PANCREATOLOGY
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2023
·
IF 3.6
Xin Wu,Xin Zhang,Peng Liu,Yao Wang
Background Pancreatic cancer is a common digestive system cancer and one of the most lethal malignancies worldwide. Ataxin-3 (ATXN3) protein is a deubiquitinating enzyme implicated in the occurrence of diverse human cancers. The potential role of ATXN3 in pancreatic cancer still remains unclear. Methods ATXN3 was screened from differentially-upregulated genes of GSE71989, GSE27890 and GSE40098 datasets. The mRNA and protein levels of ATXN3 was evaluated in pancreatic cancer samples and cell lines. Through the gain- and loss-of-function experiments, the effects of ATXN3 on cell proliferation , migration and invasion were evaluated using cell counting kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU) staining, wound healing and Transwell assays. Subsequently, the interaction between ATXN3 and HDAC6 was confirmed using double immunofluorescence staining, co-immunoprecipitation (co-IP) and proximity ligation assay (PLA). The underlying mechanism of ATXN3 was determined by knockdown of HDAC6 in ATXN3-upregulated pancreatic cancer cells. The function of ATXN3 in vivo was verified through xenograft assay. Results High expression of ATXN3 was found in pancreatic cancer tissues. Increased ATXN3 expression dramatically promoted cell proliferation, migration, and invasion. The malignant phenotypes were suppressed in ATXN3-silenced pancreatic cancer cells. ATXN3 was proved to interact with HDAC6 and regulate its degradation through deubiquitination . Downregulation of HDAC6 inhibited ATXN3-induced development of pancreatic cancer cells through regulating the expression of PCNA, vimentin and E-cadherin. ATXN3 facilitated tumor growth of pancreatic cancer and increased HDAC6 expression in vivo . Conclusions This study confirmed that ATXN3 facilitated malignant phenotypes of pancreatic cancer via reducing the ubiquitination of HDAC6.
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高影响因子
CHEMISTRY-A EUROPEAN JOURNAL
·
2023
·Vol. 29
·期 52
·e202300950
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IF 4.3
Fukun Li,Ronghe Yang,Zheng Tian,Ziting Du,Jinhang Dai,Xingmin Wang,Ning Li,Jie Zhang
Graphical Microwave-assisted one pot cascade transformation of furfural to γ-valerolactone catalyzed by Sc(OTf) 3 . γ-Valerolactone (GVL) is considered as a star biochemical which can be used as a green solvent, fuel additive and versatile organic intermediate. In this study, metal triflate (M(OTf) n ) was utilized as the catalyst for one-pot transformation of furfural (FF) to GVL in alcohol media under microwave irradiation. Alcohol plays multiple functions including solvent, hydrogen donor and alcoholysis reagent in this cascade reaction process. And process efficiency of GVL production from FF upgrading is strongly related to the effective charge density of selected catalyst and the reduction potential of selected alcohol. Complex (OTf) n -M−O(H)R, presenting both Brønsted acid and Lewis acid, is the real catalytic active species in this cascade reaction process. Among various catalysts, Sc(OTf) 3 exhibited the best catalytic activity for GVL production. Various reaction parameters including the Sc(OTf) 3 amount, reaction temperature and time were optimized by the response surface methodology with the central composite design (RSM-CCD). Up to 81.2 % GVL yield and 100 % FF conversion were achieved at 143.9 °C after 8.1 h in the presence of 0.16 mmol catalyst. This catalyst exhibits high reusability and can be regenerated by oxidative degradation of humins. In addition, a plausible cascade reaction network was proposed based on the distribution of product.
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Frontiers in Bioengineering and Biotechnology
·
2022
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IF 6.064
Wang Yiming,Luo Wenqi,Lin Feng,Liu Wanguo,Gu Rui
Purpose: Spinal cord injury (SCI) is a severely crippling injury. Scavenging reactive oxygen species (ROS) and suppressing inflammation to ameliorate secondary injury using biomaterials has turned into a promising strategy for SCI recuperation. Herein, epigallocatechin-3-gallate selenium nanoparticles (EGCG-Se NP) that scavenge ROS and attenuate inflammation were used for neuroprotection in SCI.Methods: EGCG-Se NP were arranged using a simple redox framework. The size, morphology, and chemical structure of the EGCG-Se NP were characterized. The protective effect of EGCG-Se NP for neuroprotection was examined in cell culture and in an SCI rat model.Results: EGCG-Se NP could promptly scavenge excess ROS and safeguard PC12 cells against H2O2-induced oxidative harm in vitro. After intravenous delivery in SCI rats, EGCG-Se NP significantly improved locomotor capacity and diminished the injury region by safeguarding neurons and myelin sheaths. Component studies showed that the main restorative impact of EGCG-Se NP was due to their ROS-scavenging and anti-inflammatory properties.Conclusion: This study showed the superior neuroprotective effect of EGCG-Se NP through ROS sequestration and anti-inflammatory capabilities. EGCG-Se NP could be a promising and effective treatment for SCI.
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Frontiers in Chemistry
·
2022
·
IF 5.545
Fan Zhang,Changqing Mao,Siyu Cao,Runchi Zhang,Yi Guo,Guifang Chen,Chang Feng
Bio-nanomicelles based on biomaterials such as nucleic acids, peptides, glycans, and lipids have developed rapidly in the field of bioanalysis. Although DNA and peptides have unique advantages, unfortunately, there are few bio-nanomicelles integrating DNA with peptides. Here, we designed a peptide-DNA hybrid bio-nanomicelle for the activity detection of caspase-3. The detection mechanism is based on caspase-3 specific recognition and cleavage of peptide substrates, which owns high sensitivity and selectivity. Under optimal conditions, the detection of caspase-3 activity can be achieved using our designed bio-nanomicelles and the detection limit is 0.72 nM. Furthermore, the proposed method was also successfully applied for the detection of caspase-3 in cell lysate samples after apoptosis-inducing.
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Molecular Catalysis
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2022
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IF 5.089
Yajiao Zhang,Minjie Liu,Huijing Wang,Juan Lin,Fener Chen
Non-catalytic sites are commonly present in many enzymes, but how to classify and modulate such sites for activity improvement is not well-explored. Herein a non-catalytic cavity in the 3-ketosteroid-Δ 1 -dehydrogenase (Δ 1 -KstD) from Mycobacterium smegmatis ( Ms KstD1), which could competitively bind to substrate to form non-catalytic complex, was predicted next to substrate tunnel by the CAVER/molecular dynamics. Based on that, a rational design was performed by Focused Site-directed Iterative Saturation Mutagenesis (FSISM) for blocking the non-catalytic cavity to enhance substrate enter active site to improve the Δ 1 -dehydrogenation activity of Ms KstD1. We obtained the best quadruple mutant (H132M\L113F\V419W\M51L) with 10-fold higher specific activity toward hydrocortisone than that of wild type enzyme. The Δ 1 -dehydrogenation space time yield toward hydrocortisone reached 36.0 g/L/h to produce prednisolone. This work displays how to combine focused mutagenesis with computational analysis to effectively identify and modify non-catalytic cavity to enhance enzyme activity for efficient production of Δ 1 -3-ketosteroid.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2022
·
IF 8.91
Kaidi Hu,Jianlong Li,Tianye Zhao,Qiao Zhou,Qin Li,Xinjie Hu,Guoquan Han,Shuhong Li,Likou Zou,Shuliang Liu
As a major intermediate metabolite of synthetic pyrethroids , the occurrence of 3-phenoxybenzoic acid hinders the decomposition of the parent pesticide and poses uncertain risks to environmental ecology and living organisms. Strain Aspergillus oryzae M-4 was previously reported to degrade 3-PBA and several substances were identified as downstream transformation products (TPs). But the mechanism underlying the cleavage of ether bond remains largely unclear. Here, we attempted to address such concern through identifying the peripheral TPs and analyzing transcriptomics, coupled with serial batch degradation experiments. Analysis results of chromatographic/mass spectrometry suggested that 3-PBA underwent twice hydroxylation , to yield mono- and dihydroxylated 3-PBA successively. In parallel, a mutual transformation between 3-PBA and 3-phenoxybenzyl alcohol (3-PBOH) also existed. The proposal of peripheral pathway represents an important advance towards fully understanding the whole 3-PBA metabolism in M-4. A specific altered metabolization was found for the first time, that is, resting cells of M-4 skipped the reduction step and initiate hydroxylation directly, by comparison with growing cells. Transcriptome analysis indicated that 3-PBA induced the up-regulation of genes related to energy investment, oxidative stress response, membrane transport and DNA repair. In-depth functional interpretation of differential expression genes suggested that the generation 3-PBOH and hydroxylated 3-PBA may be due to the participation of flavin-dependent monooxygenases (FMOs) and cytochrome P450 (CYP450), respectively. This study provides new insight to reveal the biodegradation mechanism of 3-PBA by A . oryzae M-4.
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JOURNAL OF MATERIALS SCIENCE-MATERIALS IN ELECTRONICS
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2022
·Vol. 33
·期 29
·23116-23127
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IF 2.779
Zhang Yu,Xiao Lei,Peng Sen,Li Qiang,Yi Tulin,Liu Weichun,Sun Yuxin
Ba[(Zn 1- x Mg x ) 1/3 Nb 2/3 ]O 3 ( x = 0 ~ 0.9) ceramics were prepared by the traditional solid-phase reaction sintering method. In this paper, the effects of MgO doping on the shrinkage, density, phase composition, crystal structure, microstructure, and microwave dielectric properties of Ba(Zn 1/3 Nb 2/3 )O 3 (BZN) ceramics were investigated. The phase constituents, crystal structure, and microstructure of the ceramics were studied by X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscope (SEM), and energy dispersive spectrometer (EDS). The results showed that Ba(Zn 1/3 Nb 2/3 )O 3 as the main phase, and the secondary phase Ba 5 Nb 4 O 15 was detected with high MgO content ( x > 0.3). However, the appearance of secondary Ba 5 Nb 4 O 15 directly led to the deterioration of the microwave dielectric properties of the samples. Ba[(Zn 1– x Mg x ) 1/3 Nb 2/3 ]O 3 ( x = 0.3) ceramics sintered at 1500 °C for 4 h possessed superior dielectric properties: ε r = 36.31, Q × f = 111,326 GHz, τ f = + 12.1 ppm/°C. Such the ceramics could be used to make dielectric resonators and stable oscillators.
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WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
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2022
·Vol. 38
·期 8
·1-11
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IF 4.253
Xue Kai,Liu Chun-Li,Yang Yankun,Liu Xiuxia,Zhan Jinling,Bai Zhonghu
d -allulose is a rare low-calorie sugar that has many fundamental biological functions. d -allulose 3-epimerase from Agrobacterium tumefaciens (AT-DAEase) catalyzes the conversion of d -fructose to d -allulose. The enzyme has attracted considerable attention because of its mild catalytic properties. However, the bioconversion efficiency and reusability of AT-DAEase limit its industrial application. Magnetic metal–organic frameworks (MOFs) have uniform pore sizes and large surface areas and can facilitate mass transport and enhance the capacity for enzyme immobilization. Here, we successfully encapsulated cobalt-type AT-DAEase into the cobalt-based magnetic MOF ZIF-67@Fe 3 O 4 using a self-assembly strategy. We confirmed the immobilization of enzyme AT-DAEase and characterized the enzymatic properties of the MOF-immobilized AT-DAEase@ZIF-67@Fe 3 O 4 . The AT-DAEase@ZIF-67@Fe 3 O 4 nanoparticles had higher catalytic activity (65.1 U mg −1 ) and bioconversion ratio (38.1%) than the free AT-DAEase. The optimal conditions for maximum enzyme activity of the AT-DAEase@ZIF-67@Fe 3 O 4 nanoparticles were 55 °C and pH 8.0, which were significantly higher than those of the free AT-DAEase (50 °C and pH 7.5). The AT-DAEase@ZIF-67@Fe 3 O 4 nanoparticles displayed significantly improved thermal stability and excellent recycling performance, with 80% retention of enzyme activity at a temperature range of 45–70 °C and > 45% of its initial activity after eight cycles of enzyme use. The AT-DAEase@ZIF-67@Fe 3 O 4 nanoparticles have great potential for large-scale industrial preparation of d -allulose by immobilizing cobalt-type AT-DAEase into magnetic MOF ZIF-67@Fe 3 O 4 .
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JOURNAL OF THE ELECTROCHEMICAL SOCIETY
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2022
·Vol. 169
·期 8
·087517
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IF 4.386
Shengnan Li,Xinhao Li,Liping Cao,Chaoxian Wang,Jintao Liang,Zhide Zhou,Guiyin Li
Glypican-3 (GPC3) is a serum marker for hepatocellular carcinoma (HCC) and has excellent specificity and sensitivity. Herein, the construction of an electrochemical aptasensor based on reduced graphene oxide-carboxymethyl chitosan-hemin-palladium nanoparticles (RGO-CMCS-Hemin/Pd NPs) and GPC3 aptamer (GPC3apt) has the function of GPC3 identification and analysis. RGO-CMCS-Hemin/Pd NPs has excellent biocompatibility, large specific surface area and good electrical conductivity, which is not only used as advanced sensing materials to modify the electrode surface to reduce the resistance and increase the signal amplitude, but also used as an electroactive substance to provide electrical signals. GPC3apt as a biometric element makes the aptasensor has good specificity and sensitivity. The GPC3apt can combine with GPC3 and form GPC3-aptamer conjugation, which increases the electron transfer impedance and changes the electrical signal. Under the optimum conditions, the aptasensor had a good linear relationship with the GPC3 concentration in the range of 1.0–100.0 ng ml−1 with R2 of 0.9573. The lower limit of detection was 1.0 ng ml−1. When the aptasensor was applied to GPC3 detection in human serum samples, the recovery was 93.73%–118.83%. In addition, the GPC3 aptasensor has excellent specificity, reproducibility and stability, which is anticipated to be applied for the clinical detection of GPC3.
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Microbiology Spectrum
·
2022
·
IF 9.043
Lujun Yin,Ping-Ping Zhang,Wei Wang,Shi Tang,Shi-Ming Deng,Ai-Qun Jia
Serratia marcescens (S. marcescens) is an environmental bacterium that causes infections with high morbidity and mortality. Notably, infections caused by multidrug-resistant S. marcescens have become a global public health issue. Therefore, the discovery of promising compounds to reduce the virulence of pathogens and restore antibiotic activity against multidrug-resistant bacteria is critical. Quorum sensing (QS) regulates virulence factors and biofilm formation of microorganisms to increase their pathogenicity and is, therefore, an important factor in the formation of multidrug resistance. In this study, we found that 3-phenylpropan-1-amine (3-PPA) inhibited S. marcescens NJ01 biofilm formation and virulence factors, including prodigiosin, protease, lipase, hemolysin, and swimming. The combination of 3-PPA (50.0 μg/mL) and ofloxacin (0.2 μg/mL) enhanced S. marcescens NJ01 sensitivity to ofloxacin. Based on crystalline violet staining, scanning electron microscopy (SEM), and confocal laser scanning microscopy (CLSM), 3-PPA (50.0 μg/mL) reduced S. marcescens NJ01 biofilm formation by 48%. Quantitative real-time PCR (qRT-PCR) showed that 3-PPA regulated the expression of virulence- and biofilm-related genes fimA, fimC, bsmB, pigP, flhC, flhD, and sodB. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that 3-PPA affected intracellular metabolites of S. marcescens NJ01, leading to reduce metabolic activity. These results suggested that 3-PPA inhibits the pathogenicity of S. marcescens NJ01 by occluding QS. Thus, 3-PPA is feasible as an ofloxacin adjuvant to overcome multidrug-resistant S. marcescens and improve the treatment of intractable infections.IMPORTANCE Multidrug-resistant bacteria have become a major threat to global public health, leading to increased morbidity, mortality, and health care costs. Bacterial virulence factors and biofilms, which are regulated by quorum sensing (QS), are the primary causes of multidrug resistance. In this study, 3-PPA reduced virulence factors and eliminated biofilm formation by inhibiting QS in S. marcescens NJ01 bacteria, without affecting bacterial growth, thus restoring sensitivity to ofloxacin. Thus, the discovery of compounds that can restore antibiotic activity against bacteria is a promising strategy to mitigate multidrug resistance in pathogens.
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CRYSTENGCOMM
·
2022
·Vol. 24
·期 17
·3217-3229
·
IF 3.756
Yang Tao,Xiaoting Liu,Yunping Zhoujin,Panpan Zhou,Sean Parkin,Tonglei Li,Ju Guo,Faquan Yu,Sihui Long
To probe the effect of substitution on the benzoic acid ring on the polymorphism of phenylaminobenzoic acids, five 3-methyl-2-(phenylamino)benzoic acids (MPABAs) were synthesized. A preliminary polymorph screen led to one form for compounds 1–4 and three forms and a solvate (5-I, 5-II, 5-III, and 5-S) for compound 5. This observation is similar to that of the structurally related compounds with no substitution on the benzoic acid ring. All crystal forms were characterized by single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), and FT-IR spectroscopy. The polymorphs of compound 5 were investigated in detail experimentally and theoretically. A conformational scan provided insight into the origin of polymorphism of 5. NBO calculations confirmed the composition and nature of the sigma bond character of the two N–C bonds in 5. Hirshfeld analysis accounted for the major intermolecular interactions contributing to the overall stability of the crystals. It is clear that conformational flexibility alone doesn't lead to polymorphism, and substitution position and pattern are the real determinant of polymorphism in the investigated compounds.
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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
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