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Complement:a global immunometabolic regulator in amyotrophic lateral sclerosis

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Neural Regeneration Research 2021年第6期16卷 1210-1211页

作者： Martin W.Lo john d.lee School of Biomedical Sciences Faculty of MedicineThe University of QueenslandSt LuciaQueenslandAustralia

Recently,Mcdonald et al.(2020)proposed that complement causes a metabolic switch to lipid consumption in amyotrophic lateral sclerosis(ALS),which raises the possibility of complement as a global immunometabolic *** ALS,neuromuscular degeneration occurs concurrently with complement-mediated inflammation,glucose intolerance,and elevated lipid ***,complement is being increasingly recognized as a metabolic regulator that can induce insulin resistance and alter fuel source ***,the authors propose that chronic complement activation may be driving metabolic reprogramming in ALS,which has broad implications for the field of immunometabolism and would be the first mechanistic explanation of the“lipid switch”in ***,it suggests that complement can drive a global shift in resources during inflammation,in which glucose is redirected from peripheral tissues to immune cells to support their inflammatory actions.

关键词： inflammation metabolism elevated

Targeting TrkB–PSd-95 coupling to mitigate neurological disorders

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Neural Regeneration Research 2025年第3期20卷 715-724页

作者： Xin Yang Yu-Wen Alvin Huang john Marshall department of Molecular Biology Cell Biology and BiochemistryBrown UniversityProvidenceRIUSA department of Neurology Warren Alpert Medical School of Brown UniversityProvidenceRIUSA Center for Translational Neuroscience Robert J.and Nancy D.Carney Institute for Brain Science and Brown Institute for Translational ScienceBrown UniversityProvidenceRIUSA

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and *** activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term ***,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term *** this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and *** with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 *** TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific *** TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

关键词： Angelman syndrome autism brain-derived neurotrophic factor depression neurodegenerative disorder neurodevelopmental disorder postsynaptic density protein-95 synaptic plasticity TrkB

Sustained virologic response following HCV eradication in two brothers with X-linked agammaglobulinaemia

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World Journal of Gastroenterology 2009年第31期15卷 3944-3946页

作者： diarmaid d Houlihan Eoin R Storan john M lee department of Gastroenterology University College Hospital Galway

X-linked agammaglobulinaemia (XLA) is a humoral immunodeficiency syndrome characterized from childhood by the absence of circulating B lymphocytes, absent or reduced levels of serum immunoglobulin and recurrent bacterial infections. For many affected patients, regular treatment with immunoglobulin is life saving. Hepatitis C viral (HCV) infection acquired through contaminated blood products is widely described in this patient cohort. The natural history of HCV infection in patients with XLA tends to follow a more rapid and aggressive course compared to immunocompetent individuals. Furthermore, standard anti-viral therapy appears to be less efficacious in this patient cohort. Here we report the cases of two brothers with XLA who contracted HCV through contaminated blood products. They were treated with a six month course of Interferon alpha-2b and Ribavirin. We report a sustained virologic response five years after completing treatment.

关键词： Hepatitis C virus X-linked agammaglo- bulinaemia Immunodeficiency Viral hepatitis Cirrhosis Hepatocellular carcinoma

A spotlight on dosage and subject selection for effective neuroprotection: exploring the central role of mitochondria

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Neural Regeneration Research 2025年第4期20卷 1081-1082页

作者： john Mitrofanis Jonathan Stone Michael R.Hamblin Pierre Magistretti Alim-Louis Benabid Glen Jeffery Fonds Clinatec UniversitéGrenoble AlpesGrenobleFrance School of Medical Science University of SydneySydneyAustralia Faculty of Health Sciences University of JohannesburgJohannesburgSouth Africa King Abdullah University of Science and Technology ThuwalSaudi Arabia Institute of Ophthalmology University College LondonLondonUK

Neurons are notoriously vulnerable cell *** the slightest change in their internal and/or external environments will cause much distress and dysfunction,leading often to their death.A range of pathological conditions,including stroke,head trauma,and neurodegenerative disease,can generate stress in neurons,affecting their survival and proper *** most neural pathologies,mitochondria become dysfunctional and this plays a pivotal role in the process of cell *** challenge over the last few decades has been to develop effective interventions that improve neuronal homeostasis under pathological *** interventions,often referred to as disease-modifying or neuroprotective,have,however,proved frustratingly elusive,at both preclinical and,in particular,clinical *** this perspective,we highlight two factors that we feel are key to the development of effective neuroprotective *** are:firstly,the choice of dose of intervention and method of application,and secondly,the selection of subjects,whether they be patients or the animal model.

关键词： protective dosage distress

(Super)paramagnetic nanoparticles as platform materials for environmental applications: From synthesis to demonstration

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Frontiers of Environmental Science & Engineering 2020年第5期14卷 15-23页

作者： Wenlu Li john d.Fortner department of Chemical and Environmental Engineering Yale UniversityNew HavenCT 06520USA

Over the past few decades,engineered,(super)paramagnetic nanoparticles have drawn extensive research attention for a broad range of applications based on their tunable size and shape,surface chemistries,and magnetic *** review summaries our recent work on the synthesis,surface modification,and environmental application of(super)paramagnetic *** utilizing high-temperature thermo-decomposition methods,first,we have broadly demonstrated the synthesis of highly monodispersed,(super)paramagnetic nanoparticles,via the pyrolysis of metal carboxylate salts in an organic *** uniform magnetic nanoparticles with various size,composition,and shape can be precisely tuned by controlled reaction parameters,such as the initial precursors,heating rate,final reaction temperature,reaction time,and the *** materials can be further rendered water stable via functionalization with surface mono/bi-layer coating structure using a series of tunable ionic/non-ionic ***,we have demonstrated platform potential of these materials for heavy metal ions sensing,sorption,and separation from the aqueous phase.

关键词： Superparamagnetic nanoparticles Surface functionalization Environmental sensing Heavy metal ion sorption

Computational Modeling of dual-Phase Ceramics with Finsler-Geometric Phase Field Mechanics

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Computer Modeling in Engineering & Sciences 2019年第8期120卷 333-350页

作者： john d.Clayton US ARL Impact Physics BranchAberdeen Proving GroundMD21005-5066USA

A theory invoking concepts from differential geometry of generalized Finsler space in conjunction with diffuse interface modeling is described and implemented in finite element(FE)simulations of dual-phase polycrystalline ceramic *** parameters accounting for fracture and other structural transformations,notably partial dislocation slip,twinning,or phase changes,are dimensionless entries of an internal state vector of generalized pseudo-Finsler *** investigated in computations are a boron carbide-titanium diboride(B4C-TiB2)composite and a diamond-silicon carbide(C-SiC)*** mechanisms-in addition to elasticity and cleavage fracture in grains of any phase-include restricted dislocation glide(TiB2 phase),deformation twinning(B4C and-SiC phases),and stress-induced amorphization(B4C phase).The metric tensor of generalized Finsler space is scaled conformally according to dilatation induced by cavitation or other fracture modes and densification induced by phase *** of pure shear consider various morphologies and lattice *** of microstructure on overall strength of each composite are *** B4C-TiB2,minor improvements in shear strength and ductility are observed with an increase in the second phase from 10 to 18%by volume,suggesting that residual stresses or larger-scale crack inhibition may be responsible for toughness gains reported *** diamond-SiC,a composite consisting of diamond crystals encapsulated in a nano-crystalline SiC matrix shows improved strength and ductility relative to a two-phase composite with isolated bulk SiC grains.

关键词： Micromechanics ceramic composites,Finsler space differential geometry phase field finite elements

Chronic liver disease in Aboriginal North Americans

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World Journal of Gastroenterology 2008年第29期14卷 4607-4615页

作者： john d Scott Naomi Garland department of Medicine Division of Allergy and Infectious Diseases University of WashingtonSeattle WA 98144 United States department of Laboratory Medicine University of WashingtonSeattle WA 98144 United States

A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLd) in Aboriginal North Americans. CLd affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLd, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLd. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLd. Future research should monitor the incidence and etiology of CLd and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLd) in this population.

关键词： Hepatitis C virus Hepatitis B virus American Indian Alaska Native Chronic liver disease

Biomarkers for diet and cancer prevention research:potentials and challenges

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Acta Pharmacologica Sinica 2007年第9期28卷 1262-1273页

作者： Cindy d dAVIS john A MILNER Nutritional Science Research GroupNational Cancer InstituteRockvilleMd 20892USA

As cancer incidence is projected to increase for decades there is a need for effec-tive preventive ***,evidence continues to mount that alteringdietary habits is an effective and cost-efficient approach for reducing cancer riskand for modifying the biological behavior of ***,validated andsensitive biomarkers,including those that reliably evaluate"intake"or exposureto a specific food or bioactive component,that assess one or more specific bio-logical"effects"that are linked to cancer,and that effectively predict individual"susceptibility"as a function of nutrient-nutrient interactions and genetics,arefundamental to evaluating who will benefit most from dietary *** must be readily accessible,easily and reliably assayed,and predictiveof a key process(es) involved in *** response to a food is determined notonly by the effective concentration of the bioactive food component(s) reachingthe target tissue,but also by the amount of the target requiring ***,this threshold response to foods and their components will vary from indi-vidual to *** key to understanding a personalized response is a greaterknowledge of nutrigenomics,proteomics and metabolomics.

关键词： exposure biomarker effect biomarker susceptibility biomarker nutrigenomics

Inverse analysis of laboratory data and observations for evaluation of backward erosion piping process

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第5期12卷 1080-1092页

作者： Sige Peng john d.Rice School of Civil Engineering and Transportation South China University of TechnologyGuangzhou510640China department of Civil and Environmental Engineering Utah State UniversityLogan84322UTUSA

An inverse analysis procedure has been developed to interpret collected pore pressure data and observations during backward erosion piping(BEP)initiation and progression in sandy *** procedure has been applied to laboratory models designed to mimic the initiation and progression of BEP through a constricted vertical *** inverse analysis uses three-dimensional(3d)finite element method(FEM)to successively produce models of the hydraulic head regime surrounding progressive stages of BEP based on observations at the sample surface and pore pressure measurements obtained from the laboratory *** inverse analysis results in a series of 3d contour plots that represent the hydraulic-head regime at each stage of the BEP development,allowing for assessing the development of BEP mechanism as well as calculating the critical hydraulic conditions required for various BEP stages to initiate and *** of the results identified four significant stages of the piping process:(1)loosened zone initiation,(2)channel initiation and progression,(3)riser sand fluidization,and(4)loosened zone *** of the hydraulic head contour plots allows assessment of the critical hydraulic gradients needed to initiate and progress various components of the BEP development.

关键词： Backward erosion piping(BEP) Laboratory modeling Inverse analysis Finite element method(FEM) Soil loosening Critical gradient