Functions of ULK1 in autophagy and non-autophagy pathways and its implications in human physiology and disease

ULK1(unc-51 like autophagy activating kinase 1),a mammalian serine/threonine kinase,is a key component of autophagy initiation complex and helps to induce all types of autophagy.Canonical autophagy is a process in which,through the interactions of a series of autophagy-related proteins,damaged organelles or misfolded proteins are engulfed by autophagosomes and then merged with lysosomes to be degraded.Thus,canonical autophagy is an important constituent part of the cellular“quality control.”Besides,accumulating evidence indicates that ULK1 exerts autophagy-independent effects in a cell-specific manner.For example,ULK1 facilitates neurite elongation through the regulation of endoplasmic reticulum(ER)–Golgi trafficking in neurons,stimulates phosphopentose pathway to help NADPH(nicotinamide adenine dinucleotide phosphate hydrogen)production,and acts as a duplex regulator in type I IFN(type I interferon)induced innate immune response.Considering the importance and diversity of ULK1 in various biological processes,this review aims to present a comprehensive overview of autophagy and non-autophagy related functions of ULK1 in a variety of human physiological,pathological,and disease processes.

Hepatic Arterioportal Fistulas: A Retrospective Analysis of 97 Cases

Background and Aims:Hepatic arterioportal fistulas(HAPFs)are abnormal shunts or aberrant functional con-nections between the portal venous and the hepatic arte-rial systems.Detection of HAPFs has increased with the ad-vances in diagnostic techniques.Presence of HAPFs over a prolonged period can aggravate liver cirrhosis and further deteriorate liver function.However,the underlying causes of HAPFs and the treatment outcomes are now well character-ized.This study aimed to summarize the clinical character-istics of patients with HAPFs,and to compare the outcomes of different treatment modalities.Methods:Data of 97 pa-tients with HAPFs who were admitted to the Second Xiang-ya Hospital between January 2010 and January 2020 were retrospectively reviewed.Demographic information,clinical manifestations,underlying causes,treatment options,and short-term outcomes were analyzed.Results:The main cause of HAPF in our cohort was hepatocellular carcinoma(78/97,80.41%),followed by cirrhosis(10/97,10.31%).The main clinical manifestations were abdominal distention and abdominal pain.Treatment methods included transcath-eter arterial embolization(n=63,64.9%),surgery(n=13,13.4%),and liver transplantation(n=2,2.1%);nineteen(19.6%)patients received conservative treatment.Among patients who underwent transcatheter arterial embolization,polyvinyl alcohol,lipiodol combined with gelatin sponge,and spring steel ring showed comparable efficacy.Conclusions:Hepatocellular carcinoma and cirrhosis are common causes of HAPFs.Transcatheter arterial embolization is a safe and effective method for the treatment of HAPFs,and polyvinyl alcohol,lipiodol combined with gelatin sponge,and spring steel ring showed comparable efficacy in our cohort.