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Pharmacological drug screening to inhibit uveal melanoma metastatic cells either via EGF-R, mAPK, mTOR or PI3K

International Journal of Ophthalmology(English edition) 2022年第10期15卷 1569-1576页

作者： Stefan Kassumeh Sebastian Arrow AndréKafka Nikolaus Luft Siegfried G.Priglinger Armin Wolf Kirsten Eibl-Lindner christian m.Wertheimer Department of Ophthalmology University HospitalLMU MunichMunich 80336Germany Department of Ophthalmology University HospitalUniversity UlmUlm 89075Germany

AIm: To screen five potential pharmacological substances specifically targeting EGF-R, mAPK, mTOR, or PI3K for their antiproliferative effects, possible impact on cell viability, as well as cell death rates on three different uveal melanoma metastasis cell lines in vitro. mETHODS: Three different uveal melanoma metastasis cell lines(Omm2.5, Omm2.3, and Omm1), that originated from human hepatic and subcutaneous metastasis, were exposed to inhibitors of different targets: erlotinib(EGF-R), everolimus(mTOR), selumetinib(mAPK), trametinib(mAPK) or the alkylphosphocholine erufosine(PI3K). Cell viability was assessed with a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide(XTT) dye reduction assay after 24 h of treatment. Antiproliferative effects were evaluated separately after a 72-hour incubation of the cells with the pharmacological substance. Subsequently, the IC_(50) was calculated. Tumor cell death was investigated using a double stain apoptosis detection assay. RESULTS: Selumetinib, trametinib, and erufosine significantly decreased cell viability of all Omm cell lines(Pmetinib and trametinib showed a significant inhibition of cell proliferation(Pmus and erlotinib solely inhibited cell proliferation at the used concentrations(Pment(Pmber of dead cells for the other substances were ***: The preliminary drug screening demonstrates five new candidates, successfully targeting the canonical mAPK/ERK and PI3K/AKT/m TOR pathways in uveal melanoma metastasis cells in vitro. Hence, these findings provide an experimental basis to explore future single or combined therapy strategies for metastatic uveal melanoma.

关键词： uveal melanoma selumetinib trametinib erufosine erlotinib

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Limb symmetry index in competitive alpine ski racers:Reference values and injury risk identification according to age-related performance levels

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Journal of Sport and Health Science 2018年第4期7卷 405-415页

作者： Lisa Steidl-müller Carolin Hildebrandt Erich müiller christian Fink christian Raschner Department of Sport Science University of InnsbruckInnsbruck 6020Austria Department of Sport Science and Kinesiology University of SalzburgSalzburg 5400Austria Research Unit for Orthopedic Sports medicine and Injury Prevention Institute of Psychology(ISA GJThe Health&Life Sciences University(UMIT)Innsbruck 6020Austria Gelenkpunkt-Sports and Joint Surgery Innsbruck 6020Austria

Purpose: The aims of this study were to assess differences of limb symmetry index(LSI) in strength-and coordination-related tasks between high-level, competitive, noninjured ski racers of different age-related performance levels and to prospectively assess limb differences as a possible risk factor for traumatic and overuse injury in youth ski ***: The study(Study 1) included 285 high-level competitive ski racers(125 females, 160 males) of 3 age-related performance levels and based on the school system: 95 youth(10à14 years, secondary modern school), 107 adolescent(15à19 years, grammar school), and 83 elite athletes(20à34 years). To investigate the second aim(Study 2), 67 of the 95 youth athletes were included and any traumatic or overuse injuries were prospectively recorded over 2 seasons. All athletes performed 4 unilateral tests(strength related: one-leg counter movement jump(OL-CmJ) and one-leg isometric/isokinetic press strength test(OL-ILS); coordination related: one-leg stability test(OL-ST) and one-leg speedy jump test(OL-SJ)). The LSI was calculated by dividing the dominant leg by the nondominant leg and multiplying by 100. Kruskal-Wallis H tests and binary logistic regression analyses were ***: There were significant differences between the LSI of the 3 age-related performance-level groups only in the strength-related tests: the OL-CmJ(x2(2, 285) = 9.09; p = 0.01) and the OL-ILS(x2(2, 285) = 14.79; p matic injury in youth ski racers(Wald = 7.08; p mb differences of ms to be appropriate for elite athletes, but for youth and adolescent athletes it has to be critically discussed. It seems to be necessary to define thresholds based o

关键词：年龄相关风险因素滑雪损害竞争大规模集成电路性能索引

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A Systematic Review on Antituberculosis Drug Discovery and Antimycobacterial Potential of Biologically Synthesized Silver Nanoparticles:Overview and Future Perspectives

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Infectious microbes & Diseases 2022年第4期4卷 139-148页

作者： christian K.Ezeh Chibuzor N.Eze Uju m.E.Dibua Stephen C.Emencheta Department of microbiology University of NigeriaNsukkaEnugu StateNigeria Department of Pharmaceutical microbiology University of NigeriaNsukkaEnugu StateNigeria

Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health ***/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial *** review focused on the biological(green)synthesis of silver nanoparticles(AgNPs)as an alternative source of antimycobacterial *** for this study were searched and screened from three electronic databases(Google Scholar,Pubmed and ScienceDirect)following the Preferred Reporting Items for Systematic Reviews and meta-analyses *** from in total 17 eligible studieswere reported in this systematic *** of the 17 studies used plants to fabricate AgNPs,whereas the remaining five studies used microorganisms(bacteria and/or fungi).Silver as part of silver nitrate(AgNO3)was themetal precursor reported for the synthesis of AgNPs in these *** nanoparticles were mostly spherical,with sizes ranging from12 *** minimum inhibitory concentrations varied between studies and were divided into three groups:(i)those more effective than the antibiotic(controls),(ii)those more effective than plant extracts,and(iii)those less effective than the antibiotic *** addition,little or no cytotoxicity effects were *** nanoparticles were also shown to be highly specific or selective toward mycobacterial *** systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs,underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.

关键词： antimycobacterial activity silver nanoparticles cytotoxicity biological synthesis tuberculosis mycobacterial

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moderate heat treatment of CoFe Prussian blue analogues for enhanced oxygen evolution reaction performance

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Journal of Energy Chemistry 2023年第3期78卷 476-486,I0013页

作者： Fangyuan Diao mikkel Rykær Kraglund Huili Cao Xiaomei Yan Pei Liu christian Engelbrekt Xinxin Xiao Department of Chemistry Technical University of DenmarkKongens Lyngby DK-2800Denmark Department of Energy Storage and Conversion Technical University of DenmarkKongens Lyngby DK-2800Denmark DTU Nanolab-National Centre for Nano Fabrication and Characterization Technical University of DenmarkKongens Lyngby DK-2800Denmark Department of Chemistry and Bioscience Aalborg UniversityAalborg 9220Denmark

Prussian blue analogues(PBAs) with inherent ordered structures and abundant metal ion sites are widely explored as precursors for various electrochemical applications,including oxygen evolution reaction(OER).Using a range of characterization techniques including Fourier-transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),X-ray diffraction(XRD) and energy dispersive spectroscopy(EDS),this work discloses the process of replacement of K^(+)by NH4^(+)in the interstitial spaces of the CoFe PBA by a hot aqueous urea solution,which influences the transformation of PBAs under further heat treatment and the OER performance of the deriva *** heat treatment at 400℃ under Ar flow,high-resolution transmission electron microscopy(HRTEm) images reveal that CoFe alloy nanoparticles grew on the crystalline cubes of CoFe PBA with K^(+),while CoFe PBA cubes with NH4^(+)become ***,the derivative of CoFe PBA with NH4^(+)(Ar-U-CoFe PBA) performs better than the derivative of CoFe PBA with K^(+)(Ar-CoFe PBA) in OER,registering a lower overpotential of 305 mV at 10 mA cm^(-2),a smaller Tafel slope of 36.1 mV dec^(-1),and better stability over a testing course of 20 h in 1.0 m KOH.A single-cell alkaline electrolyzer,using Ar-U-CoFe PBA and Pt/C for the anodic and cathodic catalyst,respectively,requires an initial cell voltage of 1.66 V to achieve 100 mA cm^(-2)at 80℃,with negligible degradation after100 h.

关键词： Prussian blue analogues PBA derivatives Oxygen evolution reaction Electrolyzer

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Influence of humidity on conduction processes in gas-insulated devices

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High Voltage 2020年第2期5卷 143-150页

作者： malte Tschentscher David Graber christian m.Franck High Voltage Laboratory ETH Zurich8092 ZurichSwitzerland

Humidity has been considered as one of the main influencing factors that determine the conduction processes and electric strength of gas-insulated *** in the past,various studies focused on the change in the partial discharge inception voltages,breakdown strength of homogeneous and inhomogeneous field arrangements,and insulator flashover voltage,recent studies have investigated the changes in ion currents measured through different gas *** the framework of this contribution,a highly precise humidity control circuit has been developed to analyse the significance of humidity in the range from−25 to−5°C frost-point,which is fully applicable to operating gas-insulated *** sulphur hexafluoride(SF6)as the insulation gas at 0.45 mPa,Al2O3-filled epoxy resin insulators,and technically rough electrodes,the humidity was found to significantly influence the intensity of microdischarges at *** generation from microdischarges at the interfaces substantially increased with increasing *** an electric field of 5 kV/mm that were applicable to the dimensioning of gas-insulated devices,humidity strongly influences the charge provision from technically rough interfaces and potentially contributes to the surface-charge accumulation at insulator *** the other hand,for low-field conduction phenomena,no increase in the ion currents from natural ionisation or electrophoretic conduction was *** the investigated range of parameters,humidity is expected to be highly relevant for the design of gas-insulated devices.

关键词： conduction humidity sulphur

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麦蒂森论语域

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中国外语 2023年第5期20卷 37-46页

作者：王博 christian m.I.m.matthiessen 马园艺澳门大学中国澳门湖南大学马德里康普顿斯大学广东科学技术职业学院

christian ***是系统功能语言学领域的领军学者之一,他在语域研究方面有着较多的重要成果。本文总结了matthiessen关于语域的观点,讨论了如何以三维视角考察语域,阐释了语域变异同方言变异和语码变异的区别,并且从实例化和层次化的角度... 详细信息

christian ***是系统功能语言学领域的领军学者之一,他在语域研究方面有着较多的重要成果。本文总结了matthiessen关于语域的观点,讨论了如何以三维视角考察语域,阐释了语域变异同方言变异和语码变异的区别,并且从实例化和层次化的角度对语域概念进行了解读。此外,本文将系统功能语言学的语域研究置于整个语言学的框架中考察,加强了系统功能语言学的语域研究同其他学派研究之间的联系。

关键词：语域系统功能语言学语域变异语域绘图学活动语场

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Catalyst-and solvent-free,thermal generation of microporous polymer networks

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Science China Chemistry 2017年第8期60卷 1103-1106页

作者： christian widling michael forster venkata m.suresh ullrich scherf bergische universitt wuppertal macromolecular chemistry group(buwmakro)and institute for polymer technologyD-42119 WuppertalGermany

multifunctional iodoaryl monomers were used for the catalyst-and solvent-free generation of microporous polymer networks of high surface areas up to 732 m^2 g^(-1). The thermal conversion of the monomers relies on the homolytic cleavage of weak iodine–carbon bonds followed by a C–C coupling of the radicalic intermediates. By using tri-or tetrafunctional monomers and by tuning reaction temperature and time, the optimum reaction conditions allow the formation of the corresponding microporous networks in good yields of 71%–86%. The resulting networks exhibit notable high CO_2 and H_2 adsorption capacities of up to 8.89wt%(273 K, 1 bar) and up to 1.31 wt%(77 K, 1 bar), respectively.

关键词： microporous polymer networks thermal generation gas uptake

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Schrodinger and Klein-Gordon theories of black holes from the quantization of the Oppenheimer and Snyder gravitational collapse

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Communications in Theoretical Physics 2023年第9期75卷 122-135页

作者： christian Corda SUNY Polytechnic Institute 13502 UticaNew YorkUSAIstituto Livi59100 PratoTuscanyItaly and International Institute for Applicable Mathematics and Information SciencesB M Birla Science CentreAdarshnagarHyderabad 500063India

The Schrodinger equation of the Schwarzschild black hole(BH) has been recently derived by the author and collaborators. The BH is composed of a particle, the 'electron', interacting with a central field, the 'nucleus'. Via de Broglie's hypothesis, one interprets the 'electron' in terms of BH horizon's modes. Quantum gravity effects modify the BH semi-classical structure at the Schwarzschild scale rather than at the Planck scale. The analogy between this BH Schrodinger equation and the Schrodinger equation of the s states of the hydrogen atom permits us to solve the same equation. The quantum gravitational quantities analogous of the fine structure constant and of the Rydberg constant are not constants, but the dynamical quantities have well-defined discrete spectra. The spectrum of the 'gravitational fine structure constant' is the set of non-zero natural numbers. Therefore, BHs are well-defined quantum gravitational systems obeying Schrodinger's theory: the 'gravitational hydrogen atoms'. By identifying the potential energy in the BH Schrodinger equation as being the gravitational energy of a spherically symmetric shell, a different nature of the quantum BH seems to surface. BHs are self-interacting, highly excited,spherically symmetric, massive quantum shells generated by matter condensing on the apparent horizon, concretely realizing the membrane paradigm. The quantum BH described as a'gravitational hydrogen atom' is a fictitious mathematical representation of the real, quantum BH, a quantum massive shell having a radius equal to the oscillating gravitational *** consequences emerge from this result:(i) BHs have neither horizons nor singularities;(ii) there is neither information loss in BH evaporation, nor BH complementarity, nor firewall paradox. These results are consistent with previous ones by Hawking, Vaz, mitra and ***, the special relativistic corrections to the BH Schrodinger equation give the BH Klein–Gordon equation and the cor

关键词： quantum black holes information paradox quantum shells quantum levels Schrodinger and Klein-Gordon theories

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High doses of catecholamines activate glucose transport in human adipocytes independently from adrenoceptor stimulation or vanadium addition

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World Journal of Diabetes 2022年第1期13卷 37-53页

作者： christian Carpéné Nathalie Boulet Jean-Louis Grolleau Nathalie morin Institut des maladies métaboliques et Cardiovasculaires INSERM UMR1297Toulouse 31432France Team Dinamix Institute of Metabolic and Cardiovascular Diseases(I2MC)Paul Sabatier UniversityToulouse 31432France Department of Plastic Surgery CHU RangueilToulouse 31059France Facultéde Pharmacie de Paris Universitéde ParisINSERM UMR-S 11393PHMParis 75006France

BACKGROUND When combined with vanadium salts,catecholamines strongly activate glucose uptake in rat and mouse *** To test whether catecholamines activate glucose transport in human *** The uptake of 2-deoxyglucose(2-DG)was measured in adipocytes isolated from pieces of abdominal subcutaneous tissue removed from women undergoing reconstructive *** approaches with amine oxidase inhibitors,adrenoreceptor agonists and antioxidants were performed to unravel the mechanisms of action of noradrenaline or adrenaline(also named epinephrine).RESULTS In human adipocytes,45-min incubation with 100μmol/L adrenaline or noradrenaline activated 2-DG uptake up to more than one-third of the maximal response to *** stimulation was not reproduced with millimolar doses of dopamine or serotonin and was not enhanced by addition of vanadate to the incubation *** various natural amines and adrenergic agonists tested,no other molecule was more efficient than adrenaline and noradrenaline in stimulating 2-DG *** effect of the catecholamines was not impaired by pargyline and semicarbazide,contrarily to that of benzylamine or methylamine,which are recognized substrates of semicarbazide-sensitive amine *** peroxide at 1 mmol/L activated hexose uptake but not pyrocatechol or benzoquinone,and only the former was potentiated by *** and the phosphoinositide 3-kinase inhibitor wortmannin inhibited adrenaline-induced activation of 2-DG *** High doses of catecholamines exert insulin-like actions on glucose transport in human *** submillimolar doses,vanadium did not enhance this catecholamine activation of glucose ***,this dismantles our previous suggestion to combine the metal ion with catecholamines to improve the benefit/risk ratio of vanadium-based antidiabetic approaches.

关键词： Human adipocytes Amine oxidases Insulin Diabetes Vanadium Obesity

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Comparative effectiveness of medical treatment *** surgery for histologically proven non-alcoholic steatohepatitis and fibrosis:a matched network meta-analysis

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Hepatobiliary Surgery and Nutrition 2022年第5期11卷 696-708,I0008-I0011页

作者： Adrian T.Billeter Beatrice Reiners Svenja E.Seide Pascal Probst Eva Kalkum christian Rupp Beat P.müller-Stich Department of General Visceral and Transplant SurgeryUniversity of HeidelbergHeidelbergGermany Institute of medical Biometry and Informatics University of HeidelbergHeidelbergGermany The Study Center of the German Surgical Society(SDGC) HeidelbergGermany Department of Gastroenterology and Hepatology University of HeidelbergHeidelbergGermany

Background:Non-alcoholic steatohepatitis(NASH)comprises a major healthcare problem affecting up to 30%of patients with obesity and the associated risk for cardiovascular and liver-related *** new drugs for NASH-treatment are currently *** study thus far directly compared surgical and non-surgical therapies for *** network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical ***:The study was conducted according to the PRISmA guidelines for network ***,CENTRAL and Web of Science were searched without restriction of time or language using a validated search *** investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were *** with liver cirrhosis were *** of bias was assessed with ROB-2 and ROBINS-I-tools.A novel method for population-adjusted indirect comparison to include and compare single-arm trials was *** outcomes were NASH-resolution and improvement of ***:Out of 7,913 studies,twelve randomized non-surgical studies and twelve non-randomized surgical trials were ***-resolution after non-surgical intervention was 29%[95%confidence interval(CI):23-40%]and 79%(95%CI:72-88%)after *** network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication[odds ratio(OR)=2.68;95%CI:1.44-4.97]while drug treatment was superior to placebo(OR=2.24;95%CI:1.55-3.24).Surgery(OR=2.18;95%CI:1.34-3.56)and medication(OR=1.79;95%CI:1.39-2.31)were equally effective to treat fibrosis compared to placebo without difference between *** results did not change when only new drugs specifically developed for the treatment of NASH were ***:metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of *** d

关键词： Non-alcoholic fatty liver disease(NAFLD) non-alcoholic steatohepatitis(NASH) metabolic surgery fatty liver

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