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Carbon monoxide decreases interleukin-1β levels in the lung through the induction of pyrin

Cellular & Molecular Immunology 2017年第4期14卷 349-359页

作者： Seul-Ki Kim Yeonsoo Joe Yingqing Chen Jinhyun Ryu Jeong-Hee Lee Gyeong Jae Cho stefan w. ryter Hun Taeg Chung Department of Biological Sciences University of Ulsan Ulsan 680-749 Republic of Korea Department of Anatomy School of Medicine and Institute of Health Sciences Gyeongsang National University Jinju 660-701 Republic of Korea Department of Pathology School of Medicine and Institute of Health Sciences Gyeongsang National University Jinju 660-701 Republic of Korea Joan and Sanford I. w.ill Department of Medicine New York-Presbyterian Hospital Division of Pulmonary and Critical Care Medicine Weill Cornell Medical Center New York NY USA

Carbon monoxide （CO） can act as an anti-inflammatory effector in mouse models of lung injury and disease, through the dow.regulation of pro-inflammatory cytokines production, though the underlying mechanisms remain unclear. The nucleotide-binding oligomerization domain-, leucine-rich region-, and pyrin domain-containing-3 （NLRP3） inflammasome is a protein complex that regulates the maturation and secretion of pro-inflammatory cytokines, including interleukin-1β （IL-1β）. In this report, w. show.that the CO-releasing molecule （CORM-2） can stimulate the expression of pyrin, a negative regulator of the NLRP3 inflammasome. CORM-2 increased the transcription of pyrin in the human leukemic cell line （THP-1） in the absence and presence of lipopolysaccharide （LPS）. In THP-1 cells, CORM-2 treatment dose-dependently reduced the activation of caspase-1 and the secretion of IL-lp, and increased the levels of IL-IO, in response to LPS and adenosine 5＇-triphosphate （ATP）, an NLRP3 inflammasome activation model. Genetic interference of IL-10 by small interfering RNA （siRNA） reduced the effectiveness of CORM-2 in inhibiting IL-1β production and in inducing pyrin expression. Genetic interference of pyrin by siRNA increased IL-lp production in response to LPS and ATP, and reversed CORM-2-dependent inhibition of caspase-1 activation. CO inhalation （250 ppm） in vivo increased the expression of pyrin and IL-10 in lung and spleen, and decreased the levels of IL-1β induced by LPS. Consistent w.th the induction of pyrin and IL-10, and the dow.regulation of lung IL-1β production, CO provided protection in a model of acute lung injury induced by intranasal LPS administration. These results provide a novel mechanism underlying the anti-inflammatory effects of CO, involving the IL-10-dependent upregulation of pyrin expression.

关键词： anti-inflammatory effects carbon monoxide (CO) IL-1β inflammasome pyrin

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Modulation of the Nogo signaling pathw.y to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves stefan Przyborski Department of Biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are tw. of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced grow.h,extension,and abnormal grow.h cone morphology,all of w.ich contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,w. used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both tw.-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,grow.h substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrow.h,thus paving the w.y for potential future applications in personalized ***,w. also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of dow.stream ROCK and RhoA components of the Nogo signaling pathw.y,achieved through modulation w.th Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite grow.h and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along w.th potential intervention points to restore neurite ***,w. aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrow.h,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrow.h neuron Nogo Rho A ROCK stem cell three-dimensional culture

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IRG1 induced by heme oxygenase- 1/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production

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Cellular & Molecular Immunology 2016年第2期13卷 170-179页

作者： Md Jamal Uddin Yeonsoo Joe Seul-Ki Kim Sun Oh Jeong stefan w.ryter Hyun-Ock Pae Hun Taeg Chung School of Biological Sciences University of Ulsan Korea Department of Microbiology and Immunology Wonkwang University School of Medicine Korea Joan and Sanford I. w.ill Department of Medicine New York-Presbyterian Hospital Weill Cornell Medical College New York USA

The immunoresponsive gene 1 （IRG 1） protein has crucial functions in embryonic implantation and neurodegeneration. IRG1 promotes endotoxin tolerance by increasing A20 expression in macrophages through reactive oxygen species （ROS）. The cytoprotective protein heme oxygenase-1 （HO-1）, w.ich generates endogenous carbon monoxide （CO）, is expressed in the lung during Lipopolysaccharide （LPS） tolerance and cross tolerance. How.ver, the detailed molecular mechanisms and functional links betw.en IRG1 and HO-1 in the innate immune system remain unknow.. In the present study, w. found that the CO releasing molecule-2 （CORM-2） and chemical inducers of HO- 1 increased I RG 1 expression in a time- and dose-dependent fashion in RAw.64.7 cells. Furthermore, inhibition of HO-1 activity by zinc protoporphyrin IX （ZnPP） and HO-1 siRNA significantly reduced expression of IRG1 under these conditions. In addition, treatment w.th CO and HO-1 induction significantly increased A20 expression, w.ich w.s reversed by ZnPP and HO-1 siRNA. LPS-stimulated TNF-a w.s significantly decreased, w.ereas IRG1 and A20 w.re increased by CORM-2 application and HO-1 induction, w.ich in turn w.re abrogated by ZnPP. Interestingly, siRNA against IRG1 and A20 reversed the effects of CO and HO-1 on LPS-stimulated TNF-a production. Additionally, CO and HO-1 inducers significantly increased IRG1 and A20 expression and dow.regulated TNF-a production in a LPS-stimulated sepsis mice model. Furthermore, the effects of CO and HO-1 on TNF-α production w.re significantly reversed w.en ZnPP w.s administered. In conclusion, CO and HO-1 induction regulates IRG1 and A20 expression, leading to inhibition of inflammation in vitroand in an in vivomice model.

关键词： A2O anti-inflammatory effects carbon monoxide HO-1 IRG1

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Generalized Sampling in Shift Invariant Spaces w.th Frames

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Acta Mathematica Sinica,English Series 2012年第9期28卷 1823-1844页

作者： stefan ERICSSON Department of Engineering Sciences and Mathematics Lule University of Technology

Generalized sampling in a shift invariant subspace V of L2（R） is considered. A function f in V is processed w.th different filters Lm and then one tries to reconstruct f from the samples L^mf（j＇k）. w. develop a theory of how.to do this in the case w.en V possesses a shift invariant frame. Special attention is paid to the question： How.to obtain dual frames w.th compact support？

关键词： Generalized sampling frames Riesz basis reproducing kernel shift invariant spaces

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Constitutive relations for the shear band evolution in granular matter under large strain

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Particuology 2008年第6期6卷 501-505页

作者： stefan Luding Multi Scale Mechanics TS CTW UTwente P.O. Box 217 7500 AE Enschede Netherlands

A so-called ＂split-bottom ring shear cell＂ leads to w.de shear bands under slow. quasi-static deformation. Unlike normal cylindrical Couette shear cells or rheometers, the bottom plate is split such that the outer part of it can move w.th the outer w.ll, w.ile the other part （inner disk） is immobile. From discrete element simulations （DEM）, several continuum fields like the density, velocity, deformation gradient and stress are computed and evaluated w.th the goal to formulate objective constitutive relations for the pow.er flow.behavior. From a single simulation, by applying time- and （local） space-averaging, a non-linear yield surface is obtained w.th peculiar stress dependence. The anisotropy is alw.ys smaller than the macroscopic friction coefficient. How.ver, the low.r bound of anisotropy increases w.th the strain rate, approaching the maximum according to a stretched exponential w.th a specific rate that is consistent w.th a shear path of about one particle diameter.

关键词： Ring shear cell Shear bands DEM simulation Micro-macro transition Objective constitutive relations Yield stress fluid

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Experimental investigation on slip conditions during thread rolling w.th flat dies

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Friction 2024年第1期12卷 136-143页

作者： stefan VOLZ Peter GROCHE Institute for Production Engineering and Forming Machines Technical University DarmstadtOtto-Berndt Straße 2Darmstadt 64287Germany

The process design of flat die rolling operations can be a tedious and costly process due to the challenges posed by small process *** this w.rk,an effort is made to closely investigate and understand the process limits caused by excessive slippage of the *** measurements are carried out to capture the characteristics of excessive slippage and the influence of the stroke rate and the tribological system on this process *** differences in slippage w.re observed,depending on the tribological *** systems w.th polymer based lubricants show.d excessive slippage at low.stroke rates,systems using oil or no lubricant endured higher stroke rates before process limits w.re *** optical measurements revealed three major forms of slippage:successful rolling w.thout slippage,failure due to excessive slippage at process start,and failure due to excessive slippage at around one w.rkpiece rotation.

关键词： rolling incremental forming thread rolling slippage profile rolling

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Influence of sample preparation on nanoindentation results of tw.nninginduced plasticity steel

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International Journal of Minerals,Metallurgy and Materials 2021年第5期28卷 877-887页

作者： Jiali Zhang stefan Zaefferer Institute for Materials Applications in Mechanical Engineering RWTH Aachen UniversityAachen 52062Germany Max-Planck-Institut für Eisenforschung Düsseldorf 40237Germany

Nanoindentation is an attractive characterization technique,as it not only measures the local properties of a material but also facilitates understanding of deformation mechanisms at submicron ***,because of the complex stress-strain field and the small scale of the deformation under the nanoindenter,the results can be easily influenced by artifacts induced during sample *** this w.rk,a systematic study w.s conducted to better understand the influence of sample preparation methods on the nanoindentation results of ductile *** experiments w.re conducted on a steel(Fe-22Mn-0.65C,w.%)w.th tw.nning-induced plasticity(Tw.P),w.ich w.s selected for its large grain size and sensitivity to different surface preparation *** grouping the results obtained from each nanoindent,chemical polishing w.s found to be the best sample preparation method w.th respect to the resulting mechanical properties of the *** contrast,the presence of a deformation layer left by mechanical polishing and surface damage induced by focused ion beam(FIB)scanning w.re confirmed by the dislocation-nucleation-induced pop-in events of nanoindentation.

关键词： Tw.P steels nanoindentation mechanical polishing chemical polishing pop-in

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Hopf algebras and Dyson-Schw.nger equations

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Frontiers of physics 2016年第3期11卷 161-177页

作者： stefan w.inzierl PRISMA Cluster of Excellence Institut fiir Physik Johannes Gutenberg- Universitiit Mainz D - 55099 Mainz Germany

In this paper I discuss Hopf algebras and Dyson-Schw.nger equations. This paper starts w.th an introduction to Hopf algebras, follow.d by a review.of the contribution and application of Hopf algebras to particle physi... 详细信息

关键词： Feynman integrals Hopf algebras Dyson-Schw.nger equations

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Simulation of spray coating in a spouted bed using recurrence CFD

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Particuology 2019年第1期17卷 92-103页

作者： Paul Kieckhefena Thomas Lichtenegger Sw.ntje Pietsch stefan Pirker stefan Heinrich Institute of Solids Process Engineering and Particle Technology Hamburg University of Technology. HamburgGermany Department for Particulate Flow.Modelling. Johannes Kepler University LinzAustria Linz Institute of Technology (LIT) Johannes Kepler UniversityLinzAustria

Although numerical models such as the computational fluid dynamics–discrete element method (CFD–DEM) have enabled the accurate simulation of laboratory-scale apparatuses, the application of these methods to large-scale apparatuses w.th many particles and time scales ranging from minutes to hours remains a challenge. The recently developed recurrence CFD (rCFD) method seeks to overcome these issues in pseudo-periodic processes by extrapolating globally recurring patterns in a physically meaningful w.y and describing the transport and interaction of passive scalars using Lagrangian tracers. Spouted beds represent an interesting target because of the associated variety of flow.regimes. They can be effectively described by CFD–DEM on the time scale of tens of seconds, w.ereas industrially relevant processes typically take hours. In this contribution, w. established the validity of applying the Lagrangian rCFD method to spouted beds by demonstrating the accurate reproduction of the particle residence time distribution in a fictitious spray zone. The deposition of spray droplets onto tracer particles w.s simulated for 1 h, and the particle surface coverage distribution w.s estimated using a statistical approach for both an unstabilized prismatic spouted bed and one stabilized by draft plates.

关键词： CFD–DEM Recurrence CFD Spray coating Time-scale decoupling Spouted bed Draft plate

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Product design based on discrete particle modeling of a fluidized bed granulator

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Particuology 2014年第1期12卷 13-24页

作者： Lennart Fries Sergiy Antonyuk stefan Heinrich Gerhard Niederreiter stefan Palzer Nestlé Research Center Institute of Solids Process Engineering and Particle Technology Hamburg University of Technology

Fluidized bed agglomeration is a process commonly used to construct pow.ered food or pharmaceuti cal products to improve their instant properties. This w.rks analyzes the influence of a w.de range of operating parameters （i.e., fluidization air flow.rate, temperature, and liquid injection rate） on grow.h rate, process stability, and product particle structure. Different granulator configurations （i.e., top spray, w.rster coater, spouted bed） are compared using identical process parameters. The impacts of both pro cess variables and granulator geometry on the fluidization regime, the particle and collision dynamics, and the resulting product structure and corresponding properties are studied in detailed simulations using a discrete particle model （DPM） and labscale agglomeration experiments w.th amorphous dextrose syrup （DE21）. The combination of numerical and experimental results allow. to correlate the kinetics of micro scale particle interactions and the final product properties （i.e., agglomerate structure and strength）. In conclusion, detailed DPM simulations are proven as a valuable tool for know.edgebased product design.

关键词： FluidizationAgglomerationDiscrete element methodFood pow.erCollision dynamics

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