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Autophagy and ethanol-induced liver injury

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World Journal of Gastroenterology 2009年第10期15卷 1178-1185页

作者： terrence M Donohue Jr Liver Study Unit The Omaha Veterans Affairs Medical Center Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68105 United States

The majority of ethanol metabolism occurs in the liver. Consequently, this organ sustains the greatest damage from ethanol abuse. Ethanol consumption disturbs the delicate balance of protein homeostasis in the liver, causing intracellular protein accumulation due to a disruption of hepatic protein catabolism. Evidence indicates that ethanol or its metabolism impairs trafficking events in the liver, including the process of macroautophagy, which is the engulfment and degradation of cytoplasmic constituents by the lysosomal system. Autophagy is an essential, ongoing cellular process that is highly regulated by nutrients, endocrine factors and signaling pathways. A great number of the genes and gene products that govern the autophagic response have been characterized and the major metabolic and signaling pathways that activate or suppress autophagy have been identified. This review describes the process of autophagy, its regulation and the possible mechanisms by which ethanol disrupts the process of autophagic degradation. The implications of autophagic suppression are discussed in relation to the pathogenesis of alcohol-induced liver injury.

关键词： Autophagy Autophagosome Ethanolmetabolism Hepatomegaly Lysosomes Signal transduction

A Review of Fluid Inclusions in Diagenetic Systems

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Acta Geologica Sinica(English Edition) 2015年第3期89卷 697-714页

作者： terrence P.MERNAGH Research School of Earth Sciences The Australian National University

The study of fluid inclusions can help constrain the conditions at which diagenetic minerals precipitated,leading to a better understanding of the geologic controls and relative timing of changes in porosity and/or mineralising *** of the diagenetic minerals are easily deformed and it is important to check for any post-entrapment changes to the *** post-entrapment changes include reaction with the host crystal,necking down,nucleation metastability and thermal *** recommended method of detecting these problems is to examine individual fluid inclusion assemblages（FIAs） and report data for each individual *** studies have been enhanced by the development of new micro-analytical techniques such as micro-fluorescence spectroscopy,micro-infrared spectroscopy,nuclear magnetic resonance,various mass spectrometry techniques and the analysis of individual fluid inclusions using laser ablation/decrepitation *** techniques have been developed for hydrocarbon-bearing inclusions such as the Grains containing Oil Inclusions（GOI）,Fluid Inclusion Stratigraphy（FIS）,and the Molecular Composition of Inclusions（MCI） *** fluid inclusions that form in some minerals during diagenesis provide the only direct means of examining the fluids present in these *** provide useful temperature,pressure,and fluid composition data that cannot be obtained by other means.

关键词： Fluid inclusions diagenesis saline formations hydrocarbons mineralisation

Alcohol-induced steatosis in liver cells

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World Journal of Gastroenterology 2007年第37期13卷 4974-4978页

作者： terrence M Donohue Jr Liver Study Unit The Omaha Veterans Affairs Medical Center the Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68105 United States

Alcohol-induced fatty liver (steatosis) was believed to result from excessive generation of reducing equivalents from ethanol metabolism, thereby enhancing fat accumulation. Recent findings have revealed a more complex picture in which ethanol oxidation is still required, but specific transcription as well as humoral factors also have important roles. Transcription factors involved include the sterol regulatory element binding protein 1 (SREBP-1) which is activated to induce genes that regulate lipid biosynthesis. Conversely, ethanol consumption causes a general down-regulation of lipid (fatty acid) oxidation, a reflection of inactivation of the peroxisome proliferator- activated receptor-alpha (PPAR-α) that regulates genes involved in fatty acid oxidation. A third transcription factor is the early growth response-1 (Egr-1), which is strongly induced prior to the onset of steatosis. The activities of all these factors are governed by that of the principal regulatory enzyme, AMP kinase. Important humoral factors, including adiponectin, and tumor necrosis factor-α (TNF-α), also regulate alcohol-induced steatosis. Their levels are affected by alcohol consumption and by each other. This review will summarize the actions of these proteins in ethanol-elicited fatty liver. Because steatosis is now regarded as a significant risk factor for advanced liver pathology, an understanding of the molecular mechanisms in its etiology is essential for development of effective therapies.

关键词： Ethanol metabolism Fatty liver Sterolregulatory element binding protein Peroxisomeproliferator activated receptor Early growth response-i Fatty acid toxicity Triglycerides Acetaldehyde Reactiveoxygen species

Film cooling performance and flow structure of single-hole and double-holes with swirling jet

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Chinese Journal of Aeronautics 2022年第3期35卷 201-213页

作者： Rui ZHU Simon terrence Shulei LI Gongnan XIE School of Mechanical Engineering Northwestern Polytechnical UniversityXi’an 710072China Research&Development Institute of Northwestern Polytechnical University in Shenzhen Shenzhen 518057China Department of Mechanical Engineering University of MinnesotaMinneapolisMN 55455USA School of Marine Science and Technology Northwestern Polytechnical UniversityXi’an 710072China

This paper presents the results of a numerical study of the effects of swirling flow in coolant jets on film cooling *** combined-hole designs with swirling coolant flow entering the delivery hole are proposed and *** film cooling effectiveness values for cases with various blowing ratios are *** flow structures and underlying mechanisms are *** results show that film cooling effectiveness is improved with jet swirl at high blowing ratios,and that swirl strength has significant influence on film cooling ***-hole designs can further improve film cooling performance using swirling jets due to mixing of coolant flows and interaction of *** largest improvements of area-averaged film cooling effectiveness for a single-hole swirl case and a combined-hole swirl case over corresponding non-swirling case results are 157%and 173%,respectively.

关键词： Combined-hole Film cooling Interactions of vortices Jet-in-cross-flow Swirling flow

Implication of altered proteasome function in alcoholic liverinjury

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World Journal of Gastroenterology 2007年第37期13卷 4931-4937页

作者： Natalia A Osna terrence M Donohue Jr Liver Study Unit The Omaha Veterans Affairs Medical Center the Department of Internal Medicine University of Nebraska Medical Center Omaha Nebraska 68105 United States

The proteasome is a major protein-degrading enzyme, which catalyzes degradation of oxidized and aged proteins, signal transduction factors and cleaves peptides for antigen presentation. Proteasome exists in the equilibrium of 26S and 20S particles. Proteasome function is altered by ethanol metabolism, depending on oxidative stress levels： low oxidative stress induces proteasome activity, while high oxidative stress reduces it. The proposed mechanisms for modulation of proteasome activity are related to oxidative modification of proteasomal proteins with primary and secondary products derived from ethanol oxidation. Decreased proteolysis by the proteasome results in the accumulation of insoluble protein aggregates, which cannot be degraded by proteasome and which further inhibit proteasome function. Mallory bodies, a common signature of alcoholic liver diseases, are formed by liver cells, when proteasome is unable to remove cytokeratins. Proteasome inhibition by ethanol also promotes the accumulation of pro-apoptotic factors in mitochondria of ethanol-metabolizing liver cells that are normally degraded by proteasome. In addition, decreased proteasome function also induces accumulation of the negative regulators of cytokine signaling （I-~B and SOCS）, thereby blocking cytokine signal transduction. Finally, ethanol-elicited blockade of interferon type 2 and 2 signaling and decreased proteasome function impairs generation of peptides for MHC class Ⅰ-restricted antigen presentation.

关键词： 20S proteasome 26S proteasome, PA28, CYP2E1, Apoptosis, Liver

Internal flow in sessile droplets induced by substrate oscillation:towards enhanced mixing and mass transfer in microfluidic systems

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Microsystems & Nanoengineering 2024年第3期10卷 369-379页

作者： Tianyi Zhang Peng Zhou terrence Simon Tianhong Cui Department of Mechanical Engineering University of MinnesotaMinneapolisMN 55455USA

The introduction of flows within sessile droplets is highly effective for many lab-on-a-chip chemical and biomedical ***,generating such flows is difficult due to the typically small droplet ***,we present a simple,non-contact strategy to generate internal flows in sessile droplets for enhancing mixing and mass *** flows are driven by actuating a rigid substrate into oscillation with certain amplitude distributions without relying on the resonance of the droplet *** oscillation characteristics and corresponding flow patterns are documented *** indices and mass transfer coefficients of sessile droplets on the substrate surface are measured using optical and electrochemical *** demonstrate complete mixing within the droplets in 1.35 s and increases in mass transfer rates of more than seven times static *** of concept was conducted with experiments of silver nanoparticle synthesis and with heavy metal ion sensing employing the sessile droplet as a microreactor for synthesis and an electrochemical cell for *** degrees of enhancement of synthesis efficiency and detection sensitivity attributed to the internal flows are experimentally documented.

关键词： mixing oscillation synthesis

On the Informational Essence of Emergence and Evolution：An Analysis of the New Dualistic Approach

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学术界 2018年第6期 214-221页

作者： terrence Deaco Wang Jian Department of Anthropology University of California Berkeley CA USA Department of Philosophy Xi'an Jiaotong University Xi'an Shaanxi 710049

Information is probably the single most important factor shaping the beginning of twenty-first century social *** Logan,in his book"What is Information",explores certain issues related toinformation on the basis of the connotation of information itself,and puts forward two importanttheories of"extended mind"and "symbolosphere".Based on the strong-emergence theory,Logandepicts the material emergence and non-material emergence,and proposes a neo-dualism view,aweak form of *** to this,different from the biosphere,the evolution andreproduction mechanism in symbolosphere do not follow the rules of genetic inheritance,but themechanisms of memes,belonging to the territory of information ***,the new dualismfaces the difficulty to correctly explain the ontological position of the symbolosphere,while thephilosophy of information provides a standard solution in its theory of human evolution.

关键词：进化二元信息扩大头两重性脑

Involvement of autophagy in alcoholic liver injury and hepatitis C pathogenesis

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World Journal of Gastroenterology 2011年第20期17卷 2507-2514页

作者： Natalia A Osna Paul G Thomes terrence M Donohue University of Nebraska Medical Center VA Medical Center

This review describes the principal pathways of macroautophagy (i.e. autophagy), microautophagy and chaperone-mediated autophagy as they are currently known to occur in mammalian cells. Because of its crucial role as an accessory digestive organ, the liver has a particularly robust autophagic activity that is sensitive to changes in plasma and dietary components. Ethanol consumption causes major changes in hepatic protein and lipid metabolism and both are regulated by autophagy, which is significantly affected by hepatic ethanol metabolism. Ethanol exposure enhances autophagosome formation in liver cells, but suppresses lysosome function. Excessive ethanol consumption synergizes with hepatitis C virus (HCV) to exacerbate liver injury, as alcohol-consuming HCV patients frequently have a longer course of infection and more severe manifestations of chronic hepatitis than abstinent HCV patients. Alcohol-elicited exacerbation of HCV infection pathogenesis is related to modulation by ethanol metabolism of HCV replication. Additionally, as part of this mechanism, autophagic proteins have been shown to regulate viral (HCV) replication and their intracel-lular accumulation. Because ethanol induces autophagosome expression, enhanced levels of autophagic proteins may enhance HCV infectivity in liver cells of alcoholics and heavy drinkers.

关键词： Autophagy Iysosome Autophagosome Hepatitis C virus Hepatitis C virus replication cycle Ethanol

Acute upper limb compartment syndrome in children: special focus on nerve recovery

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World Journal of Pediatric Surgery 2020年第3期3卷 11-22页

作者： terrence Jose Jerome Orthopedics Hand and Reconstructive MicrosurgeryOlympia Hospital&Research CentreTiruchirappalliIndia

Background Many studies have discussed acute compartment syndrome in children associated with or without fractures and have given their visible *** is known about the nerve involvement and the factors associated with recovery patterns in these *** intend to propose that ischemic nerve and muscles tend to regenerate after surgical decompression but in a different pattern and the given *** Twenty-four children with acute compartment syndrome in the upper limb were analyzed between 2009 and *** included demographic features of these patients,the time interval between the injury and surgery,and the attempt to correlate with motor and sensory *** The average follow-up was 67.3 months(range 59-80).Of the 24,14 patients(58%)had immediate recovery of motor and sensory *** remaining 10 patients had variable recovery patterns with a mean time for the radial nerve,median nerve and ulnar nerve motor recovery of 6.0,7.5 and 8.5 months,respectively,and sensory recovery at 12,12 and 13 months,*** overall study had a mean sensory recovery as per the Medical Research Council(MRC)of S3 in 3(12%)and S4 in 21(88%).The mean 2-point discrimination(2PD)was 6.9 mm(range 5-10).Twenty-one patients(88%)had a full range of movements at their final follow-up with a mean Visual Analog Scale score of 0.6;a quick Disabilities of the Arm,Shoulder and Hand score of 5.9(range 2.3-25.0)and a Mayo wrist score of *** There was a definite motor and sensory recovery in patients who underwent surgical decompression in acute compartment syndrome of the upper limb irrespective of age,gender,delay in presentation and various *** motor and nerve fibers can regenerate after ischemic sequela of compartment syndrome.

关键词： involvement children fibers