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Targeted therapy for capillary-venous malformations

Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine fraissenon Charles Bayard Marina firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie fraitag jean-paul Duong Sophie Kaltenbach Estelle Balducci Coline Lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Biomaterials and emerging technologies for tissue engineering and in vitro models

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Bio-Design and Manufacturing 2024年第3期7卷 237-239页

作者： j.Miguel Oliveira Rui L.Reis 3B’s Research Group I3Bs-Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal

The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/***-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).

关键词： breakthrough biomaterials engineer

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Adenosine A_(2A)receptor blockade attenuates excitotoxicity in rat striatal medium spiny neurons during an ischemic-like insult

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Neural Regeneration Research 2024年第2期19卷 255-257页

作者： Elisabetta Coppi federica Cherchi Alasdair j.Gibb Department of Neuroscience PsychologyDrug Research and Child HealthUniversity of FlorenceFlorenceItaly Department of Neuroscience Physiology and PharmacologyUniversity College LondonLondonUK

During brain ischemia,excitotoxicity and peri-infarct depolarization injuries occur and cause cerebral tissue ***,anoxic depolarization,consisting of massive neuronal depolarization due to the loss of membrane ion gradients,occurs in vivo or in vitro during an energy *** neuromodulator adenosine is released in huge amounts during cerebral ischemia and exerts its effects by activating specific metabotropic receptors,namely:A_(1),A_(2A),A_(2B),and A_(3).The A_(2A)receptor subtype is highly expressed in striatal medium spiny neurons,which are particularly susceptible to ischemic *** indicates that the A2Areceptors are upregulated in the rat striatum after stroke and the selective antagonist SCH58261 protects from exaggerated glutamate release within the first 4 hours from the insult and alleviates neurological impairment and histological injury in the following 24 *** recently added new knowledge to the mechanisms by which the adenosine A2Areceptor subtype participates in ischemia-induced neuronal death by performing patch-clamp recordings from medium spiny neurons in rat striatal brain slices exposed to oxygen and glucose *** demonstrated that the selective block of A2Areceptors by SCH58261 significantly reduced ionic imbalance and delayed the anoxic depolarization in medium spiny neurons during oxygen and glucose deprivation and that the mechanism involves voltage-gated K+channel modulation and a presynaptic inhibition of glutamate release by the A2Areceptor *** present review summarizes the latest findings in the literature about the possibility of developing selective ligands of A2Areceptors as advantageous therapeutic tools that may contribute to counteracting neurodegeneration after brain ischemia.

关键词： adenosine A_(2A)receptors anoxic depolarization brain ischemia glutamate excitotoxicity medium spiny neurons oxygen and glucose deprivation

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Iron regulatory protein 1: the deadly switch of ferroptosis

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Neural Regeneration Research 2024年第3期19卷 477-478页

作者： Daniel A.Bórquez Pamela j.Urrutia Center for Biomedical Research Faculty of MedicineUniversidad Diego PortalesSantiagoChile Institute of Nutrition&food Technology(INTA) Universidad de ChileSantiagoChile Geroscience Center for Brain Health and Metabolism SantiagoChile

ferroptosis,an iron-dependent cell death:ferroptosis is a type of regulated necrosis,characterized by redox-active iron accumulation and increased free radical production derived by fenton chemistry,that triggers oxidation of polyunsaturated fatty acids in phospholipids,loss of cellular membranes integrity,and leakage of intracellular contents.

关键词： integrity switch Iron

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Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

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Neural Regeneration Research 2024年第9期19卷 1861-1862页

作者： Robert Galinsky Laura Bennet Alistair j.Gunn The Ritchie Centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Obstetrics and Gynaecology Monash UniversityMelbourneVICAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal *** encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a *** cost of disability associated with preterm brain injury continues to *** of this injury,and disability,would significantly reduce this socioeconomic burden.

关键词： encephalopathy mortality hypoxic

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Laboratory Implementation of Direct Torque Controller based Speed Loop Pseudo Derivative feedforward Controller for PMSM Drive

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CES Transactions on Electrical Machines and Systems 2024年第1期8卷 12-21页

作者： Prabhakaran Koothu Kesavan Umashankar Subramaniam Dhafer j.Almakhles IEEE Renewable Energy Laboratory Department of Electrical EngineeringPrince Sultan UniversityRiyadh 12435Saudi Arabia

This paper,evaluate the effectiveness of a proposed speed loop pseudo derivative feedforward(PDff)controller-based direct torque controller(DTC)for a PMSM drive against the performance of existing PI speed controller-based DTC and hysteresis current controller(HCC).The proposed PDff-based speed regulator effectively reduces oscillation and overshoot associated with rotor angular speed,electromagnetic torque,and stator *** case studies,one using forward-to-reverse motoring operation and the other involving reverse-to-forward braking operation,has been validated to show the effectiveness of the proposed control *** proposed controller's superior performance is demonstrated through experimental verification utilizing an fPGA controller for a 1.5 kW PMSM drive laboratory prototype.

关键词： Direct torque control Pseudo derivative feedforward controller Permanent magnet synchronous motor(PMSM)

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A Tutorial Review of the Solar Power Curve: Regressions, Model Chains, and Their Hybridization and Probabilistic Extensions

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Advances in Atmospheric Sciences 2024年第6期41卷 1023-1067页

作者： Dazhi YANG Xiang’ao XIA Martin jános MAYER School of Electrical Engineering and Automation Harbin Institute of TechnologyHarbin 150001HeilongjiangChina Key Laboratory for Middle Atmosphere and Global Environment Observation(LAGEO) Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China Department of Energy Engineering Faculty of Mechanical EngineeringBudapest University of Technology and EconomicsMűegyetem rkp.3Budapest H-1111Hungary

Owing to the persisting hype in pushing toward global carbon neutrality,the study scope of atmospheric science is rapidly *** numerous trending topics,energy meteorology has been attracting the most attention *** essential skill of solar energy meteorologists is solar power curve modeling,which seeks to map irradiance and auxiliary weather variables to solar power,by statistical and/or physical *** this regard,this tutorial review aims to deliver a complete overview of those fundamental scientific and engineering principles pertaining to the solar power *** power curves can be modeled in two primary ways,one of regression and the other of model *** classes of modeling approaches,alongside their hybridization and probabilistic extensions,which allow accuracy improvement and uncertainty quantification,are scrutinized and contrasted thoroughly in this review.

关键词： review energy meteorology solar power curve model chain solar power prediction

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Blood-brain barrier pathology in cerebral small vessel disease

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Neural Regeneration Research 2024年第6期19卷 1233-1240页

作者： Ruxue jia Gemma Solé-Guardia Amanda j.Kiliaan Department of Medical Imaging Anatomy Radboud University Medical Center Donders Institute for Brain Cognition & Behavior Center for Medical Neuroscience Preclinical Imaging Center PRIME Radboud Alzheimer Center

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly. Although at first it was considered innocuous, small vessel disease is nowadays regarded as one of the major vascular causes of dementia. Radiological signs of small vessel disease include small subcortical infarcts, white matter magnetic resonance imaging hyperintensities, lacunes, enlarged perivascular spaces, cerebral microbleeds, and brain atrophy; however, great heterogeneity in clinical symptoms is observed in small vessel disease patients. The pathophysiology of these lesions has been linked to multiple processes, such as hypoperfusion, defective cerebrovascular reactivity, and blood-brain barrier dysfunction. Notably, studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease. Therefore, the purpose of this review is to provide a new foundation in the study of small vessel disease pathology. first, we discuss the main structural domains and functions of the blood-brain barrier. Secondly, we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease. finally, we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

关键词： blood-brain barrier dysfunction cerebral blood flow cerebral hypoperfusion endothelial dysfunction hypertension inflammation magnetic resonance imaging neurovascular unit oxidative stress small vessel disease tight junctions transcytosis

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Lattice Boltzmann method formulation for simulation of thermal radiation effects on non-Newtonian Al_(2)O_(3) free convection in entropy determination

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Applied Mathematics and Mechanics(English Edition) 2024年第6期45卷 1085-1106页

作者： M.NEMATI M.SEfID A.KARIMIPOUR A.j.CHAMKHA faculty of Mechanical Engineering Yazd UniversityYazd ***Iran Department of Mechanical Engineering Najafabad BranchIslamic Azad UniversityNajafabad ***Iran faculty of Engineering Kuwait College of Science and TechnologyDoha 35004Kuwait

The simultaneous investigation on the parameters affecting the flow of electrically conductive fluids such as volumetric radiation,heat absorption,heat generation,and magnetic field(Mf)is very vital due to its existence in various sectors of industry and *** present research focuses on mathematical modeling to simulate the cooling of a hot component through power-law(PL)nanofluid convection *** temperature reduction of the hot component inside a two-dimensional(2D)inclined chamber with two different cold wall shapes is *** formulation of the problem is derived with the lattice Boltzmann method(LBM)by code writing via the fORTRAN *** variables such as the radiation parameter(0–1),the Hartmann number(0–75),the heat absorption/generation coefficient(−5–5),the fluid behavioral index(0.8–1.2),the Rayleigh number(103–105),the imposed Mf angle(0°–90°),the chamber inclination angle(−90°–90°),and the cavity cold wall shape(smooth and curved)are *** findings indicate that the presence of radiation increases the mean Nusselt number value for the shear-thickening,Newtonian,and shear thinning fluids by about 6.2%,4%,and 2%,*** most cases,the presence of nanoparticles improves the heat transfer(HT)rate,especially in the cases where thermal conduction dominates *** is the lowest cooling performance index and Mf effect for the cavity placed at an angle of 90°.The application in the design of electronic coolers and solar collectors is one of the practical cases of this numerical research.

关键词： thermal performance analysis heat absorption/generation power-law(PL)Al_(2)O_(3)nanofluid magnetohydrodynamics natural convection volumetric radiation inclined cavity

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Plant triterpenoid saponins function as susceptibility factors to promote the pathogenicity of Botrytis cinerea

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Molecular Plant 2024年第7期17卷 1073-1089页

作者： francisco j.Escaray Amelia felipo-Benavent Cristian j.Antonelli Begona Balaguer Maria Pilar Lopez-Gresa Pablo Vera Instituto de Biologia Molecular y Celular de Plantas Universidad Politecnica de Valencia-C.S.l.CCiudad Politecnica de la InnovacionEdificio 8Eacceso GIngeniero Fausto Elios/n46022ValenciaSpain

The gray mold fungus Botrytis cinerea is a necrotrophic pathogen that causes diseases in hundreds of plant species,including high-value *** polyxenous nature and pathogenic success are due to its ability to perceive host signals in its *** this study,we found that laticifer cells of Euphorbia lathyris are a source of susceptibility factors required by *** to cause ***,poor-in-latex(pil)mutants,which lack laticifer cells,show full resistance to this pathogen,whereas lot-of-latex mutants,which produce more laticifer cells,are *** S factors are triterpenoid saponins,which are widely distributed natural products of vast structural *** downregulation of laticifer-specific oxydosqualene cyclase genes,which encode the first committed step enzymes for triterpene and,therefore,saponin biosynthesis,conferred disease resistance to ***,the Medicago truncatula Iha-1 mutant,compromised in triterpenoid saponin biosynthesis,showed enhanced ***,the application of different purified triterpenoid saponins pharmacologically complemented the diseaseresistant phenotype ofpil and hla-1 mutants and enhanced disease susceptibility in different plant *** found that triterpenoid saponins function as plant cues that signal transcriptional reprogramming in ***,leading to a change in its growth habit and infection strategy,culminating in the abundant formation of infection cushions,the multicellular appressoria apparatus dedicated to plant penetration and biomass destruction in *** together,these results provide an explanation for how plant triterpenoid saponins function as disease susceptibility factors to promote *** pathogenicity.

关键词： Euphorbia lathyris laticifer cell latex appressorium infection cushion necrotrophic fungi

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