JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Mengzhen Gu,Xiaoqing Xu,Xiaoping Wang,Yun Wang,Yu Zhao,Xiaoxian Hu,Lu Zhu,Zhenzhong Deng,Chao Han
Histone lysine-specific demethylase 1 (LSD1) is hyperactive in breast cancer, which is associated with the metastasis of the tumor. Current irreversible LSD1 inhibitors are all synthesized by covalently binding to the flavin adenine dinucleotide cofactor, which often have side effects due to the high affinity for a variety of targets. Here, we identified isoforsythiaside (IFA), a natural phenylpropanoid glycoside isolated from Forsythia suspensa, as a novel covalent inhibitor of LSD1. The target ligand fishing technique and LC–MS/MS analysis identified that IFA could covalently bind to the Ser817 residue of LSD1 by α,β-unsaturated ketone moiety to block the amine oxidase-like domain of LSD1. Moreover, RBMS3/Twist1/MMP2, the downstream signaling pathway of LSD1, was activated after IFA treatment to inhibit the metastasis of MDA-MB-231 cells in vitro and in vivo. This study provided novel molecular templates for development of LSD1 covalence-binding inhibitor and laid a foundation for developing agents against breast carcinoma metastasis for targeting LSD1.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Cong Xu,Jiahui Guo,Baoyue Chang,Qingyun Wang,Yiming Zhang,Xianhui Chen,Wanyi Zhu,Jiage Ma,Shanshan Qian,Zhanmei Jiang,Juncai Hou
This study was conducted to develop a W/O/W emulsion encapsulated Lactobacillus plantarum 23 – 1 ( LP23 – 1 ) to significantly enhance the survival rate of LP23-1 under simulated digestion and storage conditions. The zein particles and pectin formed a complex through electrostatic interaction and hydrogen bonding. When the proportion of zein particles to pectin was 1:1, the emulsifying stability index (ESI) was 304.17 %. Additionally, when the proportion of the internal aqueous phase to the oil phase was 1:9, the polyglycerol polyricinoleate (PGPR) concentration was 5 %, the proportion of primary emulsion to the external aqueous phase was 5:5, the zein particles concentration was 4 %, and the proportion of zein particles to pectin was 1:1, the encapsulation rate was the highest at 96.27 %. Cryo-scanning electron microscopy and fluorescence microscopy confirmed the morphology of W/O/W emulsion and successful encapsulation of LP23–1 . Furthermore, compared with free LP23–1 , the W/O/W emulsion encapsulation significantly improved the survival rate of LP23–1 to 73.36 % after simulated gastrointestinal digestion and maintained a high survival rate of 78.42 % during the 35-day storage. The W/O/W emulsion was found to effectively improve the survival rate of LP23–1 during simulated digestion and storage, which has implications for the development of probiotic functional foods with elevated survival rates.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Ying Xu,Genkuo Nie,Xiao Jiang,Hongyu Wang,Guihua Yang,Ziyi Yan,Ji-Jun Zou,Hailong Yu,Shitao Yu,Yu Liu
Metal-metal oxide catalysts are robust in selective hydrodeoxygenation of biomass derives. Herein, 1-hexanol in total yield about 76 % is firstly achieved by high selective hydrodeoxygenation of 5-hydroxymethylfurfural over Ni/MCM-41 and Pt-WO X /t-ZrO 2 . By controlling the amount ratio of Ni/Ni 2+ to 0.46, a 99.9 % yield of 2,5-tetrahydrofurandimethanol was achieved from 5-hydroxymethylfurfural by Ni/MCM-41. Subsequently high yield of 76 % of 1-hexanol was obtained by competing pathways of tandem reactions beginning at SN2 reaction at the epoxy atom of 2,5-tetrahydrofurandimethanol to enol/tautomer intermediates and ending with controllable selective hydrogenation. The reaction mechanism is explored and the reaction-oriented regulation is realized by the additional strong BrÖnsted acid sites generated by electron transfer from W to Pt and the appropriate amount of Pt 0 sites of Pt-WO X /t-ZrO 2 , where the ratios of W 5+ /W 6+ and Pt 0 /Pt 2+ are 0.31 and 4.58 respectively. This work provides a new and green method for the synthesis of 1-hexanol and expands the utilization of metal–metal oxide in making value-added products using sustainable feedstocks.
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ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Qi Chen,Yue Zhou,Xudong Zhu,Lei Xu,Ge Bai,Yaru Zhou,Nannan Zhang,Hongwen Liu,Yani Pan,Yu Liu,Lishan Wang,Xueni Fu,Jingjing Wei,Lina Zhou,Lu Xu,Yuxiang Sun,Zhangding Wang,Shanshan Shen,Yun Zhu,Lei Wang
Tumor-associated neutrophils (TANs), particularly the N2 phenotype, contribute to T cell exhaustion in cholangiocarcinoma (CCA), leading to low response rates to PD-1 inhibitor therapy. To address this issue, cancer-associated fibroblast (CAF)-derived extracellular vesicles loaded with ruxolitinib (CEVs@Ru) are developed to selectively target and reprogram N2 TANs, thereby modulating the immunosuppressive tumor microenvironment (TME). The combination of CEVs@Ru with anti-PD-1 antibody therapy significantly enhanced antitumor efficacy, reducing tumor weight by 89.86% and normalizing liver weight, without significant adverse effects. This approach improved the local concentration of ruxolitinib, increased CD8+ T cell infiltration, and reduced regulatory T cells, indicating a remodeled TME conducive to effective antitumor immunity. The findings provide a promising strategy for enhancing PD-1 inhibitor efficacy and improving patient outcomes in CCA and potentially other solid tumors.
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CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Mingwei Zhang,Cheng-Bin Hong,Zhaoying Ding,Yujing Weng,Honghui Gong,Haiyong Wang,Yulong Zhang,Yuhe Liao,Haichao Liu
Hydrogenolysis of glycerol is an important reaction in biomass valorization, and requires efficient catalysts for selectively removing its hydroxyl groups to yield valuable chemicals, such as 1-propanol and 1,2-propanediol. In this work, we synthesized a porous and non-stoichiometric tungsten oxide (WO x ) by a solvothermal method, and a serious of WO x -supported Pt and Mn ((Mn)Pt/WO x ) catalysts by reduction with H 2 at different temperatures. On these catalysts, the product selectivity in the glycerol hydrogenolysis was significantly influenced by the presence of the Mn species and reduction temperatures. The catalysts after reduction with H 2 at lower temperatures favored the formation of 1-propanol, affording a yield of 88.0 % at 240 °C, while those reduced at higher temperatures facilitated the formation of 1,2-propanediol in a yield of 93.0 % under the same reaction conditions. Extensive analysis of these catalysts by in-situ and ex-situ characterizations showed that the high-temperature reduction led to the formation of MnWO 4 on the Mn/Pt/WO x catalysts and the consequent decrease in the acidic sites and increase in the basic sites, facilitating the alkali-assisted dehydrogenation of glycerol and selective formation of 1,2-propanediol. This study provides fundamental insights into the role of the W and Mn species in tuning the selectivity of the glycerol hydrogenolysis, which will be valuable for designing catalysts towards the valorization of other biomass-based feedstocks.
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ADVANCED MATERIALS
·
2025
·
IF 26.8
Shaozhen Huang,Tianbao Li,Zhangdi Xie,Kun Li,Yuejiao Chen,Lin Mei,Gui-Chao Kuang,Zhibin Wu,Yu Zhang,Lin Gu,Libao Chen
Dendrite-free lithium anodes are crucial for developing practical high-energy-density batteries (>400 Wh/kg) with extended cycle life, but conventional interface design lack self-adaptive adjustment against dendrite growth during Li plating. Herein, we obtain a dendrite-free ultrathin Li@FcCHO anode by engineering a stress-responsive nano-interface on lithium strips via a mechanochemical reaction between ferrocene carboxaldehyde (FcCHO) and metallic Li. As proved by in situ Kelvin probe force microscopy and scanning electrochemical microscopy tests, the Li@FcCHO anode shows local potential response to the Li plating stress. Furthermore, density functional theory calculations show that the local surface potential change originates from stress-induced redistribution of anion-pair coordination. The stress-potential coupled interface layers induce uniform and dendrite-free Li deposition beneath the interface by suppressing dendritic Li from capturing Li + with the extra electric field. As a result, the Li@FcCHO anode exhibits ultralong cycling life over 5000 h under high areal capacity conditions, whilst a practical 452 Wh/kg pouch cell (9 Ah) based on the Li@FcCHO anode can survive over 470 cycles with capacity retention of 85.20%. This work pioneers a stress-potential coupled interface design to advance practical ultrathin Li anodes for next-generation high-energy-density batteries.
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Frontiers in Microbiology
·
2022
·
IF 6.064
Hexue Jia,Xiaoting Feng,Jiamin Huang,Yingjie Guo,Daolei Zhang,Xuezhi Li,Jian Zhao
Fungal cellulases usually contain a family 1 carbohydrate-binding module (CBM1), and its role was considered to recognize the substrate specifically. This study testified that the CBM1s derived from cellobiohydrolase I of Trichoderma reesei, Penicillium oxalicum , and Penicillium funiculosum could be used as an effective accessory protein in cellulase cocktails to enhance the saccharification of lignocellulose, and its enhancement effect was significantly superior to some reported accessory proteins, such as bovine serum albumin (BSA). The promoting effects of the CBM1s were related to not only the CBM1 sources and protein dosages, but also the substrate characteristics and solid consistency during enzymatic hydrolysis. The adsorption capacity of the CBM1s, the adsorption kinetic of TrCBM from T. reesei and cellobiohydrolase, endoglucanase, and β-glucosidase from P. oxalicum , and the effect of adding TrCBM on enzyme activities of free cellulases in the hydrolysis system were investigated, and the binding conformations and affinities of CBM1s to cellulose and lignin were predicted by molecular docking. It was speculated that the higher affinity of the CBM1s to lignin than cellulases could potentially enable the CBM1s to displace cellulase adsorbed on lignin or to preferentially adsorb onto lignin to avoid ineffective adsorption of cellulase onto lignin, which enhanced cellulase system efficiency during enzymatic hydrolysis of lignocellulose.
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RSC Advances
·
2019
·Vol. 9
·期 46
·26729-26733
·
IF 3.049
Ya Zhu,Jialing Han,Qian Zhang,Zhou Zhao,Jin Wang,Xiaowei Xu,Haiping Hao,Jun Zhang
Human NAD(P)H:quinone oxidoreductase (hNQO1) can be used as a biomarker for the early diagnosis of cancer. In this article, a novel fluorescent probe 1 for detecting hNQO1 was designed and synthesized by using 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) derivative (TCF-OH) as a fluorophore and quinone propionic acid (QPA) as a recognition group. The probe, which has high selectivity for hNQO1 and a Stokes shift of about 117 nm, shows a linear relationship with hNQO1 concentrations in the range of 0.25–3 μg ml−1 with the color changes from yellow to red and was successfully applied to intracellular hNQO1 imaging.
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Food Bioscience
·
2026
·
IF 6.2
Qi Wu,Xiang Ruan,Meng qi Li,Xu Yang,Jing Ren
Food allergy represents a group of disorders driven by abnormal immune responses, with a prevalence that has been rising steadily in recent years. Research indicates that human milk oligosaccharides and gut probiotics play an essential role in early-life immune regulation and the establishment of allergic tolerance. This study preliminarily explored the alleviating effects of a combined intervention with HMOs and Lc. paracasei 1 in OVA-induced food-allergic mice. The results demonstrated that the combined intervention markedly relieved allergic symptoms, reduced symptom scores, lowered serum IgE levels, rebalanced Th1/Th2 cytokines, and enhanced intestinal barrier integrity. 16S rRNA sequencing revealed that the HMOs and Lc. paracasei 1 combination significantly increased gut microbiota α-diversity and promoted the enrichment of beneficial bacteria, including Lactobacillus and Bifidobacterium . Concurrently, levels of key microbial metabolite, particularly short-chain fatty acids, rose substantially. Further untargeted Metabolomics analysis identified significant alterations in multiple differential metabolites across treatment groups, such as indole-3-acetic acid, indole-3-propionic acid, tryptophan, taurocholic acid, deoxycholic acid, and arachidonic acid. KEGG pathway enrichment analysis showed these metabolites were primarily involved in tryptophan metabolism, fatty acid metabolism, bile acid metabolism, and amino acid biosynthesis. Microbiome-metabolite correlation analysis further indicated that the abundances of Lactobacillus and Bifidobacterium were strongly positively correlated with indole metabolites and SCFAs. These findings suggest that the combined intervention of HMOs and Lc. paracasei 1 may alleviate food allergy symptoms by modulating gut microbiota composition and the metabolic profile, thereby influencing the body’s immune response.
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APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2013
·Vol. 97
·期 24
·10423-10433
·
IF 3.689
Yang Xueqing,Zhang Yalin
Carboxylesterases (CEs) are enzymes responsible for the detoxification of insecticides in insects. In the Cydia pomonella , CEs are involved in synthetic pyrethroid, neonicotinoid, carbamate, and organophosphate detoxification. However, functional overexpression of CEs proteins in Escherichia coli systems often results in insoluble proteins. In this study, we expressed the fusion protein CpCE-1 in E . coli BL21 (DE3). This recombinant protein was overexpressed as inclusion bodies at 37 °C whereas it produced a higher percentage of soluble protein at lower growth temperatures. Production of soluble proteins and enzyme activity increased in the presence of sorbitol in the growth medium. The fusion protein was purified from the lysate supernatant using a Ni 2+ -NTA agarose gel column. The enzyme exhibited a higher affinity and substrate specificity for α-naphthyl acetate (α-NA), with k
cat / K
m of 100 s −1 μM −1 for α-NA, and the value is 29.78 s −1 μM −1 for β-naphthyl acetate. The V
max and K
m were also determined to be 12.9 μmol/min/mg protein and 13.4 μM using substrate α-NA. The optimum pH was 7.0 and temperature was 25 °C. An enzyme inhibition assay shows that PMSF and DEPC strongly inhibit the enzyme activity, while the metal ions Cu 2+ and Mg 2+ significantly activated the activity. More importantly, cypermethrin, methomyl, and acephate were found to suppress enzyme activity. The data demonstrated here provide information for heterologous expression of soluble protein and further study on insecticide metabolism in C . pomonella in vitro. This is the first report of the characterization of CEs protein from C . pomonella .
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Journal of Biomaterials and Tissue Engineering
·
2020
·Vol. 10
·期 6
·874-883
·
IF 0.511
Zhang Li,Wei Shiyou,Xu Zhenkai,Sun Wen,Hang Lihua
Background: Cervical cancer is a type of malignancy with high incidence and high mortality in women all over the world. Recent findings revealed the role of sevoflurane in the inhibition of development of various cancer types. This study aimed to explore whether sevoflurane could
suppress cells proliferation and metastasis through adjusting miR-203 expression in cervical cancer. Methods: The effects of sevoflurane on HeLa cell viability was assessed using CCK-8 assay. miR-203 level in Hela cells was determined by qRT-PCR. In addition, cells apoptosis, migration
and invasion were evaluated using flow cytometry and transwell analysis respectively after sevoflurane treatment or miR-203 expression changes. Bioinformatics software (TargetScan) was used to predict the potential target genes for miR-203 and the prediction was validated using dual-luciferase
reporter system. Results: Sevoflurane effectively inhibited cell viability, metastasis and stimulated apoptosis in cervical cancer. miR-203 demonstrated a low expression in cervical cancer tissues and cells and sevoflurane significantly up-regulated miR-203 expression in cervical cancer
cells. Upregulation of miR-203 significantly suppressed cell growth and metastasis and induced apoptosis, while down-regulation of miR-203 presented the opposite effects in cervical cancer cells. In addition, the inhibitory effects of sevoflurane were eliminated by down-regulating miR-203
in cervical cancer cells. In addition, TPT1 was confirmed as a target gene for miR-203. Conclusion: Sevoflurane inhibited cervical cancer cells viability and metastasis through up-regulation of miR-203 expression by targeting TPT1.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2020
·
IF 3.347
Yang Zhang,Jiabei Zhou,Qin Ye,Kui Zeng,Jie Pan,Lu Chen,Yingying Wang,Bo Yang,Qiaojun He,Jianqing Gao,Su Zeng,Lushan Yu
Thioredoxin 1 (Trx1) and telomerase play key roles in the development and progression process of most tumors, and they both are promising drug therapy targets. We have, for the first time, discovered that Trx1 and telomerase had a dual-target synergistic effect. Based on that results, we designed a series of 6-dithio-2′-deoxyguanosine analogs (named as YLS00X) and verified whether they can inhibit Trx1 and telomerase simultaneously. TrxR1/Trx1 system activity and telomerase expression were significantly inhibited by 6-dithio-2′-deoxyguanosine analogs, especially YLS004. YLS004 can also cause ROS accumulation, and induce tumor cell apoptosis . The vitro antitumor activity of 6-dithio-2′-deoxyguanosine analogs using MTT assay on 11 different human cancer cells and found that human colon cancer cells(HCT116) and melanoma cells (A375) were the most sensitive cells to 6-dithio-2′-deoxyguanosine analogs treatment and vivo xenografts models also confirmed that. The serum biochemical parameters and multiple organs HE staining results of subacute experiments indicated that YLS004 might be mildly toxic to immune organs, including the thymus, spleen, and hematopoietic system . Besides, YLS004 was rapidly metabolized in the rats' blood. Our study revealed that YLS004, a Trx1 and telomerase inhibitor , has strong anti-tumor effects to colon cancer and melanoma cells and is a promising new candidate drug.
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