Colorectal cancer (CRC) is one of the most common malignancies worldwide with substantial mortality and morbidity. Alisertib (ALS) is a selective Aurora kinase A (AURKA) inhibitor with unclear effect and molecular interactome on CRC. This study aimed to evaluate the molecular interactome and anticancer effect of ALS and explore the underlying mechanisms in HT29 and Caco-2 cells. ALS markedly arrested cells in G2/M phase in both cell lines, accompanied by remarkable alterations in the expression level of key cell cycle regulators. ALS induced apoptosis in HT29 and Caco-2 cells through mitochondrial and death receptor pathways. ALS also induced autophagy in HT29 and Caco-2 cells, with the suppression of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), but activation of 5′ AMP-activated protein kinase (AMPK) signaling pathways. There was a differential modulating effect of ALS on p38 MAPK signaling pathway in both cell lines. Moreover, induction or inhibition of autophagy modulated basal and ALS-induced apoptosis in both cell lines. ALS potently suppressed epithelial to mesenchymal transition (EMT) in HT29 and Caco-2 cells. Collectively, it suggests that induction of cell cycle arrest, promotion of apoptosis and autophagy, and suppression of EMT involving mitochondrial, death receptor, PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways contribute to the cancer cell killing effect of ALS on CRC cells. 相似文献
To realize the controlled release property, lower cytotoxicity, and long-term bioactivity of tetracycline, the chitosan hydrogel had been prepared using genipin as the cross-linker and the tetracycline was in situ encapsulated. The formation process and strength of hydrogel were studied by rheological analysis, and the microtopography was observed by scanning electron microscope. It was found that the amount of genipin could modulate the physical property of the hydrogel. For in vitro release and antibacterial assays, the hydrogel could controllably release tetracycline and keep its bioactivity for a long time. The tetracycline-loaded chitosan hydrogel showed good antibacterial effect even under alkaline environment, which displayed better stability compared with free tetracycline. Moreover, the tetracycline-loaded chitosan hydrogel exhibited lower cytotoxicity than did tetracycline alone, suggesting that this tetracycline-loaded chitosan hydrogel could be a more useful dosage form than separate doses of tetracycline. The novel aspects of this study include the cytotoxicity study and the in vitro and in vivo assays, which might be useful for other researchers in this field.
Graphical abstract To realize the controlled release property, lower cytotoxicity, and long-term bioactivity of tetracycline, genipin cross-linked chitosan hydrogel was used as the carrier of tetracycline. The hydrogel could controllably release tetracycline with bioactivity. The hydrogel showed good antibacterial effect even under alkaline environment. The hydrogel exhibited lower cytotoxicity than did tetracycline alone.
Short‐term traffic flow prediction on a large‐scale road network is challenging due to the complex spatial–temporal dependencies, the directed network topology, and the high computational cost. To address the challenges, this article develops a graph deep learning framework to predict large‐scale network traffic flow with high accuracy and efficiency. Specifically, we model the dynamics of the traffic flow on a road network as an irreducible and aperiodic Markov chain on a directed graph. Based on the representation, a novel spatial–temporal graph inception residual network (STGI‐ResNet) is developed for network‐based traffic prediction. This model integrates multiple spatial–temporal graph convolution (STGC) operators, residual learning, and the inception structure. The proposed STGC operators can adaptively extract spatial–temporal features from multiple traffic periodicities while preserving the topology information of the road network. The proposed STGI‐ResNet inherits the advantages of residual learning and inception structure to improve prediction accuracy, accelerate the model training process, and reduce difficult parameter tuning efforts. The computational complexity is linearly related to the number of road links, which enables citywide short‐term traffic prediction. Experiments using a car‐hailing traffic data set at 10‐, 30‐, and 60‐min intervals for a large road network in a Chinese city shows that the proposed model outperformed various state‐of‐the‐art baselines for short‐term network traffic flow prediction. 相似文献
In this paper, composite shear walls with different encased steel plates (flat, horizontal corrugated, and vertical corrugated) were tested and simulated by Abaqus to investigate the seismic behavior of corrugated steel plate concrete composite shear walls (SPCSWs). The failure characteristics, deformation and energy dissipation capacity, and stiffness and bearing capacity of the structures under low‐frequency cyclic load were analyzed, and indexes of the seismic performance were obtained. The formulas of the shear‐bearing capacity of steel plate concrete composite shear walls are suggested, and the shear‐sharing ratio of each member is obtained. According to the obtained results, corrugated steel plates can bond with concrete well, and the bearing capacity of the vertical corrugated SPCSW are higher than that of the horizontal corrugated SPCSW. Compared with flat SPCSW, corrugated SPCSW has higher initial stiffness and lateral stiffness, better ductility and energy dissipation ability, and the degradation of bearing capacity and stiffness is slower. The shear‐sharing ratio of a steel plate is larger than that of reinforced concrete in the flat SPCSW and the vertical corrugated SPCSW, the shear force shared by steel plate and reinforced concrete in horizontal corrugated SPCSW is basically the same. 相似文献