mucosal IgA responses. These responses were significantly enhanced by the lipid A adjuvant. These findings showed that the <em>O. minuta</em> production system is capable of producing immunogenic Norovirus VLPs as a vaccine candidate.</div></div>","PeriodicalId":15199,"journal":{"name":"Journal of bioscience and bioengineering","volume":"141 3","pages":"Pages 165-171"},"PeriodicalIF":2.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145804660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}