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Celastrol enhances transcription factor Eb (TFEb)-mediated autophagy and mitigates Tau pathology:Implications for Alzheimer's disease therapy

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Acta Pharmaceutica sinica b 2022年第4期12卷 1707-1722页

作者： Chuanbin yang Chengfu su Ashok Iyaswamy senthil Kumar Krishnamoorthi Zhou Zhu sichang yang benjamin Chunkit Tong Jia Liu sravan G.sreenivasmurthy Xinjie Guan yuxuan Kan Aston Jiaxi Wu alexis shiying Huang Jieqiong Tan Kingho Cheung Juxian song Min Li Mr.&Mrs.Ko Chi-Ming Centre for Parkinson’s Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Department of Geriatrics Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Institute for Research and Continuing Education Hong Kong Baptist UniversityShenzhen 518057China College of Pharmacy Henan University of Chinese MedicineZhengzhou 450000China Center for Medical Genetics and Hunan Key Laboratory of Animal Model for Human Diseases School of Life SciencesCentral South UniversityChangsha 410078China Medical College of Acupuncture-Moxibustion and Rehabilitation Guangzhou University of Chinese MedicineGuangzhou 510632China

Alzheimer's disease(AD),characterized by the accumulation of protein aggregates including phosphorylated Tau aggregates,is the most common neurodegenerative disorder with limited therapeutic *** plays a critical role in the degradation of phosphorylated Tau aggregates,and transcription factor Eb(TFEb)is a master regulator of autophagy and lysosomal ***,small-molecule autophagy enhancers targeting TFEb hold promise for AD ***,we found that celastrol,an active ingredient isolated from the root extracts of Tripterygium wilfordii(Lei Gong Teng in Chinese)enhanced TFEb-mediated autophagy and lysosomal biogenesis in vitro and in mouse ***,celastrol reduced phosphorylated Tau aggregates and attenuated memory dysfunction and cognitive deficits in P301s Tau and 3xTg mice,two commonly used AD animal *** studies suggest that TFEb-mediated autophagy-lysosomal pathway is responsible for phosphorylated Tau degradation in response to ***,our findings indicate that Celastrol is a novel TFEb activator that promotes the degradation of phosphorylated Tau aggregates and improves memory in AD animal ***,Celastrol shows potential as a novel agent for the treatment and/or prevention of AD and other tauopathies.

关键词： TFEb Autophagy Lysosome biogenesis Alzheimer’s disease(AD) Tau Celastrol mTOR Therapeutic target

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A Rare Tumor of the scalp: Papilliferous Cystadenoma

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International Journal of Otolaryngology and Head & Neck surgery 2023年第6期12卷 390-396页

作者： alexis do santos Zounon bidossessi Ulrich Vodouhe Wilfrid Akpo sonia Lawson Afouda François Avakoudjo Wassi Adjibabi Faculty of Health sciences Abomey-Calavi University Abomey Calavi Bénin

Introduction: Papilliferous cystadenoma is a rare adnexal tumor of early childhood. Case Report: We report a case of papilliferous cystadenoma of the scalp in a 22-year-old adult with no previous history of the disease. she had been presenting with a slowly progressing scalp mass for about 10 years. The mass was mildly pruritic and painless, but the patient reported several painful episodes treated with local herbal applications and unspecified antibiotics. On inspection, the lesion was raised, granular, sessile and vegetated, greyish in color, with an irregular surface, nippled and hemispherical in shape. On palpation, the lesion was painless, fleshy and surrounded by crusts that were easily removed by applying a saline-moistened compress. The patient underwent excision with at least 4-mm margins. Pathological examination of the operative specimen revealed a papilliferous syringocystadenoma. There was no tumor recurrence after three years. Conclusion: Papilliferous cystadenoma is a rare benign tumor of the scalp requiring clinical analysis and surgical excision to confirm its histological nature. Post-operative follow-up is necessary due to frequent recurrences.

关键词： scalp Tumor Papilliferous Cystadenoma

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To board or Not to board： Evidence from Nutrition, Health and Education Outcomes of students in Rural China

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China & World Economy 2016年第3期24卷 52-66页

作者： Aiqin Wang alexis Medina Renfu Luo yaojiang shi Ai yue PhD candidate School of Economics and Management Northwest University China Research Fellow Freeman Spogli Institute for International Studies Stanford University USA Associate Professor School of Advanced Agricultural Sciences Peking University China Professor Center for Experimental Economics in Education Shaanxi Normal University China Associate Professor Center for Experimental Economics in Education Shaanxi Normal University China

The debate over whether boarding school is beneficial for students still exists in both developing and developed countries. In rural China, as a result of a national school merger program that began in 2001, the number of boarding students has increased dramatically. Little research has been done, however, to measure how boarding status may be correlated with nutrition, health and educational outcomes. In this paper, we compare the outcomes of boarding to those of non-boarding students using a large, aggregate dataset that includes 59 rural counties across five provinces in China. We find that for all outcomes boarding students perform worse than non-boarding students. Despite these differences, the absolute levels of all outcomes are low for both boarding and non-boarding students, indicating a need for new policies that will target all rural students regardless of their boarding status.

关键词： boarding students education health nutrition rural China

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Can We Capitalize on Central Nervous system Plasticity in young Athletes to Inoculate Against Injury?

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Journal of science in sport and Exercise 2020年第4期2卷 305-318页

作者： Jed A.Diekfuss Jennifer A.Hogg Dustin R.Grooms alexis.b.s.uts.y-ganes. Harjiv singh scott bonnette Manish Anand Gary b.Wilkerson Gregory D.Myer The sPORT Center Division of Sports MedicineCincinnati Children’s Hospital Medical Center3333 Burnet AvenueMLC 10001CincinnatiOH 45229USA Department of Health and Human Performance The University of Tennessee ChattanoogaChattanoogaTNUSA Ohio Musculoskeletal and Neurological Institute Ohio UniversityAthensOHUSA Division of Athletic Training School of Applied Health Sciences and WellnessCollege of Health Sciences and ProfessionsOhio UniversityAthensOHUSA Division of Physical Therapy School of Rehabilitation and Communication SciencesCollege of Health Sciences and ProfessionsOhio UniversityAthensOHUSA Department of Kinesiology The University of North Carolina GreensboroGreensboroNCUSA Department of Kinesiology and Nutrition sciences University of NevadaLas VegasLas VegasNVUSA Departments of Pediatrics and Orthopaedic surgery University of CincinnatiCincinnatiOHUSA The Micheli Center for sports Injury Prevention WalthamMAUSA

There are numerous physical,social,and psychological benefits of exercise,sport and play for youth ***,dynamic activities come with a risk of injury that has yet to be abated,warranting novel therapeutics to promote injury-resistance and to keep an active lifestyle throughout the *** purpose of the present manuscript was to summarize the extant literature and potential connecting framework regarding youth brain development and neuroplasticity associated with musculoskeletal *** review provides the foundation for our proposed framework that utilizes the OPTIMAL(Optimizing Performance Through Intrinsic Motivation and Attention for Learning)theory of motor learning to elicit desir-able biomechanical adaptations to support injury prevention(injury risk reduction),rehabilitation strategies,and exercise performance for youth physical activity and play across all facets of sport(Prevention Rehabilitation Exercise Play;PREP).We conclude that both young male and females are ripe for OPTIMAL PREP strategies that promote desirable movement mechanics by leveraging a unique time window for which their heightened state of central nervous system plasticity is capable of enhanced adaptation through novel therapeutic interventions.

关键词： Musculoskeletal Motor learning Neuroplasticity Development

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seasonal variability of water quality by physicochemical indexes and traceable metals in suburban area in Kikwit,Democratic Republic of the Congo

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International soil and Water Conservation Research 2017年第2期5卷 158-165页

作者： alexis b.Nienie Periyasamy sivalingam Amandine Laffte Patience Ngelinkoto Jean-Paul Otamonga Alphonse Matand Crispin K.Mulaji Josue I.Mubedi Pius T.Mpiana John Pote Universite Pedagogique Nationale(UPN) Croisement Route de Matadi et Avenue de la LiberationQuartier Binza/UPNB.P.8815 KinshasaRepublique Democratique du Congo University of Geneva Faculty of ScienceDepartment F-A.Forel for Environmental and Aquatic Sciencesand Institute of Environmental Sciences66Boulevard Carl-VogtCH-1205 GenevaSwitzerland University of Kinshasa(UNIKIN) Faculty of ScienceDepartment of ChemistryB.P.190 Kinshasa XIDemocratic Republic of the Congo

Water resource contamination is still a major concern in several regions of developing countries espe-cially in sub-saharan countries in which polluted waters pose serious risks to human health and the *** seasonal variation of the physicochemical parameters including pH,temperature(T),electrical conductivity(EC),dissolved oxygen(O_(2)),dissolved organic carbon(DOC),total organic carbon(TOC),and trace metals were assessed in water samples collected from wells(n=3)and two rivers which were the River Lukemi(RLK,n=3)and River Luini(RLN,n=2)located in the City of Kikwit(Province of Kwilu,Democratic Republic of the Congo).samples were collected during the dry and wet *** concentration of trace metals(Cr,Mn,Co,Ni,Cu,Zn,As,Mo,Ag,Cd,sn,sb,and Pb)in water was measured using Inductively Coupled Plasma Mass spectrometry(ICP-Ms),and soluble ions(Na^(+),K^(+),NH_(4)^(+),sO_(4)^(-),NO_(3),and Cl^(-))analysis was performed using lon *** results indicate the seasonal difference in the physicochemical composition of water e.g.,the pH was lower in the wet compared to the dry *** values during the wet season ranged from 4.12 to 5.60 in wells and from 5.55 to 6.31 in rivers while the dry season values ranged from 6.27 to 6.98 in wells and from 7.09 to 7.44 in *** concentrations of soluble ions and other physicochemical par ameters(O_(2),DOC and TOC)also varied with the seasons,being higher in the wet and lower in the dry *** the exception of Mn,the average concentrations of other trace metals measured in water samples from wells and rivers met the World Health Organization(WHO)guidelines for drinki ng/domestic water *** concentration in water samples analysed ranged between 634 to 812 and 1352-1741μgL^(-1) during the dry and wet seasons,*** results imply that the high concentration of Mn in the water samples may be explained by the geological origin and result of natural weathering *** general,accord

关键词： Water quality Wells Rivers Metal pollution Health risk

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Practical Training strategies to Apply Neuro-Mechanistic Motor Learning Principles to Facilitate Adaptations Towards Injury-Resistant Movement in youth

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Journal of science in sport and Exercise 2021年第1期3卷 3-16页

作者： Jed A.Diekfuss scott bonnette Jennifer A.Hogg Christopher Riehm Dustin R.Grooms Harjiv singh Manish Anand alexis.b.s.uts.y-ganes. Gary b.Wilkerson Gregory D.Myer The sPORT Center Division of Sports MedicineCincinnati Children’s Hospital Medical Center3333 Burnet AvenueMLC 10001CincinnatiOH 45229USA Department of Health and Human Performance The University of Tennessee ChattanoogaChattanoogaTNUSA Ohio Musculoskeletal and Neurological Institute Ohio UniversityAthensOHUSA Division of Athletic Training School of Applied Health Sciences and WellnessCollege of Health Sciences and ProfessionsOhio UniversityAthensOHUSA Division of Physical Therapy School of Rehabilitation and Communication SciencesCollege of Health Sciences and ProfessionsOhio UniversityAthensOHUSA Department of Kinesiology and Nutrition sciences University of NevadaLas VegasNVUSA Department of Kinesiology The University of North Carolina at GreensboroGreensboroNCUSA Departments of Pediatrics and Orthopaedic surgery University of CincinnatiCincinnatiOHUSA The Micheli Center for sports Injury Prevention WalthamMAUSA

youth may be particularly responsive to motor learning training strategies that support injury-resistant movement mechanics in youth for prevention programs that reduce injury risk,injury rehabilitation,exercise performance,and play more gener-ally(Optimizing Performance Through Intrinsic Motivation and Attention for Learning Prevention Rehabilitation Exercise Play;OPTIMAL PREP)One purpose of the present manuscript was to provide clinical applications and tangible examples of how to implement the proposed techniques derived from OPTIMAL theory into PREP strategies for youth.A secondary purpose was to review recent advances in technology that support the clinical application of OPTIMAL PREP strategies without extensive resources/programming knowledge to promote evidence-driven tools that will support practitioner feedback *** majority of examples provided are within the context of anterior cruciate ligament(ACL)injury rehabilitation,but we emphasize the potential for OPTIMAL PREP strategies to be applied to a range of populations and training scenarios that will promote injury resistance and keep youth active and healthy.

关键词： Rehabilitation Prevention Exercise performance Technology

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Individual Leaf Area of Early Flowering Arabidopsis Genotypes Is More Affected by Drought than Late Flowering Ones: A Multi-scale Analysis in 35 Genetically Modified Lines

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American Journal of Plant sciences 2015年第7期6卷 955-971页

作者： Catherine Massonnet Myriam Dauzat alexis bédiée Denis Vile Christine Granier Laboratoire d’Ecophysiologie des Plantes sous stress Environnementaux UMR 759 Institut National de la Recherche Agronomique/Ecole Nationale Supérieure d’Agronomie Place Viala Montpellier France INRA UMR Ecologie et Ecophysiologie Forestières Route d’Amance Champenoux France Université de Lorraine UMR Ecologie et Ecophysiologie Forestières Vandoeuvre France

Plants acclimate to drought optimizing the trade-off between biomass production and water loss while ensuring their survival and reproduction. Plants also modify their growth or phenology as complementary strategies in response to stress. Despite evidence of an interaction between flowering time and plant growth response to environmental stresses, this interaction in response to drought is under debate. To contribute to the analysis of this interaction, leaf growth of 35 genetically modified lines of Arabidopsis thaliana and their common wild-type, Col-0 was analyzed by a quantitative multi-scale phenotyping approach from cellular to whole plant scale both in well-watered and soil moderate water deficit conditions. These genotypes were selected for the various physiological functions potentially altered by their genetic modification and that could interact with plant growth and/or their drought responses. In all genotypes, leaf expansion decreased in response to drought both at the whole rosette and the individual leaf levels. Additionally, epidermal cell area and/or epidermal cell number decreased in response to the drought treatment. In contrast, the number of rosette leaves was reduced in only half of the genotypes and leaf growth duration was only modified in 4 of them. Despite long photoperiod conditions, the duration of the vegetative phase, i.e. the time elapsed between germination and flowering stage, varied from 12 to 27 days among genotypes under well watered conditions. Our analyses revealed that the differences of flowering time observed in well-watered condition impacted the leaf area response to drought. Early-flowering genotypes slightly decreased their final leaf number, but strongly reduced their individual leaf area compared with the late-flowering ones. This result underlines the difficulty to analyze plant response to environmental stresses when genotypes with different flowering dates are compared.

关键词： Arabidopsis thaliana soil Water Deficit Leaf Area Leaf Expansion Flowering Time

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Insight on the Ultrastructure, Physicochemical, Thermal Characteristics and Applications of Palm Kernel shells

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Materials sciences and Applications 2018年第10期9卷 790-811页

作者： Richard Ntenga Etienne Mfoumou alexis béakou Martin Tango Jordan Kamga Ali Ahmed Laboratoire de Mécanique et Productique (LMP) UFD SI Université de Douala Douala Cameroun Laboratoire d’Analyse Simulations et Essais (LASE) IUT Université de Ngaoundéré Ngaoundéré Cameroun Applied Research & Innovation Nova Scotia Community College Dartmouth Canada Institut Pascal UMR 6602-UCA-CNRs-sIGMA Clermont-Ferrand France Ivan Curry school of Engineering Acadia University Wolfville Canada

The ultrastructure and physicochemical and thermal properties of Palm Kernel shells (PKs) in comparison with Coconut Kernel shells (CKs) were investigated herein. Powder samples were prepared and characterized using surface Electron Microscopy (sEM) and Transmission Electron Microscopy (TEM). Chemical and elemental constituents, as well as thermal performance were assessed by Van soest Method, TEM/EDXA and sEM/EDs techniques. Differential scanning Calorimetry (DsC) and Thermogravimetric Analysis (TGA) were also performed for thermal characterization. sEM/EDs and TEM/EDXA revealed that most of the PKs and CKs materials are composed of particles with irregular morphology;these are mainly amorphous phases of carbon/oxygen with small amounts of K, Ca and Mg. The DsC data permitted to derive the materials’ thermal transition phases and the relevant characteristic temperatures and physical properties. Thermal Transition phases of PKs observed herein are consistent with the chemical composition obtained and are similar to those of CKs. Nonetheless, TGA/DTG showed that the combustion characteristics of PKs are higher than those of CKs. Taken together, our results reveal that PKs have nanopores and can be efficiently used for 3D printing and membrane filtration applications. Moreover, the chemical constituents found in PKs samples are in agreement with those reported in the literature for material structural applications and thus, present potential use of PKs in these applications.

关键词： biomass Materials Palm Kernel shell sEM & TEM Ultrastructure Thermal Properties Physico-Chemical Properties

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Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-b cell stage

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Cellular & Molecular Immunology 2019年第7期16卷 668-670页

作者： Nour Ghazzaui Hussein Issaoui Ophélie Alyssa Martin alexis saintamand Jeanne Cook-Moreau yves Denizot François boyer CNRs UMR 7276 Inserm U1262Universitéde LimogesLimogesFrance Present address:Inserm U1236 UniversitéRennes 1RennesFrance

Due to their impact on nuclear organization,enhancers are master regulators of cell fate.1,2 The immunoglobulin heavy chain(IgH)locus undergoes numerous changes(such as transcription,accessibility,DNA breaks,and mutations)throughout b-cell *** of these events are controlled by the IgH 3′regulatory region(3′RR).The 3′RR is the master control element of mature b-cell IgH transcription,3 somatic hypermutation(sHM),4,5 conventional class switch recombination(CsR),4,6–10 and locus suicide recombination(LsR).11 In contrast,the 3′RR is expected to be dispensable for V(D)J recombination.12,13 During bcell development,the heavy and light chain loci are poised for their VDJ and VJ rearrangements,*** IgH locus rearranges first,with D-J joining at the pro-b-cell stages,followed by V-DJ joining at the pre-b-cell *** Igk locus is poised for VJ rearrangements at the pre-b cell stage.

关键词： effect joining recombination

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substrate selection and seasonal variation in abundance and size composition of isopod Lirceus fontinalis in Ontario streams, Canada

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Chinese Journal of Oceanology and Limnology 2007年第2期25卷 215-220页

作者： ZHAO Xiaoxia Michael G FOX David C. LAsENby alexis C. ARMIT Dolly N. KOTHAWALA Watershed Ecosystems Graduate Program Trent University Peterborough Ontario K9J 7B8 Canada Environmental ＆ Resource studies Program and Department of biology Trent University Peterborough ON K9J 7B8 Canada Department of biology Trent University Peterborough ON K9J 7B8 Canada

The abundance and size composition of stream isopods Lirceus fontinalis were investigated from April 2001 to August 2002 in 3 streams in southern Ontario, Canada. Effects of current speed was released from the analysis by choosing slow flowing water. The effects of substrate, season and water depth on the abundance, distribution and size composition of the isopods were analyzed. It was found that substrate and season influence isopods the most. The rocky substrate with attached filamentous macro-algae contains an isopod abundance 7.05 times that of bare rock substrate and 14.6 times that of fine-sand and mud substrate. There was a large variation with respect to seasonality in both abundance and size composition of the isopods, with the highest abundance occurring in summer and the lowest in winter and spring; individual isopods also tend to be larger in the winter and spring. In all substrates, shallow areas tend to support higher densities of isopods than deeper areas.

关键词：加拿大安大略省河流等脚类动物底质选择丰度大小季节变异

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