METABOLIC ENGINEERING
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2020
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IF 7.263
Xi Deng,Liuqing Chen,Mohan Hei,Tiangang Liu,Yan Feng,Guang-Yu Yang
Medium-chain fatty acids (C6–C10) have attracted much attention recently for their unique properties compared to their long-chain counterparts, including low melting points and relatively higher carbon conversion yield. Thioesterase enzymes , which can catalyze the hydrolysis of acyl-ACP (acyl carrier protein) to release free fatty acids (FAs), regulate both overall FA yields and acyl chain length distributions in bacterial and yeast fermentation cultures. These enzymes typically prefer longer chain substrates. Herein, seeking to increase bacterial production of MCFAs, we conducted structure-guided mutational screening of multiple residues in the substrate-binding pocket of the E. coli thioesterase enzyme ‘TesA. Confirming our hypothesis that enhancing substrate selectivity for medium-chain acyl substrates would promote overall MCFA production, we found that replacement of residues lining the bottom of the pocket with more hydrophobic residues strongly promoted the C8 substrate selectivity of ‘TesA. Specifically, two rounds of saturation mutagenesis led to the identification of the ‘TesA RD−2 variant that exhibited a 133-fold increase in selectivity for the C8-ACP substrate as compared to C16-ACP substrate. Moreover, the recombinant expression of this variant in an E. coli strain with a blocked β -oxidation pathway led to a 1030% increase in the in vivo octanoic acid (C8) production titer. When this strain was fermented in a 5-L fed-batch bioreactor , it produced 2.7 g/L of free C8 (45%, molar fraction) and 7.9 g/L of total free FAs, which is the highest-to-date free C8 titer to date reported using the E. coli type II fatty acid synthetic pathway. Thus, reshaping the substrate binding pocket of a bacterial thioesterase enzyme by manipulating the hydrophobicity of multiple residues altered the substrate selectivity and therefore fatty acid product distributions in cells. Our study demonstrates the relevance of this strategy for increasing titers of industrially attractive MCFAs as fermentation products.
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高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Ri-Tong Lan,Yue Ren,Xin Wei,Li-Zhi Tang,Nouman Ali Shah,Lu Xu,Shi-Shu Huang,Rizwan M. Gul,Jia-Zhuang Xu,Zhong-Ming Li
Oxidative stability of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) artificial joints is significantly improved by vitamin E (VE), but there is a dilemma that VE hinders crosslinking and thus jeopardizes the wear of UHMWPE. In this effort, we proposed an efficient strategy to stabilize UHMWPE under limited antioxidant contents, where VE and D-sorbitol (DS) were used as the primary antioxidant and the secondary antioxidant respectively. For non-irradiated blends with fixed antioxidant contents, oxidative stability accessed by oxidation induction time (OIT) of VE/DS/UHMWPE blends was superior to that of VE/UHMWPE blends, while DS/UHMWPE blends showed no increase in OIT. The cooperation between DS and VE exhibited a synergistic effect on enhancing the oxidative stability of UHMWPE. Interestingly, the irradiated VE/DS/UHMWPE blends showed comparable OIT but a significantly higher crosslink density than the irradiated VE/UHMWPE blends. The crystallinity, melting point, and in vitro biocompatibility of the blends were not affected by VE and DS. The quantitative relationships of mechanical properties , oxidation stability, crystallinity and crosslink density were established to unveil the correlation of these key factors. The overall properties of VE/UHMWPE and VE/DS/UHMWPE blends were compared to elucidate the superiority of the antioxidant compounding strategy. These findings provide a paradigm to break the trade-off between oxidative stability, crosslink density and mechanical properties, which is constructive to develop UHMWPE bearings with upgraded performance for total joint replacements. Statement of significance VE-stabilized UHMWPE is the most commonly used material in total joint replacements at present. However, oxidation and wear resistance of VE/UHMWPE implants cannot be unified since VE reduces the efficiency of radiation crosslinking. It limits the use of VE. Herein, we proposed a compounding stabilization by the synergy between VE and DS. The antioxidation capability of VE was revived by DS, thus enhancing the oxidation stability of unirradiated UHMWPE. The irradiated VE/DS/UHMWPE exhibited similar oxidation stability but higher crosslink density than irradiated VE/UHMWPE, which is beneficial to combat wear of UHMWPE and to inhibit the occurrence of osteolysis . This synergistic antioxidation strategy endows the UHMWPE joint material with good overall performance, which is of clinical significance.
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EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2019
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IF 3.532
Lin Hou,Chunyu Tian,Dandan Chen,Yujie Yuan,Yingshan Yan,Qianxiao Huang,Huijuan Zhang,Zhenzhong Zhang
Multidrug resistance (MDR) is a major reason for anticancer chemotherapy failure, and P-glycoprotein (P-gp) over-expressing on tumor cells is considered as the important target to overcome MDR. Emerging reports have showed that vitamin E (VE) can cause significant reversal of MDR due to inhibition of ATPase activity . Accordingly, we synthesized hyaluronic acid (HA) conjugated vitamin E succinate (VES) polymer, which can self-assemble into micelles and thus achieve high drug (paclitaxel (PTX) used as model drug) encapsulation as well as tumor accumulation owing to the enhanced permeability and retention (EPR) effect and HA active targeting ability. In addition, the linker between HA and VES utilized in this work was disulfide bond with reduction-sensitive property, which would respond to high glutathione (GSH) concentration in tumor cytoplasmic environment and trigger HA-CYS-VES polymer disassociation and drug release. In vitro , PTX loaded HA-CYS-VES demonstrated enhanced cytotoxicity, high apoptosis-inducing activities and reversal effects of PTX on MCF-7/Adr cells, compared to PTX. Also, cellular uptake and intracellular PTX accumulation tests displayed that PTX loaded HA-CYS-VES could more efficiently enter tumor cells and selectively release drug in cytosol so as to facilitate its function on microtubule. More importantly, PTX loaded HA-CYS-VES showed better tumor targeting ability, improved antitumor efficacy and low adverse effects on tumor-bearing mice. In conclusion, PTX loaded HA-CYS-VES exhibited a great potential for reversing MDR in anticancer chemotherapeutics.
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CHEMICAL ENGINEERING JOURNAL
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2019
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IF 8.355
Xiaolan Zhou,Dong Xu,Yuancai Chen,Yongyou Hu
Mn/Fe@porous carbon (PC) was successfully fabricated through a simple carbonization of Mn-doped MIL-53(Fe) precursor and used as cathode modification in hydroxyl radical ( OH) based heterogeneous electro-Fenton (hetero-EF) process for triclosan (TCS) degradation. With co-doping of bimetal (Mn and Fe) in porous carbon, Mn/Fe@PC could markedly enhance the electrocatalysis with low oxygen reduction potential, high electrochemical active area and low resistance. Mn/Fe@PC modified cathode showed high electrocatalytic activity, great stability and low energy consumption (1.92 kWh m −1 and 0.63 kWh log −1 m −3 ) for TCS degradation over a wide pH range. The complete TCS degradation within 120 min and a 56.9 ± 2.0% TOC removal within 240 min were achieved under the condition of current 40 mA and initial pH 3. Based on the CV curves, the more negative reductive peak of Fe and Mn revealed the kinetically beneficial regeneration of Fe II /Mn II/III in Mn/Fe@PC. The electron transfer between Fe II/III and Mn II/III/IV , together with the direct regeneration of Fe II / Mn II/III on the cathode, could markedly promote the utilization of H 2 O 2, eventually leading to facilitating TCS degradation. According to the GC–MS intermediates, the possible TCS degradation pathway was deduced, including hydroxylation and dehalogenation attacked by OH. Furthermore, the TCS degradation experiments were also performed in different water matrix including river water, tap water and municipal sewage, indicating the feasibility of the TCS degradation in actual waters with Mn/Fe@PC-CP cathode in hetero-EF process. The toxicity analysis indicated that the hetero-EF process could achieve the TCS degradation and toxicity reducing.
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CHEMICAL ENGINEERING JOURNAL
·
2018
·
IF 6.735
Hui Wang,Yanwen Shen,Ziyang Lou,Nanwen Zhu,Haiping Yuan,Chunnan Liu
Concentrated leachate is collected from two-stage anaerobic/aerobic-membrane bioreactor (MBR) and nanofiltration (NF) unit in landfill leachate treatment process and featured with non-biodegradation compounds and high salts content. E + -ozonation process was developed and introduced to deal with concentrated leachate, to make good use of chlorine ions (Cl − ) and the associated O 2 during ozonation process. 74.5% and 69.7% of COD and TOC were removed in E + -ozonation under the optimum conditions with initial pH of 9 and current density of 30 mA∙cm −2 , and the corresponding enhancement factors were 1.36 and 1.13, compared to the sum of the electrolysis and ozonation individual. The co-generation of reactive oxygen species (ROS) and reactive chlorine species (RCS) made a complementary effect on the degradation of refractory substances presented in concentrated leachate. 10.1% of total COD removal was improved by non-radical RCS generated in situ and 6.5% of total COD removal was achieved by ● OH-enhanced and Cl /ClO -emerged. With the help of electrolysis, the OH quencher of Cl − was converted into non-radical RCS (such as Cl − , ClO − and Cl 2 ) at anode, and the un-reacted O 2 /O 3 was reduced into OH at the cathode simultaneously. E + -ozonation offers a synergetic degradation potential for special wastewater with refractory matters and high Cl − content.
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ACS Sustainable Chemistry & Engineering
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2018
·
IF 6.14
Hongye Cheng,Jiangsheng Li,Jingwen Wang,Lifang Chen,Zhiwen Qi
To enhance the extraction selectivity of vitamin E (VE) from the deodorizer distillate, a biphasic system with solvents of both organic chemical and the salt tetrabutylammonium chloride ([N4,4,4,4]Cl) was established. The organic solvent was tailored to extract the major component of deodorizer distillate (methyl linoleate), while the organic salt was designed to selectively extract VE by in situ forming a deep eutectic solvent. Three types of organic solvents, namely, ester, arene, and alkane, were analyzed by using the COSMO-RS model, and hexane, exhibiting stronger interaction with methyl linoleate and lower solubility of [N4,4,4,4]Cl, was screened and its suitability explained from the σ-profile and σ-potential points of view. The biphasic experiments demonstrated that the selectivity of VE by the one-pass extraction process was significantly enhanced by the biphasic system, and the important operation parameters of the dosage of solvent and initial concentration of VE were analyzed.
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高影响因子
Science Bulletin
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2016
·
IF 0
Bo-Ya Liu,Cong Wu,Xiao-Yan He,Ren-Xi Zhuo,Si-Xue Cheng
A facile self-assembly strategy to fabricate vitamin E-tocopheryl polyethylene glycol succinate (TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome multi-drug resistance, a chemotherapeutic agent (paclitaxel, PTX) and a drug resistance inhibitor (tariquidar, TQR) were co-loaded in the vitamin E-TPGS based nanoparticle to obtain TPGS/PTX/TQR nanoparticles. The sizes of mono-drug loaded TPGS/PTX nanoparticles and dual-drug loaded TPGS/PTX/TQR nanoparticles were below 150 nm with relatively narrow size distributions. The efficiencies of the drug delivery systems on tumor cells inhibition and reversal of drug resistance were evaluated in drug resistant cancer cells (MCF-7/ADR) as compared with nonresistant cells (HeLa). Due to the effective inhibition of the P-gp efflux by TQR, the dual-drug loaded nanoparticles exhibited significantly improved tumor cell inhibitory efficiency. To study the immunostimulatory effect, the effect of the drug delivery system on the production of IL-10, a cytokine related to tumor development, in the drug resistant cells was determined. After the treatment by the drug delivery systems, the concentration of IL-10 in the cell supernatant decreased. The multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery have promising applications in reversal of drug resistance in tumor treatments.
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JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
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2017
·Vol. 106
·期 5
·1827-1841
·
IF 3.189
Yikun Yang,Chunyi Tong,Juchang Zhong,Ruiying Huang,Weihong Tan,Zhikai Tan
Magnetic hyperthermia has been rapidly developed as a potential cancer treatment in recent years. Artificially induced hyperthermia close to a tumor can raise the temperature to 45°C causing tumor cell death. Herein, we introduce a novel method for rapid preparation of anti-cancer magnetocaloric PCL/Fe 3 O 4 mats capable of high-performance hyperthermia using E-jet 3D printing technology. Our 3D printed mats not only maintained the heating efficiency of traditional techniques for magnetic hyperthermia but also prolonged the effective therapy in vivo . When Fe 3 O 4 nanoparticles (NPs) were used in mats at a concentration of 6 mmol/L, 0.07 g PCL/Fe 3 O 4 mats were able to increase the temperature peripherally to 45°C under an alternating magnetic field (AMF) within 45 min. Moreover, the reproducibility experiment indicated that the maximum temperature was achieved following repeated heating and cooling cycles. Cell toxicity tests showed a high cell death rate during one treatment cycle. In vivo experiments indicated clear signs of tumor growth inhibitory and prolonged survival time of tumor-bearing mice after 4 weeks of treatment. The present magnetic mats may be a potential candidate for a novel heat-generating substrate for localized hyperthermia cancer therapy. Furthermore, the main advantage of such implantable magnetic mats is the local and precise delivery of Fe 3 O 4 NPs, ideal for the hyperthermia treatment of easily accessible tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1827–1841, 2018.
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Chemical Science
·
2024
·
IF 7.6
Wei-Xing Chen,Zi-Sheng Li,Harry W. T. Morgan,Cong-Cong Shu,Zhong-Ming Sun,John E. McGrady
We report here the synthesis and characterization of two endohedral Zintl-ion clusters, [Fe4Sn18]4− and [Fe4Pb18]4−, which contain rhombic Fe4 cores. The Fe–Fe bond lengths are all below 2.5 Å, distinctly shorter than in the corresponding Cu clusters, indicating the presence of Fe–Fe bonding. Subtle differences in the structure of the Fe4 core between the two clusters suggest that the change in tetrel element causes a change in electronic ground state, with a very short Fe–Fe bond length of 2.328 Å present across the diagonal of the rhombus in the lead case.
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RSC Advances
·
2024
·Vol. 14
·期 21
·15106-15111
·
IF 3.9
Weiyun Guo,Chaoyun Wu,Guanghui Li,Yonghui Wang,Shenghua He,Jihong Huang,Xueli Gao,Xiaoyue Yue
Glutathione (GSH) as an antioxidant greatly attenuates the reactive oxygen species (ROS) treatment strategy based on peroxidase-activity nanozymes. Therefore, nanozymes with multiple properties that generate ROS and further GSH-depletion functions would be of great benefit to improve antimicrobial efficacy. Herein, focusing on the green, safe and abundant functional prospects of metal–phenolic networks (MPNs) and the strong prospect of biomedical applications, we have synthesized copper tannic acid (CuTA) nanozymes with dual functional properties similar to peroxidase-like activity and GSH depletion. CuTA can catalyze the decomposition of H2O2 to hydroxyl radicals (˙OH). In addition, CuTA nanozymes can efficiently deplete available GSH, thus enhancing ROS-mediated antimicrobial therapy. The antibacterial results show that CuTA has an excellent antibacterial effect against E. coli.
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JOURNAL OF MOLECULAR LIQUIDS
·
2024
·
IF 5.3
Huixiang Zhang,Yang Zhang,Fumin Xue,Hui Chen,Zhenguo Gao,Shichao Du,Yan Wang
Valsartan is an angiotensin II receptor antagonist used to treat hypertension. Crystals of valsartan were prepared and the stability of the valsartan (form E) at different solvents and temperatures was investigated. The solid-liquid equilibrium solubility of valsartan (form E) in twelve pure solvents was determined by a dynamic method at the temperature from 278.15 K to 323.15 K. Among the solvents used in the experiment, the solubility of valsartan (form E) was found to be highest in methanol and lowest in acetonitrile. In straight-chain alcohols, the solubility decreases with the increase of carbon chain length. The modified Apelblat model, λh model and NRTL model were used to correlate the solubility data. The thermodynamic properties of the mixing process such as Gibbs free energy, enthalpy and entropy were estimated by applying the NRTL model. The KAT-LSER model was adopted to explore solvent effects. Hirshfeld surface analysis and molecular electrostatic potential (ESP) were employed to visualize close contacts and charge distribution of valsartan and solvents. In addition, molecular dynamics (MD) simulation was performed to calculate intermolecular interactions between solute and solvent. Radial distribution function (RDF) and the mean square displacement (MSD) analyses were also carried out to explore molecular association and molecular diffusion.
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TRANSACTIONS OF TIANJIN UNIVERSITY
·
2018
·Vol. 24
·期 3
·263-271
·
IF 0
Zhang Xubin,Hao Zhencheng,Yang Chaoqun,Ahishakiye Rosine,Wang Fumin
In this paper, 2,3,5-trimethyl-1,4-benzoquinone (TMBQ) was synthesized through the direct oxidation of 1,2,4-trimethylbenzene (pseudocumene, TMB) in the HCOOH–H 2 O 2 system. The influence of three active species was studied, including performic acid (PFA) generated in formic acid, peracetic acid (PAA) generated in acetic acid, and trifluoroperacetic (TFPA) acid generated in trifluoroacetic acid. The effects of sulfuric acid and sodium formate addition were investigated, the over-oxidation of TMB was discussed, and the main reason for the decreasing selectivity was revealed. The oxidation of TMB can be controlled and improved through adjusting the reaction temperature, mole ratio of oxidant to substrate, and reactant concentration. The TMBQ yield of 28% was achieved with a TMB concentration of 0.2 mol/L, H 2 O 2 /TMB mole ratio of 6:1, and reaction temperature 37 °C. The selectivity of 72% was obtained with a TMB concentration of 0.2 mol/L, H 2 O 2 /TMB mole ratio of 5:1, and reaction temperature of 27 °C. The reaction mechanisms were proposed and discussed based on the gas chromatography–flame ionization detection (GC–FID) and gas chromatography–mass spectrometer (GC–MS) results.
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危险品化学品经营许可证（带存储）