ABSTRACT
The process of frosting is a multiscale problem, which leads to challenges of proposing accurate numerical methods. In this study, a lattice Boltzmann model for predicting frost formation and growth on surfaces of various wettabilities is proposed based on the heterogeneous nucleation and dendrite growth theories. Three lattice Boltzmann equations are used to calculate the velocity, humidity, and temperature distributions. Furthermore, the heterogeneous nucleation theory and dendrite growth theory are used to construct the equations that govern ice production during the frosting process, so that the surface wettability can be considered. After experimental validation, the model was used in the analysis of frosting behaviors on plates and in microchannels with different wettabilities. The effects of the intrinsic contact angles and roughness on the frost layer properties were evaluated. This study will likely facilitate a better understanding of frosting on the mesoscopic level.
ABSTRACT
The inhibition of the members of aurora kinase family using ATP-competitive small molecules is an effective method for anticancer therapeutics. Based on our previous work, we synthesized 12 new N-trisubstituted pyrimidine derivatives and evaluated their biological activities and stabilities. Among them, compound 11j showed the best inhibition against aurora A kinase (IC50â¯=â¯7.1â¯nM), human leukemia cell line U937 (IC50â¯=â¯12.2â¯nM) and the growth of U937 xenograft tumors in vivo. By the flow cytometry and immunofluorescence analysis of U937, we found that compound 11j can induced polyploidy formation including (4N, 8N and 16N) and induce defects in both chromosome alignment and spindle formation. Furthermore, compound 11j exhibited good chemical, physical, and thermal stabilities. All these results suggested that 11j is a promising lead compound for further development of anticancer drugs.
Subject(s)
Antineoplastic Agents/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Aurora Kinase A/antagonists & inhibitors , Aurora Kinase A/metabolism , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Mice , Mice, Nude , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , U937 CellsABSTRACT
An efficient and direct synthetic route to epoxyisoprostane EC methyl ester has been accomplished in 8 steps (10% overall yield) from readily available starting materials using a series of asymmetric organocatalytic reactions and one-pot operations.
Subject(s)
Epoxy Compounds/chemistry , Isoprostanes/chemistry , Isoprostanes/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , StereoisomerismABSTRACT
BACKGROUND: Airway remodeling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodeling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation, migration and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentrations of triptolide before stimulated by TGF-ß1. Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle. Migration was measured by Transwell analysis. Signal proteins (NF-κB p65 and ERK1/2) were detected by western blotting analysis. LDH releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of triptolide. RESULTS: Triptolide significantly inhibited TGF-ß1 induced ASMC proliferation and migration (p<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. Western blotting analysis showed TGF-ß1 induced NF-κB p65 phosphorylation was inhibited by triptolide pretreatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of triptolide we used. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation and migration through inactivation of NF-κB pathway. This article is protected by copyright. All rights reserved.
