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.
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.
A new rearranged pentanortriterpenoid (trijugin C) and a new pregnane (3 ,4 -dihydroxypregnan-16-one) were isolated from the EtOH extract of Trichilia connaroides (Meliaceae). Trijugin C has been ...shown to be a derivative of methyl angolensate with a novel carbon skeleton. The structures were elucidated on the basis of spectral analysis including
1
H-
1
H COSY, HMQC, HMBC, and NOESY experiments. The possible biogenetic pathway of trijugin C is discussed.Key words: Trichilia connaroides, Meliaceae, pentanortriterpenoid, trijugin C, pregnane.
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.
Gravity and centrifugal investment casting processes of low-pressure turbine blades with high Nb–TiAl alloy were simulated by Procast software. Actual blade components were poured by vacuum induction ...suspended furnace with Ar protection. The experimental verification indicated that the simulation results were in good agreement with the experimental results. Comparative results had shown that the surface of centrifugal casting blade was more complete than that of gravity casting one. In gravity casting process, molten metal filled the thinnest trailing edge at last, resulting in the generation of misrun defects. Furthermore, the shrinkage porosity and crack defects of gravity casting were much more and dispersive. The internal and external quality of centrifugal casting was much better than that of gravity casting. Microstructures from edge to center of gravity casting blade had no significant change. The microstructure for centrifugal casting blade is finer than that for gravity casting blade, however, a large number of dentritic γ segregation appeared in the blade edge of centrifugal casting, which resulted from the fast cooling rate of centrifugal casting surface.
•Gravity and centrifugal investment casting processes were comparatively studied.•Good correlation between simulation and experimental.•The defects of turbine blades were comparatively studied and discussed.•Microstructures of castings were comparatively studied and discussed.
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.
Abstract
A sub-array of the Large High Altitude Air Shower Observatory (LHAASO), KM2A is mainly designed to observe a large fraction of the northern sky to hunt for γ-ray sources at energies above 10 ...TeV. Even though the detector construction is still underway, half of the KM2A array has been operating stably since the end of 2019. In this paper, we present the KM2A data analysis pipeline and the first observation of the Crab Nebula, a standard candle in very high energy γ-ray astronomy. We detect γ-ray signals from the Crab Nebula in both energy ranges of 10
100 TeV and
100 TeV with high significance, by analyzing the KM2A data of 136 live days between December 2019 and May 2020. With the observations, we test the detector performance, including angular resolution, pointing accuracy and cosmic-ray background rejection power. The energy spectrum of the Crab Nebula in the energy range 10-250 TeV fits well with a single power-law function d
N
/d
E
= (1.13
0.05
0.08
)
10
(
E
/20 TeV)
cm
s
TeV
. It is consistent with previous measurements by other experiments. This opens a new window of γ-ray astronomy above 0.1 PeV through which new ultrahigh-energy γ-ray phenomena, such as cosmic PeVatrons, might be discovered.
A novel, rapidly quenched skeletal Fe catalyst (RQ Fe) has been prepared by alkali leaching of the Fe50Al50 alloy solidified by the rapid quenching technique and tested in gas phase Fischer−Tropsch ...synthesis (FTS). Characterizations demonstrate that the RQ Fe catalyst has larger specific surface area, smaller crystallite size, and higher population of the Fe(111) surface than the conventional Raney Fe catalyst prepared from the naturally solidified Fe50Al50 alloy. As compared to Raney Fe, which has FTS activity equivalent to the precipitated Fe catalyst while higher than the fused Fe catalyst, RQ Fe is 25% more active. Promotion of the RQ Fe catalyst with Mn or K further improves the FTS activity, selectivities to alkenes and higher alkanes, as well as the catalytic stability, showing that the rapid quenching technique is promising in the preparation of skeletal Fe-based catalysts with improved FTS performance.
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