Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 (Gpx4) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4−/− mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4−/− mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
The dynamics of scientific and technological progress incorporates new content into the goals and objectives of special education in training specialists as creative and thinking individuals. As a result, it leads to specific problems that must be solved immediately. There is a need to rethink theoretical and psychoeducational foundations and accumulated practical experience of higher education institutions. The research aims to prove theoretically and to verify the effectiveness of pedagogical conditions for developing technical creativity in future engineering educators experimentally. The pedagogical conditions for developing technical creativity in future engineering educators are as follows: creating appropriate content and nature of teachers' activities; providing a creative environment for developing technical creativity. It must be noted that 261 students were involved in the experiment (a bachelor's degree): the control group (CG) consists of 134 students and the experimental group (EG) -of 127 students. Relevant control tests and questionnaires were employed during the experimental stage, which allowed assessing the effectiveness of the proposed activities. According to the results of the calculations, the statistics of the criterion is Тobs. > Тcrit. (14.94>11.34). Thus, with a probability of 0.99, one can argue that the level of technical creativity in EG students differs from the level in CG. Indeed, the high level is 29.92% G and the average level in 53.54%. At the same time, the high and average levels of CG students are 16.42% and 47.76% respectively. The analysis of experimental work shows the expediency of the justified and verified pedagogical conditions for developing the technical creativity in future engineering educators.
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