Activation of RIPK1-driven cell death and inflammation play important roles in the progression of nonalcoholic steatohepatitis (NASH). However, the mechanism underlying RIPK1 activation in NASH remains unclear. Here we identified SENP1, a SUMO-specific protease, as a key endogenous inhibitor of RIPK1. SENP1 is progressively reduced in proportion to NASH severity in patients. Hepatocyte-specific SENP1-knockout mice develop spontaneous NASH-related phenotypes in a RIPK1 kinase-dependent manner. We demonstrate that SENP1 deficiency sensitizes cells to RIPK1 kinase-dependent apoptosis by promoting RIPK1 activation following TNFα stimulation. Mechanistically, SENP1 deSUMOylates RIPK1 in TNF-R1 signaling complex (TNF-RSC), keeping RIPK1 in check. Loss of SENP1 leads to SUMOylation of RIPK1, which re-orchestrates TNF-RSC and modulates the ubiquitination patterns and activity of RIPK1. Notably, genetic inhibition of RIPK1 effectively reverses disease progression in hepatocyte-specific SENP1-knockout male mice with high-fat-diet-induced nonalcoholic fatty liver. We propose that deSUMOylation of RIPK1 by SENP1 provides a pathophysiologically relevant cell death-restricting checkpoint that modulates RIPK1 activation in the pathogenesis of nonalcoholic steatohepatitis.

HighlightsVariability is a human nature and large or small variability could directly impact our measurement and statistical data analysis practice.If not handle correctly, variability could lead to incorrect conclusion or misleading statement on research findings.Using real and hypothetical data, common errors in measurement and analyzing of variability were illustrated and how to address the errors were highlighted.There is a call for improving in measurement techniques and better statistical training for handling variability.

Moisture content is an important index to assess the grain quality and food processing conditions. A measurement system based on the traveling–standing microwave attenuation method is designed for a fast and nondestructive grain moisture content determination. The proposed system consists of a microwave cavity oscillator, microwave transmitting and receiving horn antennas, microwave detector, slide rail, sample container, weight sensor, temperature sensor, and controller. The traveling–standing wave caused by free space microwave multiple reflection is discussed. The moisture content calibration functions eliminated the interference of bulk density and temperature are proposed based on the attenuation of the maximum field strength of the transmission traveling–standing wave. The moisture content of rice, which ranges from 10.75% to 27.62%, is obtained with a standard error of prediction (SEP) of 0.586% and a coefficient of determination ( R2) of 0.988, whereas the moisture content of corn, which ranges from 7.72% to 24.46%, is obtained with a SEP of 0.340% and R2 of 0.991. The main results might provide technical support for the development of accurate and intelligent grain quality detection equipment.