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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Acta Pharmaceutica Sinica B 2023年第5期13卷 2152-2175页

作者： Damijan Knez Daniel Diez-Iriepa Mourad Chioua Andrea Gottinger Milica Denic Fabien Chantegreil Florian Nachon Xavier Brazzolotto Anna Skrzypczak-Wiercioch Ane Meden Anja Pilar Janko Kos Simon akelj Jure Stojan Kinga Saat Julia Serrano Ana Patricia Fernández Aitana Sánchez-García Ricardo Martínez-Murillo Claudia Binda Francisco López-Muoz Stanislav Gobec JoséMarco-Contelles University of Ljubljana Faculty of PharmacyLjubljana 1000Slovenia Laboratory of Medicinal Chemistry(Institute of Organic Chemistry CSIC)Madrid 28006Spain Departamento de Química Orgánicay Química Inorgánica Alcaláde HenaresMadrid 28871Spain Department of Biology and Biotechnology University of PaviaPavia 27100Italy Département de Toxicologie et Risques Chimiques Institut de Recherche Biomédicale des ArméesParis 91220France Department of Animal Anatomy and Preclinical Sciences University Centre of Veterinary Medicine JU-UAUniversity of Agriculture in KrakowKrakow 30-059Poland Institute of Biochemistry Faculty of MedicineUniversity of LjubljanaLjubljana 1000Slovenia Department of Pharmacodynamics Chair of PharmacodynamicsFaculty of PharmacyJagiellonian University Medical CollegeKrakow 30-688Poland Department of Translational Neurobiology Neurovascular Research GroupCajal Institute(CSIC)Madrid 28002Spain Biotechnology and Vegetal Biology Department Escuela Técnica Superior de Ingeniería AgronómicaAlimentaria y de BiosistemasUniversidad Politécnica de MadridMadrid 28040Spain Faculty of Health Camilo JoséCela University of Madrid(UCJC)Neuropsychopharmacology Unit“Hospital 12 de Octubre”Research InstituteMadrid 28692Spain

We describe the development of quinolylnitrones(QNs)as multifunctional ligands inhibiting cholinesterases(ChEs:acetylcholinesterase and butyrylcholinesterase—h BChE)and monoamine oxidases(hMAO-A/B)for the therapy of neurodegenerative diseases.We identified QN 19,a simple,low molecular weight nitrone,that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde.Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition,yet unexpectedly showed potent inhibition of h BChE(IC50=1.06±0.31 nmol/L)and h MAO-B(IC_(50)=4.46±0.18μmol/L).The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding,which was further studied by enzyme kinetics.Compound 19 acted as a free radical scavenger and biometal chelator,crossed the blood—brain barrier,was not cytotoxic,and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease.In addition,in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination.Importantly,chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice,underscoring the disease-modifying effect of QN 19.

关键词： Quinolylnitrone Butyrylcholinesterase Monoamine oxidase B Alzheimer's disease Multifunctional ligands 6-Hydroxydopamine model Passive avoidance task Novel object recognition

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栖息地条件对白杨与枫树林群落中高山天南星的丰富度和选定个体特征的影响

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Journal of Plant Ecology 2024年第1期17卷 33-49页

作者： Tomasz Wójcik kinga Kostrakiewicz-Gierałt Department of Nature Conservation and Landscape Ecology Institute of Agricultural SciencesLand Management and Environmental ProtectionUniversity of Rzeszow35-601 RzeszowPoland Department of Tourism Geography and Ecology Institute of TourismFaculty of Tourism and RecreationUniversity of Physical Education in Krakow31-571 KrakowPoland

本研究于2020至2021年在西喀尔巴阡山脉的山麓地区进行,研究了高山天南星(Arum alpinum)的物种数量和选定特征的空间-时间变异。调查分别在4个永久样地中进行(Patch Ⅰ、Ⅱ、Ⅲ、Ⅳ)。Patch Ⅰ和Patch Ⅲ位于以低矮植被为主的枫树-鹅耳... 详细信息

本研究于2020至2021年在西喀尔巴阡山脉的山麓地区进行,研究了高山天南星(Arum alpinum)的物种数量和选定特征的空间-时间变异。调查分别在4个永久样地中进行(Patch Ⅰ、Ⅱ、Ⅲ、Ⅳ)。Patch Ⅰ和Patch Ⅲ位于以低矮植被为主的枫树-鹅耳枥林(Tilio cordatae-Carpinetum betuli)林地中,而Patch Ⅱ和Patch Ⅳ位于以阔叶物种为主的白杨(Populetum albae)河滩林中。调查结果表明,高山天南星最丰富种群出现在Patch Ⅰ,但Patch Ⅱ和Patch Ⅳ中也存在大量的营养体和繁殖个体。个体性状的时间变异性在Patch Ⅳ最低,其次是Patch Ⅰ和Patch Ⅱ,在Patch Ⅲ最高。所有种群中均发现叶柄长度与叶片尺寸以及有性茎长度与果序特征之间的关系显著呈正相关,这一发现证实了先前的研究。这些研究结果表明,高山天南星与特定的森林群落没有密切关联。充足的遮荫和湿润富养分的土壤对该物种有利,而干燥的土壤和过多的日照可能会限制其个体的开花与结果。

关键词：高山天南星(Arum alpinum) 枫树-鹅耳枥林河滩林开花茎果序叶片山地物种

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The influence of Mycoplasma species on human and canine semen quality:a review

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Asian Journal of Andrology 2023年第1期25卷 29-37页

作者： kinga Domrazek Ilona Kaszak Szymon Kanafa Mariusz Sacharczuk Piotr Jurka Laboratory of Small Animal Reproduction Institute of Veterinary MedicineWarsaw University of Life SciencesNowoursynowska 159C StreetWarsaw 02-787Poland Institute of Genetics and Animal Biotechnology of the Polish Academy of Sciences Jastrz biec Postepu Street 36AMagdalenka 05-552Poland

Mycoplasma species(spp.)are bacteria that are difficult to detect.Currently,the polymerase chain reaction(PCR)is considered the most effective diagnostic tool to detect these microorganisms in both human and veterinary medicine.There are 13 known species of human Mycoplasma and 15 species of canine Mycoplasma.Owing to the difficulties in identifying the individual species of Mycoplasma,there is a lack of information regarding which species are saprophytic and which are pathogenic.The prevalence of the individual species is also unknown.In addition,in both humans and dogs,the results of some studies on the impact of Mycoplasma are conflicting.The presence of Mycoplasma spp.on the epithelium of reproductive tract is often associated with infertility,although they are also detected in healthy individuals.The occurrence of Mycoplasma spp.is more common in dogs(even 89%)than in humans(1.3%–4%).This is probably because the pH of a dog's genital is more conducive to the growth of Mycoplasma spp.than that of humans.Phylogenetically,human and canine Mycoplasma are related,and majority of them belong to the same taxonomic group.Furthermore,40%of canine Mycoplasma spp.are placed in common clusters with those of human.This suggests that species from the same cluster can play a similar role in the canine and human reproductive tracts.This review summarizes the current state of knowledge about the impact of Mycoplasma on canine and human male fertility as well as the prospects of further development in this field.

关键词： Mycoplasma sperm morphology sperm motility

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Applying Rational Envelope curves for skinning purposes

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Frontiers of Information Technology & Electronic Engineering 2021年第2期22卷 202-209页

作者： kinga KRUPPA Faculty of Informatics University of DebrecenDebrecen H-4028Hungary Doctoral School of Informatics University of DebrecenDebrecen H-4028Hungary

Special curves in the Minkowski space such as Minkowski Pythagorean hodograph curves play an important role in computer-aided geometric design,and their usages are thoroughly studied in recent years.Bizzarri et al.(2016)introduced the class of Rational Envelope(RE)curves,and an interpolation method for G1 Hermite data was presented,where the resulting RE curve yielded a rational boundary for the represented domain.We now propose a new application area for RE curves:skinning of a discrete set of input circles.We show that if we do not choose the Hermite data correctly for interpolation,then the resulting RE curves are not suitable for skinning.We introduce a novel approach so that the obtained envelope curves touch each circle at previously defined points of contact.Thus,we overcome those problematic scenarios in which the location of touching points would not be appropriate for skinning purposes.A significant advantage of our proposed method lies in the efficiency of trimming offsets of boundaries,which is highly beneficial in computer numerical control machining.

关键词： Medial axis transform Envelope Interpolation Skinning Circle

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Protocadherin gamma C3:a new player in regulating vascular barrier function

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Neural Regeneration Research 2023年第1期18卷 68-73页

作者： Victoria Kaupp kinga G.Blecharz-Lang Christina Dilling Patrick Meybohm Malgorzata Burek Department of Anesthesiology Intensive CareEmergency and Pain MedicineUniversity of WürzburgUniversity Hospital WürzburgWürzburgGermany Department of Experimental Neurosurgery Charité-UniversitätsmedizinBerlinGermany

Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.

关键词： blood-brain barrier brain microvascular endothelial cells permeability protein interaction protocadherin gamma C3 protocadherins tight junctions

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Effect of Compression with Oscillatory Torsion Processing on Structure and Properties of Cu

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Journal of Materials Science & Technology 2011年第11期27卷 1083-1088页

作者： kinga Rodak Jacek Pawlicki Department of Materials Science Silesian University of Technology Department of Materials Technology Silesian University of Technology

The results presented in this study were concerned with microstructures and mechanical properties of poly- crystalline Cu subjected to plastic deformation by a compression with oscillatory torsion process. Different deformation parameters of the compression with oscillatory torsion process were adopted to study their effects on the microstructure and mechanical properties. The deformed microstructure was characterized quantitatively by electron backscattered diffraction （EBSD） and scanning transmission electron microscopy （STEM）. Mechanical properties were determined on an MTS QTest/10 machine equipped with digital image correlation. From the experimental results, processes performed at high compression speed and high torsion frequency are recommended for refining the grain size. The size of structure elements, such as average grain size （D） and subgrain size （d）, reached 0.42 μm and 0.30 μm, respectively, and the fraction of high angle boundaries was 35% when the sample was deformed at a torsion frequency f = 1.6 Hz and compression rate v= 0.04 mm/s. These deformation parameters led to an improvement in the strength properties. The material exhibited an ultimate tensile strength （UTS） of 434 MPa and a yield strength （YS） of 418 MPa. These values were about two times greater than those of the initial state.

关键词： Severe plastic deformation Copper Fine-grained microstructure Electronbackscattered diffraction （EBSD） Scanning transmission electronmicroscopy （STEM）

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Socialism as Social Imaginary:An Analysis of the Political Discourse of Deng Xiaoping’s Reform

Socialism as Social Imaginary:An Analysis of the Political D...

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作者： Soós kinga 华东师范大学

学位级别：硕士

It is well known from Michel Foucault how different perspectives of looking back into the history can advance our knowledge on seemingly well-known facts and events.Accordingly,this research tends to offer a new understanding of Deng Xiaoping’s reform era.The analysis of the initiation of the reform（specially between 1978 and 1982）conducted through a political perspective,using the enhancement of the legitimacy of the Communist Party in China as an objective.The thesis is built on the political discourse theory of Laclau and Mouffe,which claims that every social action（textual by nature or not）as far as it aims to create new meanings in the socio-political realm,can be understood as a discourse.The researcher applies discourse analysis on crucial political texts（editorials,speeches）and on political activities（e.***.institutional reforms）of Deng Xiaoping.Discourses,in the Chinese case,contribute to the Party’s legitimacy,keep on with the Marxist base,as well as fix a style of political communication,and maintain a Chinese from of Marxist political theory to explain the current reforms.Through the analysis,it has been shown that the described discursive（re）forms are creating hegemonic relations（in the sense of Laclau and Mouffe）,thus they serve as the consolidation of the political line of Deng Xiaoping and preserve the continuity of the Party’s rule.The economic reform and opening of the Post-Mao era came along with fundamental political restructuring where socialism became a totality instead of the guidance of the revolutionary mobilization,and transcended from the realm of social actions to the social imaginary.

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瞬时受体电位通道TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性和神经病理性疼痛模型中的镇痛作用(英文)

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2015年第3期16卷 167-178页

作者： kinga SALAT Barbara FILIPEK Department of Pharmacodynamics Faculty of PharmacyJagiellonian University

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇... 详细信息

目的:评价瞬时受体电位通道(TRP通道)TRPV1、TRPA1和TRPM8拮抗剂在小鼠神经源性、持续性和神经病理性疼痛模型中的作用。方法:通过辣椒素实验、异硫氰酸烯丙酯(AITC)实验和福尔马林实验,评估TRP通道拮抗剂在小鼠神经源性疼痛模型中的镇痛作用;通过建立紫杉醇诱导的小鼠神经病理性疼痛模型,对TRP通道拮抗剂的抗痛觉(冷、热、触觉)过敏效应进行评估;通过旋转法实验对小鼠的运动协调性进行评估。结论:TRP通道家族包含了不同的小鼠疼痛模型。TRP通道拮抗剂能减轻神经源性、持续性和神经病理性疼痛,但是其镇痛效果与疼痛模型有关。

关键词：异硫氰酸烯丙酯辣椒素福尔马林神经源性疼痛瞬时受体电位通道紫杉醇诱导的感觉神经病变

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Peacekeeping and Non-intervention:Understanding China’s Attitude Towards United Nations Peacekeeping

Peacekeeping and Non-intervention:Understanding China’s Att...

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作者： kinga Jacques（唐华）山东大学

学位级别：硕士

在21世纪的第一个十年中,整个世界背负着众多的冲突。联合国、欧盟以及像美国、中国这样的大国已经提出如何维护世界和平与安全这个议题。但是要达到这个共同的目标,就意味这这些机构或大国之间的分析。讨论到解决冲突的追索权,是通过...

在21世纪的第一个十年中,整个世界背负着众多的冲突。联合国、欧盟以及像美国、中国这样的大国已经提出如何维护世界和平与安全这个议题。但是要达到这个共同的目标,就意味这这些机构或大国之间的分析。讨论到解决冲突的追索权,是通过干预和向交战双方提供援助还是通过干预,这让作者提出一个新的议程。本文的目的是了解中国对联合国维和政策模式的变化,从尊重不干涉一个主权国家的内政,到成为全球的重要决策者。本文的议题是了解为什么中国改变对联合国维和的态度。应该考虑几个问题,包括联合国维和部队的角色和目标,不干预政策在维护世界和平与稳定是怎么样成为一个很好的方式的。从这些问题,本研究将突出强调联合国维和行动的过程,经过讨论联合国维和行动,其任务分别称为联索行动（Ⅰ和Ⅱ）和联刚特派团。当世界体系（包括联合国所有分支机构,当然,联合国维和机构）是一个霸权下的率性和反复无常的冷战结束后,联合国在非洲开展了这两项操作。它也将强调在理解中国国情的情况下,中国作为联合国安理会的成员,反对大多数联合国在干预方面的决定,之前和现在都非常积极参与。本文也将涵盖中国’的外交政策,在同一时期冲突塑造联合国安理会的决策和行动中的作用。该分析将更加强调两个原则的相互作用（维和不干预）。在这样做时,作家将能够获得承认决策者采取不同的选择,特别是研究员对中国政策的演变将有一个更清晰地理解,也希望从这项工作中得出结论,一个国家的发展可能会改变政策决定草案。第一章将重点突出研究的目的性和合理性,但更重要的是审查当前的研究。首先提出实现和平与安全是21世纪的国际社会最重要主题。然而,要达到这一目标,意味着决策者和政治家之间的分歧。一方面,在解决两个交战地区的冲突时是需要干预的,经过证明,维持和平是某种形式的干预,作者认为,这种操作通常是被联合国用来构建和维护世界和平的一个方式。另一方面,自从中国建国以来,中国尊重和促进的不干预政策也是实现世界和平的另外一种途径。不干预政策是指超出这个角度来看,因为它也可以看作是尊重国家主权和其内部事务的最佳方式。第二章将论述维持和平的概念和不干预的相关理论。首先阐述国际学校是怎样理解和定义这些理论的。谈到维和,和平与安全,维持和平行动必须从现实主义和新现实主义的角度来看,从自由主义和新自由主义和建构主义理论来看。现实主义者提出了在世界体系下关于和平与安全的非常悲观的观点。自由主义认为,世界体系不仅是权力,各国社会利益和价值观的理想主义。然而,建构一直是容易被“创意中心”。它基于这样一个事实,即世界和平与安全的基础上共享的价值,而不是物质力量。关于不干预,主权和民族自决是本文关键思想理论,根据相同的国际学校提出的观点论文第三章研究的案例是从联合国在非洲进行的几个任务中抽取的两个案例,为了理解维持和平和不干预的理念,我们将讨论这两个案例,分别称为联索行动（Ⅰ和Ⅱ）和联刚特派团。联合国在索马里Ⅰ和Ⅱ的操作是自1992年至1995年联合国在索马里监测的两项任务。这两项的任务设置是为了方便对被内战和饥荒所困的人提供人道主义援助。该任务发展成为一个广泛的尝试,以帮助制止冲突和重建基本可行的国家机构。在这次行动中将解释为什么中国对联合国维和行动一直保持被动。第二种情况是,联刚特派团（法语名字的缩写）在2010年1999年6月30日被称为刚果民主共和国的联合国特派团。此任务是中国在非洲参加的任务之一,但更重要的是超越了亚洲大陆的任务. 在第四章中,对题目的分析将从在世界政治的背景下,旧世界政治格局正在改变,新的世界秩序正在形成。研究者认为,冷战结束后打乱了的世界体系在许多方面促进了中国对联合国政策的不断变化。接下来将论述随着中国经济的日益增长,中国在国际社会的地位逐渐提高。在这种情况下,中国担心这个世界,尤其是发展中国家,看到她作为一个非负责任的大国,这可能阻碍其快速增长。总结这一章,它也有要注意联合国维持和平行动部（UN-维和部）的演变,帮助中国更好地了解维和行动的目标。我们知道,在冷战期间,维和行动视为传统的只注重展示权力和武器。最后这一章将总结本文。首先评估了维和行动和不干预的意义。本文还提出维持和平和不干预是两种对立的观点,都有其优点和限制。作家指出有关问题的解决方案,一方面批评联合国维和部缺乏重点;另一方面,提出中国对联合国维和态度的转变可能是由于其巨大的能源需求。最后,展望未来,提出预测中国在世界体系中的作用,将会达到其历史的巅峰。

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Evaluation of the nutritional status of patients with liver cirrhosis

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World Journal of Hepatology 2023年第7期15卷 914-924页

作者： Barbara Janota Aneta Krupowicz kinga Noras Ewa Janczewska Department of Basic Medical Sciences Faculty of Public Health in BytomMedical University of Silesia in KatowiceBytom 41-902Poland ID Clinic Mysłowice 41-400Poland Department of Biometry Warsaw University of Life SciencesWarsaw 02-787Poland

BACKGROUND Progressive malnutrition coexists with liver diseases,particularly in patients with cirrhosis.Early diagnosis of malnutrition in patients with advanced stages of chronic liver disease and the implementation of appropriate nutritional treatment for malnourished patients should be an integral part of the therapeutic process.AIM To evaluate the nutritional status of patients with various severities of advanced liver fibrosis,using various nutritional status parameters.METHODS This study involved 118 patients with liver cirrhosis who were classified into three groups according to their Child-Pugh score.The nutritional status of the patients in each group was assessed using different methods.The average values obtained from the measurements were calculated for each research group.The influence of disease stage on the examined parameters of nutritional status was determined using one-way analysis of variance.To investigate the relationship between the parameters determining nutritional status and the stage of disease advancement,a correlation analysis was performed.RESULTS The Child-Pugh A group had the highest mean body weight(76.42 kg),highest mean body mass index(BMI)(26.72 kg/m²),and largest mean arm circumference(27.64 cm).In the Child-Pugh B group,the mean scores of all examined variables were lower than those of the Child-Pugh A group,whereas the mean body weight and BMI of the Child-Pugh C group were higher than those of the Child-Pugh B group.There was a very strong correlation between the Child-Pugh classification and subjective global assessment score;a very strong correlation between the Child-Pugh classification and arm circumference;a strong correlation between the Child-Pugh classification and body weight,albumin concentration,fat-free mass index,muscle mass index,phase angle,and BMI;and an average correlation between Child-Pugh classification and fat mass index.Notably,these indicators deteriorated with disease progression.CONCLUSION Advanced liver fibrosis leads to the deterioration of many

关键词： Liver cirrhosis Fibrosis Nutritional status Malnourishment Sarcopenia

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