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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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SmartMicro Grid Energy System Management Based on Optimum Running Cost for Rural Communities in Rwanda

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Energy Engineering 2024年第7期121卷 1805-1821页

作者： fabien Mukundufite Jean Marie Vianney Bikorimana Alexander Kyaruzi Lugatona Electrical and Electronic Engineering Department University of RwandaKigaliRwanda Electrical Engineering Department University of Dar es SalaamDar es SalaamTanzania

The governmental electric utility and the private sector are joining hands to meet the target of electrifying all households by 2024.However,the aforementioned goal is challenged by households that are scattered in remote areas.So far,Solar Home Systems(SHS)have mostly been applied to increase electricity access in rural areas.SHSs have continuous constraints to meet electricity demands and cannot run income-generating activities.The current research presents the feasibility study of electrifying Remera village with the smart microgrid as a case study.The renewable energy resources available in Remera are the key sources of electricity in that village.The generation capacity is estimated based on the load profile.The microgrid configurations are simulated with HOMER,and the genetic algorithm is used to analyze the optimum cost.By analyzing the impact of operation and maintenance costs,the results show that the absence of subsidies increases the levelized cost of electricity(COE)five times greater than the electricity price from the public utility.The microgrid made up of PV,diesel generator,and batteries proved to be the most viable solution and ensured continuous power supply to customers.By considering the subsidies,COE reaches 0.186$/kWh,a competitive price with electricity from public utilities in Rwanda.

关键词： Load demand load profile optimum running cost power demand satisfaction smart meters and smart micro grid

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Why China Still Has Room to Grow

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Beijing Review 2024年第18期67卷 20-21页

作者： fabien Pacory French Chamber of Commerce and Industry in China

The world economy is experiencing what the World Bank calls"the slowest halfdecade of GDP growth in 30 years."As some of China's key growth catalysts weaken against this backdrop,a few stakeholders in the Western econ... 详细信息

关键词： economy Room Still

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Numerical Study of the Vibrations of Beams with Variable Stiffness under Impulsive or Harmonic Loading

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World Journal of Engineering and Technology 2024年第2期12卷 401-425页

作者： Moussa Sali fabien Kenmogne Jean Bertin Nkibeu Abdou Njifenjou Laboratory of Materials Mechanics and Civil Engineering National Higher Polytechnic School of Maroua University of Maroua Maroua Cameroon Department of Civil Engineering Advanced Teachers Training College of the Technical Education University of Douala Douala Cameroon Laboratory Engineering Civil and Mechanics National Advanced School of Engineering University of Yaound&#233 1 Yaound&#233 Cameroon Laboratory of Energy Materials Modeling and Method (E3M) National Advanced School of Engineering University of Douala Douala Cameroon Laboratory of Mathematical Engineering and Information Systems National Advanced School of Engineering University of Yaound&#233 1 Yaound&#233 Cameroon

The behavior of beams with variable stiffness subjected to the action of variable loadings (impulse or harmonic) is analyzed in this paper using the successive approximation method. This successive approximation method is a technique for numerical integration of partial differential equations involving both the space and time, with well-known initial conditions on time and boundary conditions on the space. This technique, although having been applied to beams with constant stiffness, is new for the case of beams with variable stiffness, and it aims to use a quadratic parabola (in time) to approximate the solutions of the differential equations of dynamics. The spatial part is studied using the successive approximation method of the partial differential equations obtained, in order to transform them into a system of time-dependent ordinary differential equations. Thus, the integration algorithm using this technique is established and applied to examples of beams with variable stiffness, under variable loading, and with the different cases of supports chosen in the literature. We have thus calculated the cases of beams with constant or variable rigidity with articulated or embedded supports, subjected to the action of an instantaneous impulse and harmonic loads distributed over its entire length. In order to justify the robustness of the successive approximation method considered in this work, an example of an articulated beam with constant stiffness subjected to a distributed harmonic load was calculated analytically, and the results obtained compared to those found numerically for various steps (spatial h and temporal τ ¯ ) of calculus, and the difference between the values obtained by the two methods was small. For example for ( h=1/8 , τ ¯ =1/ 64 ), the difference between these values is 17%.

关键词： Successive Approximations Method Direct Integration Differential Equations Beams of Variable Stiffness Quadratic Parabola Impulse and Harmonic Loads

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Preclinical and clinical evidence of the association of colibactinproducing Escherichia coli with anxiety and depression in colon cancer

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World Journal of Gastroenterology 2024年第21期30卷 2817-2826页

作者： fabien Rondepierre Maëva Meynier Johan Gagniere Vincent Deneuvy Anissa Deneuvy Gwenaelle Roche Elodie Baudu Bruno Pereira Richard Bonnet Nicolas Barnich Frédéric Antonio Carvalho Denis Pezet Mathilde Bonnet Isabelle Jalenques Service de Psychiatrie de l’Adulte A et Psychologie Médicale CHU Clermont-FerrandClermont-Ferrand 63000France M2iSH UMR 1071INSERMUniversity of Clermont AuvergneINRAE USC 1382Clermont-Ferrand 63001France NeuroDol UMR 1107INSERMUniversity of Clermont AuvergneClermont-Ferrand 63001France Department of Digestive Surgery CHU de Clermont-FerrandClermont-Ferrand 63001France Biostatistics Unit Department of Clinical Research and InnovationCHU Clermont-FerrandClermont-Ferrand 63000France Department of Bacteriology CHU de Clermont-FerrandClermont-Ferrand 63001France UniversitéClermont Auvergne INPCNRSClermont Auvergne Institut PascalClermont-Ferrand 63000France

BACKGROUND The association between the intestinal microbiota and psychiatric disorders is becoming increasingly apparent.The gut microbiota contributes to colorectal carcinogenesis(CRC),as demonstrated with colibactin-producing Escherichia coli(CoPEC).AIM To evaluate the association between CoPEC prevalence and anxiety-and depressive-like behaviors with both preclinical and clinical approaches.METHODS Patients followed after a CRC surgery and for whom the prevalence of CoPEC has been investigated underwent a psychiatric interview.Results were compared according to the CoPEC colonization.In parallel C57BL6/J wild type mice and mice with a CRC susceptibility were chronically infected with a CoPEC strain.Their behavior was assessed using the Elevated Plus Maze test,the Forced Swimming Test and the Behavior recognition system PhenoTyper®.RESULTS In a limited cohort,all patients with CoPEC colonization presented with psychiatric disorders several years before cancer diagnosis,whereas only one patient(17%)without CoPEC did.This result was confirmed in C57BL6/J wildtype mice and in a CRC susceptibility mouse model(adenomatous polyposis colimultiple intestinal neoplasia/+).Mice exhibited a significant increase in anxiety-and depressive-like behaviors after chronic infection with a CoPEC strain.CONCLUSION This finding provides the first evidence that CoPEC infection can induce microbiota-gut-brain axis disturbances in addition to its procarcinogenic properties.

关键词： Colorectal cancer Colibactin Escherichia coli Colibactin-producing Escherichia coli Inflammation Anxiety Depression Behavior

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Spatial Variation and Trend of Extreme Precipitation in Africa during 1981-2019 and Its Projected Changes at the End of 21^st Century

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Journal of Geoscience and Environment Protection 2024年第3期12卷 192-221页

作者： fabien Habiyakare Tong Jiang Ibrahim Yahaya Daudi Ndabagenga James Kagabo Buda Su School of Atmospheric Sciences Key Laboratory of Meteorological Disaster of Ministry of Education Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science and Technology Nanjing China Rwanda Meteorology Agency (Meteo Rwanda) Kigali Rwanda Institute for Disaster Risk Management/School of Geographical Sciences Nanjing University of Information Science & Technology Nanjing China Department of Geography Gombe State University Gombe State Nigeria

This study comprehensively examines the patterns and regional variation of severe rainfall across the African continent, employing a suite of eight extreme precipitation indices. The analysis extends to the assessment of projected changes in precipitation extremes using five General Circulation Models (GCMs) from Coupled Model Intercomparison Project Phase 6 (CMIP6) under four Shared Socioeconomic Pathways (SSPs) scenarios at the long-term period (2081-2100) of the 21st century. Furthermore, the study investigates potential mechanisms influencing precipitation extremes by correlating extreme precipitation indices with oceanic system indices, specifically Ni?o 3.4 for El Ni?o-Southern Oscillation (ENSO) and Dipole Mode Index (DMI) for the Indian Ocean Dipole (IOD). The findings revealed distinct spatial distributions in mean trends of extreme precipitation indices, indicating a tendency toward decreased extreme precipitation in North Africa, Sahel region, Central Africa and the Western part of South Africa. Conversely, West Africa, East Africa and the Eastern part of South Africa exhibit an inclination toward increased extreme precipitation. The changes in precipitation extreme indices indicate a general rise in both the severity and occurrence of extreme precipitation events under all scenarios by the end of the 21st century. Notably, our analysis projects a decrease in consecutive wet days (CWD) in the far-future. Additionally, correlation analysis highlights significant correlation between above or below threshold rainfall fluctuation in East Africa and South Africa with oceanic systems, particularly ENSO and the IOD. Central Africa abnormal precipitation variability is also linked to ENSO with a significant negative correlation. These insights contribute valuable information for understanding and projecting the dynamics of precipitation extreme in Africa, providing a foundation for climate adaptation and mitigation efforts in the region.

关键词： Extreme Precipitation Mann-Kendall Trend Projections Oceanic System Africa

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Vaccination and Measles Epidemic in the Republic of Congo

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Open Journal of Epidemiology 2024年第1期14卷 45-55页

作者： Léa Gwladys Gangoue Yanne Mavougou fabien Rock Niama Pembe Issamou Mayengue Etienne Nguimbi National Public Health Laboratory (LNSP) Ministry of Health and Population Brazzaville Republic of Congo Cellular and Molecular Biology Laboratory (BCM) Faculty of Sciences and Techniques Marien Ngouabi University Brazzaville Republic of Congo

Measles is a highly infectious, vaccine-preventable viral disease. Often forgotten, it is potentially fatal. Its main symptoms are: fever, cough, conjunctivitis, rhinitis and skin rash. Serological diagnoses by ELISA test based on the detection of anti-measles virus immunoglobulins M and G (IgM and IgG), are used respectively for the confirmation of suspected cases notified by means of clinical signs of the disease in health structures of the twelve departments of the Republic of Congo involved in the epidemiological surveillance of the disease, and for the evaluation of the immunity conferred by vaccination. During 2021, 459 suspected cases of measles were reported and sampled throughout the country, despite the administration under the Expanded Routine Immunization Program (EPI), of 2 doses of the combined measles-rubella vaccine (RR1 and RR2) in 2020. The notification rate was higher in the south of the country, more precisely in the health structures of the departments of Pointe-Noire (42%) and Brazzaville (11%). During the year 2021, 459 suspected cases of measles were notified and sampled throughout the country with a high notification rate in the south of the country, more precisely in the health structures of the Pointe-Noire departments (42%) and Brazzaville (11%). The samples consisting of human blood (serum) were sent to the National Public Health Laboratory and analyzed by various ELISA tests for the detection of anti-measles immunog-lobulins M and G. The analysis of the results obtained shows that the measles virus circulated in all departments of the country. 154 cases (33.55%) were confirmed positive by IgM ELISA and 98 positive cases (63.63%) were patients vaccinated against measles. Vaccination coverage in RR1 of [50%-95% [(first dose) as well as the lowest RR2 < 50% (second dose) undoubtedly because the COVID-19 pandemic could be the cause of the high frequency of cases positive vaccinated. The non-detection of IgG immunoglobulins in vaccinated patients observed by IgG ELISA tests revealed that

关键词： Vaccination Measles Epidemic

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Profile of Factors of Arduous Work among Healthcare Professionals in Healthcare Facilities in Northern Benin in 2021

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Occupational Diseases and Environmental Medicine 2024年第1期12卷 41-48页

作者： Gounongbé Ahoya Christophe fabien Mama Cissé Ibrahim Lompo Marthe Sandrine Azandjèmè Colette Bèhanzin Luc Faculty of Medicine University of Parakou Parakou Benin Health Sciences Training and Research Unit Joseph Ki-Zerbo University Ouagadougou Burkina Faso Regional Institute of Public Health of Ouidah University of Abomey-Calavi Abomey-Calavi Benin National Training School for Senior Technicians in Public Health and Epidemiological Surveillance University of Parakou Parakou Benin

Introduction: Work environments create the basis for arduous nursing work. This is what led us to research the factors of arduousness in the exercise of the health profession in North Benin, through this study. Methods: This is a cross-sectional and descriptive study which focused on health professionals in the health zones of Parakou-N’dali and Tchaourou. The sampling was an exhaustive census. All health workers who had given their free and informed consent were included. The data was collected using a questionnaire. The variables studied were the factors of arduous work and socio-professional characteristics. The data collected was processed and analyzed with the Epi info 7.***.0.1 software. Results: A total of 692 were surveyed, the participation rate was 85.11% and the sex ratio (M/F) equal to 0.7. The average age was 38 years old. Nurses made up 32.66% of the sample. They were 86.42% subject to night work and 82.66% to alternating work. Overall, 70.23% worked more than 40 hours per week. Between 78.12% and 96.46% of non-specialist doctors, nurses, midwives and biomedical analysis technicians were required to work night shifts. Nurses, midwives, radiology and laboratory technicians were between 89.53% and 97.35%, organized in alternating work. In the sample, 55.20% complained about the insufficient number of work materials, 26.29% handled harmful chemical substances. Among those surveyed, 58.14% had been attacked. Conclusion: All professional categories of caregivers are subject to arduous work. Measures are needed to reverse the situation.

关键词： Hard Work Professionals Health North-Bénin

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Prevalence and Factors Associated with Diabetes among City Hall Workers, Bohicon, Benin

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Open Journal of Epidemiology 2024年第2期14卷 366-377页

作者： Adjobimey Mênonli Djohoun Frimège Mama Cissé Ibrahim Mikponhoué Rose Gounongbé fabien Ayélo Paul Hinson Vikkey Antoine Unité de Recherche et d&#8217Enseignement en Sant&#233 au Travail et Environnement FSS Cotonou Cotonou Benin Service de Santé au Travail du Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou Cotonou Benin Laboratoire d’ Epid&#233miologie des Maladies Chroniques et Neurologiques FSS Cotonou Benin Ecole de Mé decine Universit&#233 de Parakou Parakou Benin

Introduction: Living and working conditions are increasingly conducive to a sedentary lifestyle. Many administrative workers are exposed daily to long hours of work in a prolonged sitting position, which can favour the onset of diabetes. The aim of the study was to determine the prevalence and factors associated with diabetes among workers at a town hall in Benin in 2019. Methods: This was a descriptive cross-sectional study conducted from December 2018 to January 2019. Exhaustive recruitment was carried out. Data were collected during a face-to-face interview, using a standardized questionnaire including socio-professional factors, behavioral factors, anthropometric measurements, and blood glucose. Frequencies were calculated. Frequencies were compared using the chi-square and Fisher tests. The significance threshold was 5%. Results: A total of 85 workers were included. Their mean age was 41.55 ± 9.82 years, with a sex ratio of 6.1. = The prevalence of diabetes was estimated at 8.2% [95% CI: 3.38 - 16.23%] and 3 of the workers knew they had diabetes. A family history of diabetes was associated with diabetes (p = 0.032). Occupationally, 10.77% of permanent employees had diabetes, compared with 0.0% of non-permanent employees;12.50% of employees with at least 10 years’ seniority had diabetes, compared with 7.25% of those with less seniority;19.05% of employees who spent at least 6 hours a day sitting at work had diabetes, compared with 4.69% of those who spent less time sitting. Conclusion: Preventing chronic disease in the workplace is part of promoting workers’ health, and must take into account occupational factors such as prolonged sitting.

关键词： Diabetes Prolonged Sitting Workers-Benin

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Evaluation of Water Losses by Evaporation in the Nakanbe Basin

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Atmospheric and Climate Sciences 2024年第1期14卷 29-41页

作者： Bayala Alfred Kabre Sayouba Yonli Hamma fabien Chesneau Xavier Thierry Sikoudouin Maurice Ky Zeghmati Belkacem Kieno P. Florent Kam Sié Unité de Formation et de Recherche en Sciences Exactes et Appliquées (UFR/SEA) Laboratoire d’Energies Thermiques Renouvelables (LETRE) Université Joseph KI-ZERBO Ouagadougou Burkina Faso Unité de Formation et de recherche en Science Exactes et Appliquées Centre Universitaire de Kaya (CU-K) Perpignan France Laboratoire de Modélisation Pluridisciplinaire et Simulation Université de Perpignan Via Domitia Perpignan France Unité de Formation et de Recherche en Sciences Exactes et Appliquées (UFR/SEA) Laboratoire de Matériaux et Environnement Uni-versité Joseph KI-ZERBO Ouagadougou Burkina Faso Laboratoire de Physique et Chimie de l’ Environnement (LPCE) Université Joseph KI-ZERBO Ouagadougou Burkina Faso

A numerical approach to heat and mass transfer in a large water reservoir is presented. This water reservoir is likened to a parallelepiped reservoir whose vertical and lower walls are adiabatic and impermeable. The equations that govern natural convection in water are solved by the finite volume method and Thomas’salgorithm. The adequacy between the velocity and pressure fields is ensured by the SIMPLE algorithm. We are going to evaluate the water losses by evaporation from three dams in the Nakanbé basin in Burkina Faso for a period of thirty years, that is to say from January 1, 1991, to March 15, 2020. The three dams have a rate of evaporation greater than 40% of the volume of water stored. Indeed the rate of evaporation in each dam increases with the water filling rate in the reservoir: we have observed the following results for each dam in the Nakanbé basin;for the date of 02/27/1988 to 03/13/2020., the Loumbila dam received a total volume of stored water of 22.02 Mm3 and 10.57 Mm3 as the total volume of water evaporated at the same date. At the Ouaga dam (2 + 3), it stored a water volume of 4.06 Mm3 and evaporated 2.03 Mm3 of its storage volume from 01/01/1988 to 05/07/2016. Finally, with regard to the Bagré dam, it stored 745.16 Mm3 of water and 365.13 Mm3 as the volume of water evaporated from 01/01/1993 to 03/31/2020.

关键词： Numerical Study Evaporation Meteorological Data Natural Convection Basins Dams

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