PROCESS BIOCHEMISTRY
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2022
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IF 4.885
Hai-Bin Qin,Jun-Ping Zhou,Bo Zhang,Zhi-Qiang Liu,Yu-Guo Zheng
Microbial production of D-pantothenic acid (D-PA) has become an important research area, as D-PA is an essential vitamin widely applied in food, feed, chemical and pharmaceutical industries. Here both dynamic regulations of redox metabolism and fermentation strategies were applied to enhancing D-PA biosynthesis in Escherichia coli W3110. Firstly, a quorum-sensing (QS) system for redox regulation developed, in which zwf and nadK overexpression were shown to be effective for enhancing D-PA production. Based on this, a strain DPA11/p LBCWK was constructed with D-PA titer at 4.19 g/L in flask. Moreover, the fermentation strategies including pH-feedback feeding and gradient β-alanine feeding were introduced, under optimal conditions, the strain DPA11/p LBCWK could produce 48.21 g/L D-PA in 5 L fermenter, with the specific productivity of 0.72 g/L·h and the yield of 0.33 g/g glucose. These modification strategies were proved effective and would provide valuable reference for biosynthesis of other chemicals.
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高影响因子
Food & Function
·
2022
·Vol. 13
·期 14
·7560-7571
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IF 6.317
Shuai Lu,Jinyi Zhou,Chen Yang,Xiaoxue Zhang,Yingying Shi,Jie Liu,Xintong Yan,Juanjuan Liang,Xianli Liu,Lan Luo,Da Zhou,Zhimin Yin
Aging is a natural process accompanied by inflammation and oxidative stress and is closely associated with age-related diseases. As a direct precursor of glutathione, γ-glutamylcysteine (γ-GC) possesses antioxidant and anti-inflammatory properties; however, whether γ-GC plays an important role in anti-aging remains unknown. Here, we investigated the protective effects and mechanisms of γ-GC in D-galactose (D-gal)-induced senescence in PC12 cells and aging mice. Our results showed that γ-GC treatment significantly reduced the percentage of senescence-associated-β-galactosidase (SA-β-Gal)-positive cells and inhibited D-gal-induced cell cycle arrest in PC12 cells. The results of Nissl and hematoxylin and eosin (H&E) staining in mouse brain showed that γ-GC treatment markedly reversed the damage in the hippocampus of D-gal-induced aging mice. Moreover, γ-GC increased the phosphorylation of AMP-activated protein kinase (AMPK) to promote the nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) while inhibiting the nuclear translocation of deleted in breast cancer 1 (DBC1), which leads to the activation of sirtuin 1 (SIRT1) and deacetylation of p53 in the nucleus. Therefore, γ-GC may be a potential therapeutic candidate compound for the prevention and treatment of age-related diseases.
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高影响因子
GENE
·
2022
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IF 3.913
Xiaohong Chen,Yueya Zhang,Haifeng Yan,Meiyun Niu,Yuping Xiong,Xinhua Zhang,Yuan Li,Jaime A. Teixeira da Silva,Guohua Ma
The commercial value of Santalum album L. lies in its aromatic heartwood and essential oil. Sesquiterpenes are the main components of sandal essential oil, and these are synthesized through the plant’s mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. In this study, the first key rate-limiting enzyme, 1-deoxy- d -xylulose-5-phosphate synthase (SaDXS), was investigated to provide a theoretical molecular basis for the sandalwood MEP sesquiterpene biosynthetic pathway. The biofunctions of SaDXS were also analyzed. SaDXS promoters were successfully cloned from a seven-year-old S. album tree. SaDXS1A/1B promoter activity was verified by a β-glucuronidase (GUS) assay and by analyzing cis -acting elements of the promoters, which carried light- and methyl jasmonate (MeJA)-responsive signals. In an experiment involving yellow S. album seedlings, exposure to light upregulated SaDXS1A/1B expression and increased chlorophyll and carotenoid contents when overexpressed in Arabidopsis thaliana . Analysis of the expression of SaDXS1A/1B and SaSSy , key genes of santalol biosynthesis, revealed SaDXS1A expression in all tissues whereas SaDXS1B was expressed in tissues that contained photosynthetic pigments, such as stems, leaves and flowers. Sandal seedlings exogenously treated with two hormones, MeJA and ethylene, revealed similar expression patterns for SaDXS1A/1B and SaSSy . Sandal seedlings were treated with an inhibitor of DXS, clomazone, but showed no significant changes in the contents of α-santalene, β-santalene and α-santalol between treatment and control groups. These results suggest that SaDXS1A/1B play a role in the synthesis of sandalwood sesquiterpenes, providing carbon for downstream secondary metabolites. SaDXS1A/1B also play a role in the biosynthesis of chlorophyll, carotenoids, and primary metabolites.
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高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
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2022
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IF 3.915
Ziyi Li,Zhenghua Li,Jianhua He,Jianping Liu
Salvianolic acid B (SAB) is a widely used cardioprotective agent, while its clinical application was limited by poor intestinal absorption and low oral bioavailability. In this study, SAB phospholipid (SP) complex was first prepared to improve the lipophilicity of SAB and then combined with d-glucose to further enhance intestinal absorption. Compared with free SAB, SP or the mixture of SAB and d-glucose, combination of SP and d-glucose showed higher intestinal absorption evidenced by increased effective permeation coefficient (Peff) in the in situ single-pass intestinal perfusion (SPIP) assay. Subsequently, SP and d-glucose at mass ratio of 1:6, with the highest Peff of SAB, were chosen for the preparation of complexed pellets to improve oral absorption efficiency of SAB. As expected, the obtained pellets significantly enhanced oral bioavailability of SAB in the pharmacokinetic study characterized by increasing Cmax and AUC0–t of SAB by 14.88-fold and 5.02-fold than free SAB, respectively. In conclusion, combination of d-glucose in SP pellets can effectively improve the intestinal absorption and oral bioavailability of SAB.
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高影响因子
FOOD HYDROCOLLOIDS
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2023
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IF 10.7
Xin Wang,Jiayi Sun,Shenghan Zhao,Fang Zhang,Xianghong Meng,Bingjie Liu
The objective of this work was to develop nanostructured lipid carriers (NLCs) with preservation effect by using pea protein isolate (PPI) nanoparticles as emulsifiers, candelilla wax (CW) as organo-gelator and d -limonene (DL) as antifungal agent. The optimal formulation parameters of NLCs were firstly determined based on results of particle size, poly-dispersity index and zeta potential, and then NLCs prepared by optimal formulation were further characterized. The results showed that DL was successfully encapsulated inside NLCs. Moreover, the encapsulation of amorphous DL led to more disordered crystalline state of NLCs. In addition, in comparing the properties of NLCs and nanoemulsions (NEs) without CW, it was found that the addition of CW seemed to have several beneficial effects on NLCs: 1) NLC droplets were well dispersed, whereas NE droplets exhibited coalescence and flocculation; 2) compared with NEs, NLCs displayed excellent storage stability and inhibition ability of DL release. Furthermore, antifungal activity of NLCs was observed by in vitro and in vivo study. The acquired information in current research can provide novel insight into development of stable and antifungal nanocarriers that own a promising application in tomato preservation.
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Journal of Advanced Research
·
2023
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IF 10.7
Wenjuan Tang,Yu Hu,Kaihui Tu,Zhengyan Gong,Man Zhu,Tianfeng Yang,Ammar Sarwar,Bingling Dai,Dongdong Zhang,Yingzhuan Zhan,Yanmin Zhang
Introduction Tumor-associated calcium signal transducer 2 (Trop2) has been used as a transport gate for cytotoxic agents into cells in antibody–drug conjugate designs because of its expression in a wide range of solid tumors. However, the specific role of Trop2 itself in breast cancer progression remains unclear and small molecules targeting Trop2 have not yet been reported. Objectives To screen small molecules targeting Trop2, and to reveal its pharmacological effects and the molecular mechanisms of action. Methods Small molecule targeting Trop2 was identified by cell membrane chromatography, and validated by cellular thermal shift assay and point mutation analyses. We investigated the pharmacological effects of Trop2 inhibitor using RNA-seq, human foreskin fibroblast (HFF)-derived extracellular matrix (ECM), Matrigel drop invasion assays, colony-forming assay, xenograft tumor model, 4T1 orthotopic metastasis model and 4T1 experimental metastasis model. The molecular mechanism was determined using immunoprecipitation, mass spectrometry, immunofluorescence, immunohistochemistry and Western blotting. Results Here we identified Bruceine D (BD) as the inhibitor of Trop2, and demonstrated anti-metastasis effects of BD in breast cancer. Notably, Lys307 and Glu310 residues of Trop2 acted as critical sites for BD binding. Mechanistically, BD suppressed Trop2-induced cancer metastasis by blocking the formation of Trop2/β-catenin positive loop, in which the Trop2/β-catenin complex prevented β-catenin from being degraded via the ubiquitin-proteosome pathway. Destabilized β-catenin caused by BD reduced nucleus translocation, leading to the reduction of transcription of Trop2, the reversal of epithelial-mesenchymal transition (EMT) process, and the inhibition of ECM remodeling, further inhibiting cancer metastasis. Additionally, the inhibitory effects of BD on lung metastatic colonization and the beneficial effects of BD on prolongation of survival were validated in 4T1 experimental metastasis model. Conclusions These results support the tumor-promoting role of Trop2 in breast cancer by stabilizing β-catenin in Trop2/β-catenin positive loop, and suggest Bruceine D as a promising candidate for Trop2 inhibition.
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高影响因子
Journal of Energy Storage
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2023
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IF 9.4
Yu Bai,Shuangfeng Wang
Accelerate the development of medium-temperature phase change materials (PCMs) with high enthalpy of phase change and light absorption capability is very important for medium-temperature energy storage and solar thermal utilization. However, low energy conversion capacity and easy leakage limit the practical application of PCMs. To improve these properties of materials, a MXene/DM aerogel composite phase change material was prepared by self-assembly followed by freeze-drying of d -mannitol (DM) and MXene nanosheets using a simple solution blending method. The MXene/DM containing 20 wt% MXene has a high enthalpy (H m ) of phase change (202.7 J/g) with phase change temperature (T m ) of 153.3 °C, and still has good shape stability at 170 °C without leakage. In addition, MXene/DM has strong absorption ability in UV–Vis-NIR regions, with significant solar-thermal conversion efficiency of 88.1 %. The results indicate that the MXene/DM aerogel have comprehensive performance and have promising applications in medium-temperature thermal storage and photothermal conversion.
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ENZYME AND MICROBIAL TECHNOLOGY
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2023
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IF 3.4
Shuangshuang Duan,Yonghua Chen,Guodong Wang,Zebin Li,Shitong Dong,Yingshuai Wu,Yuanwei Wang,Chunling Ma,Ruiming Wang
D -Allose is a rare cis-caprose with a wide range of physiological functions, which has a wide range of applications in medicine, food, and other industries. L -Rhamnose isomerase ( L -Rhi) is the earliest enzyme found to catalyze the production of D -allose from D -psicose. This catalyst has a high conversion rate, but its specificity for substrates is limited; thus, it cannot fulfill the requirements of industrial production of D -allose. In this study, L -Rhi derived from Bacillus subtilis was employed as the research subject, and D -psicose as the conversion substrate. Two mutant libraries were constructed through alanine scanning, saturation mutation, and rational design based on the analysis of the secondary structure , tertiary structure , and interactions with ligands of the enzyme. The yield of D -allose produced by these mutants was assessed; it was found that the conversion rate of mutant D325M to D -allose was increased by 55.73 %, and the D325S improved by 15.34 %, while mutant W184H increased by 10.37 % at 55 °C, respectively. According to modeling analysis, manganese (Mn 2+ ) had no significant effect on the production of D -psicose from D -psicose by L -Rhi. The results of molecular dynamics simulation demonstrated that the mutants W184H, D325M, and D325S had more stable protein structures while binding with the substrate D -psicose, as evidenced by its root mean square deviation (RMSD), root mean square fluctuation (RMSF), and binding free energy values. It was more conducive to binding D -psicose and facilitating its conversion to D -allose, providing the basis for the production of D -allose.
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高影响因子
Molecular Catalysis
·
2021
·
IF 5.062
Teng Li,Guangyu Sun,Lu Xiong,Boying Zheng,Yaqi Duan,Rui Yu,Jun Jiang,Yantao Wang,Weiran Yang
As a useful chemical, furan can be produced from bio-based chemicals, such as furfural and furoic acid (FA). There were few reports on the preparation of furan from bio-based C6 aldaric acids . Herein, a new method was developed to produce furan from D-glucaric acid (GA) without transition metals, and nearly 80% yield of furan was produced in the water/toluene biphasic system with SnCl 4 at 200 °C in 2 h. 3-Hydroxy-2-pyrone (3-HP) and FA were proved to be the key intermediates in the formation of furan from GA, and the reaction pathway was proposed to be GA→ 3-HP→ FA→ furan based on the kinetic study , model substrate reaction, and isotope labeling experiments. SnCl 4 gave the highest furan yield among the common acid catalysts, and the contrast experiments suggested that H + , Cl − and Sn 4+ all have promoting effect on GA conversion to furan. This method was also applicable with other C6 aldaric acids.
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高影响因子
FOOD SCIENCE AND BIOTECHNOLOGY
·
2023
·
IF 2.9
Zheng Qian,Long Si,Chen Zhi,Fu Jiaolong,Ju Xin,Li Liangzhi
Enzymatic preparation of rare sugars as an alternative to traditional sweeteners is an effective strategy to achieve a low-calorie healthy diet. Ribose-5-phosphate isomerase B (RpiB) is a key enzyme in the non-oxidative branch of the catalytic pentose phosphate pathway. Here, we investigated the potential of Curtobacterium flaccumfaciens ZXL1 ( C. flaccumfaciens ZXL1) derived RpiB (CfRpiB) in D-allose preparation. The optimal reaction conditions for recombinant CfRpiB were found experimentally to be pH 7.0, 55 °C, and no metal ions. The kinetic parameters K m , k cat , and catalytic efficiency k ca t / K m were 320 mM, 4769 s −1 , and 14.9 mM −1 s −1 respectively. The conversion of D-allulose by purified enzyme (1 g L −1 ) to D-allose was 13% within 1 h. In addition, homology modeling and molecular docking were used to predict the active site residues: Asp13, Asp14, Cys72, Gly73, Thr74, Gly77, Asn106, and Lys144.
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高影响因子
MOLECULES
·
2023
·Vol. 29
·期 1
·21
·
IF 4.6
Xue Wang,Xiaomei Fu,Xiurong Luo,Yiyi Lai,Chuipu Cai,Yanfang Liao,Zhao Dai,Shuhuan Fang,Jiansong Fang
Osthole, a natural coumarin found in various medicinal plants, has been previously reported to have neuroprotective effects. However, the specific mechanism by which Osthole alleviates dysmnesia associated with Alzheimer’s disease (AD) remains unclear. This study aimed to investigate the neuroprotective properties of Osthole against cognitive impairment in rats induced by D-galactose and elucidate its pharmacological mechanism. The rat model was established by subcutaneously injecting D-galactose at a dose of 150 mg/kg/day for 56 days. The effect of Osthole on cognitive impairment was evaluated by behavior and biochemical analysis. Subsequently, a combination of in silico prediction and experimental validation was performed to verify the network-based predictions, using western blot, Nissl staining, and immunofluorescence. The results demonstrate that Osthole could improve memory dysfunction induced by D-galactose in Sprague Dawley male rats. A network proximity-based approach and integrated pathways analysis highlight two key AD-related pathological processes that may be regulated by Osthole, including neuronal apoptosis, i.e., neuroinflammation. Among them, the pro-apoptotic markers (Bax), anti-apoptotic protein (Bcl-2), the microgliosis (Iba-1), Astro-cytosis (GFAP), and inflammatory cytokines (TNF-R1) were evaluated in both hippocampus and cortex. The results indicated that Osthole significantly ameliorated neuronal apoptosis and neuroinflammation in D-galactose-induced cognitive impairment rats. In conclusion, this study sheds light on the pharmacological mechanism of Osthole in mitigating D-galactose-induced memory impairment and identifies Osthole as a potential drug candidate for AD treatment, targeting multiple signaling pathways through network proximity and integrated pathways analysis.Keywords:Alzheimer’s disease;cognitive disorder;Osthole;neuronal apoptosis;neuroinflammation;network proximity
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高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Fangxiu Li,Yue Sun,Xiaoxia Sun,Yu Hu,Yanli Wu
Due to the hydrophilicity of furan ring and hydroxyl group, and hydrophobicity of benzene ring and cyclohexyl group, the compounds are easy to form hydrophilic and hydrophobic amphoteric vesicles through self-assembly. The self-assembled vesicles were designed and facilely synthesized using the 2-furanboronic acid and H 8 -BINOL by Suzuki coupling reaction, which could serve as a novel probe with high enantioselectivity for D/L-Phe. In SEM and TEM images, after adding the L-Phe, the vesicle structure of the H 8 -BINOL derivatives changed from spherical to dendritic nanotube structures. On the contrary, after the addition of D-Phe, the spherical vesicle structure changed only slightly, indicating that the material had specific recognition for L-Phe. Moreover, the new fluorescent probes had unique rigid structures and obvious enantioselective recognition for phenylalanine in fluorescence testes. In the methanol solution, after adding the L-Phe, the fluorescence intensity of R - 1 and S - 1 decreased significantly at 368 nm and increased at 306 nm, but D-Phe had no obvious fluorescence effect on the probes, which indicated that the fluorescent probes had a good guiding effect on the recognition of amino acids by chiral compounds.
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