Esophageal squamous cell carcinoma (ESCC) is a common human malignancy characterized by late-stage diagnosis, metastasis, and poor prognosis. Cisplatin (DDP)-based chemotherapy has been the most predominant treatment for patients with ESCC. However, the high rate of DDP resistance and toxicity seriously hinder its clinical application. Then, the optimized strategy and mechanisms for ESCC to enhance DDP sensitivity are in great demand. Accumulating evidence have shown that chaperone proteins are closely related to the tumorigenesis and drug resistance of cancers. Chaperonin containing TCP1 complex 4 (CCT4) is a recent identified member of the family. However, its expression and function in ESCC have not been well illustrated. In this study, we found that CCT4 was highly expressed in human ESCC tissues and cell lines, and closely related to the poor prognosis. Moreover, CCT4 silence raised oxidative stress and inhibited glycolysis of ESCC cells, which significantly inhibited cell proliferation and migration, promoted apoptosis and caused cell cycle arrest in ESCC cells. Interestingly, CCT4 knockdown enhanced the sensitivity of KYSE150 cells to DDP by regulating AMPK/AKT/Nrf2 signaling pathway and inhibiting glycolysis ability. Taken together, our results indicate that targeting CCT4 may be a therapeutic target in ESCC patients, which provides a theoretical basis to enhance the sensitivity of DDP in ESCC.
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest human malignancies characterized by late-stage diagnosis, drug resistance, and poor prognosis. Pyruvate dehydrogenase kinase 1 (PDK1) plays an important role in regulating the metabolic reprogramming of cancer cells. However, its expression, function, and regulatory mechanisms of PDK1 in ESCC have not been reported. In this study, we found that PDK1 silence and dichloroacetic acid (DCA) significantly inhibited the growth of ESCC cells and induced cell apoptosis. Interestingly, PDK1 is a direct target of miR-6516-5p, and miR-6516-5p/PDK1 axis suppressed the growth of ESCC cell by inhibiting glycolysis. Moreover, DCA and cisplatin (cis-diamminedichloroplatinum, DDP) synergistically inhibited the progression and glycolysis ability of ESCC cells both in vitro and in vivo by increasing oxidative stress via the inhibition of the Keap1/Nrf2 signaling pathway. And, Tert-butylhydroquinone (TBHQ), a specific activator of the Keap1/Nrf2 signaling, could diminish the synergic antitumor effects of DCA and DDP on ESCC cells. Collectively, our findings indicate that PDK1 may regulate the progression of ESCC by metabolic reprogramming, which provides new strategy for the treatment of ESCC.
Huge space and shape lead college sports buildings a lot of energy-consumption. Reduce the running energy-consumption is of great importance to save energy and decrease the running cost. This article introduced the using of computer simulation to analysis the design progress in 3 aspects: space efficiency, low running energy-consumption and innocuous design of the life-cycle of building; discussed how to use appropriate low-cost technologies to save energy and make comfortable indoor environment of college sports buildings, and finally argued that using low-cost technologies is effective way to design a green college sports building.
With the water tourism developed, making the development of water landscape rising rapidly. How to ensure the safety of hydraulic engineering technology under normal circumstances, and protect the ecological environment, play tourism economic benefits are an important problem in landscape design. Under the premise of following the principle of water conservancy landscape planning and design, applying AHP to research Xiya ditch waterfall landscape and optimize design program, then set up the preferred plan from ecological effect, waterfalls and technological factors three aspects of evaluation index. This provides theory basis for model test and engineering implementation in Xiya ditch waterfall landscape. In recent years, water conservancy projects relying on water industry form a large number of humanities landscape, natural landscape. The development of water tourism, gradually achieved a certain economic, social and environmental benefits. Giving full play to the comprehensive benefits of water conservancy projects, Ministry of Water Resources has granted water tourism as three major elements in water economy with water supply, power generation.
This article aimed to introduce a building design method to reduce energy-consumption, improve indoor comfort. The article discussed under the climate condition of the Central Plains area in China , the coefficient ventilation effect of double-roof and atrium, lighting effect of atrium’s skylight and impounding glass-wall, and the utilization of solar PV, wind power generation, biomass power generation, ground-source heat pump, solar air heater and other applications of renewable energy in building designs.
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