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Statins markedly potentiate aminopeptidase inhibitor activity against(drug-resistant)human acute myeloid leukemia cells

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Cancer Drug Resistance 2023年第3期6卷 430-446页

作者： Gerrit Jansen Marjon Al Yehuda G.Assaraf Sarah Kammerer Johan van Meerloo gert J.Ossenkoppele Jacqueline Cloos Godefridus J.Peters Department of Rheumatology and Clinical Immunology Amsterdam Rheumatology and immunology CenterAmsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands The Fred Wyszkowsky Cancer Research Laboratory Faculty of BiologyThe Technion-Israel Institute of TechnologyHaifa 3200003Israel Department of Medical Oncology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands Institute of Biotechnology Molecular Cell BiologyBrandenburg University of Technology Cottbus-SenftenbergSenftenberg 01968Germany Department of Hematology Amsterdam University Medical Centerlocation VUmcAmsterdam 1081 HVThe Netherlands Department of Biochemistry Medical University of GdanskGdansk 80-210Poland

Aim: This study aimed to decipher the molecular mechanism underlying the synergistic effect of inhibitors of the mevalonate-cholesterol pathway (i.e., statins) and aminopeptidase inhibitors (APis) on APi-sensitive and -resistant acute myeloid leukemia (AML) ***: U937 cells and their sublines with low and high levels of acquired resistance to (6S)-[(R)-2-((S)-Hydroxy-hydroxycarbamoyl-methoxy-methyl)-4-methyl-pentanoylamino]-3,3 dimethyl-butyric acid cyclopentyl ester (CHR2863), an APi prodrug, served as main AML cell line models. Drug combination effects were assessed with CHR2863 and in vitro non-toxic concentrations of various statins upon cell growth inhibition, cell cycle effects, and apoptosis induction. Mechanistic studies involved analysis of Rheb prenylation required for mTOR ***: A strong synergy of CHR2863 with the statins simvastatin, fluvastatin, lovastatin, and pravastatin was demonstrated in U937 cells and two CHR2863-resistant sublines. This potent synergy between simvastatin and CHR2863 was also observed with a series of other human AML cell lines (e.g., THP1, MV4-11, and KG1), but not with acute lymphocytic leukemia or multiple solid tumor cell lines. This synergistic activity was: (i) specific for APis (e.g., CHR2863 and Bestatin), rather than for other cytotoxic agents;and (ii) corroborated by enhanced induction of apoptosis and cell cycle arrest which increased the sub-G1 fraction. Consistently, statin potentiation of CHR2863 activity was abrogated by co-administration of mevalonate and/or farnesyl pyrophosphate, suggesting the involvement of protein prenylation;this was experimentally confirmed by impaired Rheb prenylation by ***: These novel findings suggest that the combined inhibitory effect of impaired Rheb prenylation and CHR2863-dependent mTOR inhibition instigates a potent synergistic inhibition of statins and APis on human AML cells.

关键词： Aminopeptidase statins mevalonate pathway carboxyl esterase Rheb mTOR

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污泥作为污水厂内碳源的水解特性及工艺选择

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中国给水排水 2011年第22期27卷 30-35页

作者：刘智晓 Sille Bendix Larsen gert Petersen 马宝玲首创爱华天津市政环境工程有限公司天津300191 EnviDan Denmark

随着各地污水厂出水水质对氮、磷要求的日益提高,强化脱氮除磷成为必然要求,但是我国多数污水厂由于多种原因导致进水碳源不足,尤其是进水SCOD、VFAs的匮乏,直接影响了生物脱氮除磷的效率,甚至不得已采用人工投加外碳源脱氮或者化学除... 详细信息

随着各地污水厂出水水质对氮、磷要求的日益提高,强化脱氮除磷成为必然要求,但是我国多数污水厂由于多种原因导致进水碳源不足,尤其是进水SCOD、VFAs的匮乏,直接影响了生物脱氮除磷的效率,甚至不得已采用人工投加外碳源脱氮或者化学除磷方式以满足严格的出水氮、磷要求,但这无疑大大提高了污水厂的产泥率及运行成本。充分挖掘污水厂的"内碳源",利用污泥水解产生VFAs,不仅能有效提高除磷脱氮效率,而且可以降低污水厂的污泥产量,是可持续的资源化技术。比较了初沉污泥和活性污泥的水解特性差异,介绍了污泥水解工艺的常用构型及参数选择,以及国内外一些成功的实施案例。

关键词：初沉污泥活性污泥侧流水解发酵强化生物除磷 RBCOD VFAs

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The role of radiation therapy and particle therapy in renal cell carcinoma: current evidence and future perspectives

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 775-784页

作者： Charlien Berghen Maarten Albersen Robin De Roover Kato Rans Benoit Beuselinck KarelDecaestecker Kenneth Poels Francois-Xavier Otte Steven Joniau Karin Haustermans gert De Meerleer Department of Radiation Oncology University Hospitals LeuvenLeuven 3000Belgium Department of Urology University Hospitals LeuvenLeuven 3000Belgium Department of General Medical Oncology University Hospitals LeuvenLeuven Cancer Instituteand Laboratory of experimental OncologyDepartment of OncologyCatholic University LeuvenLeuven 3000Belgium Department of Urology Ghent University HospitalLeuven 3000Belgium Department of Radiation Oncology Institut Jules BordetBrussels 1000Belgium

For both primary and metastatic renal cell carcinoma(RCC),treatment with stereotactic body radiotherapy(SBRT)has found its way into clinical *** a non-invasive outpatient procedure,SBRT requires only a few visits to the radiation department and may be of interest for the elderly or,in the case of primary RCC,for patients who are not considered surgical candidates due to technical limitations,medical comorbidities,or in the event that the maintenance of kidney function is *** the treatment landscape of oligometastatic RCC,SBRT shows promise in eradicating metastatic disease and delaying the initiation of systemic *** advancements in the planning and administration of radiation treatment and improvements in movement management allow irradiating the tumor and/or metastatic lesions with very high doses in few fractions while maximally sparing the surrounding organs at risk,thus minimizing *** that context,the increasing availability of particle therapy,such as proton beam radiotherapy or carbon ion radiotherapy,could further optimize the delivery of radiation treatment in order to reduce toxicity and improve outcome.

关键词： Particle therapy proton therapy carbon ion radiation therapy

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中国的低碳转型与生态现代化

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中国人口·资源与环境 2012年第9期22卷 15-19页

作者：刘文玲王灿 Spaargaren gert Mol Arthur P J 清华大学环境学院北京100084 瓦赫宁根大学环境政策系

生态现代化理论探讨了国家在社会体制、经济发展和社会思想意识形态等方面的生态化转向,为政府、企业以及非政府团体和个人在面对环境问题时应该如何做出调整提供了一种新的思路。本文综述了生态现代化理论的核心思想和基本要素,并探讨... 详细信息

生态现代化理论探讨了国家在社会体制、经济发展和社会思想意识形态等方面的生态化转向,为政府、企业以及非政府团体和个人在面对环境问题时应该如何做出调整提供了一种新的思路。本文综述了生态现代化理论的核心思想和基本要素,并探讨了该理论发展过程中的主要争论。考虑目前国内经济的发展动态和发展低碳经济的迫切需求,这一理论对推动我国经济的低碳转型有着重要的借鉴意义。尤其是该理论发展过程中关于生产与消费的讨论,更为探讨发展低碳经济的核心定位等问题提供了参考。结合生态现代化观点和争论,本文提出我国经济的低碳转型,需要从尤其强调生产端导向的碳减排向同时兼顾上下游并重视消费者作用的战略思路转变;经济变革同时强调制度变革,转变行政命令控制为主的规制格局,促进多角色的参与;作为生产的微观主体,企业需强调以保护生态为己任的机构和管理改革,长远的发展更需要构建一种生产者与消费者之间有效衔接的消费导向战略。这些转变都将有利地推动中国经济的低碳现代化。

关键词：生态现代化低碳转型生产导向消费者战略

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低碳源条件下利用侧流活性污泥水解技术强化生物脱氮除磷

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给水排水 2013年第1期39卷 53-57页

作者：刘智晓 gert Petersen 张伟 Alexander Grossmann 詹卫东首创爱华天津市政环境工程有限公司天津300191 EnviDan A/S 2770 KastrupDenmark Lund Institute of Technology Lund 北京首创股份有限公司北京100028

污水水质特性是决定生物脱氮除磷工艺处理效能的关键性影响因素,尤其是进水中可快速降解有机物(rbCOD)及挥发性脂肪酸(VFA)浓度与N、P浓度比值的高低,直接制约了N、P的去除效率,补加外部碳源往往成为污水处理厂迫不得已的选择,但是外部... 详细信息

污水水质特性是决定生物脱氮除磷工艺处理效能的关键性影响因素,尤其是进水中可快速降解有机物(rbCOD)及挥发性脂肪酸(VFA)浓度与N、P浓度比值的高低,直接制约了N、P的去除效率,补加外部碳源往往成为污水处理厂迫不得已的选择,但是外部商业碳源会导致高昂的运行费用及其他运行问题。近十年来,充分挖掘优先利用污水处理厂内碳源技术在国外得到发展和应用。介绍了回流活性污泥(RAS)进行水解补充碳源的技术优势及工艺选择,就采用RAS侧流水解发酵在国内某厂实施技术示范项目进行了介绍,以期为国内在开发活性污泥可持续性利用技术方面提供借鉴。

关键词：活性污泥污泥水解可快速降解有机物挥发性脂肪酸生物脱氮除磷内碳源

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Species diversity and chemotype analysis of Fusarium from Chinese barley

Species diversity and chemotype analysis of Fusarium from Ch...

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中国植物病理学会2006年学术年会

作者： Theo van der Lee Cees Waalwijk gert Kema Plant Research International BV Biointeractions and Plant Health6700AA Wageningenthe Netherlands Plant Research International BV Biointeractions and Plant Health6700AA Wageningenthe Netherlands Plant Research International BV Biointeractions and Plant Health6700AA Wageningenthe Netherlands

＜正＞China is an increasing stakeholder in the barley/malt/beer chain, both as producer as well as consumer. Fusarium is a major problem in wheat and barley due to the production of mycotoxins, and malt/beer producers have a zero tolerance for mycotoxins. We therefore monitored the presence of Fusarium species during the growing season of 2005. We performed hierarchical sampling of

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Identification of habitat requirements of farmland birds based on a hierarchical structured monitoring scheme

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Chinese Birds 2013年第4期4卷 265-280页

作者： Jrg HOFFMANN Udo WITTCHEN Ulrich STACHOW gert BERGER 德国战略与技术评价研究所栽培植物联邦研究中心德国土地利用系统研究所莱布尼兹农业景观研究中心

Agricultural landscapes are essential for the conservation of biodiversity. Nevertheless, a negative trend continues to be observed in many rural areas for the most prominent indicator species group, the farmland birds. However, clear cause-effect relationships are rarely reported and sometimes difficult to deduce, especially from monitoring data which are based only on the detection of species and counts of the numbers of individuals. Because the identification of habitat preferences is a precondition for farmland bird biodiversity conservation efforts, a monitoring scheme for the simultaneous collection and analysis of bird and land use data was developed and tested. In order to assign the occurrence of bird species to land characteristics at various spatial scales and different land use and crop types, we applied a hierarchical structured sampling design. The spatial scales were ‘agricultural landscape', ‘agricultural landscape types', ‘field crops and other habitats' and ‘vegetation structures'. These scales were integrated with a novel concept, the ‘habitat matrix'(HM). This method was applied to farmland breeding bird abundances on 29 plots, each 1 km2 in size, by the use of the territory mapping method. The same plots were enlarged by a 100 m buffer and the sizes and location of habitats documented. Vegetation height, coverage and density were also recorded for all crop fields in the study area. We propose that this monitoring method facilitates the identification of scale dependent relationships between farmland bird habitat characteristics and bird abundance. This is demonstrated by the farmland bird species Corn Bunting(Emberiza calandra), Skylark(Alauda arvensis), and Whinchat(Saxicola rubetra). The breeding territories of these species reveal large differences within the various spatial scales ‘agricultural landscape', ‘agricultural landscape types' and ‘field crops'. Throughout the breeding season the abundances varied, dependent on the field crop and t

关键词： farmland birds hierarchical monitoring scheme agricultural landscape vegetation structures habitat matrix biodiversity

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Effect of rapamycin on hepatic osteodystrophy in rats with portasystemic shunting

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World Journal of Gastroenterology 2006年第28期12卷 4504-4510页

作者： Schalk W van der Merwe Maria M Conradie Robert Bond Brenda J Olivier Elongo Fritz Martin Nieuwoudt Rhena Delport Tomas Slavik gert Engelbrecht Del Kahn Enid G Shephard Maritha J Kotze Nico P de Villiers Stephen Hough Department of Internal Medicine and Gastroenterology ImmunologyHepatology and GI- research laboratoryUniversity of PretoriaSouth Africa Department of Internal Medicine and Endocrinology University of StellenboschSouth Africa Department of Internal Medicine and Gastroenterology1 Hepatology and GI- research laboratoryUniversity of PretoriaSouth Africa Department of Hepatology and GI- research laboratory University of PretoriaSouth Africa Department of Chemical Pathology University of PretoriaSouth Africa Department of Ampath pathology PretoriaSouth Africa Department of Surgery Grootte Schuur HospitalUniversity of Cape TownSouth Africa MRC Liver Research Centre Grootte Schuur HospitalUniversity of Cape TownSouth Africa Department of Genecare Molecular Genetics Christiaan Barnard Memorial HospitalCape TownSouth Africa

AIM： TO study if T-cell activation related to portasystemic shunting causes osteoclast-mediated bone loss through RANKL-dependent pathways. We also investigated if T-cell inhibition using rapamycin would protect against bone loss in rats. METHODS： Portasystemic shunting was performed in male Sprague-Dawley rats and rapamycin 0.1 mg/kg was administered for 15 wk by gavage. Rats received powderized chow and supplemental feeds to prevent the effects of malnutrition on bone composition. Weight gain and growth was restored after surgery in shunted animals. At termination, biochemical parameters of bone turnover and quantitative bone histology were assessed. Markers of T-cell activation, inflammatory cytokine production, and RANKL-dependent pathways were measured. In addition, the roles of IGF-1 and hypogonadism were investigated. RESULTS： Portasystemic shunting caused low turnover osteoporosis that was RANKL independent. Bone resorbing cytokine levels, including IL-1, IL-6 and TNFα, were not increased in serum and TNFα and RANKL expression were not upregulated in PBMC. Portasystemic shunting increased the circulating CD8＋ T-cell population. Rapamycin decreased the circulating CD8＋ T-cell population, increased CD8＋ CD25＋ T-regulatory cell population and improved all parameters of bone turnover. CONCLUSION： Osteoporosis caused by portasystemic shunting may be partially ameliorated by rapamycin in the rat model of hepatic osteodystrophy.

关键词： Osteopenia Liver disease Portasystemic shunting T-lymphocyte Rapamycin

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Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR CLEAN Registry

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Stroke & Vascular Neurology 2023年第1期8卷 17-25页

作者： Sabine L Collette Reinoud P H Bokkers Aryan Mazuri Geert J LycklamaàNijeholt Robert J van Oostenbrugge Natalie E LeCouffe Faysal Benali Charles B L M Majoie Jan Cees de Groot gert Jan R Luijckx Maarten Uyttenboogaart 无 Department of Radiology Medical Imaging CentreUniversity Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands Department of Radiology Haaglanden Medical CentreThe Haguethe Netherlands Department of Neurology Cardiovascular Research Institute Maastricht(CARIM)Maastricht University Medical CentreMaastrichtthe Netherlands Department of Neurology Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Radiology Maastricht University Medical CentreMaastrichtthe Netherlands Department of Radiology and Nuclear Medicine Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Neurology University Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands On behalf of the MR CLEAN Registry investigators

Introduction The efficacy and safety of local intra-arterial(IA)thrombolytics during endovascular thrombectomy(EVT)for large-vessel occlusions is *** analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR CLEAN)Registry,whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA *** In this observational study,we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR CLEAN Registry(March 2014-November 2017).The primary endpoint was favourable functional outcome,defined as an modified Rankin Scale score≤2 at 90 *** endpoints were reperfusion status,early neurological recovery and symptomatic intracranial haemorrhage(sICH).Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were *** Of the 2263 included patients,95(4.2%)received IA thrombolytics during *** IA thrombolytics administered were urokinase(median dose,250000 IU(IQR,193750-250000))or alteplase(median dose,20 mg(IQR,12-20)).No association was found between IA thrombolytics and favourable functional outcome(adjusted OR(aOR),1.16;95%CI 0.71 to 1.90).Successful reperfusion was less often observed in those patients treated with IA thrombolytics(aOR,0.57;95%CI 0.36 to 0.90).The odds of sICH(aOR,0.82;95%CI 0.32 to 2.10)and early neurological recovery were comparable between patients treated with and without IA *** primary and adjuvant revascularisation attempts,IA thrombolytics were more often administered for proximal than for distal *** outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation *** Local IA thrombolytics were rarely used in the MR CLEAN *** the relatively small st

关键词： arterial throm acute

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战斗老农

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模型世界 2020年第4期 32-38页

作者： gert MERTENS

城市作战并不仅发生在市区内,城郊或周边的田野都有可能爆发冲突。当我偶然发现一张拖拉机的照片,上面搭载一挺DShK1938重机枪和生锈钢板制成的装甲板,脑海中立马浮现出情景模型的创意。照片中最显眼的是一个散落着工具和农具的棚屋。...

城市作战并不仅发生在市区内,城郊或周边的田野都有可能爆发冲突。当我偶然发现一张拖拉机的照片,上面搭载一挺DShK1938重机枪和生锈钢板制成的装甲板,脑海中立马浮现出情景模型的创意。照片中最显眼的是一个散落着工具和农具的棚屋。由于这些元素在市面上找不到相应的模型,就算有类似的产品也和我们脑中的形象相去甚远,因此只能选择自制。情景中的拖拉机选用Balaton Model出品的MTZ-80,编号为BM-3542,这是一套带蚀刻片的全树脂

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