Search

High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy. [ABSTRACT FROM AUTHOR]

In this paper, a novel hybrid wave energy converter (WEC)‐floating breakwater system consisting of three floating pontoons with power take‐off (PTO) modules is developed to extract wave energy from heave motion and attenuate waves to protect the coast. Unlike previous studies of this subject, the present three pontoons are in close proximity so that they may share the same foundation to reduce the cost further and both pontoons with step change drafts and same drafts are investigated. A systematic experimental study was carried out in a wave flume to examine the hydrodynamic characteristics of the hybrid system under regular waves. The experimental results are used to assess the influences of the WEC‐breakwater integration and the configuration of pontoons on the hydrodynamic performance of the hybrid system as a WEC and a breakwater. It was found that the integration of multiple energy‐extracting pontoons is robust in smoothing out the power output fluctuations, and the floating pontoons with same drafts gave arise to higher energy conversion efficiency while the floating pontoons with step change drafts are more effective in attenuating wave energy. A parametric analysis is able to identify the balanced performance of the system as a WEC and a breakwater. [ABSTRACT FROM AUTHOR]

The present paper aims to clarify the mechanism of infragravity wave (IGW) energy amplification over nearshore shoals reported in recent studies. Wave transformation and energy transfer between short waves (SWs) and IGWs were investigated using SWASH model for nonbreaking random waves propagating over trapezoid shoals with different bottom slopes. It was found that the time lag of IGWs relative to SW groups is the major mechanism for energy transfer from SWs to IGWs and the amplification of IGW energy over all segments of the shoal. The time lag is generated on the front slope and enlarged on the plateau of the shoal, decreases on the rear slope with higher decreasing rates on milder slopes. Over the rear slope, the evolution of IGWs depends on the relative importance of deshoaling and nonlinear energy transfer. It was found that nonlinear energy transfer dominates over the rear slope gentler than 1/60, causing the IGW energy to increase over the first half of the deshoaling process and decrease over the second half whereas deshoaling dominates for steeper rear slope and the IGW energy decay over the whole slope. It is demonstrated numerically and theoretically that the shoals with gentler bottom slopes amplify the IGW energy more effectively by providing longer distance for nonlinear energy transfer to build up. The persistent nonlinear energy transfer on the plateau indicates the important role of wave spatial evolution history in the subsequent IGWs evolution. Strong free IGWs were detected on leeward of the shoal, possibly due to release of topography‐induced additional bound IGWs. Key Points: Wave spatial evolution history has significant effects on the subsequent evolution of infragravity wavesInfragravity wave energy is significantly amplified in the direction of wave propagation by a near shore shoalShort waves continually transfer energy to infragravity waves when propagating across the shoal even in the deshoaling zone [ABSTRACT FROM AUTHOR]

Abstract: A Reynolds‐Averaged Navier‐Stokes (RANS) flow solver with a Volume of Fluid (VOF) surface capturing scheme is used to investigate wave breaking and blocking due to strong opposing currents. The Shear Stress Transport (SST) k − ω model is modified in order to capture the turbulence properly. The unique capability of the RANS‐VOF model allows us to reveal the distinct features of current‐induced wave breaking and blocking. The limiting wave steepness at breaking onset is reduced considerably by the opposing current from the Stokes' limit for stationary waves. Although the wave height grows faster before breaking under a more rapidly varying current, the maximum height at the breaking onset remains almost the same. The locations of incipient breaking are slightly shifted downstream/upwave by the increased current gradient. It was found that the wave radiation stress alters the mean water level by competing with the pressure gradient arising from the current‐induced surface tilting. The wave set‐down and set‐up is more pronounced for more intensive breakers occurring under a larger incident wave and current gradient. Our model results indicate an undertow‐like change to the current profile due to wave breaking. The turbulence and vorticity generated by the current‐induced breaking wave persist and are advected downstream and interact with those generated by the following wave and current. [ABSTRACT FROM AUTHOR]