The role of enhanced velocity shears in rapid ocean cooling during Super Typhoon Nepartak 2016.

Typhoon is a major cause of multiple disasters in coastal regions of East Asia. To advance our understanding of typhoon-ocean interactions and thus to improve the typhoon forecast for the disaster mitigation, two data buoys were deployed in the western North Pacific, which captured Super Typhoon Nepartak (equivalent to Category 5) in July 2016 at distances <20 km from the typhoon's eye center. Here we demonstrate that the unprecedented dataset combined with the modeling results provide new insights into the rapid temperature drop (~1.5 °C in 4 h) and the dramatic strengthening of velocity shear in the mixed layer and below as the driving mechanism for this rapid cooling during the direct influence period of extremely strong winds. The shear instability and associated strong turbulence mixing further deepened the mixed layer to ~120 m. Our buoys also observed that inertial oscillations appeared before the direct wind influence period.

Foxp3 enhances HIF-1α target gene expression in human bladder cancer through decreasing its ubiquitin-proteasomal degradation.

Hypoxia-inducible factor-1α (HIF-1α) can control a transcriptional factor forkhead box P3 (Foxp3) protein expression in T lymphocyte differentiation through proteasome-mediated degradation. In this study, we unveil a reverse regulatory mechanism contributing to bladder cancer progression; Foxp3 expression attenuates HIF-1α degradation. We first demonstrated that Foxp3 expression positively correlates with the metastatic potential in T24 cells and can increase the expression of HIF-1α-target genes, such as vascular endothelial growth factor (VEGF) and glucose transporter (GLUT). Foxp3 protein can bind with HIF-1α, particularly under hypoxia. In vivo ubiquination assay demonstrated that Foxp3 can decrease HIF-1α degradation in a dose-dependent manner. Knocking-down of Foxp3 expression blocks in vivo tumor growth in mice and prolongs mice's survival, which is associated with von Willebrand factor expression. Thirty-three of 145 (22.8 %) bladder tumors exhibit Foxp3 expression. Foxp3 expression is an independent predictor for disease progression in superficial bladder cancer patients (p = 0.032), associated with less number of intratumoral CD8+ lymphocyte. The metaanalysis from 2 published datasets showed Foxp3 expression is positively associated with GLUT-4,-9, and VEGF-A, B-, D expression. This reverse post-translational regulation of HIF-1α protein by Foxp3 provides a new potential target for developing new therapeutic strategy for bladder cancer.