Cucurbitacin-I (Cu-I, also known as Elatericin B or JSI-124) is developed to inhibit constitutive and abnormal activation of STAT3 in many cancers, demonstrating a potent anticancer activity by targeting disruption of STAT3 function. Here, we for the first time systematically studied the underlying molecular mechanisms of Cu-I-induced gastric cancer cell death both in vitro and in vivo. In our study, we show that Cu-I markedly inhibits gastric cancer cell growth by inducing G2/M phase cell cycle arrest and apoptosis at low nanomolar concentrations via a STAT3-independent mechanism. Notably, Cu-I significantly decreases intracellular GSH/GSSG ratio by inhibiting NRF2 pathway to break cellular redox homeostasis, and subsequently induces the expression of GADD45α in a p53-independent manner, and activates JNK/p38 MAPK signaling. Interestingly, Cu-I-induced GADD45α and JNK/p38 MAPK signaling form a positive feedback loop and can be reciprocally regulated by each other. Therefore, the present study provides new insights into the mechanisms of antitumor effects of Cu-I, supporting Cu-I as an attractive therapeutic drug in gastric cancer by modulating the redox balance.

The impact of Al 2 O 3 -InAlN interface traps on the switching characteristics of Al 2 O 3 -InAlN-GaN MOSHEMTs was examined using temperature-dependent current-voltage characterization. A steep subthreshold swing (SS) as low as 37 mV/dec at 25 °C is obtained, and shows negative temperature dependence up to 180 °C. We attribute this behavior to the dynamic threshold voltage (V th ) induced by the de-trapping of the acceptor-like interface traps near the InAlN conduction-band edge, which acts as a positive feedback in increasing the drain current during the switch-on process. At elevated temperature, the thermally activated de-trapping of the deeper traps results in a more sufficient dynamic shift in V th and then leads to a steeper SS. The traps contributing to the steep SS were found within the energy levels ranging from E C − 0.55 to E C − 0.833 eV for the measured temperature range (25-180 °C). On the other hand, the interface traps near the midgap or at deeper energy levels act as quasi-fixed charges, which feature negligible impact on the switching behavior of the device.