BIOORGANIC & MEDICINAL CHEMISTRY
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2016
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IF 2.923
Xiaohui Bai,Youhong Niu,Jingjing Zhu,An-Qi Yang,Yan-Fen Wu,Xin-Shan Ye
Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clinical use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, we employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N -methylated analogues 2 – 6 were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogues 7 – 13 were synthesized. By two rounds of screening, analogue 10 was identified. Analogue 10 greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approximately a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.
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高影响因子
BRAIN & DEVELOPMENT
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2023
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IF 1.7
Hai Xu,Xuetao Yu,Rong Xie,Yangyang Wang,Chunli Li
Background RE1 Silencing Transcription factor (REST) corepressor 1 (RCOR1) has been reported to orchestrate neurogenesis, while its role in cerebral palsy (CP) remains elusive. Besides, RCOR1 can interact with Endothelin-1 (EDN1), and EDN1 expression is related to brain damage. Therefore, this study aimed to explore the effects of RCOR1/EDN1 on brain damage during the progression of CP. Methods CP rats were established via hypoxia–ischemia insult, and injected with lentivirus-RCOR1, followed by examination of brain pathological conditions. The RCOR1 and EDN1 interaction was recognized using hTFtarget. Healthy rat cortical neuron cells received interference of RCOR1/EDN1 expression, and underwent oxygen-glucose deprivation/reoxygenation (OGD/R) treatment, after which phenotypic and molecular assays were conducted through the biochemical method, qRT-PCR and/or western blot. Results RCOR1 was low-expressed but EDN1 was high-expressed in CP model rats and OGD/R-treated neurons. RCOR1 overexpression ameliorated rat neurobehaviors, alleviated brain pathological conditions, reduced TUNEL-positive cells, decreased the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), increased superoxide dismutase (SOD) level and repressed EDN1 expression in the brains of CP model rats. In neurons, RCOR1 overexpression counteracted OGD/R-induced viability decrease, reduction of the levels of RCOR1, SOD, Bcl-2, caspase-3, p-Akt/Akt and p-GSK-3β/GSK-3β, and elevation of the levels of EDN1, ROS, Bax, and cleaved caspase-3, while EDN1 overexpression did contrarily on these events. Moreover, there was a negative interplay between RCOR1 overexpression and EDN1 overexpression in OGD/R-induced neurons. Conclusion RCOR1 ameliorates neurobehaviors and suppresses neuronal apoptosis and oxidative stress in CP through EDN1 targeting-mediated upregulation of Akt/GSK-3β.
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EXPERIMENTAL CELL RESEARCH
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2023
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IF 3.7
Yizhen Guo,Xianchen Lu,Yan Zhou,Wen-Hua Chen,Kin Yip Tam
Many cancer cells exhibit enhanced glycolysis, which is seen as one of the hallmark metabolic alterations, known as Warburg effect. Substantial evidence shows that upregulated glycolytic enzymes are often linked to malignant growth. Using glycolytic inhibitors for anticancer treatment has become appealing in recent years for therapeutic intervention in cancers with highly glycolytic characteristic, including non-small cell lung cancer (NSCLC). In this work, we studied the anticancer effects and the underlying mechanisms of combination of benzerazide hydrocholoride ( Benz ), a hexokinase 2 (HK2) inhibitor and 64 , a pyruvate dehydrogenase kinase 1 (PDK1) inhibitor, in several NSCLC cell lines. We found that combination of Benz and 64 exhibited strong synergistic anticancer effects in NCI–H1975, HCC827, NCI–H1299 and SK-LU-1 cell lines. With this combination treatment, we observed changes of certain mechanistic determinants associated with metabolic stress caused by glycolysis restriction, such as mitochondrial membrane potential depolarization, overproduction of reactive oxygen species [1], activation of AMPK and down-regulation of mTOR, which contributed to enhanced apoptosis. Moreover, Benz and 64 together significantly suppressed the tumor growth in HCC827 cell mouse xenograft model. Taken together, our study may suggest that combined inhibition of HK2 and PDK1 using Benz and 64 could be a viable anticancer strategy for NSCLC.
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JOURNAL OF PERIODONTAL RESEARCH
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2023
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IF 3.5
Yifan Ma,Yi Qian,Yuteng Chen,Xiaoxu Ruan,Xiaoya Peng,Yi Sun,Jue Zhang,Jingjing Luo,Songlin Zhou,Chao Deng
Objective The purpose of this study was to investigate resveratrol's specific role as an anti-inflammatory and osteogenic differentiation of hPDLSCs in periodontitis and to reveal the mechanisms involved. Background Numerous studies have shown that inhibiting the inflammatory response of periodontal tissues and promoting the regeneration of alveolar bone are crucial treatments for periodontitis. Resveratrol has been found to have certain anti-inflammatory property. However, the anti-inflammatory mechanism and osteogenic effect of resveratrol in periodontitis are poorly understood. Materials and Methods We constructed an in vitro periodontitis model by LPS stimulation of hPDLSCs and performed WB, RT-qPCR, and immunofluorescence to analyze inflammatory factors and related pathways. In addition, we explored the osteogenic ability of resveratrol in in vitro models. Results In vitro, resveratrol ameliorated the inflammatory response associated with activation of the NF-κB pathway through activation of the NRF2/HO-1 pathway, characterized by inhibition of p65/p50 nuclear translocation and the proinflammatory cytokines interleukin-1β levels. Resveratrol also has a positive effect on osteogenic differentiation. Conclusions Observations suggest that resveratrol modulates the inflammatory response in hPDLSCs via the NRF2/HO-1 and NF-κB pathways and promotes osteogenic differentiation.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2023
·Vol. 21
·期 1
·1-22
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IF 10.2
Zhang Shushan,Huang Yongquan,Pi Songying,Chen Hui,Ye Feile,Wu Chaoqun,Li Liujun,Ye Qing,Lin Yuhong,Su Zhongzhen
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.Graphical Abstract
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CERAMICS INTERNATIONAL
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2023
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IF 5.2
Wei Liu,Yuanxun Li,Xinyan Liu,Yongcheng Lu
In millimeter-wave communication, signal delay becomes increasingly pronounced as the operating frequency of the equipment rises. To accelerate signal transmission, substrates with low dielectric constants (ε r < 6) are required. This study synthesized a novel microwave dielectric material, NaMg (1- x ) Zn x (PO 3 ) 3 (NMZPO), using the conventional solid-phase method. The microwave dielectric properties of NaMg(PO 3 ) 3 ceramics were enhanced by substituting Mg 2+ with Zn 2+ . Specifically, Zn 2+ doping increased the ceramics' densification and reduced dielectric loss. The NaMg 0.9625 Zn 0.0375 (PO 3 ) 3 ceramic exhibited optimal microwave dielectric properties at sintering temperature 880 °C for 4h: ε r = 4.49, Q × f = 58237.2 GHz (at 17.792 GHz), τ f = −50.6 ppm/°C. In addition, NMZPO ceramics demonstrate excellent chemical compatibility with Ag electrodes. These findings indicate that NMZPO represents a promising candidate for the next generation of ultra-low dielectric constant LTCC materials.
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MICROPOROUS AND MESOPOROUS MATERIALS
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2023
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IF 5.2
Yanyang Wu,Jiabo Rao,Qing Yi,Zhihui Ma,Bin Wu,Kui Chen,Lijun Ji
Metal-organic frameworks (MOFs) with sensitive nanospace and selective binding sites are widely used to discriminate the subtle structural. Adsorption performances of 2-Phenylethanol, 1-Phenyl-2-propanol, and 2-Ethylphenol on MOFs were studied in this paper. Eight MOFs were prepared hydrothermally and NH 2 -UiO-66(1) was chosen as the subsequent adsorbent based on the larger selectivity for both 1-Phenyl-2-propanol/2-Phenylethanol and 2-Ethylphenol/2-Phenylethanol. Studies on adsorption kinetics showed that pseudo-first-order model was suitable for adsorption performances of 1-Phenyl-2-propanol on NH 2 -UiO-66(1), while pseudo-second-order model was suitable for both 2-Phenylethanol and 2-Ethylphenol. The adsorption isotherm revealed that Langmuir model was suitable for 1-Phenyl-2-propanol, 2-Ethylphenol, and 2-Phenylethanol. Thermodynamic parameters including Gibbs free energy, enthalpy, and entropy indicated that adsorption of 1-Phenyl-2-propanol on NH 2 -UiO-66(1) was a spontaneous and exothermic physisorption process, while those of 2-Ethylphenol and 2-Phenylethanol were spontaneous and endothermic physisorption processes. The adsorption process indicated that the separation of 2-Phenylethanol from 1-Phenyl-2-propanol and 2-Ethylphenol on NH 2 -UiO-66(1) was due to the Lewis acid-base interactions and sieving effect. NH 2 -UiO-66(1) was also treated the simulated enriched 2-Phenylethanol solutions and 99.5% 2-Phenylethanol was obtained. In conclusion, NH 2 -UiO-66(1) can be a feasible adsorbent to separate 2-Phenylethanol from 1-Phenyl-2-propanol and 2-Ethylphenol for industrial application.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Jianrong Chen,Dengfeng Yang,Yunkai Zhang,Liyan Yang,Qingyan Wang,Mingguo Jiang,Lixia Pan
In order to better utilize chitinolytic enzymes to produce high-value N -acetyl-D-glucosamine (GlcNAc) from chitinous waste, there is an urgent need to explore bi-functional chitinases with exceptional properties of temperature, pH and metal tolerance. In this study, we cloned and characterized a novel bi-functional cold-adaptive chitinase called Ca Chi18A from a newly isolated strain, Chitinilyticum aquatile CSC-1, in Bama longevity village of Guangxi Province, China. The activity of Ca Chi18A at 50 °C was 4.07 U/mg. However, it exhibited significant catalytic activity even at 5 °C. Its truncated variant Ca Chi18A_ΔChBDs, containing only catalytic domain, demonstrated significant activity levels, exceeding 40 %, over a temperature range of 5–60 °C and a pH range of 3 to 10. It was noteworthy that it displayed tolerance towards most metal ions at a final concentration of 0.1 mM, including Fe 3+ and Cu 2+ ions, retaining 122.52 ± 0.17 % and 116.42 ± 1.52 % activity, respectively. Additionally, it exhibited favorable tolerance towards organic solvents with the exception of formic acid. Interestedly, Ca Chi18A and Ca Chi18A_ΔChBDs had a low K m value towards colloidal chitin (CC), 0.94 mg mL −1 and 2.13 mg mL −1 , respectively. Both enzymes exhibited chitobiosidase and N -acetyl-D-glucosaminidase activities, producing GlcNAc as the primary product when hydrolyzing CC. The high activities across a broader temperature and pH range, strong environmental adaptability, and hydrolytic properties of Ca Chi18A_ΔChBDs suggested that it could be a promising candidate for GlcNAc production.
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JOURNAL OF MEMBRANE SCIENCE
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2021
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IF 8.742
Yehao Jin,Qiangqiang Song,Na Xie,Weigang Zheng,Jing Wang,Junyong Zhu,Yatao Zhang
Advanced organic solvent nanofiltration (OSN) membranes with high permeance and stability are highly needed in petrochemical and pharmaceutical industries. Recently, polymers of intrinsic microporosity (PIMs) have attracted significant attention for the development of advanced membranes, because of their high porosity and solution processability. In this study, a thin film composite membrane based on an amidoxime-functionalized PIM (AOPIM-1) was prepared by spin coating followed by solvent activation. The activation approach could dramatically improve the solvent permeance of the membrane without compromising its rejection performance. The changes in porosity of the AOPIM-1 layer before and after activation were confirmed by positron annihilation Doppler spectroscopy. The optimum membrane exhibited an impressively high ethanol permeance of 15.5 L m −2 h −1 bar −1 , nearly one orders of magnitude higher than that of Starmem240 (a commercial polyimide-based OSN membrane) with a comparable rejection of Rose Bengal (MW 1017 Da). In addition, the present membrane exhibited outstanding stability in polar solvents and a remarkably high rejection of active pharmaceutical ingredients (vitamin B12) from ethanol. This work could provide a new avenue for developing highly permeable OSN membranes and is expected to stimulate the use of PIM membranes in OSN applications.
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DESALINATION
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2021
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IF 9.501
Wenwei Zhong,Yingnan Zhao,Shunquan Chen,Jialun Zhong,LiWei Guo,Dongyang Zheng,Chun Xie,Chao Ji,Yi Guo,Guangxi Dong,Fengyuan Zhang,Alicia An,Shaoping Li,Sheng Li
TCM wastewater treatment is a significant environmental issue in China. This study investigated the effectiveness of the UF-MD hybrid system on recycling valuable resources in TCM wastewater. Synthetic TCM wastewater was prepared and separated with the self-assemble UF-MD hybrid system. Moreover, the feed temperature (45 °C, 55 °C, 65 °C) and membrane materials' influence on MD performance were also evaluated. Results show that the UF-MD hybrid system is efficient to achieve a complete separation and resources recycle from the TCM wastewater. The MD flux production increased with the increment of feed temperature. However, some bioactive compounds could not be concentrated in MD due to their potential degradation at high temperatures, and membrane wetting might be an issue in long-term operation. Although PP membranes exhibited the highest flux among PP , PTFE and PVDF membranes, considering the wetting and fouling resistance , PTFE membranes would be a better option for long-term MD operation at 65 °C.
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Biomedical Materials
·
2021
·Vol. 16
·期 4
·044104
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IF 3.715
Yashuang Miao,Peirong Chen,Miao Yan,Jianmin Xiao,Biao Hong,Ke Zhou,Guilong Zhang,Junchao Qian,Zhengyan Wu
Single-mode magnetic resonance imaging (MRI) contrast agents (CAs) in clinical settings are easily disturbed by calcification, bleeding, and adipose signals, which result in inaccurate diagnoses. In this study, we developed a highly efficient T1–T2 dual-mode MRI CA using an ultra-small gadolinium oxide-decorated magnetic iron oxide nanocrystal (GMIO). The gadolinium element could effectively alter the magnetic properties of the GMIO from soft-ferromagnetism to superparamagnetism. In addition, when the Gd/Fe ratio was 15% (designated as GMIO-2), the GMIO-2 possessed the best superparamagnetism and highest magnetism. Subsequently, T1 and T2 values of GMIO-2 were measured through a series of turbo spin-echo images and then multi-spin echo sequence, respectively. Based on this, T1 and T2 relaxivities of GMIO-2 were calculated and were the highest (r1: 1.306 m M−1 s−1 and r2: 234.5 m M−1 s−1) when compared to other groups. The cytotoxicity of GMIO-2 was negligible under a wide range of dosages, thus exhibiting excellent cell biocompatibility. Moreover, GMIO-2 could quickly diffuse into cells, leading to its effective accumulation. The systemic delivery of GMIO-2 resulted in an excellent T1–T2 dual-mode MRI contrast effect in kidneys, which is expected to improve the diagnosis of kidney lesions. Therefore, this work provides a promising candidate for the development of a T1–T2 dual-mode MRI CA.
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ENVIRONMENTAL MICROBIOLOGY
·
2021
·Vol. 23
·期 6
·3265-3273
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IF 5.491
Mingliang Zhang,Yijun Ren,Shilong Du,Yidong Zhou,Wankui Jiang,Zhijian Ke,Mingli Jiang,Jiguo Qiu,Jian He,Qing Hong
Summary Pymetrozine is a synthetic pesticide that can be utilized as the sole carbon source by Pseudomonas sp. strain BYT-1. However, the genes involved in the degradation of pymetrozine remain unknown. We used transposon mutagenesis to create a mutant that unable to hydrolyze pymetrozine. The transposon interrupted the gene pyzH , which was cloned by self-formed adaptor PCR. PyzH hydrolyzed the C=N double bond of pymetrozine to produce 4-amino-6-methyl-4,5-dihydro-2 H -[1,2,4]triazin-3-one (AMDT) and nicotinaldehyde; the latter inhibits PyzH activity. PyzH can completely hydrolyze pymetrozine in the presence of dehydrogenase ORF6, which can convert nicotinaldehyde into nicotinic acid and relieve the inhibition. H 2 18 O-labeling experiments showed that the oxygen atom of nicotinaldehyde came from water instead of oxygen. PyzH homologous genes were also found in other soil isolates able to degrade pymetrozine.
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危险品化学品经营许可证（带存储）