Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L

Generation of PI3P in the normally PI3P-deficient ER membrane makes the organelle a platform for autophagosome formation

Experimental and Numerical Study on Disc-RDE: Flow Structure and its Performances

The present study discusses disc-type rotating detonation engine (DRDE) experimentally and numerically. The experimental work shows that the detonation propagates in three different modes; single, dual, and hybrid. The operating frequency of dual-wave mode is 1.8-2.1 times faster than that of single wave mode. The number of detonation wave can be predicted based on the pressure history and the operating frequency signal. The numerical work shows the performance of 3D numerical analysis of DRDE with uniform injection case and multiport injection case. By increasing the wave number from one to two, the detonation propagation velocity decreases by 18.7 %. The one-detonation head case gives some better performance to the flow than the two-detonation head case. The inlet flow angle to the radial turbine becomes about 50 degrees to the radial direction no matter how large the plenum chamber is.AIAA Scitech 2021 Forum, 11–15 & 19–21 January, 2021, Virtual Even

A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β1 pathways

Renal fibrosis is closely related to chronic inflammation and is under the control of epigenetic regulations. Because the signaling of transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) play key roles in progression of renal fibrosis, dual blockade of TGF-β1 and TNF-α is desired as its therapeutic approach. Here we screened small molecules showing anti-TNF-α activity in the compound library of indole derivatives. 11 out of 41 indole derivatives inhibited the TNF-α effect. Among them, Mitochonic Acid 35 (MA-35), 5-(3, 5-dimethoxybenzyloxy)-3-indoleacetic acid, showed the potent effect. The anti-TNF-α activity was mediated by inhibiting IκB kinase phosphorylation, which attenuated the LPS/GaIN-induced hepatic inflammation in the mice. Additionally, MA-35 concurrently showed an anti-TGF-β1 effect by inhibiting Smad3 phosphorylation, resulting in the downregulation of TGF-β1-induced fibrotic gene expression. In unilateral ureter obstructed mouse kidney, which is a renal fibrosis model, MA-35 attenuated renal inflammation and fibrosis with the downregulation of inflammatory cytokines and fibrotic gene expressions. Furthermore, MA-35 inhibited TGF-β1-induced H3K4me1 histone modification of the fibrotic gene promoter, leading to a decrease in the fibrotic gene expression. MA-35 affects multiple signaling pathways involved in the fibrosis and may recover epigenetic modification; therefore, it could possibly be a novel therapeutic drug for fibrosis

ザイショク ロウドウシャ ノ ショクギョウ ノウリョク ケイセイ オ メグル イチカダイ ニツイテ

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Efficacy of intraoperative fluorescence imaging using indocyanine green‐containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report

Abstract In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green‐containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography