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Engineered SPIONs functionalized with endothelin a receptor antagonist ameliorate liver fibrosis by inhibiting hepatic stellate cell activation

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Bioactive Materials 2024年第9期39卷 406-426页

作者： Marit ten Hove Andreas Smyris richell Booijink Lydia Wachsmuth uwe Hansen Lejla Alic Cornelius Faber Carsten Hӧltke ruchi Bansal Personalized Diagnostics and Therapeutics Department of Bioengineering TechnologiesTechnical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedethe Netherlands Clinic of radiology University Hospital MuensterMuensterGermany Institute for Musculoskeletal Medicine University Hospital MuensterMuensterGermany Department of Magnetic Detection and Imaging Technical Medical CentreFaculty of Science and TechnologyUniversity of TwenteEnschedethe Netherlands

Endothelin-1/endothelin A receptor(ET-1/ETAr)pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells(HSCs)-a key cell type involved in the pathogenesis of liver *** HSCs by blocking the ET-1/ETAr pathway using a selective ETAr antagonist(ErA)represents a promising therapeutic approach for liver ***,small-molecule ErAs possess limited clinical potential due to poor bioavailability,short half-life,and rapid renal *** improve the clinical applicability,we conjugated ErA to superparamagnetic iron-oxide nanoparticles(SPIONs)and investigated the therapeutic efficacy of ErA and ErA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging(MrI),HSCs-specific localization,and ET-1/ETAr-pathway antagonism in *** murine and human liver fibrosis/cirrhosis,we observed overexpression of ET-1 and ETAr that correlated with HSC activation,and HSC-specific localization of *** and successfully synthesized ErA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation,ECM production,migration,and *** an acute CCl4-induced liver fibrosis mouse model,ErA-SPIONs exhibited higher liver uptake,HSC-specific localization,and ET-1/ETAr pathway *** resulted in significantly reduced liver-to-body weight ratio,plasma ALT levels,andα-SMA and collagen-I expression,indicating attenuation of liver *** conclusion,our study demonstrates that the delivery of ErA using SPIONs enhances the therapeutic efficacy of ErA in *** approach holds promise as a theranostic strategy for the MrI-based diagnosis and treatment of liver fibrosis.

关键词： Endothelin A receptor SPIONs Hepatic stellate cells Liver fibrosis

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US-Kongress stimmt fr Clintons Vermchtnis Die Aufnahme Pekings in die WTO wurde in den USA als die Frage,,Krieg oder Friede“debattiert

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德语人文研究 2000年第4期 53-55页

作者： Von uwe Schmitt

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Modelling reliability-adaptive Multi-system Operation

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International Journal of Automation and computing 2006年第2期3卷 192-198页

作者： uwe K. rakowsky Vossloh Kiepe

This contribution discusses the concept of reliability-Adaptive Systems （rAS） to multi-system operation. A fleet of independently operating systems and a single maintenance unit axe considered. It is the objective in this paper to increase overall performance or workload respectively by avoiding delay due to busy maintenance units. This is achieved by concerted and coordinated derating of individual system performance, which increases reliability. Quantification is carried out by way of a convolution-based approach. The approach is tailored to fleets of ships, aeroplanes, spacecraft, and vehicles （trains, trams, buses, cars, trucks, etc.） - Finally, the effectiveness of derating is validated using different criteria. The rAS concept makes sense if average system output loss due to lowered performance level （yielding longer time to failure） is smaller than average loss due to waiting for maintenance in a non-adaptive case.

关键词： reliability-adaptive systems multi-system operation performance maintenance effectiveness criteria.

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Parameters Influencing the Noise Emission of Planing Machines

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Journal of Environmental Science and Engineering(A) 2016年第2期5卷 102-108页

作者： Lucia Gross uwe Heisel LGTECH GmbH Steinhausen 6312 Switzerland Institute for Machine Tools University of Stuttgart Stuttgart 70174 Germany

regarding woodworking machines, machine acoustics are of particular significance due to the high noise emission of these machines. Among other things, this can be attributed to the adoption of the European Commission Machinery Directive as a national law, which demands protection against noise emission in the design phase of new machines. In order to accomplish this, it is necessary to examine and locate the causes of emissions on existing machines. In this paper, the sound source is located through sound intensity measurements, using planing machines as an example, which are particularly noise-intensive woodworking machines. In addition, different influencing parameters on noise emission are analyzed, such as manual and automatic feed, rotational speed and the influence of the type of wood of the workpiece.

关键词： Production process noise emission woodworking machines.

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Stereodivergent catalytic asymmetric allylic alkylation(AAA)

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Science Bulletin 2020年第22期65卷 1865-1868,M0003页

作者： Subarna Jyoti Kalita Yi-Yong Huang uwe Schneider Department of Chemistry School of ChemistryChemical Engineering and Life ScienceWuhan University of TechnologyWuhan 430070China EaStCHEM School of Chemistry The University of EdinburghEdinburgh EH93FJUK

Chirality or handedness,i.e.,the non-superimposability of a structure(lacking a plane or center of symmetry)with its mirrorimage,strongly impacts various chemistry/biology areas,and plays an important role,e.g.,in materials chemistry[1].In medicinal chemistry it is critical to evaluate the therapeutic and toxicological properties of all stereoisomers of a drug molecule because diastereoisomers and enantiomers may exhibit distinct biological and pharmacological activities[2].

关键词：烯丙基化反应 isomers 发散型

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Multi-material multi-photon 3D laser microand nanoprinting

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Light(Advanced Manufacturing) 2021年第3期2卷 14-30页

作者： Liang Yang Frederik Mayer uwe H.F.Bunz Eva Blasco Martin Wegener Institute of Nanotechnology Karlsruhe Institute of Technology(KIT)76128 KarlsruheGermany Institute of Applied Physics Karlsruhe Institute of Technology(KIT)76128 KarlsruheGermany Institut für Organische Chemie Ruprecht-Karls-Universität HeidelbergIm Neuenheimer Feld 27069120 HeidelbergGermany Centre for Advanced Materials(CAM) Ruprecht-Karls-Universität HeidelbergIm Neuenheimer Feld 225 and 27069120 HeidelbergGermany

Three-dimensional(3D)laser micro-and nanoprinting based upon multi-photon absorption has made its way from early scientific discovery to industrial manufacturing processes,e.g.,for advanced microoptical ***,so far,most realized 3D architectures are composed of only a single polymeric ***,we review 3D printing of multi-materials on the nano-and *** start with material properties that have been realized,using multi-photon *** materials include bulk polymers,conductive polymers,metals,nanoporous polymers,silica glass,chalcogenide glasses,inorganic single crystals,natural polymers,stimuliresponsive materials,and polymer ***,we review manual and automated processes achieving dissimilar material properties in a single 3D structure by sequentially photo-exposing multiple photoresists as 3D analogs of 2D multicolor *** examples from biology,optics,mechanics,and electronics are *** emerging approach–without counterpart in 2D graphical printing–prints 3D structures combining dissimilar material properties in one 3D structure by using only a single photoresist.A controlled stimulus applied during the 3D printing process defines and determines material properties on the voxel *** of laser power and/or wavelength,or application of quasi-static electric fields allow for the seamless manipulation of desired materials properties.

关键词： properties sequentially struc

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xtraction of internal phase motions in femtosecond soliton molecules using an orbital-angular-momentum-resolved method

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Photonics research 2020年第10期8卷 1580-1585页

作者： YuweI ZHAO JNTAO FAN YOUJIAN SONG uwe MOrGNEr MINGLIE HU Uitrafast Laser Laboratory Key Laboratory of Opto-electronic Information Science and Technology of Mlinistry of EducationSchool of Precision Instruments and Opto-electronics EngineeringTianjin UniversityTianjin 300072China Institut fiur Quanteroptik Leibniz Universitat HannoverWelfengarten 130167 HaninaverGermeny Cluster of Excellence PhoenixD(Photonics Opticsand Engineering-rnrnovation Across Disciplines)30167 HannoverGermany Laser Zentrum Hannover e.V Hollerithalice 830419 HannoverGermany

Internal motions in femtosecond soliton molecules provide insight into universal collective dynamics in various nonlinear *** we introduce an orbital-angular-momentum(OAM)-resolved method that maps the relative phase motion within a femtosecond soliton molecule into the rotational movement of the interferometric beam profile of two optical *** this means,long-term relative phase evolutions of doublet and triplet soliton molecules generated in an all-polarization-maintaining mode-locked Er-fiber laser are *** simple and practical OAM-resolved method represents a promising way to directly visualize the complex phase dynamics in a diversity of multisoliton structures.

关键词： polarization soliton resolved

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Evaluation of bone remodeling in regard to the age of scaphoid non-unions

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World Journal of Orthopedics 2016年第7期7卷 418-425页

作者： Susanne rein uwe Hanisch Hans-Eberhard Schaller Hans Zwipp Stefan rammelt Stefan Weindel Department of Plastic and Hand Surgery Burn UnitTrauma Center Bergmannstrost Center of Orthopaedics and Traumatology University Medicine "Carl Gustav Carus" DresdenTechnicalUniversity Dresden Institute of Pathology "Carl Thiem" Hospital Deptartment of Plastic Hand Reconstructive and Burn SurgeryTrauma Center Tuebingen University Deptartment of Hand Aesthetic and Plastic SurgeryHospital of Linth

AIM: To analyse bone remodeling in regard to the age of scaphoid non-unions(SNU) with ***: Thirty-six patients with symptomatic SNU underwent surgery with resection of the pseudarthrosis. The resected material was evaluated histologically after staining with hematoxylin-eosin(HE), tartrate resistant acid phosphatase(TrAP), CD 68, osteocalcin(OC) and osteopontin(OP). Histological examination was performed in a blinded ***: The number of multinuclear osteoclasts in the TrAP-staining correlated with the age of the SNU and was significantly higher in younger SNU(P = 0.034; r = 0.75). A higher number of OP-immunoreactive osteoblasts significantly correlated with a higher number of OC-immunoreactive osteoblasts(P = 0.001; r = 0.55). Furthermore, a greater number of OP-immunoreactive osteoblasts correlated significantly with a higher number of OP-immunoreactive multinuclear osteoclasts(P = 0.008; r = 0.43). SNU older than 6 mo showed a signifi-cant decrease of the number of fibroblasts(P = 0.04). Smoking and the age of the patients had no influence on bone remodeling in ***: Multinuclear osteoclasts showed a significant decrease in relation to the age of SNU. However, most of the immunhistochemical findings of bone remodeling do not correlate with the age of the SNU. This indicates a permanent imbalance of bone formation and resorption as indicated by a concurrent increase in both osteoblast and osteoclast numbers. A clear histological differentiation into phases of bone remodeling in SNU is not possible.

关键词： Bone remodeling Histology Immunohistological staining Scaphoid non-union Scaphoid Wrist joint

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Pelagic Nitrogen Cycling in Jiaozhou Bay, a Model Study I: the Conceptual Model

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Chinese Journal of Oceanology and Limnology 2003年第4期21卷 358-367页

作者：任玲张曼平 Brockmann uwe H. 冯士笮 College of Chemistry and Chemical Engineering Ocean University of China Institute of Physical Oceanography Ocean University of China Institute of Biogeochemistry and Marine Chemistry University of Hamburg

A zero dimensional box model (PNCMjzb) with six state variables (ammonium, nitrate, dissolved organic nitrogen, phytoplankton, zooplankton and detritus) was developed to study nitrogen cycling in the Jiaozhou Bay pelagic ecosystem. The dominant processes within these compartments are considered with nitrogen as flow currency. Phytoplankton and zooplankton are treated as separate state variables, assuming that the species composition was dominated by two or three species the dynamic constants of which are similar and that they represent the entire plankton community. The microbial loop has not been integrated explicitly in the model. The turnover of bacteria is included implicitly in processes such as detritus decomposition, DON remineralization, pelagic nitrification and denitrification. The model is driven by two forcing variables, viz. water temperature and light intensity. Historical data from the1980s and 1990s were compiled and used for model calibration. In this paper (part I), the consideration of every main compartment in the model is interpreted in detail. And the applied equations and parameters are presented. The main results from the simulations together with discussion about phytoplankton dynamics and primary production in Jiaozhou Bay are presented in the next paper (part II).

关键词： nitrogen ecosystem modelling phytoplankton nitrate ammonium pelagic Jiaozhou Bay

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PI 3-kinase pathway is responsible for antiapoptotic effects of atrial natriuretic peptide in rat liver transplantation

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World Journal of Gastroenterology 2006年第7期12卷 1049-1055页

作者： uwe Grutzner Melanie Keller Michael Bach Alexandra K Kiemer Herbert Meissner Manfred Bilzer Stefan Zahler Alexander L Gerbes Angelika M Vollmar Institute for Surgical research Klinikum GroBhadernUniversity of MunichD-81377 MunichGermany Department of Pharmacy University of MunichD-81377 MunichGermany Department Institute of Pathology University of MunichD-81377 MunichGermany

AIM： To investigate the in vivo effect of atrial natriuretic peptide （ANP） and its signaling pathway during orthotopic rat liver transplantation.METHODS： rats were infused with NaCI, ANP （5 μg/ kg）, wortmannin （WH, 16μg/kg）, or a combination of both for 20 min. Livers were stored in UW solution （4℃） for 24 h, transplanted and reperfused. Apoptosis was examined by caspase-3 activity and TUNEL staining. Phosphorylation of Akt and Bad was visualized by Western blotting and phospho-Akt-localization by confocal microscopy.rESULTS： ANP-pretreatment decreased caspase-3 activity and TUNELopositive cells after cold ischemia, indicating antiapoptotic effects of ANP in vivo. The an- tiapoptotic signaling of ANP was most likely caused by phosphorylation of Akt and Bad, since pretreatment with PI 3-kinase inhibitor WM abrogated the ANP-induced reduction of caspase-3 activity. Interestingly, analysis of liver tissue by confocal microscopy showed translocation of phosphorylated Akt to the plasma membrane of hepa- tocytes evoked by ANP.CONCLUSION： ANP activates the PI-3-kinase pathway in the liver in vivo leading to phosphorylation of Bad an event triggering antiapoptotic signaling cascade in ischemic liver.

关键词： Bad Apoptosis Hormonal preconditioning Ischemia reperfusion injury

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