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Alcoholic liver disease:Utility of animal models

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World Journal of gastroenterology 2018年第45期24卷 5063-5075页

作者： Arantza Lamas-Paz Fengjie Hao Leonard J Nelson Maria Teresa Vázquez Santiago Canals manuel gómez del Moral Eduardo Martínez-Naves Yulia A Nevzorova Francisco Javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain Institute for Bioengineering(IBioE) School of EngineeringFaraday BuildingThe University of EdinburghEdinburgh EH9 3 JLScotlandUnited Kingdom Department of Human Anatomy and Embryology Complutense University School of MedicineMadrid 28040Spain Instituto de Neurociencias Consejo Superior de Investigaciones CientíficasUniversidad Miguel HernándezSan Juan de Alicante 03550Spain Department of Cell Biology Complutense University School of MedicineMadrid 28040Spain Department of genetics Physiology and MicrobiologyFaculty of BiologyUniversidad ComplutenseMadrid 28040Spain Department of Internal Medicine Ⅲ University Hospital RWTH AachenAachen 52062Germany

Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.

关键词： Steatohepatitis Cirrhosis Hepatocellular carcinoma Alcoholic liver disease Reactive oxygen species

Steatosis and insulin resistance in hepatitis C: A way out for the virus?

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World Journal of gastroenterology 2009年第40期15卷 5014-5019页

作者： José A del Campo manuel Romero-gómez Unit for The Clinical Management of Digestive Diseases and CIBERehd Hospital Universitario de Valme

The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

关键词： Steatosis Insulin resistance Hepatitis Cvirus

Modulation of host lipid metabolism by hepatitis C virus: role of new therapies

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World Journal of gastroenterology 2015年第38期21卷 10776-10782页

作者： José A del Campo manuel Romero-gómez Digestive Diseases and CIBERehd Valme University Hospital

It is well established that hepatitis C virus(HCV) infection and replication relies on host lipid metabolism. HCV proteins interact and associate with lipid droplets to facilitate virion assembly and production. Besides,circulating infective particles are associated with verylow-density lipoprotein. On the other hand,higher serum lipid levels have been associated with sustained viral response to pegylated interferon and ribavirin therapy in chronic HCV infection,suggesting a relevant role in viral clearance for host proteins. Host and viral genetic factors play an essential role in chronic infection. Lipid metabolism is hijacked by viral infection and could determine the success of viral replication. Recently development of direct acting antiviral agents has shown a very high efficacy(> 90%) in sustained viral response rates even for cirrhotic patients and most of the viral genotypes. HCV RNA clearance induced by Sofosbuvir has been associated with an increased concentration and size of the low-density lipoprotein particles. In this review,host genetic factors,viral factors and the interaction between them will be depicted to clarify the major issues involved in viral infection and lipid metabolism.

关键词： Hepatitis C virus Lipid metabolism Direct acting a

Catenoidal Layers for the Allen-Cahn Equation in Bounded Domains

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Chinese Annals of Mathematics,Series B 2017年第1期38卷 13-44页

作者： Oscar AgUdelO manuel del PINO Juncheng WEI Department of Mathematics Zapadocescka Univerzita v PlzniPlzenCzech Republic Departamento de Ingenieria Matematica and CMM Universidad de ChileCasilla 170 Correo 3SantiagoChile Department of Mathematics University of British ColumbiaVancouver BC V6T 1Z2Canada

This paper presents a new family of solutions to the singularly perturbed Allen-Cahn equation α~2Δu + u(1- u^2) = 0 in a smooth bounded domain Ω R^3, with Neumann boundary condition and α > 0 a small parameter. These solutions have the property that as α→ 0, their level sets collapse onto a bounded portion of a complete embedded minimal surface with finite total curvature intersecting ?Ω orthogonally and that is non-degenerate respect to ?Ω. The authors provide explicit examples of surfaces to which the result applies.

关键词： Allen-Cahn equation Critical minimal surfaces Critical catenoid Infinite dimensional gluing method Neumann boundary condition

Stepping up after spinal cord injury:negotiating an obstacle during walking

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Neural Regeneration Research 2025年第7期20卷 1919-1929页

作者： Alain Frigon Charly g.Lecomte Department of Pharmacology-Physiology Faculty of Medicine and Health SciencesUniversitéde SherbrookeCentre de recherche du Centre Hospitalier Universitaire de SherbrookeSherbrookeQCCanada

Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate *** spinal cord injury,stepping over an obstacle becomes *** over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor *** information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain *** spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an ***,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.

关键词： biomechanics locomotion neurophysiology obstacle negotiation spinal cord injury

Type Ⅱ Blow-up in the 5-dimensional Energy Critical Heat Equation

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Acta Mathematica Sinica,English Series 2019年第6期35卷 1027-1042页

作者： manuel del PINO Monica MUSSO Jun Cheng WEI Department of Mathematical Sciences University of Bath Departamento de Ingeniería Matemática-CMM Universidad de Chile Departamento de Matemáticas Universidad Católica de Chile Department of Mathematics University of British Columbia

We consider the Cauchy problem for the energy critical heat equation ■ in dimension n = 5. More precisely we find that for given points q_1, q_2,..., q_k and any sufficiently small T > 0 there is an initial condition u0 such that the solution u(x, t) of(0.1) blows-up at exactly those k points with rates type Ⅱ, namely with absolute size ～(T-t)^(-α) for α >3/4. The blow-up profile around each point is of bubbling type, in the form of sharply scaled Aubin–Talenti bubbles.

关键词： Singularity formation bubbling phenomena critical parabolic equations

An SPH Framework for Earthquake-Induced Liquefaction Hazard Assessment of geotechnical Structures

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 251-277页

作者： Sourabh Mhaski g.V.Ramana Department of Civil Engineering Indian Institute of Technology DelhiNew Delhi110016India

Earthquake-induced soil liquefaction poses significant risks to the stability of geotechnical structures *** understanding of the liquefaction triggering,and the post-failure large deformation behaviour is essential for designing resilient *** present study develops a Smoothed Particle Hydrodynamics(SPH)framework for earthquake-induced liquefaction hazard assessment of geotechnical *** coupled flowdeformation behaviour of soils subjected to cyclic loading is described using the PM4Sand model implemented in a three-phase,single-layer SPH framework.A staggered discretisation scheme based on the stress particle SPH approach is adopted to minimise numerical inaccuracies caused by zero-energy modes and tensile ***,non-reflecting boundary conditions for seismic analysis of semi-infinite soil domains using the SPH method are *** numerical framework is employed for the analysis of cyclic direct simple shear test,seismic analysis of a level ground site,and liquefaction-induced failure of the Lower San Fernando *** agreement for liquefaction triggering and post-failure behaviour demonstrates that the SPH framework can be utilised to assess the effect of seismic loading on field-scale geotechnical *** present study also serves as the basis for future advancements of the SPH method for applications related to earthquake geotechnical engineering.

关键词： Earthquake seismic liquefaction stress particle PM4Sand smoothed particle hydrodynamics(SPH)

Bioelectronic medicine in modulation of cortical spreading depolarization and beyond

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Neural Regeneration Research 2025年第2期20卷 481-482页

作者： Khaled Alok Timothy g.White Chunyan Li Department of Neurosurgery Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellHempsteadNYUSA Translational Brain Research Laboratory The Feinstein Institutes for Medical ResearchManhassetNYUSA

Bioelectronic interventions,specifically trigeminal nerve st imulat ion(TNS),have attracted considerable attention in conditions where cortical spreading depolarizations(CSDs)accompanied by compromised cerebral perfusion may exacerbate neurological *** pharmacological interventions have demonstrated initial potential in addressing CSDs,a standardized treatment approach has not yet been *** objective of this perspective is to explore emerging bioelectronic methodologies for addressing CSDs,particularly emphasizing TNS,and to underscore TNS’s capacity to enhance neurovascular coupling and cerebral perfusion.

关键词： cerebral perfusion electronic

Impact of Zika virus non-structural protein mutations on hippocampal damage

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Neural Regeneration Research 2025年第8期20卷 2307-2308页

作者： Larissa M.g.Cassiano Roney S.Coimbra Neurogenômica/Imunopatologia Instituto RenéRachouFiocruzBelo HorizonteBrazil Departamento de Bioquímica e Imunologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

The Zika virus(ZIKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in ***,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNS)in both children and adults,leading to enduring cognitive and behavioral impairments.

关键词： damage fetal neonatal