Yes-associated protein (YAP) and its paralog transcriptional co-activator with PDZ-binding motif (TAZ) are two co-activators downstream of Hippo tumor suppressor cascade. Both have been implicated in the development of hepatocellular carcinoma (HCC). However, whether YAP and TAZ have distinct or overlapping functions during hepatocarcinogenesis remains unknown. Expression patterns of YAP and TAZ were analyzed in human HCC samples. The requirement of Yap and/or Taz in Akt/NRas driven liver tumorigenesis was analyzed using conditional Yap, Taz, and Yap;Taz knockout mice. Transcriptional programs regulated by YAP and/or TAZ were identified via RNASeq. We found that in human HCC samples, an almost ubiquitous activation of YAP or TAZ occurs, underlying their role in this tumor type. Intriguingly, 70% of HCC samples displayed only nuclear YAP or TAZ immunoreactivity. In the Akt/NRas liver tumor model, where nuclear Yap and Taz can be readily detected, deletion of Yap or Taz alone only mildly delayed liver tumor development, whereas their concomitant ablation strongly inhibited tumor cell proliferation and significantly suppressed Akt/NRas driven hepatocarcinogenesis. In HCC cell lines, silencing of either YAP or TAZ led to decreased expression of both overlapping and distinct sets of genes, with the most prominent gene signatures related to cell cycle progression and DNA replication. YAP and TAZ have overlapping and distinct roles in hepatocarcinogenesis. HCCs may display unique activation of YAP or TAZ, thus relying on either YAP or TAZ for their growth.
The honeycomb structure demonstrates exceptional stability, efficient mechanical performance, outstanding load-bearing capacity, and energy-saving and lightweight properties, rendering it extensively employed in various fields such as industrial manufacturing, radiation protection building, aerospace engineering, and wave-absorbing stealth materials. Bionic design can enhance the performance of structures, making bionic honeycomb design valuable in engineering. This study employs a bionic optimization design based on the original honeycomb size to investigate the impact of a new composite honeycomb core structure on mechanical properties. Orthogonal experiments are conducted to explore the effect of honeycomb size on mechanical properties and determine the optimal size. Combining numerical simulation and 3D printing experiments, we examine the mechanical properties of both nano-Fe3O4 particle-distributed honeycomb structure and common structures, analyzing mechanisms behind their tensile and compressive properties.
2 March 2024 in International Archives of Occupational and Environmental Health