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Unraveling pathological mechanisms in neurological disorders:the impact of cell-based and organoid models

Neural Regeneration Research 2022年第10期17卷 2131-2140页

作者： Jake Langlie Rahul Mittal Ariel Finberg nathalie b.bencie Jeenu Mittal Hossein Omidian Yadollah Omidi Adrien A.Eshraghi Department of Otolaryngology Hearing Research and Communication Disorders LaboratoryUniversity of Miami Miller School of MedicineMiamiFLUSA College of Pharmacy Nova Southeastern UniversityFort LauderdaleFLUSA Department of Neurological Surgery University of Miami Miller School of MedicineMiamiFLUSA Department of biomedical Engineering University of MiamiCoral GablesFLUSA Department of Pediatrics University of Miami Miller School of MedicineMiamiFLUSA

Cell-based models are a promising tool in deciphering the molecular mechanisms underlying the pathogenesis of neurological disorders as well as aiding in the discovery and development of future drug *** greatest challenge is creating cell-based models that encapsulate the vast phenotypic presentations as well as the underlying genotypic etiology of these *** this article,we discuss the recent advancements in cell-based models for understanding the pathophysiology of neurological *** reviewed studies discussing the progression of cell-based models to the advancement of three-dimensional models and organoids that provide a more accurate model of the pathophysiology of neurological disorders in *** better we understand how to create more precise models of the neurological system,the sooner we will be able to create patient-specific models and large libraries of these neurological *** three-dimensional models can be used to discover the linking factors to connect the varying phenotypes,such models will also help to understand the early pathophysiology of these neurological disorders and how they are affected by their *** three-dimensional cell models will allow us to create more specific treatments and uncover potentially preventative measures in neurological disorders such as autism spectrum disorder,Parkinson’s disease,Alzheimer’s disease,and amyotrophic lateral sclerosis.

关键词： Alzheimer’s disease amyotrophic lateral sclerosis autism spectrum disorder cell-based model central nervous system induced pluripotent stem cells mesenchymal stem cells organoid model organ-on-a-chip Parkinson’s disease three-dimensional model

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Recent advancements in noninvasive brain modulation for individuals with autism spectrum disorder

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Neural Regeneration Research 2023年第6期18卷 1191-1195页

作者： Jessica R.Griff Jake Langlie nathalie b.bencie Zachary J.Cromar Jeenu Mittal Idil Memis Steven Wallace Alexander E.Marcillo Rahul Mittal Adrien A.Eshraghi Hearing Research and Communication Disorders Laboratory Department of OtolaryngologyNeurotology DivisionUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Neurological Surgery University of Miami Miller School of MedicineMiamiFLUSA Department of biomedical Engineering University of MiamiCoral GablesFLUSA Department of Pediatrics University of Miami Miller School of MedicineMiamiFLUSA

Autism spectrum disorder is classified as a spectrum of neurodevelopmental disorders with an unknown definitive *** with autism spectrum disorder show deficits in a variety of areas including cognition,memory,attention,emotion recognition,and social *** no definitive treatment or cure,the main interventions for individuals with autism spectrum disorder are based on behavioral ***,noninvasive brain modulation techniques including repetitive transcranial magnetic stimulation,intermittent theta burst stimulation,continuous theta burst stimulation,and transcranial direct current stimulation have been studied for their therapeutic properties of modifying neuroplasticity,particularly in individuals with autism spectrum *** evidence from small cohort studies,pilot studies,and clinical trials suggests that the various noninvasive brain stimulation techniques have therapeutic benefits for treating both behavioral and cognitive manifestations of autism spectrum ***,little data is available for quantifying the clinical significance of these findings as well as the long-term outcomes of individuals with autism spectrum disorder who underwent transcranial *** objective of this review is to highlight the most recent advancements in the application of noninvasive brain modulation technology in individuals with autism spectrum disorder.

关键词： autism spectrum disorder behavior cognition neurostimulation interventions noninvasive brain modulation theta burst stimulation transcranial direct current stimulation transcranial magnetic stimulation

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Computational fluid dynamics simulation of Hyperloop pod predicting laminar–turbulent transition

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Railway Engineering Science 2020年第1期28卷 97-111页

作者： nathalie Nick Yohei Sato Department of Mechanical and Process Engineering Swiss Federal Institute of TechnologyETH ZurichLEO B 9.1Leonhardstrasse 278092 ZurichSwitzerland Nuclear Energy and Safety Research Division Paul Scherrer InstituteForschungsstrasse 1115232 Villigen PSISwitzerland

Three-dimensional compressible flow simulationswere conducted to develop a Hyperloop pod. Thenovelty is the usage of Gamma transition model, in whichthe transition from laminar to turbulent flow can be ***, a mesh dependency study was undertaken,showing second-order convergence with respect to themesh refinement. Second, an aerodynamic analysis for twodesigns, short and optimized, was conducted with thetraveling speed 125 m/s at the system pressure 0.15 *** concept of the short model was to delay the transitionto decrease the frictional drag;meanwhile that of theoptimized design was to minimize the pressure drag bydecreasing the frontal area and introduce the transitionmore toward the front of the pod. The computed resultsshow that the transition of the short model occurred moreon the rear side due to the pod shape, which resulted in 8%smaller frictional drag coefficient than that for the optimizedmodel. The pressure drag for the optimized designwas 24% smaller than that for the short design, half ofwhich is due to the decrease in the frontal area, and theother half is due to the smoothed rear-end shape. The totaldrag for the optimized model was 14% smaller than that forthe short model. Finally, the influence of the systempressure was investigated. As the system pressure and theReynolds number increase, the frictional drag coefficientincreases, and the transition point moves toward the front,which are the typical phenomena observed in the transitionregime.

关键词： Computational fluid dynamics(CFD) Drag Subsonic compressible flow Hyperloop Laminar-turbulent transition

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Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats

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World Journal of biological Chemistry 2022年第1期13卷 15-34页

作者： Christian Carpéné Luc Marti nathalie Morin Institut des Maladies Métaboliques et Cardiovasculaires INSERMToulouse 31342France Facultéde Pharmacie de Paris Paris UniversityParis 75270France

bACKGROUND Despite overt insulin resistance,adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of *** To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide,since it is produced by monoamine oxidase(MAO)and semicarbazide-sensitive amine oxidase(SSAO)in *** 3H-2-deoxyglucose uptake(2-DG)was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine.14C-tyramine oxidation and binding of imidazolinic radioligands[3H-Idazoxan,3H-(2-benzofuranyl)-2-imidazoline]were studied in adipocytes,the liver,and *** influence of in vivo administration of tyramine+vanadium on glucose handling was assessed in lean and obese *** 2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats,when compared to their lean *** and benzylamine activation of hexose uptake was vanadate-dependent and was also limited,while MAO was increased and SSAO *** changes were adipocyte-specific and accompanied by a greater number of imidazoline I2 binding sites in the obese rat,when compared to the *** vitro,tyramine precluded the binding to I2 sites,while in vivo,its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese CONCLUSION The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site ***,probably as a consequence of SSAO down-regulation,the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant *** adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.

关键词： Obesity Adipocyte Amine oxidases Imidazoline binding sites Creatine kinase b Idazoxan Lipogenesis Hydrogen peroxide Glucose uptake

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Evolution of germination strategy in the invasive species Ulex europaeus

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Journal of Plant Ecology 2017年第2期10卷 375-385页

作者： nathalie Udo Michèle Tarayre Anne Atlan Laboratoire ECObIO UMR 6553CNRSUniversitéde Rennes 1Bâtiment 14ACampus de Beaulieu263 avenue du Général Leclerc35042 Rennes CedexFrance

Aims The study of the adaptive potential of the germination patterns of invading species enables us to identify some traits linked with their capacity to colonize new sites,and to gain a better understanding of their area of *** aim of this study is to determine the germination pattern of Ulex europaeus,a cosmopolitan invasive species,in relation to temperature and to explore its potential evolu-tion and invasiveness in a tropical region,following its introduction from *** We studied the germination pattern of ***(the com-mon gorse)to test both physical dormancy and germination capacity within the range of temperatures found in the native and invasive *** understand its germination pattern and its evolution,the rate and the speed of germination,as well as the percentage of seeds that became mouldy during the experi-ment,have been compared between a native habitat,France and a habitat into which it has been introduced,the tropical island of La *** Findings The results show that gorse seeds germinate in large quantities,pos-sess the ability to germinate under a wide range of temperatures and they confirm the physical dormancy of the seeds(caused by seed coat impermeability).The decrease in germination from 25℃ upwards,coupled with an increase in the rate of moulding help to explain its restricted distribution at altitude in tropical *** scari-fied seeds,we have not detected any difference between the two regions,neither in the percentage of germinated seeds,nor in the per-centage of mouldy ***,seeds from Reunion germinate faster at 20℃ than seeds from France and a greater number of seeds from Reunion are able to germinate without scarification(10-60%for Reunion versus 0-10%for France).These results suggest that while preserving the advantages of the native habitat,in Reunion gorse develops a strategy which favours the rapid occupation of new sites.

关键词： Ulex europaeus invasive species germination physical dormancy

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体外眼刺激性全面分类的新策略和SkinEthicTMHCE重建角膜上皮模型多时间点暴露眼刺激性试验在中国的建立

体外眼刺激性全面分类的新策略和SkinEthicTMHCE重建角膜上皮模型...

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中国毒理学会第十次全国毒理学大会

作者：刘砚枫 nathalie ALEPEE 李楠欧莱雅中国研发和创新中心欧莱雅法国研发和创新中心

目的随着体外替代测试技术的发展,目前已经有多种眼刺激性替代检测方法经OECD验证并采纳为测试指南,用于区分严重眼刺激(UNGHSCat 1)和/或无眼刺激(UNGHSNo Cat)。但是针对可逆的眼部反应(UNGHSCat 2)的分类测试方法尚存挑战。今年6月,... 详细信息

目的随着体外替代测试技术的发展,目前已经有多种眼刺激性替代检测方法经OECD验证并采纳为测试指南,用于区分严重眼刺激(UNGHSCat 1)和/或无眼刺激(UNGHSNo Cat)。但是针对可逆的眼部反应(UNGHSCat 2)的分类测试方法尚存挑战。今年6月,针对眼部风险的评估和预测,OECD发布了最新的测试指南(TestGuideline,TG)467和492b。OECDTG467由两组规定性方法(DefinedApproaches,DAs)组成,可应用于非表面活性剂液体化学品,通过对现有体外方法和化学品物理化学性质的整合进行评估。OECDTG492b提出了一种全新的,基于重建人角膜上皮模型的单一的测试方法,可应用于液体和固体化学品。不论是OECDTG467当中采纳的DAs进行整合测试,还是OECDTG492b中采纳的新方法,两者都可以作为体内动物测试(DraizeTest)的完全替代。基于所使用方法限定的可应用化学品范围,可以实现化学品眼刺激性的全面分类(Cat 1,Cat2和NoCat)。其中TG492b中采纳的SkinEthic?HCE重建角膜上皮模型的多时间点暴露方法(TTT),第一次实现了单一方法对化学品眼刺激性的全面分类(Cat 1,Cat2和NoCat)。本研究的目的是实现该方法在中国实验室的转移和建立。材料和方法 SkinEthic?HCE组织暴露于待测化学品不同的处理时间进行测试。液体化学品分别为5分钟(纯的),16分钟(20%水溶液)和120分钟(20%水溶液)。固体化学品分别为30分钟和120分钟。该方法的OECD验证工作完成了151个化学品(70个液体,81个固体)的评估测试,涵盖不同的眼刺激性UNGHS分类(Cat 1,Cat 2和NoCat)以及不同种类的化学品类别。已发表的数据显示该方法获得74.4%的整体准确率(balancedaccuracy),其中Cat 1准确率79%,Cat 2准确率69%,No Cat准确率75%。本研究使用在中国商品化的SkinEthic?HCE模型,选择OECD验证工作中已测试过的45个参考化学品进行评估测试。第一阶段评估完成了18个化学品的三轮测试,考察该方法的重复性,可转移性和预测能力。第二阶段评估完成了27个化学品的一轮测试,进一步考察该方法的预测能力。结果第一阶段评估的18个化学品均分类正确,且三轮测试结果一致。重复性100%,整体准确率100%(Cat 1:100%,Cat 2:100%,NoCat:100%)。结合两个阶段共45个化学品的评估测试结果,整体准确率82%(Cat 1:77%,Cat 2:100%,NoCat:78%)。结论本研究在中国实验室,使用在国内商品化的SkinEthic?HCE模型,成功转移和建立了OECD最新的测试指南492b中采纳的SkinEthic?HCETTT方法。该方法的成功建立,首次在国内实现了单一方法对化学品眼刺激性的全面分类,为国内的眼刺激性非动物测试提供有效可靠的科学技术基础,进一步促进替代方法在中国的推广。

关键词：体外测试方法眼刺激性 OECDTG 492b 重建角膜上皮模型

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Inflamed phenotype of splenic marginal zone b-cell lymphomas with expression of PD-L1 by intratumoral monocytes/macrophages and dendritic cells

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Cellular & Molecular Immunology 2019年第6期16卷 621-624页

作者： Christelle Vincent-Fabert Isabelle Soubeyran Valérie Velasco Marie Parrens Robin Jeannet Emilie Lereclus nathalie Gachard Jean Feuillard nathalie Faumont CNRS-UMR 7276 INSERM U1262 CRIbL University of Limogesand Hematology Laboratory of Dupuytren Hospital University Center(CHU)of LimogesLimogesFrance Laboratory of Pathology Institut BergoniéBordeauxFrance Pathology Department Hospital University Center of BordeauxBordeauxFrance

Splenic marginal zone lymphoma(SMZL)is an incurable indolent small b-cell lymphoma that primarily involves the spleen and arises in elderly patients,who have a median age of 65 years old at diagnosis.1 Splenomegaly is... 详细信息

关键词： lymphoma spleen patients

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IKKβ binds NLRP3 providing a shortcut to inflammasome activation for rapid immune responses

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4022-4024页

作者： Yaw Asare Margarita Shnipova LukaŽivković Christina Schlegl Federica Tosato Arailym Aronova Markus brandhofer Laura Strohm nathalie beaufort Rainer Malik Christian Weber Jürgen bernhagen Martin Dichgans Institute for Stroke and Dementia Research(ISD) University HospitalLudwig-Maximilians-University(LMU)MunichGermany Munich Cluster for Systems Neurology(SyNergy) MunichGermany Institute for Cardiovascular Prevention(IPEK) LMUMunichGermany

Dear Editor,A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring *** response is largely mediated by the concerted action of pattern recognition receptors(PRRs).Such cooperativity has been described for Toll-like receptors(TLRs)and NACHT,LRR,and pyrin domain-containing protein 3(NLRP3),but the underlying molecular mechanisms remain incompletely *** are multi-protein complexes defined by a cytosolic innate immune sensor,usually a PRR,which recruits the adaptor molecule apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC)to activate the effector caspase-1 leading to the release of matured IL-1βand *** caspase-1 further cleaves gasdermin D(GSDMD)allowing the N-terminal domain of GSDMD(GSDMD-N)to form pores in the plasma membrane,thus facilitating the release of matured IL-1βand ***-forming GSDMD-N further induces pyroptosis,an inflammatory form of cell death.

关键词： NLRP3 release activation

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bactericera cockerelli(Sulc), a potential threat to China’s potato industry

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Journal of Integrative Agriculture 2020年第2期19卷 338-349页

作者： Oluwashola OLANIYAN Neus RODRÍGUEZ-GASOL nathalie CAYLA Eleonor MICHAUD Steve D.WRATTEN bio-Protection Research Centre Lincoln UniversityLincoln 7647New Zealand Institute for Research and Technology in Food and Agriculture(IRTA) Lleida 25003Spain Agrocampus Ouest Institut National Supérieur des Sciences AgronomiquesAgroalimentairesHorticoles et du PaysageRennes Cedex 35000France

The potato psyllid bactericera cockerelli(Hemiptera:Triozidae)has recently emerged as a serious pest of potatoes and other solanaceous *** causes direct feeding damage and also vectors Candidatus Liberibacter solanaceaerum(Lso),a pathogen that causes zebra chip disease in potatoes and which potentially costs growers millions of dollars each *** producers rely on frequent sprays of pesticides for psyllid control but the results are unsatisfactory and there are negative side *** psyllid has spread beyond its native range in southwest US and northern Mexico to Canada,El Salvador,Honduras,Guatemala and Nicaragua via medium to long range dispersal flights perhaps aided by wind currents,and through anthropogenic *** was accidentally introduced into New Zealand in 2006 and most recently Australia,most likely through the importation of infested plant *** review summarizes information from studies on the biology,impact and management of ***,and highlights the imminent risk of this insect and its associated pathogen invading China,the world’s largest producer of fresh *** of risk maps leading to increased surveillance,could prevent or delay an incursion and facilitate early detection or eradication should this ***-term management with Lso-tolerant potato cultivars and psyllid control using the parasitic wasp Tamarixia triozae and other natural enemies should be pursued,rather than depending on synthetic pesticides.

关键词： bactericera cockerelli tomato-potato psyllid invasive pest Candidatus Liberibacter solanaceaerum biological control Tamarixia triozae

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Impact of sarcopenia on tumor response and survival outcomes in patients with hepatocellular carcinoma treated by trans-arterial (chemo)-embolization

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World Journal of Gastroenterology 2022年第36期28卷 5324-5337页

作者： Gael Roth Yann Teyssier Maxime benhamou Mélodie Abousalihac Stefano Caruso Christian Sengel Olivier Seror Julien Ghelfi Arnaud Seigneurin nathalie Ganne-Carrie Elia Gigante Lorraine blaise Olivier Sutter Thomas Decaens Jean-Charles Nault Univ.Grenoble-Alpes Grenoble 38058France Department of Hepatology Gastroenterology and Digestive OncologyCHU Grenoble AlpesGrenoble 38043France Institute for Advanced biosciences INSERM U1209/CNRS UMR 5309Grenoble 38043France Department of Radiology CHU Grenoble AlpesGrenoble 38043France Department of Radiology CHU Avicenne-APHPBobigny 93000France Functional Genomics of Solid Tumors Laboratory Centre de Recherche des Cordeliers-INSERM UMR 1138InsermUniversitéParisParis 75006France Unitéde Formation et de Recherche SantéMédecine et biologie Humaine UniversitéParis NordParis 93430France Service d'Epidémiologie et Evaluation Médicale CHU Grenoble AlpesGrenoble 38043France Department of Hepatology CHU Avicenne-APHPBobigny 93000France

bACKGROUND At the diagnosis of hepatocellular carcinoma(HCC),more than 90%of HCC patients present cirrhosis,a clinical condition often associated to *** is an indirect marker of malnutrition assessable on computed tomography(CT).AIM To evaluate the prognostic value of sarcopenia in patients with HCC treated by trans-arterial(chemo)-*** Patients with HCC treated by a first session of trans-arterial(chemo)embolization and an available CT scan before treatment were *** was assessed using skeletal muscle index at baseline and at the first radiological *** response was recorded after the first session of treatment using *** Of 225 patients treated by trans-arterial bland embolization(n=71)or trans-arterial chemoembolization(n=154)for HCC between 2007 and 2013,barcelona Clinic of Liver Cancer stage was A,b,and C in 27.5%,55%,and 16.8%of cases,*** was present in 57.7%of the *** with sarcopenia presented a higher rate of progressive disease(19%vs 8%,P=0.0236),a shorter progression-free survival(8.3 vs 13.2 mo,P=0.0035),and a shorter median overall survival(19.4 mo vs 35.5 mo,P=0.0149)compared with non-sarcopenic ***,patients whose sarcopenia appeared after first transarterial treatment had the worst prognosis(P=0.0004).CONCLUSION Sarcopenia is associated with tumor progression and poor survival outcomes after trans-arterial(chemo)-embolization for HCC.

关键词： Hepatocellular carcinoma Transarterial chemoembolization bland embolization Sarcopenia Skeletal muscle index

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