Pan-histone deacetylase (HDAC) inhibitors often have some toxic side effects. In this study, three series of novel polysubstituted
N
-alkyl acridone analogous were designed and synthesised as HDAC isoform-selective inhibitors. Among them,
11b
and
11c
exhibited selective inhibition of HDAC1, HDAC3, and HDAC10, with IC
50
values ranging from 87 nM to 418 nM. However, these compounds showed no inhibitory effect against HDAC6 and HDAC8. Moreover,
11b
and
11c
displayed potent antiproliferative activity against leukaemia HL-60 cells and colon cancer HCT-116 cells, with IC
50
values ranging from 0.56 μM to 4.21 μM. Molecular docking and energy scoring functions further analysed the differences in the binding modes of
11c
with HDAC1/6.
In vitro
anticancer studies revealed that the hit compounds
11b
and
11c
effectively induced histone H3 acetylation, S-phase cell cycle arrest, and apoptosis in HL-60 cells in a concentration-dependent manner.
Abstract:Based on the momentum conservation approach, a theoretical model was developed to predict the superficial liquid velocity, and a correlation equation was established to calculate the gas holdup of an annular external-loop airlift reactor(AELAR)in the bubble flow and developing slug flow pattern. Experiments were performed by using tap-water and silicone oil with the viscosity of 2.0 mm 2 /s(2cs-SiO)and 5.0 mm 2 /s(5cs-SiO)as liquid phases. The effects of liquid viscosity and flow pattern on the AELAR performance were investigated. The predictions of the proposed model were in good agreement with the experimental results of the AELAR. In addition, the comparison of the experimental results shows that the proposed model has good accuracy and could be used to predict the gas holdup and liquid velocity of an AELAR operating in bubble and developing flow pattern.
The cover of a cylindrical explosion containment vessel would suffer an extremely intense impact because the shock wave and blast products would converge at the cover area. To reduce the impact of shock waves to the cover, cases with aluminum foam placed at the end of the vessel and in the interior of the cylindrical portion are studied by numerical simulation and experiment. The result shows that aluminum foam located at the end of the vessel can have a great effect on the protection of the cover because it can absorb the energy of the shock wave that has spread to the end of the vessel. Aluminum foam located in the interior of the cylindrical portion would have a negative effect on the protection of the cover because it would reduce the distance between the charge and the cylindrical portion, the effect of which is more significant than the effect of energy absorption. These results can contribute to the design of cylindrical explosion containment vessels.
Since the DC-link of the dual-inverter two-stage matrix converter (TSMC) has no energy storage element, its grid-side current waveform is closely related to the load-side condition. The conventional modulation strategy of the dual-inverter TSMC is only the stack of the double inverters, without considering the cooperation between both modulation strategies. Thus, the fluctuations in the grid-side currents synthesized by both load-side currents will be obvious. To solve this problem, this paper analyzes the effect of the current pulse position on the grid-side current waveform quality, and relevant relationship between the pulse position and current harmonics is obtained according to Fourier transform. On this basis, the harmonic attenuation strategy for the dual-inverter TSMC is proposed. In the proposed strategy, the grid-side current harmonic is reduced based on the optimal duty-cycle combination, obtained from the harmonic optimization problem. The simulation and experimental results are provided to verify that the theoretical analysis of grid-side current harmonic content is consistent with the actual condition, and the proposed modulation strategy can effectively reduce the grid-side current harmonic.
A tooth-lock cover is a kind of convenient closure used in explosive containment vessels. But in experiments, it is found that a small amount of explosive exploded in cylindrical vessels could cause severe deformation to the tooth-lock covers. In some situations, the cover would even be blown out of the vessel with severe distortion. The spreading and superposition of the shock waves in the cylindrical vessel is studied in this paper. Impulse is chosen as the evaluation parameter instead of the peak pressure because of the reflection and superposition of the shock waves. The piston method is used to calculate the impulse and the result is verified in 8-tooth cover vessels. This method can evaluate the intensity of the shock wave loaded on the cover. It would be useful in the optimization of the explosion containment vessels.
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