Long noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.
A new type of nonsmooth surface inspired by the shape of barchan dunes has been proposed and is intended to reduce skin friction, a major cause of overall drag. Simulations were carried out to obtain skin friction reduction characteristics for the nonsmooth surface using the commercial computational fluid dynamics software Fluent. A realizable k-ε model was employed to assess the influence of the nonsmooth structure on turbulent flow and velocity fields. The numerical simulation results showed that the new nonsmooth surface possesses the desired skin friction reduction effect and that the maximum skin friction reduction percentage reached 33.63% at a fluid speed of 30 m/s. Various aspects of the skin friction reduction mechanism were discussed, including the distribution of velocity vectors and shear stress contours and the variations in boundary layer thickness. The accuracy of the flow field for the nonsmooth unit was further verified by particle image velocimetry test results. The new bionic nonsmooth surface, which exceeds the limitations of existing nonsmooth bionic structures, can effectively reduce skin friction and should provide insights into engineering applications in the future.
Circular RNAs (circRNAs) play critical roles in clear cell renal cell carcinoma (ccRCC). However, their involvement in sunitinib resistance remains largely unknown. Herein, we identified a novel circRNA, named circME1, which contributes to sunitinib resistance development in ccRCC. CircME1 also promoted proliferation, migration, and invasion of ccRCC cells. Further mechanism analysis showed that circME1 interacted with U1 snRNP at the promoter of its parental gene ME1, thereby upregulating the expression of ME1, enhancing aerobic glycolysis of ccRCC, and promoting its malignant phenotype. Furthermore, ME1 specific inhibitor could effectively repress the oncogenic functions of circME1. Taken together, our study demonstrates that the circME1/ME1 pathway is involved in ccRCC progression and sunitinib resistance development, which may be exploited for anticancer therapy.
Aiming at aerodynamic drag reduction for transportation systems, a new active surface is proposed that combines a bionic nonsmooth surface with a jet. Simulations were performed in the computational fluid dynamics software STAR-CCM+ to investigate the flow characteristics and drag reduction efficiency. The SST K-Omega model was used to enclose the equations. The simulation results showed that when the active surface simultaneously reduced the skin friction and overcame the sharp increase of pressure drag caused by a common nonsmooth surface, the total net drag decreased. The maximum drag reduction ratio reached 19.35% when the jet velocity was 11 m/s. Analyses of the turbulent kinetic energy, pressure distribution, and velocity profile variations showed that the active surface reduced the peak pressure on the windward side of the nonsmooth unit cell, thereby reducing the total pressure drag. Moreover, the recirculation formed in the unit cell transformed the fluid–wall sliding friction into fluid–fluid rolling friction like a rolling bearing, thereby reducing the skin friction. This study provides a new efficient way for turbulent drag reduction to work.
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