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A series of peptidomimetic aldehydes were designed, synthesized, and evaluated for their biochemical activity against 3C protease (3C pro ) and anti-enterovirus 71 (EV71) activity in vitro . Molecular docking revealed that 5s (IC 50 = 0.22 ± 0.07 μM, EC 50 = 0.18 ± 0.05 μM) could bind well to the active site of EV71 3C pro , which was consistent with the biological data compared to reference 5a (IC 50 = 0.54 ± 0.02 μM, EC 50 = 0.26 ± 0.07 μM). Structure and relationship study led to the discovery of aldehyde 5x (IC 50 = 0.10 ± 0.02 μM, EC 50 = 0.11 ± 0.07 μM), which exhibited the most potent 3C pro inhibitory and antiviral activity. [ABSTRACT FROM AUTHOR]

A series of polyamine conjugates of flavonoids with a naphthalene motif were synthesized and evaluated for their anti-hepatocellular carcinoma properties using in vitro and in vivo assays. Compound 8a displayed favorable selectivity between hepatocellular carcinoma cells and normal hepatocyte cells, and the combination of 8a with aspirin resulted in additive inhibition of in vitro tumor cell growth and migration. The 8a -aspirin combination also inhibited H22 liver tumor growth and pulmonary metastasis and improved body weight index in animal models. Preliminary mechanistic studies indicated that 8a increased the expression of apoptosis-related proteins such as p-p38, p-JNK, p53 and Bcl-2, an effect that was further amplified by aspirin. Therefore, a cocktail therapy of flavonoid-polyamine conjugates with aspirin has potential use as an antitumor therapy. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC 50 of 37.0 nM with low cytotoxicity (CC 50 > 200 μM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3C pro . The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD. [ABSTRACT FROM AUTHOR]

Quadrotor AUV is a new and promising vehicle in applications due to its special advantages. However, the problem of dynamic modeling of quadrotor AUV has not been investigated yet. In this study, a new dynamic modeling method for a quadrotor AUV is proposed by using a novel CFD simulation to calculate the hydrodynamic coefficients. Star CCM + is used to simulate the uniform and variable motion of each degree of freedom of a quadrotor AUV to decouple original high coupling dynamic model. Through the simulation of the AUV and the propeller motion, the main hydrodynamic coefficients are calculated, while the mathematical relationship between the rotation velocity and the thrust/torque is concluded. Specifically, the static mesh and dynamic mesh models are used to simulate the uniform and variable motion of the quadrotor AUV respectively. The calculation of added mass and drag coefficient does not interfere with each other, leading to accurate results. A numerical method is also proposed to separate the linear and nonlinear parts of the total drag coefficients. Then a six DOF dynamic model of a quadrotor AUV is established. The proposed CFD simulation also provides a reliable, repeatable and low-cost method for dynamic modeling of underwater vehicles. • The hydrodynamic coefficients of a type of quadrotor AUV are calculated. • The mathematical relationship between the propeller speed and its thrust/torque is obtained. • A novel mesh configuration method for star CCM+ simulation is proposed. • A numerical method is proposed to separate the linear and nonlinear parts of the total drag coefficients. • The complete six degree of freedom dynamic model of the quadrotor AUV is obtained. [ABSTRACT FROM AUTHOR]