ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Lingling Cai,Yanxing Wang,Xiangrong Peng,Wenjing Li,Ying Yuan,Xiaofeng Tao,Xinwei Yao,Ruichan Lv
Oral squamous cell carcinoma (OSCC) is the most common cancer in the oral and maxillofacial region. Due to the special physiological and anatomical position of the oral cavity, the disease often has a significant impact on the chewing, swallowing, language, and breathing functions of patients. In recent years, with the development of medical molecular biology, molecular targeted therapy has received increasing clinical attention and has gradually become a new method for the treatment of malignant tumors. In this research, gold nanostars with a high photothermal effect combined with the searched targeted antibody were used for OSCC therapy. We use the data set in the public database and construct a gene co-expression module by weighted gene co-expression network analysis (WGCNA). It was found that the turquoise module and the midnight blue module had the greatest connection to tumorigenesis. Cytoscape software was used to analyze the important modules, and the top 10 genes of each module were selected; the survival analysis of the top 10 genes was carried out by gene expression profiling interactive analysis (GEPIA), which indicated that these genes (SERPINH1, MMP11, ADAM12, FADS3, SLC36A2, C1QTNF7, SCRG1, and APOBEC2) have statistical significance as key genes that are related to the tumorigenesis of OSCC. Then, the anti-SERPINH1 antibody targeted to SERPINH1 was chosen as the inhibitor and combined with gold nanostars for photothermal assisted targeted therapy. Thus, the searched key genes can be regarded as biomarkers and therapeutic targets for further precise diagnosis.
研究领域:
肿瘤学
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分子生物学
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生物信息学
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诊疗学
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DOI
PubMed
高影响因子
Catalysts
·
2020
·Vol. 10
·期 9
·947
·
IF 3.52
Hongjie Hui,Yajun Bai,Tai-Ping Fan,Xiaohui Zheng,Yujie Cai
Putrescine, a biogenic amine, is a highly valued compound in medicine, industry, and agriculture. In this study, we report a whole-cell biocatalytic method inEscherichia colifor the production of putrescine, using L-arginine as the substrate. L-arginine decarboxylase and agmatine ureohydrolase were co-expressed to produce putrescine from L-arginine. Ten plasmids with different copy numbers and ordering of genes were constructed to balance the expression of the two enzymes, and the best strain was pACYCDuet-speB-speA. The optimal concentration of L-arginine was determined to be 20 mM for this strain. The optimum pH of the biotransformation was 9.5, and the optimum temperature was 45 °C; under these conditions, the yield of putrescine was 98%. This whole-cell biocatalytic method appeared to have great potential for the production of putrescine.Keywords:L-arginine;putrescine;Escherichia coli;whole-cell catalysis;co-expression
研究领域:
生物技术
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生物化学
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微生物学
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产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 9
·2809
·
IF 4.927
Qi-Ting Fang,Wen-Wen Luo,Ya-Nan Zheng,Ying Ye,Mei-Juan Hu,Xin-Qiang Zheng,Jian-Liang Lu,Yue-Rong Liang,Jian-Hui Ye
Chemicals underlying the floral aroma of dry teas needs multi-dimensional investigations. Green, black, and freeze-dried tea samples were produced from five tea cultivars, and only ‘Chunyu2’ and ‘Jinguanyin’ dry teas had floral scents. ‘Chunyu2’ green tea contained the highest content of total volatiles (134.75 μg/g) among green tea samples, while ‘Jinguanyin’ black tea contained the highest content of total volatiles (1908.05 μg/g) among black tea samples. The principal component analysis study showed that ‘Chunyu2’ and ‘Jinguanyin’ green teas and ‘Chunyu2’ black tea were characterized by the abundant presence of certain alcohols with floral aroma, while ‘Jinguanyin’ black tea was discriminated due to the high levels of certain alcohols, esters, and aldehydes. A total of 27 shared volatiles were present in different tea samples, and the contents of 7 floral odorants in dry teas had correlations with those in fresh tea leaves (p< 0.05). Thus, the tea cultivar is crucial to the floral scent of dry tea, and these seven volatiles could be promising breeding indices.Keywords:floral scent;tea cultivars;processing;volatiles;alcohols;principal component analysis;co-expression analysis
研究领域:
食品科学
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植物化学
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产品关联
DOI
PubMed
高影响因子
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY
·
2018
·Vol. 187
·期 4
·1143-1157
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IF 1.797
Jin Li-Qun,Xu Wei,Yang Bo,Liu Zhi-Qiang,Zheng Yu-Guo
Xylitol is an important functional sugar alcohol which is widely used in industries. To efficiently produce xylitol from xylose by xylose reductase in a single step, the coupled system and the coexpression system using xylose reductase (XR) from Rhizopus oryzae and glucose dehydrogenase (GDH) from Exiguobacterium sibiricum were constructed, the latter of which was used for cofactor regeneration. One hundred fifty grams/liter of xylose could be fully converted to xylitol by employing the two-enzyme coupled system with cell-free extract, and xylitol productivity of 21.2 g/L/h was reached by biotransformation in vitro. The whole-cell biocatalyst coexpressing xylose reductase and glucose dehydrogenase was successfully used to synthesize xylitol via enzymatic reduction of xylose. After optimization of the induction condition, the enzyme activity reached 1533 U/L. Two hundred grams/liter of xylose could be completely converted to xylitol, and the highest xylitol productivity of 6.37 g/L/h was obtained under the optimal transformation conditions. Thus, recombinant Escherichia coli coexpressing xylose reductase and glucose dehydrogenase is a promising candidate for xylitol production from xylose.
研究领域:
生物化学
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代谢工程
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合成生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
·
IF 6.953
Lin Yao,Xinyi Wang,Rui Xue,Hong Xu,Rui Wang,Lujia Zhang,Sha Li
Mussel foot proteins (Mfps), which help mussels attach to various surfaces, are considered to be promising biomaterials due to their outstanding adhesive properties. However, limited production and lack of post-translational modifications of tyrosine residues into 3,4-dihydroxyphenylalanine (Dopa) in bacterial expression systems have hampered their applications. In the present study, for the first time we established the expression of recombinant Mytilus galloprovincialis foot protein type 3 variant B (fp-3B) in Escherichia coli ; and achieved its viable production (~51 mg/L). Additionally, the Dopa content and adhesive properties of fp-3B co-expressed using various types of tyrosinases were compared. Consequently, the co-expression of fp-3B construct together with tyrosinase from Verrucomicrobium spinosum (TyrVs) yielded up to 87 mg/L of modified fp-3B; hydroxylation of tyrosine residues accounted for 57.18% by acid-borate difference spectroscopy. The modified fp-3B also showed significant coating and adhesive ability, and its bulk-scale adhesive strength was 2.9-fold higher than that of unmodified fp-3B. Compared with other type 3 mussel foot proteins, the high-yield expression and extensive hydroxylation level of the recombinant protein indicate that fp-3B co-expressed with TyrVs (3B-Vs) has the potential to be widely used as bioglues.
研究领域:
生物技术
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材料科学
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海洋生物学
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DOI
PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 103
·期 1
·e14363
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IF 3
Chun Li,Yuxin Xie,Shaoyu Hu,Hong Yu,Yunke Xu,Hongping Shen,Yuan Yuan,Long Gu,Bangming Pu
Hepatocellular carcinoma (HCC) is a life-threatening disease for which there is no cure. Traditional Chinese medicine is a treasure trove of Medicinals that has been used for thousands of years. In China, the traditional herb pair, Curcumae Rhizoma and Sparganii Rhizoma (CR-SR) represent a classic herbal combination used for the treatment of HCC. However, the drug targets and pharmacological mechanism of action of CR-SR in the treatment of HCC are unclear. To address this, we screened the active components and drug targets of CR-SR from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and a high-throughput experiment- and reference-guided database of traditional Chinese medicines (HERB database). Combined with the weighted co-expression network analysis of dataset GSE76427, we constructed an active component-target-disease regulatory network. It was found that CR-SR's active components for HCC treatment included trans-gondoic acid, beta-sitosterol, stigmasterol, hederagenin, and formononetin. These compounds specifically targeted the genes Estrogen Receptor 1 ( ESR1 ), Cyclin A2 ( CCNA2 ), Checkpoint Kinase 1 ( CHEK1 ), and Nuclear Receptor Coactivator 2 ( NCOA2 ). ESR1 , CCNA2 , and CHEK1 genes showed significant differences in survival prognosis, expression levels, and statistical significance during the pathological stage. Moreover, their high affinity for formononetin was determined through molecular docking analysis. Cell assays and high-throughput sequencing were performed to reveal that the inhibitory effect of formononetin on HepG2 cell proliferation was related to hepatocyte metabolism and cell cycle regulation-related pathways. This study provides insights into potential HCC treatments.
研究领域:
肿瘤学
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药理学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Catalysts
·
2022
·Vol. 12
·期 3
·304
·
IF 4.501
Xinxing Gao,Qianqian Pei,Nianqing Zhu,Yi Mou,Jilei Liang,Xin Zhang,Shoushuai Feng
(S)-N-Boc-3-hydroxypiperidine is an important intermediate of the anticancer drug ibrutinib and is mainly synthesized by the asymmetric reduction catalyzed by ketoreductase coupled with glucose dehydrogenase at present. In this study, the coexpression recombinant strainsE. coli/pET28-K-rbs-G with single promoter andE. coli/pETDuet-K-G with double promoters were first constructed for the coexpression of ketoreductase and glucose dehydrogenase in the same cell. Then, the catalytic efficiency ofE. coli/pET28-K-rbs-G for synthesizing (S)-N-Boc-3-hydroxypiperidine was found to be higher than that ofE. coli/pETDuet-K-G due to the more balanced activity ratio and higher catalytic activity. On this basis, the catalytic conditions ofE. coli/pET28-K-rbs-G were further optimized, and finally both the conversion of the reaction and the optical purity of the product were higher than 99%. In the end, the cell-free extract was proved to be a better catalyst than the whole cell with the improved catalytic efficiency of different recombinant strains. This study developed a better coexpression strategy for ketoreductase and glucose dehydrogenase by investigating the effect of activity ratios and forms of the biocatalysts on the catalytic efficiency deeply, which provided a research basis for the efficient synthesis of chiral compounds.Keywords:(S)-N-Boc-3-hydroxypiperidine;coexpression strategy;activity ratio;ketoreductase;glucose dehydrogenase
研究领域:
生物化学
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生物技术
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药物化学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Dianhui Wu,Ziqiang Chen,Mingtao Ma,Wenzhe Li,Zhengcong Peng,Zhenbao Shi,Jinglong Zhang,Hua Liu,Guangfa Xie,Jian Lu
Aging plays a crucial role in enhancing the flavor of Huangjiu. This study aims to elucidate the changes in taste attributes of aged Huangjiu and explore the correlation between non-volatile compounds. It showed that aging made the sourness, bitterness, and astringency more pronounced. The content of organic acids and amino acids exhibited specific patterns with aging years. The total taste activity value of organic acids showed an increasing trend, peaking at 54.40 in Huangjiu aged 15 years, which served as a key indicator of sourness intensity. A total of 22 potential contributors to umami and 18 to bitterness were screened based on weighted gene coexpression network analysis. The total content of potential umami contributors was significantly higher in fresh Huangjiu and aging stage I, but declined in later periods, while bitterness contributors increased gradually throughout the aging process. This study provided theoretical support for the taste characteristics of aged Huangjiu.
研究领域:
食品科学
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代谢组学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL
·
2025
·
IF 42.5
Xing Guo,Yichuan Wang,Caiyao Zhao,Cong Tan,Wei Yan,Sunhuan Xiang,Dan Zhang,Hui Zhang,Mengting Zhang,Liujing Yang,Meng Yan,Pingli Xie,Yi Wang,Li Li,Dongming Fang,Xuanmin Guang,Wenwen Shao,Fang Wang,Haoxuan Wang,Sunil Kumar Sahu,Min Liu,Tong Wei,Yang Peng,Yuping Qiu,Tao Peng,Yi Zhang,Xuemei Ni,Zhicheng Xu,Haorong Lu,Zhonghai Li,Huanming Yang,Ertao Wang,Michael Lisby,Huan Liu,Hongwei Guo,Xun Xu
With rapid advancements in single-cell RNA sequencing (scRNA-seq) technologies, exploration of the systemic coordination of critical physiological processes has entered a new era. Here, we generated a comprehensive Arabidopsis single-nucleus transcriptomic atlas using over 1 million nuclei from 20 tissues encompassing multiple developmental stages. Our analyses identified cell types that have not been characterized in previous single-protoplast studies and revealed cell-type conservation and specificity across different organs. Through time-resolved sampling, we revealed highly coordinated onset and progression of senescence among the major leaf cell types. We originally formulated two molecular indexes to quantify the aging state of leaf cells at single-cell resolution. Additionally, facilitated by weighted gene co-expression network analysis, we identified hundreds of promising hub genes that may integratively regulate leaf senescence. Inspired by the functional validation of identified hub genes, we built a systemic scenario of carbon and nitrogen allocation among different cell types from source leaves to sink organs.
研究领域:
植物学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
AAPS Journal
·
2016
·Vol. 19
·期 1
·203-214
·
IF 3.819
Zhong Shilong,Han Weichao,Hou Chuqi,Liu Junjin,Wu Lili,Liu Menghua,Liang Zhi,Lin Haoming,Zhou Lili,Liu Shuwen,Tang Lan
Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles ( n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs. The relationship among 17 defined TFs, CYPs/UGTs expression, and activity were evaluated in 30 liver samples from Chinese patients. The positive controls (e.g., PPARA, NR1I2, NR1I3) and hub TFs (NFIA, NR3C2, and AR) in the Grey sWGCNA Module were significantly and positively associated with CYPs/UGTs expression. And the cancer- or inflammation-related TFs (TEAD4, NFKB2, and NFKB1) were negatively associated with mRNA expression of CYP2C9/CYP2E1/UGT1A9. Furthermore, the effect of NR1I2, NR1I3, AR, TEAD4, and NFKB2 on CYP450/UGT1A gene transcription translated into moderate influences on enzyme activities. To our knowledge, this is the first study to integrate Gene Expression Omnibus (GEO) datasets and supervised weighted correlation network analysis (sWGCNA) for defining TFs potentially related to CYPs/UGTs. We detected several novel TFs involved in the regulatory network of hepatic CYPs and UGTs in humans. Further validation and investigation may reveal their exact mechanism of CYPs/UGTs regulation.
研究领域:
药理学
·
分子生物学
·
基因组学
✓ 已验证
DOI
PubMed
高影响因子
Catalysts
·
2023
·Vol. 14
·期 1
·23
·
IF 3.9
Zi-Han Zhang,An-Qi Wang,Bao-Di Ma,Yi Xu
The effective synthesis ofN-benzyl cyclo-tertiary amines using imine reductase, key components in natural products and pharmaceutical synthesis, is a green approach. Traditional methods faced challenges with enzyme activity and selectivity. This study focused on enhancingMesorhizobiumimine reductase (MesIRED) for betterN-benzyl cyclo-tertiary amine production. Through alanine scanning and consensus mutation, 12 single-siteMesIRED mutants were identified from 23 candidates, showing improved conversion ofN-benzylpyrrolidine andN-benzylpiperidine. Notably, mutants from I177, V212, I213, and A241 significantly boosted conversions. The best-performing mutant forN-benzylpyrrolidine,MesIREDV212A/I213V(M1), increased conversion from 23.7% to 74.3%. ForN-benzylpiperidine,MesIREDV212A/I177A/A241I(M2) enhanced conversion from 22.8% to 66.8%. Tunnel analysis revealed M1 and M2 have more efficient tunnels for larger product movement compared to wild-typeMesIRED. Using recombinantE. colicoexpressingMesIRED and glucose dehydrogenase (GDH), high conversions were achieved: 75.1% forN-benzylpyrrolidine (M1) and 88.8% forN-benzylpiperidine (M2). A preparative experiment resulted in 86.2% conversion and 60.2% yield forN-benzylpiperidine. This research offers an efficient method for engineering IRED, significantly improving conversion and selectivity forN-benzyl cyclo-tertiary amines, aiding drug synthesis and providing insights into rational design of other enzymes.Keywords:imine reductase;N-benzyl cyclo-tertiary amines;alanine scanning;consensus mutation;whole-cell biocatalysis;coexpression
研究领域:
生物化学
·
酶工程
·
药物合成
✓ 已验证
DOI
高影响因子
Frontiers in Plant Science
·
2025
·
IF 4.8
Zhangting Xu,Guihua Zhang,Feixiong Zheng,Xiaoji Deng,Yiming Sun,Jaime A Teixeira da Silva,Xiaoxia Shen,Zhenming Yu
Introduction Dendrobium is a multi-purpose medicinal orchid that grows on the edge of highaltitude cliffs. The content of water-soluble polysaccharides (WSPs), which primarily play a pharmacological role, is the main criterion for evaluating the quality of Dendrobium orchid. Therefore, it is necessary to study the regulatory manner involved in the accumulation of WSPs. Methods D. officinale were treated with methyl jasmonate (MeJA), and WSPs content was measured at different time points to assess the dynamic accumulation pattern. To clarify the role of one finger (Dof) family genes in the MeJA-mediated WSP metabolic pathway, a bioinformatics analysis identified Dof members in D. huoshanense , D. nobile and D. officinale . Based on expression patterns and co-expression analysis, a regulatory factor, DoDof4 was identified. Results In this study, the elicitation of D. officinale by methyl jasmonate (MeJA) increased WSP production, which was further amplified by extending the treatment period. Analysis of transcriptomic data revealed that members of the DNA-binding with Dof gene family members accounted for 4% of all differentially expressed genes coding for transcription factors, following MeJA induction. To clarify the role of Dof family genes in the MeJA-mediated WSP metabolic pathway, a bioinformatics analysis identified 29, 29 and 22 Dof members in D. huoshanense , D. nobile and D. officinale , respectively and these were divided into four groups. DoDof4 was encoded a 31.16 kDa protein composed of 292 amino acids, and was targeted on chromosome 3. Furthermore, DoDof4 was a typical transcription factor that localized in the nucleus, displayed transcriptional activity and increased the WSPs accumulation. DoDof4 was co-expressed with 15 genes involved in the WSP metabolic pathway, eight of which displayed a positive Pearson's correlation coefficient. Additionally, correlation analysis revealed the possible downstream targets ( KM980199 and KP203853 ) of DoDof4 . Discussion The results of the present study suggest that DoDof4 acts as an important regulator in the WSPs metabolic pathway, exhibiting potential values for the improvement of WSPs in Dendrobium species.
研究领域:
植物学
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分子生物学
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遗传学
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生药学
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植物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）