Targeting Aurora-A inhibits tumor progression and sensitizes thyroid carcinoma to Sorafenib by decreasing PFKFB3-mediated glycolysis.

Thyroid cancer (TC) is the most common endocrine tumor, amongst which anaplastic thyroid carcinoma (ATC) is the most deadly. Aurora-A usually functions as oncogenes, and its inhibitor Alisertib exerts a powerful antitumor effect in various tumors. However, the mechanism of Aurora-A in regulating TC cell energy supply remains unclear. In the present study, we demonstrated the antitumor effect of Alisertib and an association between high Aurora-A expression and shorter survival. Multi-omics data and in vitro validation data suggested that Aurora-A induced PFKFB3-mediated glycolysis to increase ATP supply, which significantly upregulated the phosphorylation of ERK and AKT. Furthermore, the combination of Alisertib and Sorafenib had a synergistic effect, further confirmed in xenograft models and in vitro. Collectively, our study provides compelling evidence of the prognostic value of Aurora-A expression and suggests that Aurora-A upregulates PFKFB3-mediated glycolysis to enhance ATP supply and promote TC progression. Combining Alisertib with Sorafenib has huge prospects for application in treating advanced thyroid carcinoma.

A comparison of variability and gait dynamics in spatiotemporal variables between different self-paced treadmill control modes.

This study investigates the effects of treadmill control algorithms on spatiotemporal variables when walking on a self-paced (SP) treadmill. Ten healthy subjects walked at their preferred walking speed for 15 min under three different treadmill control modes. Stride time, stride length, and stride speed were measured using an inertial measurement unit. The mean, coefficient of variance, Poincaré descriptors, and gait dynamics were calculated for each parameter. The mean values of stride length and stride speed were significantly increased when the treadmill had a quick response speed to the user's walking behavior. The long-term variability of stride length and stride speed was significantly affected by the treadmill control algorithms. A reduced strength of long-range correlations of stride time and stride speed was found when walking on the SP treadmill with suppressed treadmill accelerations and small velocity variations. We suggest that the suppression of treadmill acceleration provides more adaptability and less constraint to the user during SP treadmill walking. Although further research is required, the present work provides a basis for interpreting the influence of treadmill control algorithms on human gait.