CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Dezhi Feng,Chengtao Xu,Biao Ma,Chao Zhao,Hong Liu
Chemically synthesized DNA has been considered a promising medium for data storage. Among various methods, electrochemical synthesis is simple and easy to miniaturize, attracting much attention. However, conventional DNA synthesis uses phosphoramidite chemistry involving multi-step liquid-phase reactions and complicated liquid manipulation, restricting scalability and practical application. Here, we report the quasi-solid-state electrochemical DNA synthesis based on gels. All reagents required for different synthesis steps are contained in separate gels without mixing or dilution. Instead of complicated liquid manipulation, DNA synthesis on the electrode requires only relative motion between the electrode and gels. Similarly, blank gels with only acetonitrile are reused to clean the electrode surface without washing with plenty of liquid. We demonstrate our method is scalable using an electrode array for parallel DNA synthesis.
研究领域:
数据存储
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电化学
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分子生物学
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生物技术
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产品关联
DOI
高影响因子
BIOCHEMISTRY
·
2018
·
IF 2.997
Qianwei Zhao,Wen Yang,Tong Qin,Zhen Huang
RNA is a key player in the cellular central dogma, including RNA transcription and protein synthesis. However, it is unknown whether RNA can directly interfere with DNA synthesis. Recently, we have found in vitro that while binding to DNA polymerase nonspecifically, RNA can transform DNA polymerase to display a moonlighting activity, dNTP phosphatase, in turn interfering with DNA synthesis. This phosphatase activity removes the γ-phosphate from dNTPs (generating dNDPs) and subsequently removes the β-phosphate from the formed dNDPs (generating dNMPs), confirmed by the noncleavable α,β-CH2-dGTP and β,γ-CH2-dGTP analogues. We also found that dGTP is the best substrate for the phosphatase, and the dNTP phosphatase activity is sensitive to the reaction medium. In addition, we have revealed that RNA can tune the activity of closely related proteins and give rise to new catalytic functions with subtle differences. Moreover, we have demonstrated in vitro that at the lower dNTP level, this phosphatase can directly inhibit DNA synthesis by dNTP depletion, though the phosphatase activity is 690-fold slower than the polymerase activity. Our observation in vitro suggests a plausible strategy for RNA to directly interfere with DNA polymerase and DNA synthesis in vivo.
研究领域:
分子生物学
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生物化学
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DOI
PubMed
高影响因子
NATURE BIOTECHNOLOGY
·
2025
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IF 41.7
Zhang Xiandi,Jiang Xiang’er,Wang Yun,Chen Qinzhen,Jiang Hao,Zhang Hu,Beltran Antoni,Yang Weiya,Chen Tai,Liang Chenglong,Cheng Ning,Huang Yun,Ding Guqiao,Xie Chengwang,Gao Nanfeng,Liu Juntao,Xu Wei,Huang Jinlei,Cai Dong,Zhu Lihao,Mo Songjin,Shen Mengzhe,Zhang Wenwei,Lehner Ben,Ni Ming,Wang Jian,Xu Xun,Shen Yue
Current high-throughput DNA synthesis technologies use intricate chip and microfluidic systems to produce large-scale synthetic oligonucleotides but with low concentration and limited compatibility for long DNA assembly. Here we report a massive-in-parallel synthesis system, with an ‘identification–sorting–synthesis–recycling’ iteration mechanism applied to microchips for high-throughput DNA synthesis. This approach increases DNA product concentration by four to six orders of magnitude and simplifies downstream processes for large-scale gene synthesis.
研究领域:
分子生物学
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合成生物学
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生物技术
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基因工程
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高通量筛选
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING SCIENCE
·
2023
·
IF 4.7
Xiao Su,Xiaoping Li,Yi Zhang,Qing Guo,Xingguo Zhang,Haixia Yu,Dachao Li
This paper presents a facile and cost-effective fabrication method of microreactor array chip for high-throughput DNA synthesis with three orders of mangnitude enhancement in synthesis capacity. Inkjet printing was used to dispense a massive droplet array of silica nanoparticle slurry on chemically-modified surface. Dense microreactor array can be simply obtained by following the procedure of three-phase contact line (TCL)-confined nanoparticle aggregating, which is dominated by the receding contact angle (RCA) of the modified substrates. Chip with RCAs greater than 90° transfers the resultant force to a lifting statu as well as enhances the inward force effect, which leading to a dense and compact packing synergistically on limited chip area. Herein, a consequential increasement in effective reaction area contributes to the significant enhancement in synthesis capacity as compared to a planar or porous substtrate. The proposed microarray chip demonstrates great prospects for both high-throughput and high-capacity DNA synthesis.
研究领域:
生物技术
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材料科学
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化学工程
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 11
·期 1
·99-108
·
IF 7.571
Yongtao Wang,Nana Wang,Yazhou Chen,Yingjun Yang
Breast cancer is considered as a worldwide disease due to its high incidence and malignant metastasis. Although numerous techniques have been developed well to conduct breast cancer therapy, the influence of micropattern-induced interfacial heterogeneity on the molecular mechanism and nuclear signalling transduction of carcinogenesis is rarely announced. In this study, PDMS stencil-assisted micropatterns were fabricated on tissue culture plates to manage cell clustering colony by adjusting initial cell seeding density and the size of microholes. The curvature of each microholes was controlled to construct the interfacial heterogeneity of MDA-MB231 cancer cells at the periphery of micropatterned colony. The distinguished focal adhesion (FA) and cytoskeleton distribution at the central and peripheral regions of the cell colony were regulated by heterogeneous properties. The interfacial heterogeneity of FA and cytoskeleton would induce the biased tension force to encourage more ezrin expression at the periphery and further promote DNA synthesis, therefore disclosing a stem-like phenotype in heterogeneous cells. This study will provide a value source of information for the development of micropattern-induced heterogeneity and the interpretation of metastatic mechanism in malignant breast cancer cells.
研究领域:
癌症生物学
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细胞生物学
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生物医学工程
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Hydrocolloids for Health
·
2024
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IF 4.6
Zhongcan Peng,Shurong Tian,Depo Yang,Longping Zhu,Jianing Zhang,Wenfeng Li,Guodong Zheng,Zhimin Zhao
ABSTRACT Citri Reticulatae Pericarpium ‘Chachi’ ( Citrus reticulata ‘Chachi’) is a traditional Chinese medicine with dual medicinal and dietary uses. As its main component, pectin exhibited various biological activities. However, research and development on it, especially pectin oligosaccharides, remain limited. In this study, ‘Chachi’ pectin oligosaccharides (CPOS) was extracted and prepared for the first time, resulting in the purification of two oligosaccharide components, CPOS3 and CPOS4. Structural characterization of the predominant oligosaccharide, CPOS3, revealed it to be composed of a backbone α-D-Gal p A-(1→2)-α-L-Rha p -(1→4)-α-D-3-OAc-Gal p A-(1→4)-α-D-Gal p A-(1→4)-α-D-Gal p A and a side chain [→5)-α-L-Ara f -(1→] 4 attached at the C-4 of Rha p . Subsequent experiments have shown that CPOS3 can significantly promote the proliferation and migration of human immortalized keratinocyte cell. Further investigation revealed that it facilitated cell proliferation by stimulating DNA synthesis in the S phase of the cell cycle. Additionally, CPOS3 exhibited good thermal stability and rheological characteristics. Based on the good wound healing activity and favorable physicochemical properties of CPOS3, its prospects in the fields of wound dressings and tissue repair are promising.
研究领域:
药理学
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细胞生物学
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伤口愈合
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生物医学工程
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产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Dezhi Feng,Biao Ma,Chengtao Xu,Jingyi Xu,Yiyang Zhang,Yi Chen,Gangsheng Chen,Yakun Gao,Duxin Chen,Wenwu Yu,Chao Zhao,Hong Liu
Synthetic DNA is essential for various areas. Array-based synthetic technologies have been developed, and owing to scalability their synthetic throughput can be dramatically increased with reduced time and cost. However, the traditional arrays are usually fabricated on solid and rigid substrates which can hardly be renewed, their scalability is still limited, which hinders further advance of the synthetic technology. Here, a renewable array based on transformable gallium (Ga) electrode for DNA synthesis and facilitate its downstream manipulation is reported. After the DNA synthesis based on electrochemically triggered phosphoramidite chemistry on the Ga electrode, the electrode can be simply renewed by converting its tip into a drop of liquid metal (LM) so that the remaining electrode can be used for a new synthetic cycle. It also found that by repeated deformations of the LM drop, producing increased oxidation layer on the Ga, the surface DNA can be encapsulated within the LM drop for protection and easy manipulation. It is demonstrated that programmable DNA synthesis and manipulation can be accomplished on a microfluidic chip, which can be used for highthroughput, low-cost DNA synthesis and manipulation for data storage.
研究领域:
合成生物学
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生物电子学
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纳米技术
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微流控技术
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分子生物学
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产品关联
DOI
高影响因子
Green Energy & Environment
·
2021
·
IF 8.207
Liteng Li,Xiaofang Li,Susu Zhang,Hongyuan Yan,Xiaoqiang Qiao,Hongyan He,Tao Zhu,Baokun Tang
Acrylic acid (AA) is an important and widely used industrial chemical, but its high toxicity renders its use incompatible with the concept of green development. By leveraging its terminal carboxyl group and unsaturated bond, we designed and explored a new strategy to increase the greenness of AA via its eutectic melting using a quaternary ammonium salt (choline chloride) to form a deep eutectic solvent (DES), followed by polymerisation of the DES to form a polymer (poly(DES)). The greenness of AA, DES, and poly(DES) was evaluated via an in vitro test using MGC80-3 cells and an in vivo test using Kunming mice. The toxicity improved from Grade 2 (moderately toxic) for AA to Grade 1 (slightly toxic) for DESs and Grade 0 (non-toxic) for poly(DES) in the in vitro test. Moreover, the poly(DES)s showed a lower toxicity in mice than the DESs in the in vivo test. Thus, greenness enhancement was successfully achieved, with the greenness following the order AA < DES < poly(DES). Furthermore, the mechanisms underlying the change in toxicity were explored through microscopy and flow cytometry, which revealed that the DES can permeate the MGC80-3 cell membrane during the G 0 /G 1 phase to adversely affect DNA synthesis in the S phase, but the poly(DES) cannot. Finally, the green poly(DES), which showed good adsorption properties and flexible functionality, was successfully applied as a carrier or excipient of drugs. Through the novel strategy reported herein, greenness enhancement and the broadening of the application scope of a toxic organic acid were achieved, making such acids applicable for green development.
研究领域:
化学工程
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材料科学
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毒理学
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生物技术
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产品关联
DOI
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Likun Yan,Xiao Zhang,Jie Fu,Qiang Liu,Xiaohua Lei,Zhenyu Cao,Ju Zhang,Yaoli Shao,Qing Tong,Wei Qin,Xinxu Liu,Chun Liu,Zhiqiang Liu,Zhenghao Li,Jueliang Lu,Xundi Xu
Transient receptor potential vanilloid 3 (TRPV3) is a member of the TRP superfamily. Previous studies have demonstrated that TRPV3 is associated with myocardial fibrosis. However, the role of TRPV3 in hepatic fibrosis and its underlying mechanisms are still unclear. This study aimed to elucidate the underlying effects of TRPV3 on hepatic fibrosis at multiple biological levels. First, immunohistochemical staining was performed to examine TRPV3 expression in human hepatic cirrhosis tissues. Then, we established a CCl 4 -induced hepatic fibrosis mouse model. The TRPV3 selective agonist drofenine and its inhibitor, forsythoside B, were intraperitoneally injected to investigate the relationship between TRPV3 and liver fibrosis progression. Finally, in vitro studies were performed using hepatic stellate cells (HSCs) to discover the potential molecular biological mechanisms. Immunohistochemistry revealed TRPV3 overexpression in liver cirrhosis. In the liver fibrosis groups, TRPV3 inhibitor treatment significantly reduced liver fibrosis, while TRPV3 agonist exacerbated its progression. In HSCs, knocking down TRPV3 with siRNA impaired DNA synthesis and cell proliferation and increased cell apoptosis. Furthermore, we found that knockdown of TRPV3 could reduce the lectin like oxidized lowdensity lipoprotein receptor-1 (LOX-1) protein levels. Our research suggests that lower expression or functional levels of TRPV3 can ameliorate the inflammatory response and fibrotic tissue proliferation.
研究领域:
药理学
·
肝病学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2021
·
IF 5.858
Mingming Sun,Hao Sheng,Tingfeng Wu,Jiaqi Song,Huanran Sun,Yingzhi Wang,Jiyan Wang,Zhen Li,Huifang Zhao,Junzhen Tan,Yanping Li,Guo Chen,Qingrong Huang,Yuan Zhang,Bei Lan,Shuangping Liu,Changliang Shan,Shuai Zhang
Reprogramming of energy metabolism is a hallmark of cancer, and the pentose phosphate pathway (PPP) is a major glucose metabolic pathway important for meeting the cellular demands of biosynthesis and anti-oxidant defense. Our previous study showed that phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) plays an important role in glioblastoma cell survival and growth under cellular energy stress condition. However, the crucial functions of PIKE-A in cancer energy metabolism are poorly understood. In the present study, we show that PIKE-A promotes DNA biosynthesis, NADPH production and inhibits reactive oxygen species (ROS) production, leading to increasing proliferation and growth of glioblastoma cell and suppressing cellular senescence. Mechanistically, PIKE-A binds to STAT3 and stimulates its phosphorylation mediated by tyrosine kinase Fyn , which enhances transcription of the rate-limitting enzyme glucose-6-phosphate dehydrogenase (G6PD) in the PPP. Finally, targeting PIKE-A-G6PD axis sensitizes glioblastoma to temozolomide (TMZ) treatment. This study reveals that STAT3 is a novel binding partner of PIKE-A which recruits Fyn to phosphorylate STAT3, contributing to the expression of G6PD, leading to promoting tumor growth and suppressing cellular senescence. Thus, the PIKE-A/STAT3/G6PD axis strongly links the PPP to carcinogenesis and may become a promising cancer therapeutic target.
研究领域:
癌症生物学
·
分子生物学
·
细胞生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2023
·
IF 5.1
Shuai Wang,Jian-Tao Shi,Xing-Rong Wang,Hong-Xia Mu,Xue-Ting Wang,Kai-Yan Xu,Qing-Shan Wang,Shi-Wu Chen
The PI3K/AKT/mTOR signaling pathway is one of the most common abnormal activation pathways in tumor cells, and has associated with multiple functions such as tumor cell growth, proliferation, migration, invasion, and tumor angiogenesis. Here, a series of 3-amino-1 H -indazole derivatives were synthesized, and their antiproliferative activities against HT-29, MCF-7, A-549, HepG2 and HGC-27 cells were evaluated. Among them, W24 exhibited the broad-spectrum antiproliferative activity against four cancer cells with IC 50 values of 0.43–3.88 μM. Mechanism studies revealed that W24 inhibited proliferation by affecting the DNA synthesis, induced G 2 /M cell cycle arrest and apoptosis by regulating Cyclin B1, BAD and Bcl-xL, meanwhile induced the change of intracellular ROS and mitochondrial membrane potential in HGC-27 cells. Moreover, W24 inhibited the migration and invasion of HGC-27 cells by decreasing EMT pathway related proteins and reducing the mRNA expression levels of Snail, Slug and HIF-1α. Furthermore, W24 displayed low tissue toxicity profile and good pharmacokinetic properties in vivo . Therefore, 3-amino-1 H -indazole derivatives might serve as a new scaffold for the development of PI3K/AKT/mTOR inhibitor and anti-gastric cancer reagent.
研究领域:
肿瘤学
·
药理学
·
化学
·
细胞生物学
·
分子生物学
✓ 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）