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益肾方对db/db糖尿病小鼠肾保护作用的疗效观察

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暨南大学学报（自然科学与医学版） 2021年第6期42卷 600-607页

作者：邓丽娥卢汉祺董晶晶李云逸姚淑焕洪嘉玲林捷范丽静曹锐董向楠卢永平叶明君 Bernhard Kr mer Berthold Hocher 尹良红李强东莞市中医院内十科广东东莞523000 暨南大学附属第一医院肾内科广东广州510630 德国海德堡大学蔓海姆医学院肾脏病医院德国海德堡市69117

目的:探讨益肾方对db/db糖尿病小鼠肾保护作用的效果.方法:60只db/db糖尿病小鼠随机分为模型组、益肾方低剂量组、益肾方高剂量组和洛汀新组,15只同背景db/m小鼠为正常对照组,分别灌胃12周,检测肾功能相关生化指标,并对肾组织进行HE、PA... 详细信息

目的:探讨益肾方对db/db糖尿病小鼠肾保护作用的效果.方法:60只db/db糖尿病小鼠随机分为模型组、益肾方低剂量组、益肾方高剂量组和洛汀新组,15只同背景db/m小鼠为正常对照组,分别灌胃12周,检测肾功能相关生化指标,并对肾组织进行HE、PAS染色.结果:与对照组相比,模型组、益肾方低剂量组、益肾方高剂量组和洛汀新组的血糖、尿肌酐/尿微量白蛋白比(ACR)、胱抑素C和肾病病理学评分均显著升高,提示模型构建成功;与模型组对比,益肾方低剂量组、益肾方高剂量组和洛汀新组的ACR、胱抑素C和肾病病理学评分均显著降低,且益肾方高剂量组上述指标的改善优于益肾方低剂量组和洛汀新组,而各组的血糖无显著性差异,益肾方可有效改善db/db糖尿病小鼠的生化指标,减轻肾脏病理变化.结论:益肾方对db/db糖尿病小鼠的肾保护作用疗效确切,且其疗效呈剂量依赖性,并独立于血糖水平.

关键词：益肾方糖尿病肾病 db/db糖尿病小鼠肾保护

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《底层表达》介绍

当代语言学 2014年第4期16卷 494-497页

作者： Martin krmer 于辉南开大学汉语言文化学院

《底层表达》（Underlying Representations）是“音系学中的核心论题”系列丛书之一，2012年由剑桥大学出版社出版发行。该书作者Martinkraimer是挪威特罗姆瑟大学语言学系教授。作者带着大家一起回顾了过去近一百年“底层表达”在音... 详细信息

《底层表达》（Underlying Representations）是“音系学中的核心论题”系列丛书之一，2012年由剑桥大学出版社出版发行。该书作者Martinkraimer是挪威特罗姆瑟大学语言学系教授。作者带着大家一起回顾了过去近一百年“底层表达”在音系学领域的发展，对很多长期存在的音系问题做了思考，并对OT视角的底层表达提出了一些独特的修订意见。

关键词：剑桥大学出版社音系学系列丛书出版发行修订意见语言学作者论题

Starving out brain tumors: a reprogrammed lysine catabolism serves as a novel target for glioblastoma treatment

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5136-5138页

作者： Désirée Gül Oliver H.krämer Christoph Reinhardt Molecular and Cellular Oncology Department of Otorhinolaryngology Head and Neck SurgeryUniversity Medical CenterJohannes Gutenberg-University Mainz55131MainzGermany Department of Toxicology University Medical CenterJohannes Gutenberg-University Mainz55131 MainzGermany Center for Thrombosis and Hemostasis(CTH) University Medical CenterJohannes Gutenberg-University MainzLangenbeckstrasse 155131 MainzGermany German Center for Cardiovascular Research(DZHK) Partner Site Rhine-MainUniversity Medical CenterJohannes Gutenberg-University Mainz55131 MainzGermany

In their recent study published in Nature,Yuan and colleagues enlighten the role of histone lysine crotonylation(Kcr)in brain tumor biology.They report a novel lysine-dependent mechanism through which glioblastoma ste... 详细信息

关键词： glioblastoma interferon treatment

Chemistry-led investigations into the mode of action of NAMPT activators,resulting in the discovery of non-pyridyl class NAMPT activators

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Acta Pharmaceutica Sinica B 2023年第2期13卷 709-721页

作者： Siyuan Tang Miguel Garzon Sanz Oliver Smith Andreas krämer Daniel Egbase Paul W.Caton Stefan Knapp Sam Butterworth Division of Pharmacy and Optometry School of Health SciencesManchester Academic Health Sciences CentreUniversity of ManchesterManchester M139PLUK Structural Genomics Consortium(SGC) 60438 Frankfurt Am MainGermany Buchmann Institute for Life Sciences(BMLS) 60438 Frankfurt Am MainGermany Institut für Pharmazeutische Chemie Goethe University60438 Frankfurt Am MainGermany Frankfurt Cancer Institute(FCI) 60596 Frankfurt Am MainGermany Department of Diabetes School of Cardiovascular and Metabolic Medicine&SciencesFaculty of Life Sciences&MedicineKing's College LondonLondon SE11ULUK

The cofactor nicotinamide adenine dinucleotide(NAD+)plays a key role in a wide range of physiological processes and maintaining or enhancing NAD+levels is an established approach to enhancing healthy aging.Recently,several classes of nicotinamide phosphoribosyl transferase(NAMPT)activators have been shown to increase NAD+levels in vitro and in vivo and to demonstrate beneficial effects in animal models.The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors,however the basis for the switch from inhibitory activity to activation is not well understood.Here we report an evaluation of the structure activity relationships of NAMPT activators by designing,synthesising and testing compounds from other NAMPT ligand chemotypes and mimetics of putative phosphoribosylated adducts of known activators.The results of these studies led us to hypothesise that these activators act via a through-water interaction in the NAMPT active site,resulting in the design of the first known urea-class NAMPT activator that does not utilise a pyridine-like warhead,which shows similar or greater activity as a NAMPT activator in biochemical and cellular assays relative to known analogues.

关键词： Nicotinamide phosphoribosyl transferase activator Healthy aging Drug discovery Bioisosteres Medicinal chemistry

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危机倒逼法治完善

中华环境 2015年第11期 55-56页

作者： Ludwig kr?mer 德国不莱梅大学

对于环保来说,最困难的不是立法,而是执法。立法看起来再好,但终归不过一张纸而已。法律,只有在日常生活中得以贯彻执行,才能够真正改变环境,更好的保护环境。突发事件驱动立法更新在欧盟环境法的发展初始,各行各业都是比较抵触的,不想... 详细信息

对于环保来说,最困难的不是立法,而是执法。立法看起来再好,但终归不过一张纸而已。法律,只有在日常生活中得以贯彻执行,才能够真正改变环境,更好的保护环境。突发事件驱动立法更新在欧盟环境法的发展初始,各行各业都是比较抵触的,不想在环保方面做出改变。因而,环境法案取得突破一般都是源于事故。在1976年的意大利,发生了一次巨大的环保灾难,造成了大气污

关键词：政府官僚化学品成员国化工行业布鲁塞尔

Reactions with Aminobenzoic Acids via Diazonium Salts Open New Routes to Bio-Derived Aromatics

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International Journal of Organic Chemistry 2016年第2期6卷 95-99页

作者： Anthony Farlow Jens Olaf krömer School of Chemical and Molecular Biosciences The University of Queensland Brisbane Australia Instituto de Biociências Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP) Botucatu Brazil Centre for Microbial Electrochemical Systems The University of Queensland Brisbane Australia Advanced Water Management Centre The University of Queensland Brisbane Australia

Aromatics have a broad application in our everyday life ranging from plastics, coatings and fibres, to food and pharmaceuticals. To date the bulk of these aromatics is derived from naphtha-based pet-rochemistry. However, recent progress in the fermentative production of metabolites using renew-able resources and engineered microbes has enabled the production of bio-precursors, such as 4-amino benzoic acid (pABA) and 2-amino benzoic acid (oABA). In this work we explored the feasibility of Sandmeyer reactions for the conversion of pABA to terephthalic and oABA salicylic acid, providing two very important platform chemicals for the chemical and pharmaceutical industries. We could demonstrate that both acids can be obtained from the amino benzoic acids derived from the shikimate pathway in microbes and plants. Good conversions could be achieved using Sandmeyer reactions at mild conditions with biodegradable reagents and without organic solvents.

关键词： Aminobenzoic Acid Terephthalic Acid Salycilic Acid Sandmeyer Cyanations

Pore characterization of PM Mg–0.6Ca alloy and its degradation behavior under physiological conditions

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Journal of Magnesium and Alloys 2021年第2期9卷 686-703页

作者： Eshwara Phani Shubhakar Nidadavolu Diana krüger Berit Zeller-Plumhoff Domonkos Tolnai Björn Wiese Frank Feyerabend Thomas Ebel Regine Willumeit-Römer Division Metallic Biomaterials Institute of Materials ResearchHelmholtz-Zentrum GeesthachtMax-Planck-Str.1Geesthacht 21502Germany Magnesium Innovation Center(MagIC) Institute of Materials ResearchHelmholtz-Zentrum GeesthachtMax-Planck-Str.1Geesthacht 21502Germany

Several material parameters affect degradation characteristics of Mg and its alloys under physiological conditions.Porous Mg materials are interesting for their simultaneous degradation and drug delivery capabilities.However,an increase in pore surface area is detrimental to both degradation resistance and subsequent mechanical properties.The present work aims at determining the threshold porosity value in Mg–0.6 Ca specimens produced by powder metallurgy(PM)below which low degradation rates persist with acceptable mechanical properties.Seven different porous Mg–0.6 Ca specimens containing both closed and open pore structures were fabricated with porosities ranging from 3%to 21%.Degradation profiles were obtained via a semi static immersion test over 16 days under physiological conditions using Dulbecco’s modified Eagle’s medium with Glutamax and 10%fetal bovine serum as supplements.The results are related to morphological pore parameters like pore size distribution,pore interconnectivity and pore curvatures that were quantified using an ex situμCT analysis.In general,with decreasing porosity a decrease in pore interconnectivity is seen followed by rounding of the pores.Low degradation rates(MDR<0.3 mm/year)are observed in specimens until 10%porosity,however,the upper bound for reproducible degradation is observed to be in specimens until 12%porosity.This porosity level also marks the transition from closed to open pore nature with a simultaneous change in pore interconnectivity from less than 10%to greater than 95%,below and above this porosity level,respectively.The tensile strength and elongation to failure recorded for specimens with 10%porosity were 70 MPa and 2%,respectively displaying positive traits of both homogenous degradation and mechanical properties.The results suggest that high pore interconnectivity is the dominant factor controlling degradation and mechanical properties in porous Mg-0.6 Ca specimens.The results also indicate a good sintering response of Mg-0.6 Ca specimens providing further mater

关键词： Porous Mg-0.6Ca In vitro Degradation μCT Sintering

Assessing the microstructure and in vitro degradation behavior of Mg-xGd screw implants using μCT

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Journal of Magnesium and Alloys 2021年第6期9卷 2208-2223页

作者： Diana krüger Berit Zeller-Plumhoff Björn Wiese Sangbong Yi Marcus Zuber D.C.Florian Wieland Julian Moosmann Regine Willumeit-Römer Institute of Metallic Biomaterials Helmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Institute of Material and Process Design Helmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Institute for Photon Science and Synchrotron Radiation Karlsruhe Institute of TechnologyHerrmann-von-Helmholtz-Platz 1Eggenstein-Leopoldshafen 76344Germany Laboratory for Applications of Synchrotron Radiation Karlsruhe Institute of TechnologyKaiserstr.12KarlsruheGermany Institute of Materials Physics Helmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany

Biodegradable implants are taking an increasingly important role in the area of orthopedic implants with the aim to replace permanent implants for temporary bone healing applications.During the implant preparation process,the material’s surface and microstructure are being changed by stresses induced by machining.Hence degradable metal implants need to be fully characterized in terms of the influence of machining on the resulting microstructure and corrosion performance.In this study,micro-computed tomography(μCT)is used for the quantification of the degradation rate of biodegradable implants.To our best knowledge,for the first time quantitative measures are introduced to describe the degradation homogeneity in 3D.This information enables a prediction in terms of implant stability during the degradation in the body.Two magnesium gadolinium alloys,Mg-5Gd and Mg-10 Gd(all alloy compositions are given in weight%unless otherwise stated),in the shape of M2 headless screws have been investigated for their microstructure and their degradation performance up to 56 days.During the microstructure investigations particular attention was paid to the localized deformation of the alloys,due to the machining process.In vitro immersion testing was performed to assess the degradation performance quantified by subsequent weight loss and volume loss(usingμCT)measurements.Although differences were observed in the degree of screw’s near surface microstructure being influenced from machining,the degradation rates of both materials appeared to be suitable for application in orthopedic implants.From the degradation homogeneity point of view no obvious contrast was detected between both alloys.However,the higher degradation depth ratios between the crests and roots of Mg-5Gd ratios may indicated a less homogeneous degradation of the screws of these alloys on contract to the ones made of Mg-10Gd alloys.Due to its lower degradation rates,its more homogeneous microstructure,its weaker texture and better degradation performance extruded Mg-1

关键词： Magnesium alloys Biodegradable implant Degradation rate Degradation homogeneity Micro-comptued tomography

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文化与社会交互对情绪知觉的影响

文化与社会交互对情绪知觉的影响