We studied the effect of TFP5 on MIN6 cells (cultured mouse islet β cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control;
n
=12) ...and db/db mice with type 2 diabetes mellitus (
n
=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic β cells from apoptosis
in vitr
o and
in vivo
. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-β1, TNFα, and IL-1β. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.
Liver cancer is a malignant cancer with great harmfulness. Fenofibrate is a peroxisome proliferation activated receptor (PPARα) agonist widely used in the treatment of dyslipidemia. Previous studies ...have shown that fenofibrate may promote cell proliferation, but the underlying mechanism has not been fully characterized. The aim of this study was to investigate the role of PPARα agonist fenofibrate in cell proliferation of SMMC-7721 cells compared with that of THLE-2 cells. SMMC-7721 and THLE-2 cells were treated with different concentrations of fenofibrate. Cell proliferation was analyzed by MTT, using flow cytometry for cell cycle analysis, and CyclinD1, Cyclin-dependent kinases2 (CDK2) and Proliferating Cell Nuclear Antigen (PCNA) were analyzed by Western blotting. RT-qPCR method was used to assess CDK2, CyclinD1 and PCNA mRNA levels. The results showed that 10−9–10−4 mol/L fenofibrate could induce cell growth and 10−4, 10−5, 10−6 mol/L fenofibrate could reduce the number of G0/G1 phase cells and increased in the number of cells in S and G2/M phase of cell cycle in SMMC-7721 cells. Furthermore, fenofibrate could significantly increase the expression of cell cycle related protein (CyclinD1, CDK2)and cell proliferation related proteins (PCNA). The use of PPARα inhibitor MT886 inhibited cell cycle progression and promote tumor cell apoptosis. But fenofibrate had no obvious effect on THLE-2 cells. These results revealed the effect of fenofibrate on the cell cycle of liver cancer cells, and provided a reasonable explanation for studying how fenofibrate promotes cell proliferation.
A mesogenic crosslinking agent M-1 was synthesized to minimize the perturbations of non-mesogenic crosslinking agents in liquid crystalline elastomers. The synthesis of new side chain liquid ...crystalline elastomers containing the rigid mesogenic crosslinking agent M-1 and nematic monomer M-2 by a one-step hydrosilylation reaction is described. The chemical structures of the monomers and network polymers obtained were confirmed by FTIR and
1
H NMR spectroscopy. The mesomorphic properties and phase behaviour were investigated by differential scanning calorimetry, polarizing optical microscopy, and X-ray diffraction. The influence of the crosslinking units on phase behaviour is discussed. Liquid crystalline elastomers containing less than 15 mol % of the crosslinking units showed elasticity, reversible phase transitions and a threaded texture. The experimental results demonstrated that the glass transition temperature of polymers P-1-7 increased with increasing concentration of crosslinking agent M-1; but the isotropic temperature and liquid crystalline range decreased slightly.
The Nanjing University of Information Science and Technology Earth System Model version 3 (NESM v3) has been developed, aiming to provide a numerical modeling platform for cross-disciplinary Earth ...system studies, project future Earth climate and environment changes, and conduct subseasonal-to-seasonal prediction. While the previous model version NESM v1 simulates the internal modes of climate variability well, it has no vegetation dynamics and suffers considerable radiative energy imbalance at the top of the atmosphere and surface, resulting in large biases in the global mean surface air temperature, which limits its utility to simulate past and project future climate changes. The NESM v3 has upgraded atmospheric and land surface model components and improved physical parameterization and conservation of coupling variables. Here we describe the new version's basic features and how the major improvements were made. We demonstrate the v3 model's fidelity and suitability to address global climate variability and change issues. The 500-year preindustrial (PI) experiment shows negligible trends in the net heat flux at the top of atmosphere and the Earth surface. Consistently, the simulated global mean surface air temperature, land surface temperature, and sea surface temperature (SST) are all in a quasi-equilibrium state. The conservation of global water is demonstrated by the stable evolution of the global mean precipitation, sea surface salinity (SSS), and sea water salinity. The sea ice extents (SIEs), as a major indication of high-latitude climate, also maintain a balanced state. The simulated spatial patterns of the energy states, SST, precipitation, and SSS fields are realistic, but the model suffers from a cold bias in the North Atlantic, a warm bias in the Southern Ocean, and associated deficient Antarctic sea ice area, as well as a delicate sign of the double ITCZ syndrome. The estimated radiative forcing of quadrupling carbon dioxide is about 7.24 W m.sup.-2, yielding a climate sensitivity feedback parameter of -0.98 W m.sup.-2 K.sup.-1, and the equilibrium climate sensitivity is 3.69 K. The transient climate response from the 1 % yr.sup.-1 CO.sub.2 (1pctCO2) increase experiment is 2.16 K. The model's performance on internal modes and responses to external forcing during the historical period will be documented in an accompanying paper.
Activity-guided fractionation of a chloroform-soluble extract of the leaves of Ormosia sumatrana, using a proteasome inhibition assay, led to the isolation of a new A-type proanthocyanidin ...derivative, 3'-O-cinnamoylprocyanidin A-2 (1), and a new cerebroside, sumatranoside (2). The structures of these two isolates were determined as epicatechin-(2 beta-->O-->7',4 beta-->8')-epicatechin-3'-O-cinnamate (1) and 1-O-(beta-d-glucopyranosyl)-(2S,3S,4R)-2N-(2'R)-2'-hydroxy-tetracosanoyl-9Z-octadecene-1,3,4-triol (2), respectively, by spectroscopic and chemical methods. Sumatranoside (2) exhibited proteasome inhibitory activity with an IC(50) value of 30 microM.
Surfactant (S) induced room-temperature phosphorescence (RTP) from 1-bromonaphthalene (1-BrN) in aerated aqueous solution of
β-cyclodextrin (
β-CD) has been investigated in detail. Benesi-Hildebrand ...analyses indicate that bright phosphorescence arises from a stable 1/S-BrN:
β-CD ternary complex in aqueous solution. Of the surfactants employed, cetylpyridinium bromide (CPB) shows much lower phosphorescence enhancement than cetyltrimethylammonium bromide (CTAB) and polyethylene tert-octyl phenyl ether (OP), and sodium dodecylbenzene sulfonate (SDBS) shows higher phosphorescence enhancement than Tween-20 and sodium dodecyl sulfate (SDS), respectively since the intermolecular energy transfer occurs between 1-BrN in the cavity and an aromatic group of a surfactant in a ternary complex. Simultaneously, the external heavy-atom effect of 1-BrN results in the fluorescence quenching of OP and SDBS, In combination with equilibrium constants, surface tension of solutions and spectral structure, a comparison of molecular size shows that part of the hydrocarbon chain of surfactants is included in the cavity of
β-CD and the hydrophobic part with the polar head group located outside the cavity coils at the mouth of
β-CD cavity. As a result, the excited I-BrN is shielded from the efficient phosphorescence quenching oxygen molecules dissolving in water and intense RTP is obtained.
A spectrofluorimetric method, involving alkaline degradation and formation of a magnesium complex, is described for the determination of tetracycline (TC) and anhydrotetracycline (ATC) in their mixed ...solution. Tetracycline is degraded and determined in alkaline solution. This treatment of ATC produces almost no fluorescence, but a fluorescent magnesium complex forms at pH 7.5. Several synthetic samples of TC and ATC, with TC:ATC ratios ranging from 50:1 to 1:50, were analysed. The recoveries of TC and ATC are about 71-76 and 61-63% in serum, respectively, and are all about 100% in urine.
DNA nanotechnology provides a versatile foundation for the chemical assembly of nanostructures. Plasmonic nanoparticle assemblies are of particular interest because they can be tailored to exhibit a ...broad range of electromagnetic phenomena. In this Letter, we report the assembly of DNA-functionalized nanoparticles into heteropentamer clusters, which consist of a smaller gold sphere surrounded by a ring of four larger spheres. Magnetic and Fano-like resonances are observed in individual clusters. The DNA plays a dual role: it selectively assembles the clusters in solution and functions as an insulating spacer between the conductive nanoparticles. These particle assemblies can be generalized to a new class of DNA-enabled plasmonic heterostructures that comprise various active and passive materials and other forms of DNA scaffolding.
N-(substituted-benzoyl)-1-aminonaphthalenes and N-(substituted-benzoyl)-2-aminonaphthalenes (1-NBAs and 2-NBAs) with varied substituents at the para- or meta-position of benzoyl phenyl ring were ...prepared to probe the difference between 1-aminonaphthalene (1-AN) and 2-aminonaphthalene (2-AN) as electron donors, using benzanilide-like charge transfer as a probe reaction. An abnormal long-wavelength emission was found for all of the prepared aminonaphthalene derivatives in cyclohexane and was assigned to the CT state by the observation of a substantial red shift with increasing solvent polarity or with increasing electron-withdrawing ability of the substituent. The CT emission energies were found to follow a linear relationship with the Hammett constant of the substituent and the value of the linear slope for 1-NBAs (-0.45 eV) was higher than that of 2-NBAs (-0.35 eV), the latter being close to that of the aniline derivatives (BAs, -0.345 eV). This pointed to a higher extent of charge separation in the CT state of 1-NBAs in which a full charge separation was established by the reduction potential dependence of the CT emission energy with a linear slope of -1.00. The possible contribution of the difference in the steric effect and the electron donating ability of the donors in 1-NBAs and 2-NBAs was ruled out by the observation that the corresponding linear slopes of benzoyl-substituted BAs remained unchanged when para-, meta-, ortho-, or ortho,ortho-methyls were introduced into the aniline moiety. It was therefore concluded that 1-AN enhanced the charge transfer in 1-NBAs and the proximity of its 1La and 1Lb states was suggested to be responsible. Results showed that the charge transfers in 1-NBAs and 2-NBAs were not the same and 1-AN and 2-AN as electron donors were different not only in electron donating ability but in shaping the charge transfer pathway as well.
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