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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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Possibilities and concerns of implementing precision agriculture technologies on small farms in Slovenia

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International Journal of Agricultural and Biological Engineering 2022年第3期15卷 16-21页

作者： Jurij Rakun Erik Rihter damijan Kelc Stajnko Denis Peter Vindiš Peter Berk Peter Polič Miran Lakota Faculty of Agriculture and Life Sciences University of MariborPivola 102311 HočeSlovenia

Precision agriculture(PA)through the use and utilization of innovative technologies is a concept in agricultural management that enables long-term efficiency gains,control of unforeseen changes,and a reduction of negative impacts on the environment.However,there are even more reasons and benefits to using precision agriculture technologies(PATs)on farms,but the actual use on small farms is often questionable.The main objective of this research was to evaluate and analyze the current state of PA and its potential on a set of small farms.In addition,a comparison was made between small farms located in less favored areas(LFAs)and more favored areas(MFAs)to find if specific characteristics of the surrounding environment affect the(non-)implementation of these technologies by farm owners,with respect to the given regional possibilities.The result shows that 57.5%of respondents on these farms have never implemented PATs before and 20%are beginners in their respective fields.It was found that there were no statistically significant differences in the integration between fewer LFAs and MFAs technologies and their use in this study.The majority of respondents believe that the main changes need to occur on the level of politics.The results show that the level of cost or initial investment is the main reason and the main obstacle in the implementation of PATs on the surveyed farms.

关键词： precision agriculture small farm technological innovations implementation situation overview survey ICT

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Reduction of environmental pollution by using RTK-navigation in soil cultivation

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International Journal of Agricultural and Biological Engineering 2019年第5期12卷 173-178页

作者： damijan Kelc Denis Stajnko Peter Berk Jurij Rakun Peter Vindiš Miran Lakota Faculty of Agriculture and Life Sciences University of MariborPivola 102311 HočeSlovenia

The concept of precision farming is wide,and it represents the efficiency which is achieved with the help of precision.For the navigation of field machines,the RTK(Real Time Kinematic)navigation is needed.In order to verify the positive effects in practice,RTK navigation system equipped with Fentd 828 was applied to test the width of overlap,and fuel and time that could be saved compared with manual driving.The experiment was conducted on two areas of land size of 172 m×58 m with two working machines width 3 m and 6 m.Results indicated that 15.7%of the time and 8.66%of the fuel were saved on a working machine of 3 meters width,and 12.6%of the time and 8.28%of the fuel were saved on a working machine of 6 m width.The width of the overlap represent 10%of the working width of the machine,and with the method of turning,which RTK navigation allows,additional time was saved.Ecological footprint,CO2 emissions and global warming potential(GWP)was estimated under different guiding systems.The largest footprint was related to manual tillage with 3 m width working machine,while estimation on CO2(kg)emissions and GWP obtained the same result.The use of precision agriculture technologies allows better planning and analyzing of working procedures.The air,water and soil pollution are less intensive.

关键词： precision farming RTK technology ecological footprint environmental pollution tillage

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在斯洛文尼亚小农场实施精准农业技术的可行性和关注点

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农业工程技术 2023年第2期 116-116页

作者： Jurij Rakun Erik Rihter damijan Kelc Stajnko Denis Peter Vindi? Peter Berk Peter Poli? Miran Lakota 马里博尔大学农业与生命科学学院皮沃拉

通过创新技术的运用实现精准农业(PA)是农业管理中的一个概念，可长期提高效率，控制不可预见的变化，并减少对环境的负面影响。在大型农场使用精准农业技术(PAT)或许还有更多的理由和好处，但小型农场的实际体验却未必如此。该研究的... 详细信息

通过创新技术的运用实现精准农业(PA)是农业管理中的一个概念，可长期提高效率，控制不可预见的变化，并减少对环境的负面影响。在大型农场使用精准农业技术(PAT)或许还有更多的理由和好处，但小型农场的实际体验却未必如此。该研究的主要目的是评估和分析PA的当前状态及其在一组小型农场中的潜力。此外，对处于相对荒凉区域(LFA)和相对受关注区域(MFA)的小型农场进行了比较，以证明周围环境的具体特征在特定区域条件下是否会影响农场主采用或不采用这些技术。结果显示，这些农场中57.5%的受访者以前从未实施过精准农业技术，20%在各自领域里刚开始采用PAT。研究发现，LFA和MFA之间的技术整合及其应用在统计学上没有明显差异。大多数受访者认为，应在政策层面做出重大改变。结果表明，成本或初始投资水平是这些受调研农场是否实施精准农业技术的主要原因和主要障碍。

关键词：精准农业小农场技术创新实施情况概述调研 ICT

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