PHYSICAL CHEMISTRY CHEMICAL PHYSICS
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2022
·Vol. 24
·期 35
·21157-21164
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IF 3.945
Z. Z. Liu,K. P. Li,X. B. Yang,Y. Q. Zhang,Z. X. Xie,Z. Q. Duan,B. Zhou,Y. M. Hu
Pt counter electrodes (CEs) have been widely used in dye-sensitized solar cells (DSSCs) due to their high conductivity and electrocatalytic activity. However, industrialization of DSSCs is limited by shortcomings of Pt CEs such as being expensive, and weak corrosion resistance in electrolytes. Reported in this paper is two simple approaches to Pt-free Cu1.8S1−xSex CEs. Nanocrystalline Cu1.8S1−xSex CEs were fabricated via two processes, that is, a solvothermal process to Cu1.8S1−xSex powder followed by CE fabrication, and a solvothermal process and CE fabrication to Cu1.8S films followed by selenylation to Cu1.8S1−xSex CEs. Photoelectric conversion efficiencies (PCE) of 4.02% and 4.16% were achieved respectively by the as-fabricated Cu1.8S1−xSex CEs. Compared with the cells with Cu1.8S CEs fabricated by the same processes, increases of 19% and 45% were achieved, respectively. The PCE improvement comes from the enhancement of charge transfer at the CE/electrolyte interface induced by the selenylation of the CEs.
研究领域:
材料科学
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能源研究
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2020
·
IF 4.96
Hongwei Yao,Jingkai Gu,Yuqin Shan,Yani Wang,Xue Chen,Dong Sun,Yingjie Guo
Patients with diabetic mellitus tend to have a poor response to clopidogrel (Clop) due to reduced generation of active metabolite (Clop-AM). However, the underlying mechanism is not elucidated. A type 2 diabetic mellitus (T2DM) rat model was established by combining high-fat diet feeding and low-dose streptozotocin (STZ) injection. The reduced Clop-AM exposure was observed in T2DM rats after oral administration of Clop. However, in vitro liver microsomes incubated with Clop exhibited increased Clop-AM levels in T2DM rats due to a significant decrease in carboxylesterase (CES)1 expression and activity and a significant increase in the expression or activity of CYP1A2 and CYP3A . Interestingly, different from oral administration, the significantly increased C max of Clop-AM was observed in T2DM rats after intravenous injection, with no difference in AUC 0-t and t 1/2 values between the two strains. Meanwhile, in situ single -pass intestinal perfusion study showed lower absorption rate constant ( K a) and effective apparent permeability values ( P eff ) of Clop in T2DM rats than in control rats. It is explained by the increased expression or function of P-glycoprotein (P-gp) and pregnane X receptor (PXR) in duodenum and jejunum of T2DM rats. Moreover, the decreased Clop-AM level in T2DM rats was eliminated by the pretreatment of cyclosporin A , a P-gp inhibitor. It suggests that intestinal absorption, not hepatic metabolism is responsible for the reduced Clop-AM exposure in T2DM rats. P-gp might be the key factor causing the reduction of Clop absorption, consequently making less Clop available for Clop-AM formation.
研究领域:
药理学
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糖尿病研究
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药学
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代谢
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DOI
PubMed
高影响因子
RSC Advances
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2022
·Vol. 12
·期 54
·35477-35483
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IF 4.036
Lihong Li,Qi Zhang,Jiaojiao Li,Yafei Tian,Jinyao Li,Wen Liu,Haipeng Diao
Phototheranostic probes have been proven to be a promising option for cancer diagnosis and treatment. However, near-infrared phototheranostic probes with specific tumor microenvironment responsiveness are still in demand. In this paper, a carboxylesterase (CES)-responsive near-infrared phototheranostic probe was developed by incorporating 6-acetamidohexanoic acid into a hemicyanine dye through an ester bond. The probe exhibits highly sensitive and selective fluorescence enhancement towards CES because CES-catalyzed cleavage of the ester bond leads to the release of the fluorophore. By virtue of its near-infrared analytical wavelengths and high sensitivity, the probe has been employed for endogenous CES activatable fluorescence imaging of tumor cells. Moreover, under 660 nm laser irradiation, the probe can generate toxic reactive oxygen species and efficiently kill tumor cells, with low cytotoxicity in dark. As far as we know, the probe was the first CES-responsive phototheranostic probe with both near-infrared analytical wavelengths and photosensitive capacity, which may be useful in the real-time and in situ imaging of CES as well as imaging-guided photodynamic therapy of tumors. Therefore, the proposed probe may have wide application prospect in cancer theranostics.
研究领域:
癌症诊断与治疗
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生物医学工程
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分子成像
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光动力治疗
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
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2021
·Vol. 31
·期 42
·2104418
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IF 18.808
Can Wu,Chunlu Wang,Yaoyao Zheng,Yaxin Zheng,Ziqi Liu,Keming Xu,Wenying Zhong
Cancerous cells exhibit overexpression of multiple enzymes in various cellular compartments. These enzymes are often undruggable, yet display unique advantages in regulating intracellular self-assembly and dis-assembly of small molecules for cancer targeting. Herein, a self-assembling molecule (LND-1p-ES) for carrier-free delivery of lonidamine specifically to cancerous cells is designed, where LND-1p-ES executes as both a drug and a carrier with combined benefits thereof. Under the precise regulation of phosphatase (ALP) and esterase (CES), LND-1p-ES is capable of self-assembling intracellularly in a spatiotemporal manner, to confer lonidamine-borne nanofibers with enhanced cellular uptake. These nanofibers also facilitate controlled drug release with the aid of cellular proteases. Taking advantages of overexpressing ALP and CES as well as proteases in cancerous cells, the LND-1p-ES formulation demonstrates enhanced potency and selectivity against melanoma cells A375 in vitro and in vivo. In comparison, none/single enzyme responsive compounds fail to show a similar potency or selectivity, further confirming the indispensable roles of these enzymes in the delivery system. Collectively, the research provides a viable strategy to utilize multiple enzymes in cancerous cells for regulation of intracellular self-assembly, which can be expanded to design smart soft materials responsive to multiple biologically relevant biomolecules for enhanced therapeutic efficacy.
研究领域:
癌症研究
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药物递送系统
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生物医学工程
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材料科学
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药学
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产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2018
·
IF 4.235
Mengjing Zhao,Tianpeng Zhang,Fangjun Yu,Lianxia Guo,Baojian Wu
Carboxylesterases (CES) are a family of phase I enzymes that play an important role in xenobiotic clearance and lipid metabolism. Here, we investigate a potential role of E4 promoter-binding protein 4 (E4bp4) in regulation of Ces and CPT-11 (irinotecan, a first-line drug for treating colorectal cancer) pharmacokinetics in mice. Mouse hepatoma Hepa-1c1c7 cells were transfected with Rev-erbα expression plasmid or siRNA targeting E4bp4. The relative mRNA and protein levels of Ces enzymes in the cells or the livers of wild-type and E4bp4-deficient (E4bp4 −/− ) mice were determined by qPCR and Western blotting , respectively. Transcriptional regulation of Ces by E4bp4/Rev-erbα were investigated using luciferase reporter, mobility shift, and co-immunoprecipitation (Co-IP) assays. Pharmacokinetic studies were performed with wild-type and E4bp4 −/− mice after intraperitoneal injection of CPT-11. E4bp4 ablation down-regulated an array of hepatic Ces genes in mice. E4bp4 −/− mice also showed reduced Ces-mediated metabolism and elevated systemic exposure of CPT-11, a well-known Ces substrate. Consistently, E4bp4 knockdown reduced the expression of Ces genes ( Ces2b , Ces2e and Ces2f ) in Hepa-1c1c7 cells. Furthermore, Rev-erbα repressed the transcription of Ces2b, whereas E4bp4 antagonized this repressive action. Co-IP experiment confirmed a direct interaction between E4bp4 and Rev-erbα. Through a combination of promoter analysis and mobility shift assays, we demonstrated that Rev-erbα trans-repressed Ces (Ces2b) through its specific binding to the -767 to-754 bp promoter region. In conclusion, E4bp4 regulates Ces enzymes through inhibition of the transrepression activity of Rev-erbα, thereby impacting the metabolism and pharmacokinetics of Ces substrates.
研究领域:
药理学
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分子生物学
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遗传学
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肝病学
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DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Qiong Wu,Jing Yu,Mingjin Zhang,Yinran Xiong,Lijia Zhu,Bo Wei,Ting Wu,Yiping Du
The liver is a major organ in metabolism, and alterations in serum lipids are associated with liver disorders. Here, a rapid, easy, and reliable screening technique based on lipidomic profiling was developed using machine learning and surface-assisted laser desorption ionization mass spectrometry (SALDI MS) for liver cancer diagnosis. A graphitized carbon matrix (GCM) was created for serum lipid profiling in SALDI MS and demonstrated a better performance for neutral lipids analysis than conventional organic matrices. The fingerprint of serum lipids, including triacylglycerols (TGs), diacylglycerols (DGs), cholesteryl esters (CEs), glycerophospholipids (GPs), and other components, could be directly obtained by GCM-assisted LDI MS without extraction. Five machine learning methods were applied to distinguish liver cancer (LC) patients from healthy controls (HC) and chronic hepatitis B (CHB) patients. The best diagnostic performance was attained by linear discriminant analysis (LDA), which has a confusion matrix accuracy of 98.3 %. The receiver operating characteristic (ROC) curve for liver cancer exhibited an area under the curve (AUC) of 0.99, indicating a high degree of prediction accuracy. One-way ANOVA analysis revealed that numerous TGs were down-regulated in LC group. The results demonstrated the viability of GCM-assisted LDI MS as a valuable diagnostic tool for liver cancer.
研究领域:
医学诊断
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质谱技术
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机器学习
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癌症研究
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脂质组学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Zhengming Xu,Shuang Liu,Huining Lai,Lijun You,Zhengang Zhao
Arbutin, salidroside, polydatin, and phlorizin are typically natural bioactive phenolic glycosides. To improve the liposolubility and bioavailability, highly liposoluble derivatives including 6′-O-lauryl arbutin, 6′-O-lauryl salidroside, 6″-O-lauryl polydatin, and 6″-O-lauryl phlorizin were efficiently synthesized by enzymatic acylation in a green solvent 2-MeTHF. Their reaction conversions reached 84.4, 99.5, 99.8, and 89.1%, respectively, when catalyzed by Lipozyme 435 at 20 mg/mL at 50 °C. As expected, the derivatives had high log P (1.66–2.37) and retained good antioxidant activity, making them potential alternatives to butylated hydroxytoluene (BHT) and tert-butyl-hydroquinone (TBHQ) in lipid systems. Then, the intestinal permeability characteristics and metabolism of phenolic glycosides and their derivatives were investigated based on Caco-2 monolayers. The permeability of polydatin and phlorizin was mainly through active transport, but that of arbutin and salidroside involved both passive diffusion and active uptake. The acylated derivatives suffered from severe CES-mediated hydrolysis but exhibited a larger transported amount than phenolic glycosides.
研究领域:
药学
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有机化学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子