Weigeng Liu, Jiamin Cao, Di Wu, Yue Wu, Yi Qin, Yanlin Liu, Xixi Zhao, Yuyang Song
{"title":"Development of an advanced acetaldehyde detection solution based on yeast and bacterial surface display technology","authors":"Weigeng Liu, Jiamin Cao, Di Wu, Yue Wu, Yi Qin, Yanlin Liu, Xixi Zhao, Yuyang Song","doi":"10.1016/j.jbiotec.2024.11.020","DOIUrl":"10.1016/j.jbiotec.2024.11.020","url":null,"abstract":"<div><div>Acetaldehyde, a carcinogen widely present in various beverages and the natural environment, necessitates convenient and efficient detection methods. In this work, two different host strains were used to develop a sensitive, convenient, and efficient whole-cell optical biosensor for acetaldehyde detection. Acetaldehyde dehydrogenase (AldH) was displayed on the cell surface of <em>Saccharomyces cerevisiae</em> and <em>E. coli</em> using flocculin protein and the N-terminal ice nucleation protein (INP), respectively. The successful construction of yeast and bacteria surface display platforms was confirmed by laser scanning confocal microscopy. Then, the optimal AldH-display system for yeast and bacteria was confirmed. The optimum reaction conditions were determined by changing testing temperatures and pH values. The differences between the two display systems were compared. The highest whole-cell activities of yeast and bacteria under optimal conditions were 3.68 ± 0.07 U/mL/OD<sub>600</sub> for BY-S6G and 6.95 ± 0.04 U/mL/OD<sub>600</sub> for E-32-I<sub>r</sub>A. The strains with the best performance were chosen for the detection of acetaldehyde in wine and other beverage samples and showed substrate specificity and accuracy, in which the recovery rate ranged between 94.4 % and 110.1 %. The results demonstrated that the AldH surface display strains could be used as an optical biosensor to detect acetaldehyde in beverages and red wine.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"398 ","pages":"Pages 42-50"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769262","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}
Jiamin Chen , Ping Wang , Zhanpeng Li , Jieyi Wu , Fang Tang , Niao Yang , Bohong Cen , Cuiyin Xie , Yufan Yang , Ziyan Yang , Chuwen Zhang , Xiangcao Yao , Zhongyuan Xu
{"title":"An in vitro 3D spheroid model with liver steatosis and fibrosis on microwell arrays for drug efficacy evaluation","authors":"Jiamin Chen , Ping Wang , Zhanpeng Li , Jieyi Wu , Fang Tang , Niao Yang , Bohong Cen , Cuiyin Xie , Yufan Yang , Ziyan Yang , Chuwen Zhang , Xiangcao Yao , Zhongyuan Xu","doi":"10.1016/j.jbiotec.2025.01.019","DOIUrl":"10.1016/j.jbiotec.2025.01.019","url":null,"abstract":"<div><div>Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease worldwide, affecting more than 30 percent of adults. The most severe form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is characterized by necrotizing inflammation and rapid fibrosis progression, often leading to cirrhosis and hepatocellular carcinoma. Currently, only Resmetirom is approved for the treatment of MASH one of the main reasons is the absence of representative in vivo or in vitro models for MASH. To address this challenge, we developed a high-throughput 3D spheroid model consisting of human hepatocellular carcinoma cells (HepG2) and human hepatic stellate cells (LX-2) on microwell arrays. This model, induced with free fatty acids (FFA) to simulate steatosis and fibrosis, enables the assessment of efficacy and mechanisms for potential anti-MASH drugs. Our findings demonstrate that this in vitro spheroid model replicates key pathological features of human MASLD, including steatosis, oxidative stress, and fibrosis. Upon validation, we selected pirfenidone (PFD) and yinfenidone (AC-003), which are commonly used to treat idiopathic pulmonary fibrosis (IPF), to test their anti-MASH efficacy. Treatment with these drugs showed that they could regulate lipid synthesis and metabolism genes, reduce lipid accumulation, oxidative stress, and fibrosis levels. This 3D spheroid model represents a straightforward and efficient tool for screening anti-MASH drugs and investigating the molecular mechanisms of drug action.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 153-163"},"PeriodicalIF":4.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074341","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}
{"title":"Bifunctional chimeras of myeloperoxidase and glucose oxidase. Antimicrobial, topological and enzymatic properties","authors":"Parfait Kenfack Ymbe , Claire Céré , Brigitte Delord , Gilles Pecastaings , Isabelle Ly , Aurélien Thureau , Laura Rodriguez , Zoran Ivanovic , Véronique Schmitt , Xavier Lafarge , Jean-Paul Chapel , Claire Stines-Chaumeil","doi":"10.1016/j.jbiotec.2025.01.018","DOIUrl":"10.1016/j.jbiotec.2025.01.018","url":null,"abstract":"<div><div>Enhancing the local substrate concentration is a crucial strategy in nature for facilitating the proximity of two enzymes. The substrate of the first enzyme is transformed into a by-product that travels to the active site of the second enzyme without external diffusion, then transformed into a product and eventually expelled from the complex. In an effort to optimize the antimicrobial properties of myeloperoxidase from <em>Rhodopirellula baltica</em> (RbMPO), we created a library of fused chimeras between a glucose oxidase (GOx) and RbMPO so that H<sub>2</sub>O<sub>2</sub> could be continuously perfused in the vicinity RbMPO, enabling the production of HOCl or HOSCN, well-known antimicrobial agents. The enzymes were characterized biochemically, enzymatically, and physically using low-resolution techniques such as AFM, SAXS, and cryofracture. SAXS experiments revealed that the chimeras were properly folded and existed in different oligomeric states. The kinetic parameters of the chimeras were determined and used for classification, revealing that all chimeras exhibited varying levels of activity and were microbicidal. The mixture of different oligomeric states of LEGGEAEA displayed both activity and microbicidal properties. AFM was used to visualize the chimeras in different oligomeric states, with their overall shapes ranging from round, oblong, to hooked, depending on the linker used.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 127-140"},"PeriodicalIF":4.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143065881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linbo Gou , Di Liu , Tai-ping Fan , Huaxiang Deng , Yujie Cai
{"title":"Efficient spermidine production using a multi-enzyme cascade system utilizing methionine adenosyltransferase from Lactobacillus fermentum with Reduced Product Inhibition and Acidic pH Preference","authors":"Linbo Gou , Di Liu , Tai-ping Fan , Huaxiang Deng , Yujie Cai","doi":"10.1016/j.jbiotec.2025.01.016","DOIUrl":"10.1016/j.jbiotec.2025.01.016","url":null,"abstract":"<div><div>Methionine adenosyltransferases (MATs; EC 2.5.1.6) are key enzymes that catalyze a crucial step in the spermidine biosynthesis pathway. Due to MAT's significant product inhibition, S-adenosylmethionine (SAM) and spermidine production faces challenges. We evaluated MATs from 20 lactic acid bacteria (LAB) to identify enzymes with acidic preference and lower susceptibility to product inhibition. <em>Lactobacillus fermentum</em>'s MAT (LfMAT) emerged as a candidate with desirable characteristics. LfMAT exhibited strong activity in acidic environments, maintaining over 85 % activity between pH 6.0–8.5 for 60 min, with peak efficacy at pH 7.0. LfMAT produced 4.2 mM SAM from 5 mM substrate, indicating reduced product inhibition. Ultimately, using an <em>in vitro</em> multi-enzyme cascade system containing LfMAT, S-adenosylmethionine decarboxylase, and spermidine synthase, we successfully produced 12.9 g·L<sup>−1</sup> of spermidine. This study establishes a cascade reaction platform, offering a novel approach for the efficient synthesis of spermidine and other polyamines.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 141-152"},"PeriodicalIF":4.1,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046730","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}
Kang Li , Shaojie Yang , Tengfei Wang , Chunjun Zhan , Zhonghu Bai , Yankun Yang
{"title":"Enhanced methanol-xylose co-utilization strategy in Komagataella phaffii","authors":"Kang Li , Shaojie Yang , Tengfei Wang , Chunjun Zhan , Zhonghu Bai , Yankun Yang","doi":"10.1016/j.jbiotec.2025.01.017","DOIUrl":"10.1016/j.jbiotec.2025.01.017","url":null,"abstract":"<div><div>Bio-manufacturing based on non-food carbon sources is conducive to alleviating the global food crisis and greenhouse effect. However, the mechanism of the utilization of methanol and xylose in <em>Komagataella phaffii</em> based on endogenous metabolic pathways has not been fully explored. In this study, transcriptomics revealed a positive correlation between methanol metabolic efficiency and the transcription level of genes related to xylose metabolism and phosphate metabolism. By providing sufficient phosphate to the strain, the methanol utilization rate of the <em>Komagataella phaffii</em> GA01 strain was improved, and the final biomass reached 7.5 g DCW/L. Metabolomics further confirmed that methanol could effectively activate xylose metabolism of the strain, and the consumption rates of methanol and xylose of the <em>Komagataella phaffii</em> GA01 strain could reach 3.87 g/L/d and 1.83 g/L/d, which were 34 % and 357.5 % higher than that of the wild-type strain, respectively. This study further promotes the application of methanol and xylose in microbial fermentation.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 117-126"},"PeriodicalIF":4.1,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059120","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}
Linbing Yu , Xin Song , Guangqiang Wang , Yongjun Xia , Zibo Song , Gong Chen , Lianzhong Ai , Zhiqiang Xiong
{"title":"Construction and characterization of a mutant library for the P23 constitutive promoter in lactic acid bacteria","authors":"Linbing Yu , Xin Song , Guangqiang Wang , Yongjun Xia , Zibo Song , Gong Chen , Lianzhong Ai , Zhiqiang Xiong","doi":"10.1016/j.jbiotec.2025.01.015","DOIUrl":"10.1016/j.jbiotec.2025.01.015","url":null,"abstract":"<div><div>Promoters are crucial elements for controlling gene expression in cells, yet lactic acid bacteria (LAB) often lack a diverse set of available constitutive promoters with quantitative characterization. To enrich the LAB promoter library, this study focused on the known strong constitutive promoter P<sub>23</sub> in LAB. Through error-prone PCR and dNTP analog-induced random mutagenesis, a library of 247 mutants of P<sub>23</sub> was generated by using the red fluorescent protein (RFP) fluorescence intensity as a high-throughput screening indicator in <em>Streptococcus thermophilus</em>. The activity of P<sub>23</sub> mutants varied from 0.01 to 3.63 times that of P<sub>23</sub>. Similar trends of promoter strength were observed in <em>Lactobacillus plantarum</em> and <em>Lactococcus lactis</em>, but significant differences in <em>Escherichia coli</em>, indicating the library's specificity to LAB. To assess the application potential of this P<sub>23</sub> library, seven promoters with different strengths (0.28–2.58) were selected. The mutant promoters significantly enhanced the enzyme activities of superoxide dismutase (SOD), β-glucuronidase (GusA), and β-galactosidase (β-gal) in <em>S. thermophilus</em>. Notably, the mutant P<sub>23–203</sub> expressing SOD exhibited an enzyme activity of 382.9 U/mg, which was 1.65 times higher than the control (P<sub>23</sub>). Similarly, the expression of GusA and β-gal were 1.82 and 1.28 times higher than those of P<sub>23</sub>, respectively. This study provided a set of significantly different P<sub>23</sub> constitutive promoter mutant elements for the first time, laying the foundation for metabolic engineering and synthetic biology applications in LAB.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 99-107"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028708","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}
{"title":"Enhancement of the production of terpenoid and flavonoid secondary metabolites in the ground and aerial parts of licorice composite plant in a hydroponic system","authors":"Behrooz Mohammadparast , Zahra Shirazi","doi":"10.1016/j.jbiotec.2025.01.014","DOIUrl":"10.1016/j.jbiotec.2025.01.014","url":null,"abstract":"<div><div>Hairy roots mediated by <em>Agrobacterium rhizogenes</em> can be obtained from the composite plants (plants with hairy roots and untransformed aerial parts) by <em>ex vitro</em> method. Composite plants can produce higher amounts of secondary metabolites by merging hydroponic systems. This provides a stable condition for composite plants, in which various metabolites are produced in different parts. In the present study, composite plants of <em>Glycyrrhiza glabra</em> were produced under <em>ex vitro</em> conditions and transferred into a hydroponic culture medium to produce and extract secondary metabolites. The results showed a 4.8- and 1.8-fold enhancement in the expressions of <em>SQS1</em> and <em>bAS</em> genes in the roots of the composite plants compared to the control group, respectively. The levels of glycyrrhizin (1.7) and glabridin (3.5) were higher in the leaves of the composite plants compared to the controls. Moreover, higher amounts of glabridin (1.7) were observed in the roots of the composite plants compared to the control group. Investigation of the oxidative enzymes in the composite plants and control group revealed that the plants used more secondary metabolites through <em>Agrobacterium</em> inoculation. The plants needed more antioxidant enzymes to counter the release of oxygen-free radicals in control conditions, but composite plants used secondary metabolites as scavengers. Data revealed that composite plants managed to produce high amounts of various secondary metabolites in a hydroponic system.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 164-171"},"PeriodicalIF":4.1,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028623","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}
Viviana Chiappini, Debora Casbarra, Anna Maria Girelli
{"title":"Hemp tea waste-immobilized lipase for the synthesis of alkyl oleates in solvent free systems","authors":"Viviana Chiappini, Debora Casbarra, Anna Maria Girelli","doi":"10.1016/j.jbiotec.2025.01.013","DOIUrl":"10.1016/j.jbiotec.2025.01.013","url":null,"abstract":"<div><div>This study explores the immobilization of lipase from <em>Candida rugosa</em> (CRL) on hemp tea waste to catalyze the esterification of oleic acid with primary aliphatic C2-C12 alcohols in a solvent-free system. The immobilization method employed was adsorption, chosen for its simplicity, low cost, and ability to preserve enzyme activity. The esterification of undecanoic acid, lauric acid, and oleic acid with alcohols of varying chain lengths (ethanol, 1-propanol, 1-butanol, 1-octanol, 1-decanol, and 1-dodecanol) was studied. The esterification efficiency was found to be influenced by the type of alcohol, the molar ratio of oleic acid to alcohol, and the water content in the reaction medium. The highest conversions were achieved with ethanol (23 % conversion with 18.5 % water and a molar ratio of 1:5) and 1-decanol (30 % conversion with no added water and a molar ratio of 1:2). Comparatively, the soluble lipase achieved slightly higher conversion of oleic acid using decanol (38 %), indicating that the performance may be attributed to origin of lipase, rather than the immobilization procedure. The study demonstrated that the immobilization of lipase on hemp tea waste did not hinder enzyme activity. Additionally, the biocatalyst developed can function in a completely solvent-free system, offering a green solution by repurposing waste materials for industrial ester production.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 108-116"},"PeriodicalIF":4.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023578","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}
Myeong-Seop Sim , Sung-ho Park , Jong-il Choi , Tae Wan Kim
{"title":"Development of a highly efficient microbial fermentation process of recombinant Escherichia coli for GABA production from glucose","authors":"Myeong-Seop Sim , Sung-ho Park , Jong-il Choi , Tae Wan Kim","doi":"10.1016/j.jbiotec.2025.01.011","DOIUrl":"10.1016/j.jbiotec.2025.01.011","url":null,"abstract":"<div><div>This study was aimed to develop a highly productive microbial fermentation process for gamma-aminobutyric acid (GABA) production from glucose. For this, an efficient GABA-producing <em>E. coli</em> strain was firstly developed through metabolic engineering with a strategy of increasing the flux of GABA biosynthetic pathway and deleting or repressing the GABA shunt pathways that compete with GABA biosynthesis. According to this strategy, three metabolically engineered <em>E. coli</em> strains of GTB, GTS, and A1S1 were constructed, and through batch cultivation of these strains, <em>E. coli</em> GTS was ultimately selected as the most efficient GABA-producing strain. From flask cultures, <em>E. coli</em> GTS was found to produce 3.96 g/L of GABA, a titer 2.1 times or 17 % higher than that produced by <em>E. coli</em> GTB or <em>E. coli</em> A1S1, respectively. To maximize GABA production from glucose, pH-stat fed-batch culture conditions of the <em>E. coli</em> GTS were optimized in a one-factor-at-a-time manner. Fed-batch cultivation of the <em>E. coli</em> GTS under optimal conditions resulted in the highest GABA production performance with a concentration of 85.9 g/L and a volumetric productivity of 2.37 g/L/h. This result shows that the microbial fermentation process developed in this study has outstanding potential for the mass production of GABA.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 72-80"},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005979","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}
Sebastian-Juan Reyes , Lucas Lemire , Yves Durocher , Robert Voyer , Olivier Henry , Phuong Lan Pham
{"title":"Investigating the metabolic load of monoclonal antibody production conveyed to an inducible CHO cell line using a transfer-rate online monitoring system","authors":"Sebastian-Juan Reyes , Lucas Lemire , Yves Durocher , Robert Voyer , Olivier Henry , Phuong Lan Pham","doi":"10.1016/j.jbiotec.2025.01.008","DOIUrl":"10.1016/j.jbiotec.2025.01.008","url":null,"abstract":"<div><div>Shake flasks are a foundational tool in early process development by allowing high throughput exploration of the design space. However, lack of online data at this scale can hamper rapid decision making. Oxygen transfer rate (OTR) monitoring has been readily applied as an online process characterization tool at the benchtop bioreactor scale. Recent advances in modern sensing technology have allowed OTR monitoring to be available at the shake flask level. It is now possible to multiplex time-of-action (e.g., Induction, temperature shift, pH shift, feeding initiation, point of harvest) characterization studies by relying on careful analysis of OTR profile kinetics. As a result, there is potential to save time and capital expenditures while exploring process intensification studies though accurate and physiologically relevant online data. In this article, we detail the application of OTR monitoring to characterize the impact that recombinant protein production has on an inducible CHO cell line expressing Palivizumab. We then test out time-of-action studies to intensify protein production outcomes. We observe that recombinant protein expression causes a metabolic load that diminishes potential biomass growth. As a result, when compared to a control standard process, delaying induction and temperature shift has the potential to improve viable cell densities (VCD) by 2-fold thus increasing recombinant protein yield by over 30 %. The study also demonstrates that OTR can serve as a useful tool to detect cessation of exponential growth. Consequently, time-of-action points that are characteristic of inducible systems can be formulated accurately and reliably to maximize production performance.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"399 ","pages":"Pages 47-62"},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}