Molecular Catalysis
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2020
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IF 3.687
Ping Wei,Peng Chao,Yao-Ying Wang,Dong-Li Li,Qing-Jian Zou,Min-Hua Zong,Wen-Yong Lou
( S )-1-Phenyl-1,2-ethanediol (PED) is a vital chiral block in specialty chemical industries. The biotransformation of 2-hydroxyacetophenone (2-HAP) to ( S )-PED was conducted successfully catalyzed with BL21(DE3)(pETDuet- gst -mut- accr - gdh ) which harboring a carbonyl reductase mutant (mut-AcCR). The catalytic activity of the biocatalyst was 15.9 times higher than the recombinant cells harboring original AcCR. 250 mM 2-HAP was reduced, under optimal conditions, and the yield and space-time yield were 95.2 % and 1.89 M/d in the buffer system. Then C 4 MIMI·PF 6 was chosen to be the second phase to improve the catalytic efficiency, and the substrate concentration was increased to 450 mM in the C 4 MIMI·PF 6 /buffer system. After a reaction duration of 3 h, the product yield was over 92 %, and the space-time yield increased to 2.88 M/d which was 1.52 folds higher than that in the buffer system. Also, the product e.e. was over 99 % consistently. Overall, the preparative scale reduction of 2-HAP (450 mM) in C 4 MIMI·PF 6 /buffer system was conducted with promising result. The developed effective C 4 MIMI·PF 6 /buffer system of asymmetric reduction catalyzed by BL21(DE3)(pETDuet- gst -mut- accr - gdh ) will promote the preparation of the enantiomeric pureity chiral alcohol at industrial scale.
研究领域:
生物化学
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工业微生物学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
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2015
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IF 6.723
Jia Yang,Fang Zhou,Rubo Xing,Yuan Lin,Yanchun Han,Chunbo Teng,Qian Wang
The generation of transplantable β-cells from pancreatic progenitor cells (PPCs) could serve as an ideal cell-based therapy for diabetes. Because the transplant efficiency depends on the size of islet-like clusters, it becomes one of the key research topics to produce PPCs with controlled cluster sizes in a scalable manner. In this study, we used inkjet printing to pattern biogenic nanoparticles, i.e., mutant tobacco mosaic virus (TMV), with different spot sizes to support the formation of multicellular clusters by PPCs. We successfully achieved TMV particle patterns with variable features and sizes by adjusting the surface wettability and printing speed. The spot sizes of cell-adhesive TMV mutant arrays were in the range of 50–150 μm diameter. Mouse PPCs were seeded on the TMV-RGD (arginine–glycine–aspartate)-patterned polystyrene (PS) substrate, which consists of areas that either favor (TMV-RGD) or prohibit (bare PS) cell adhesion. The PPCs stably attached, proliferated on top of the TMV-RGD support, thus resulting in the formation of uniform and confluent PPC clusters. Furthermore, the aggregated PPCs also maintained their multipotency and were positive for E-cadherin, indicating that the formation of cell–cell junctions is critical for enhanced cell–cell contact.
研究领域:
生物医学工程
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细胞生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
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2020
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IF 5.186
Xu Chenxi,Zhuang Jianjian,Zhang Xiaobo
P53 is a transcriptional factor that plays important roles in apoptosis and is mutated in more than 50% of tumor cells. However, the restoration of mutated p53 to the level similar to wild-type p53 by a natural compound has not been explored intensively. In this study, the 2-[(4-hydroxybenzyl) amino] phenol (HBAP) compound, obtained from deep-sea virus-challenged thermophile Geobacillus sp. E263, interacted specifically with the mutated p53 protein. HBAP was able to induce apoptosis of p53-mutated breast cancer cells, but not normal breast cells and p53-unmutated breast cancer cells. HBAP activated the mutant p53 transcriptional activity by restoring the function of mutant p53 to that of wild-type p53. Further analysis indicated that HBAP bound only to the DNA binding domain of mutant p53 and that the interaction was dependent on the HBAP hydroxyl groups. In vivo data demonstrated that HBAP was toxicity-free and could suppress tumor growth by inducing tumor cell apoptosis. Therefore our findings revealed that recovering mutated p53 function to that of wild-type p53 caused by HBAP triggered cancer cell apoptosis and that metabolites from deep-sea virus-challenged thermophiles could be a promising source of anti-tumor drugs.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYPERTHERMIA
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2024
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IF 3
Yijin Fan,Xi Wang,Yao Liu,Huajun Tang,Chengzhi Li
Objective In this study, we established a Sprague-Dawley rat model of vulvar squamous intraepithelial lesions and investigated the impact of focused ultrasound on the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and mutant type p53 (mtp53) in the vulvar skin of rats with low-grade squamous intraepithelial lesions (LSIL).Materials and methods The vulvar skin of 60 rats was treated with dimethylbenzanthracene (DMBA) and mechanical irritation three times a week for 14 weeks. Rats with LSIL were randomly allocated into the experimental group or the control group. The experimental group was treated with focused ultrasound, while the control group received sham treatment.Results After 14 weeks treatment of DMBA combined with mechanical irritation, LSIL were observed in 44 (73.33%) rats, and high-grade squamous intraepithelial lesions (HSIL) were observed in 14 (23.33%) rats. 90.91% (20/22) of rats showed normal pathology and 9.09% (2/22) of rats exhibited LSIL in the experimental group at four weeks after focused ultrasound treatment. 22.73% (5/22) of rats exhibited LSIL, 77.27% (17/22) of rats progressed to HSIL in the control group. Compared with the control-group rats, the levels of HIF-1α, VEGF and mtp53 were significantly decreased in experimental-group rats (p < 0.05).Conclusions These results indicate that DMBA combined with mechanical irritation can induce vulvar squamous intraepithelial lesion in SD rats. Focused ultrasound can treat LSIL safely and effectively, prevent the progression of vulvar lesions, and improve the microenvironment of vulvar tissues by decreasing the localized expression of HIF-1α, VEGF, and mtp53 in rats.
研究领域:
肿瘤学
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妇科
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医学影像学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
CURRENT ISSUES IN MOLECULAR BIOLOGY
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2024
·Vol. 46
·期 4
·3694-3712
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IF 2.8
Kai Li,Yuan Wang,Xiao Guo,Bo Wang
Establishing a multi-enzyme synergistic lignocellulosic biodegradation system using lytic polysaccharide monooxygenase (LPMO) and polyphenol oxidases is vital for efficiently utilizing plant biomass waste, ultimately benefiting the carbon cycle and promoting environmental protection. Single-residue mutations of LPMO can improve the efficiency of lignocellulosic biomass degradation. However, the activity of mutant-type LPMO in relation to lignin-diverted reducing agents has not been sufficiently explored. In this study, laccase and tyrosinase were initially investigated and their optimal conditions and impressive thermal stability were revealed, indicating their potential synergistic abilities with LPMO in lignocellulose biodegradation. When utilizing gallic acid as a reducing agent, the activities of LPMOs were increased by over 10%, which was particularly evident in mutant-type LPMOs after the addition of polyphenol oxidases. In particular, the combination of tyrosinase with either 4-hydroxy-3-methoxyphenylacetone orp-coumaric acid was shown to enhance the efficacy of LPMOs. Furthermore, the highest activity levels of wild-type LPMOs were observed with the addition of laccase and 3-methylcatechol. The similarities between wild and mutant LPMOs regarding their activities in lignin-diverted phenolic compounds and reducing agents are almost identical, suggesting that the single-residue mutation of LPMO does not have a detrimental effect on its performance. Above all, this study indicates that understanding the performance of both wild and mutant types of LPMOs in the presence of polyphenol oxidases and various reducing agents constitutes a key link in the industrialization of the multi-enzyme degradation of lignocellulose.
研究领域:
生物技术
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生物化学
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环境科学
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酶学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2021
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IF 7.46
Jiaying Zhao,Danqun Huo,Xintong Geng,Jing Bao,Jingzhou Hou,Zhengfan Shui,Huisi Yang,Yanli Qi,Yian Hu,Mei Yang,Changjun Hou
p53 gene is one of the most important anticancer genes and has been recognized as a typical biomarker for the early diagnosis, classification, and prognosis evaluation of cancers. In this work, a novel biosensing strategy integrating MoS 2 -AuNPs modified carbon paper (CP) conductive substrate and enzyme signal amplification technique was developed for p53 gene detection. We constructed an immobilized DNA S1 probe and a biotinylated DNA S3 probe, which could induce the formation of an S1-p53-S3 DNA sandwich complex in the presence of target sequence p53. After conjugating avidin-HRP via biotin-avidin reaction, 3,3’,5,5’-tetramethylbenzidine would be catalyzed for signal amplification in the presence of H 2 O 2 so that the induced electrochemical response would change with proportional to the abundance of p53 gene. The proposed biosensor exhibited two linearities in the range of 1.0 × 10 −15 ∼ 1.0 × 10 -12 M and 1.0 × 10 -12 ∼ 1.0 × 10 -6 M, and the limit of detection (LOD) was 68 fM. No significant interferences were observed during detecting real serum samples. Moreover, it is worth pointing out that the biosensor together with its disposable, low-cost, and stable features can discriminate well between the mutated and wild type p53 gene extracted from tumor cells (wtTP53 in MCF-7 and mutated in SK-BR-3), demonstrating a promising applicability for clinical test.
研究领域:
生物传感器
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癌症诊断
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纳米技术
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电化学
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分子生物学
✓ 已验证
DOI
高影响因子
TALANTA
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2019
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IF 4.916
Ni Zeng,Juan Xiang
KRAS G12D point mutation plays an important role in the incidence of non-small-cell lung cancer (NSCLC) as well as colorectal cancer, pancreatic cancer and breast cancer. Here, we developed a novel anchor-like DNA (alDNA) electrochemical sensor for the detection of KRAS point mutation level (the concentration ratio of the specific KRAS point mutant DNA (M-DNA) to the total DNA (t-DNA) of both mutant and wild-type DNAs carrying the same allele). Compared to those conventional ligation-based DNA sensors, the proposed alDNA sensor achieved the one-step capture of both wild-type and mutant DNA, and the subsequent detection on one chip, which effectively decreased systematic errors from the uncertain differences on the interfacial structural and microenvironmental changes, improved the detection accuracy. Also, with the usage of formamide-NaCl solution, the whole detection process including the denaturation of double-stranded DNA was performed under mild temperature conditions (~40 °C). It greatly decreased the cost and improved the reproducibility and feasibility of the method. Based on it, the linear correlations with the logarithm of concentration in wide range from 0.1 pM to 10 nM for t-DNA and from 100 pM to 10 nM for M-DNA were achieved, respectively. The analysis of t-DNA- and M-DNA-spiked human serum samples revealed the high accuracy of the method. This alDNA sensor is convenient, low-cost and time-saving, with broad dynamic range, high sensitivity and selectivity . It can meet the demands of the clinical detection on the KRAS point mutation level in blood samples, which means significant for the earlier NSCLC diagnosis, individualized treatment, and therapeutic efficacy evaluation.
研究领域:
癌症生物学
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分子诊断学
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电化学
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临床化学
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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）