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The effective voltage of soil refers to the actual voltage which is acting on the soil. When electroosmosis is adopted to strengthen the soft foundation, the soil effective voltage is less than the applied power supply voltage. The effective voltage of the soil gradually decreases with the progress of electroosmosis and tends to reach a stable value. In this regard, based on the analysis of the experimental results that the soil effective voltage first undergoes a linear decrease over time and then remains unchanged, the classical electroosmotic consolidation theory proposed by Esrig is modified in this paper in order to obtain a new analytical solution of excess pore water pressure. Then, the analytical solution is verified by a specific experimental case and compared with Esrig's theory. The results indicate that the theoretical value of excess pore water pressure, which was obtained from the modified electroosmotic consolidation equation, is closer to the measured value and caters better to the actual situation in comparison with Esrig's theory. This provides evidence for the rationality of the analytical solution and further improves the existing electroosmotic consolidation theory. [ABSTRACT FROM AUTHOR]

Necroptosis is a form of regulated cell death that depends on the receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL). The molecular mechanisms underlying distinct instances of necroptosis have only recently begun to emerge. In the present study, we characterized RABGEF1 as a positive regulator of RIPK1/RIPK3 activation in vitro. Based on the overexpression and knockdown experiments, we determined that RABGEF1 accelerated the phosphorylation of RIPK1 and promoted necrosome formation in L929 cells. The pro-necrotic effect of RABGEF1 is associated with its E3 ubiquitin ligase activity and guanine nucleotide exchange factor (GEF) activity. We further confirmed that RABGEF1 interacts with cIAP1 protein by inhibiting its function and plays a regulatory role in necroptosis, which can be abolished by treatment with the antagonist Smac mimetic (SM)-164. In conclusion, our study highlights a potential and novel role of RABGEF1 in promoting TNF-induced cell necrosis. • RABGEF1 promotes the phosphorylation of RIPK1 and formation of complex Ⅱb in L929 cells. • RABGEF1 does not affect TNF-induced activation of NF-kB and MAPK signaling pathways. • Knockdown of RABGEF1 levels inhibits TNF-induced necroptosis and necrosome formation. • The pro-necrotic effect of RABGEF1 is associated with the A20-type zinc finger and Vps9 domains. • RABGEF1 interacts with cIAP1 but does not affect cIAP1 protein levels. [ABSTRACT FROM AUTHOR]

Necroptosis is a form of regulated cell death that has been implicated in multiple diseases. TNF-induced necroptosis is regulated by necrosomes, complexes consisting of RIPK1, RIPK3 and MLKL. In this study, by screening of a small-compound library, we identified dozens of compounds that inhibited TNF-induced necroptosis. According to the mechanisms by which they inhibited necroptosis, these compounds were classified into different groups. We then identified Ibrutinib as an inhibitor of RIPK3 and found that Quizartinib protected against the TNF-induced systemic inflammatory response syndrome in mice by inhibiting the activation of RIPK1. Altogether, our work revealed dozens of necroptosis inhibitors, suggesting new potential approaches for treating necroptosis-related diseases. Screening a library of compounds identifies several inhibitors of TNF-induced necroptosis, including Ibrutinib as an inhibitor of RIPK3 and Quizartinib as an indirect RIPK1 kinase activity inhibitor. [ABSTRACT FROM AUTHOR]