Increased integrin β4 (ITGB4) level is accompanied by malignant progression of multiple carcinomas. However, selective therapeutic strategies against cancer cells expressing a high level of ITGB4 have not been reported. Here, for the first time, we report that a chiral small molecule, SEC, selectively promotes apoptosis in cancer cells expressing a high level of ITGB4 by inducing ITGB4 nuclear translocation. Nuclear ITGB4 can bind to the ATF3 promoter region and activate the expression of ATF3, then upregulate the downstream pro-apoptosis genes. Furthermore, SEC promoted the binding of annexin A7 (ANXA7) to ITGB4 and increased ANXA7 GTPase activity. Activated ANXA7 promoted ITGB4 nuclear translocation by triggering ITGB4 phosphorylation at Y1494. SEC also inhibited the growth of xenograft tumors in the avian embryo model. We identified a small molecule, SEC, with selective pro-apoptosis effects on cancer cells with high expression of ITGB4, both in vitro and in vivo, by triggering the binding of ITGB4 and ANXA7, ITGB4 nuclear trafficking, and pro-apoptosis gene expression.
Choose appropriate preventive maintenance measures is the key link to the pavement preventive maintenance successfully and effectively. According to the characteristics of highway asphalt pavement preventive maintenance technology, it summarizes the applicable and inapplicable occasions and application note of existing preventive maintenance measures, puts forward the preventive maintenance technology characteristics and adaptability, sets up the frame of decision-making for the preventive maintenance measures to provide guarantee for successful implementation of effective preventive maintenance.
The warm mix asphalt technology was introduced to breaks through the low reclaimed asphalt pavement (RAP) ratio in central plant hot recycled engineering. Firstly, performance tests for traditional hot mix asphalt and central plant warm recycled asphalt mixture with different RAP ratios (0%,40%,50%,70%,100%) were conducted. It was concluded that the performance of warm mix asphalt was as good as hot mix asphalt, and the RAP ratio could increase to 60% by central plant warm recycling technology. Then a practical central plant warm recycled engineering with RAP ratio 50% was analyzed. It was concluded that not only the performance of the recycled asphalt mixture met the standard requirements absolutely, but also the compaction quality of the recycled pavement was improved.
Because of the heating limitation of old pavement and the restriction of climate, the quality of hot in-place recycled pavement was different to control. The warm m,ix asphalt technology was introduced to improve the heterogeneity and compactness of the hot in-place recycled pavement and decrease its construction temperature. The compaction characteristics of warm in-place recycled asphalt mixture were analyzed and its molding temperature was determined through the Marshall test. The pavement performance of warm in-place recycled asphalt mixture was analyzed whose results indicated that the introduction of warm mix asphalt technology was able to improve the compactness, the high temperature stability and water stability of hot in-place recycled asphalt mixture and reduce the influence of environment over its construction quality. A warm in-place recycled engineering of Shian expressway was introduced to verify the feasibility of warm in-place recycling technology which demonstrated that the warm in-place recycling technology was able to improve the heterogeneity and compaction quality of the recycled pavement and weaken the environmental pollution.
Combinning at home and abroad research results, a new method of ‘sinking ball’ was put forward to evaluate the workability of self-compacting mortar (SCM). The size of ‘sinking ball’ and the volume of mortar vessel have been optimized by experiments. The results show that: when the ball with 20mm in diameter, the mortar vessel with 60mm in diameter and 160mm in heigh, the results of sinking ball test are best; Meanwhile, results indicate that the time of curve reflects the flow ability of SCM, the slope changing of curve indicates the anti-segregate ability of SCM, the integral area of curve has great relation with self-compacting ability of SCM.
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