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Growth differentiation factor 5:a neurotrophic factor with neuroprotective potential in Parkinson’s disease

Neural Regeneration Research 2022年第1期17卷 38-44页

作者： Susan R.Goulding Jayanth Anantha Louise m.collins Aideen m.Sullivan Gerard W.O’Keeffe Department of Anatomy and Neuroscience and Cork Neuroscience CentreUniversity College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the most common movement disorder worldwide,affecting over 6 million *** is an age-related disease,occurring in 1%of people over the age of 60,and 3%of the population over 80 *** disease is characterized by the progressive loss of midbrain dopaminergic neurons from the substantia nigra,and their axons,which innervate the striatum,resulting in the characteristic motor and non-motor symptoms of Parkinson’s *** is paralleled by the intracellular accumulation ofα-synuclein in several regions of the nervous *** therapies are solely symptomatic and do not stop or slow disease *** promising disease-modifying strategy to arrest the loss of dopaminergic neurons is the targeted delivery of neurotrophic factors to the substantia nigra or striatum,to protect the remaining dopaminergic neurons of the nigrostriatal ***,clinical trials of two well-established neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have failed to meet their primary *** failure is thought to be at least partly due to the downregulation byα-synuclein of Ret,the common co-receptor of glial cell line-derived neurorophic factor and ***/differentiation factor 5 is a member of the bone morphogenetic protein family of neurotrophic factors,that signals through the Ret-independent canonical Smad signaling ***,we review the evidence for the neurotrophic potential of growth/differentiation factor 5 in in vitro and in vivo models of Parkinson’s *** discuss new work on growth/differentiation factor 5’s mechanisms of action,as well as data showing that viral delivery of growth/differentiation factor 5 to the substantia nigra is neuroprotective in theα-synuclein rat model of Parkinson’s *** data highlight the potential for growth/differentiation factor 5 as a disease-modifying therapy for Parkinson’s disease.

关键词： adeno-associated virus bone morphogenetic protein dopaminergic neurons growth/differentiation factor 5 neurodegeneration neuroprotection neurotrophic factor Parkinson’s disease Smad signaling α-synuclein

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Hybrid LES/RANS Simulations of Compressible Flow in a Linear Cascade of Flat Blade Profiles

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Journal of Thermal Science 2024年第5期33卷 1839-1850页

作者： Jaromír PRIHODA Petr STRAKA david SImURDA Petr SIDLOF Jan LEPICOVSKY Institute of Thermomechanics of the Czech Academy of Sciences Dolejskova 1402/518200 Prague 5Czech Republic Aerospace Research and Test Centre Beranovych 13019905 PragueCzech Republic Technical University of Liberec Faculty of MechatronicsStudentska 246117 Liberec 1Czech Republic

The paper reports on 3D numerical simulations of unsteady compressible airflow in a blade cascade consisting of flat profiles using a hybrid LES/RANS approach including a transition *** a first step towards simulation of blade flutter in turbomachinery,various incidence angle offsets of the middle blade were *** simulations were run for the flow regime characterized by outlet isentropic mach number m_(is)=0.5and zero *** results of the LES/RANS simulations(pressure and mach number distributions)were compared to a baseline RANS model,and to experimental data measured in a high-speed wind *** numerical results show that both methods overpredict flow separation taking place at the leading *** this regard,the hybrid LES/RANS method does not provide superior results compared to the traditional RANS ***,the LES/RANS results also capture vortex shedding from the blunt trailing *** frequency of the trailing edge vortex shedding in CFD simulations matches perfectly the spectral peak recorded during wind tunnel measurements.

关键词： numerical simulation blade cascade hybrid LES/RANS

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青藏高原地表变暗与北极气候变化间的共振

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Science Bulletin 2024年第3期69卷 367-374页

作者：汤舒畅朴世龙 david m.Holland 阚飞汪涛姚檀栋李熙晨 Sino-French Institute for Earth System Science College of Urban and Environmental SciencesPeking UniversityBeijing 100871China State Key Laboratory of Tibetan Plateau Earth System Resources and EnvironmentInstitute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100085China Courant Institute of mathematical Sciences New York UniversityNew YorkNY 0711USA Institute of Atmospheric Physics Chinese Academy of SciencesBeijing 100029China

The Tibetan Plateau(TP)exerts a profound influence on global climate over million-year timescales due to its past ***,whether the ongoing climate changes over the TP,particularly the persistent reduction in its local albedo(referred to as“TP surface darkening”),can exert global impacts remains *** this study,a state-of-the-art coupled land–atmosphere global climate model has been employed to scrutinize the impact of TP darkening on polar climate *** indicate that the projected TP darkening has the potential to generate a stationary Rossby wave train,thereby modulating the atmospheric circulation in the high-latitudes of the Northern Hemisphere and instigating a dipole-like surface air temperature anomaly pattern around the Arctic *** additional experiment suggests that the projected Arctic warming may in return warm the TP,thus forming a bi-directional linkage between these two climate *** their association with vast ice reservoirs,the elucidation of this mechanism in our study is crucial in advancing our comprehension of Earth system climate projections.

关键词： Tibetan Plateau High-latitude Northern Hemisphere Arctic Climate change Albedo Surface darkening

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Navigating the controversy regarding antibiotic prophylaxis in acute variceal bleeding

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World Journal of Gastroenterology 2024年第18期30卷 2485-2487页

作者： david Aguirre-Villarreal Ignacio García-Juárez Department of Gastroenterology and Liver Transplant Unit Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránMexico City 14080Mexico

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical ***,with recent evidence arguing against antibiotic prophylaxis,the role of this... 详细信息

关键词： Cirrhosis Acute variceal bleeding Antibiotic prophylaxis Endoscopic band ligation Spontaneous bacterial peritonitis

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Glyphosate Exposure Associated with Human Neurodegenerative Disorders: A Scoping Review

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Journal of Behavioral and Brain Science 2024年第7期14卷 187-209页

作者： Hannah Hutchins david m. Compton Kris Dougherty Behavioral Neuroscience Program Palm Beach Atlantic University West Palm Beach Florida USA Department of Biology Palm Beach Atlantic University West Palm Beach Florida USA

Chemically engineered agricultural products such as pesticides, insecticides, and herbicides, although used considerably for both industrialized and personal agricultural use, have recently been associated with a number of serious human health disorders. This rapid literature review aims to accumulate and analyze research from the last ten years, focusing specifically on the effects of exposure to glyphosate-based herbicide products such as Roundup as associated with the formation of various neurological disorders. Specifically, this review focuses on laboratory research using animal models or human cell cultures as well as human population-based epidemiological studies. It associates exposure to glyphosate or glyphosate-based products with the formation or exacerbation of neurological disorders such as Parkinson’s disease, Alzheimer’s disease, seizures, and autism spectrum disorder. In addition, it examines the correlation between the gut-brain axis, exposure to glyphosate, and neurodegeneration.

关键词： Herbicide Glyphosate Roundup Neurodegeneration Neurodegenerative Disorder Parkinson’s Disease Alzheimer’s Disease Seizures Autism Spectrum Disorder Gut-Brain Axis

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The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease

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Neural Regeneration Research 2020年第8期15卷 1432-1436页

作者： Susan R.Goulding Aideen m.Sullivan Gerard W.O’Keeffe Louise m.collins Department of Biological Sciences Cork Institute of TechnologyCorkIreland Department of Anatomy and Neuroscience and Cork Neuroscience Centre University College CorkCorkIreland Department of Physiology University College CorkCorkIreland

Parkinson’s disease is the second most common neurodegenerative disorder;it affects 1%of the population over the age of *** number of people with Parkinson’s disease is set to rapidly increase due to changing demographics and there is an unmet clinical need for disease-modifying *** pathological hallmarks of Parkinson’s disease are the progressive degeneration of dopaminergic neurons in the substantia nigra and their axons which project to the striatum,and the aggregation ofα-synuclein;these result in a range of debilitating motor and non-motor *** application of neurotrophic factors to protect and potentially regenerate the remaining dopaminergic neurons is a major area of research ***,this strategy has had limited success to *** trials of two well-known neurotrophic factors,glial cell line-derived neurotrophic factor and neurturin,have reported limited efficacy in Parkinson’s disease patients,despite these factors showing potent neurotrophic actions in animal *** is therefore a need to identify other neurotrophic factors that can protect againstα-synuclein-induced degeneration of dopaminergic *** bone morphogenetic protein(BmP)family is the largest subgroup of the transforming growth factor-βsuperfamily of *** are naturally secreted proteins that play crucial roles throughout the developing nervous ***,many BmPs have been shown to be potent neurotrophic factors for dopaminergic *** we discuss recent work showing that transcripts for the BmP receptors and BmP2 are co-expressed with several key markers of dopaminergic neurons in the human substantia nigra,and evidence for downregulation of BmP2 expression at distinct stages of Parkinson’s *** also discuss studies that explored the effects of BmP2 treatment,in in vitro and in vivo models of Parkinson’s *** studies found potent effects of BmP2 on dopaminergic neurites,which is important given that axon deg

关键词： axon growth BmP2 dopaminergic neurons neuroprotection neurotrophic factor neuroregeneration Parkinson’s disease α-synuclein

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Uncovering the dominant contribution of intermediate volatility compounds in secondary organic aerosol formation from biomass-burning emissions

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National Science Review 2024年第3期11卷 150-158页

作者： Kun Li Jun Zhang david m.Bell Tiantian Wang Houssni Lamkaddam Tianqu Cui Lu Qi mihnea Surdu Dongyu Wang Lin Du Imad El Haddad Jay G.Slowik Andre S.H.Prevot Environment Research Institute Shandong University Laboratory of Atmospheric Chemistry Paul Scherrer Institute

Organic vapors from biomass burning are a major source of secondary organic aerosols(SOAs). Previous smog chamber studies found that the SOA contributors in biomass-burning emissions are mainly volatile organic compounds(VOCs). While intermediate volatility organic compounds(IVOCs) are efficient SOA precursors and contribute a considerable fraction of biomass-burning emissions, their contribution to SOA formation has not been directly observed. Here, by deploying a newly-developed oxidation flow reactor to study SOA formation from wood burning, we find that IVOCs can contribute ～70% of the formed SOA, i.e.>2 times more than VOCs. This previously missing SOA fraction is interpreted to be due to the high wall losses of semi-volatile oxidation products of IVOCs in smog chambers. The finding in this study reveals that SOA production from biomass burning is much higher than previously thought, and highlights the urgent need for more research on the IVOCs from biomass burning and potentially other emission sources.

关键词： atmospheric chemistry biomass burning secondary organic aerosol intermediate volatility organic compounds

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Old-growth mixed dipterocarp forests show variable losses and gains in aboveground biomass and standing carbon over forty years

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Forest Ecosystems 2024年第1期11卷 14-23页

作者： Sisira Ediriweera Champika Bandara Tithira Lakkana Shanika Jayasinghe david Woodbury Arun Dayanandan B.m.P.Singhakumara Xiangcheng mi I.A.U.N.Gunatilleke C.V.S.Gunatilleke mark SAshton Department of Science and Technology Uva Wellassa UniversityBadullaSri Lanka The Forest School Yale School of the EnvironmentYale UniversityNew HavenCT06511USA Department of Forestry and Environmental Science University of Sri JayewardenepuraNugegodaSri Lanka State Key Laboratory of Vegetation and Environmental Change Institute of BotanyChinese Academy of SciencesBeijing100093China Botany Department University of PeradeniyaPeradeniyaSri Lanka

Background:No studies have documented long-term trends in aboveground biomass(AGB)for mixed-dipterocarp forests(mDF),the dominant rain forest type in tropical wet equatorial *** our study,we sought to document such trends over forty years across three sites representing lowland to lower montane ***:To do this,we established fifty 100 m×25 m plots in 1978 across three sites sampled along an elevation gradient,identified as mature old-growth *** measured trees for diameter at breast height that we identified to species and *** took wood samples to calculate species wood-specific *** re-measured plots in 1998 and again in ***:We show standing AGB for all sites combined to be 517.52 mg·ha^(-1)in 1978,but this declined by 17%over 40 years to 430.11 mg·ha^(-1).No differences exist among sites in AGB primarily because of considerable within site variation;but interactions of time with site show declines across sites were not uniform,one remained about the *** few species represented a high proportion of the AGB with the top five species comprising between 34%and 65%,depending upon site and year *** species,mesua nagassarium,represented a disproportionately large amount of AGB and decline over time,particularly at the low elevation ***:Our results are directly relevant to estimating AGB and standing carbon sequestered in *** study is the first to demonstrate varying but overall,declining trends in amounts of AGB among forests making predictions of biomass and standing carbon in mDF difficult over wide regions.

关键词： Western ghats Shorea spp. Southeast Asia Sri Lanka Tropical rain forest Wood specific gravity

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Bilateral nephrolithiasis and upper tract transitional cell carcinoma in horseshoe kidney

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Current Urology 2024年第3期18卷 247-249页

作者： Jacob m.Gaines Eric J.macdonald Arun Rai david Hoenig Arthur Smith Zeph Okeke Tareq Aro The Smith Institute for Urology Donald and Barbara Zucker School of Medicine at Hofstra/NorthwellLake SuccessNYUSA

Nephroureterectomy is currently the criterion-standard treatment for high-grade upper tract urothelial carcinoma(UTUC).Current guidelines and expert opinions propose some exceptions to this approach based on patient characteristics,disease status,and function of the contralateral *** present a rare case of a patient with horseshoe kidney,bilateral large nephrolithiasis,high-grade UTUC in one moiety,and relative parenchymal thinning of the contralateral *** patient was treated with a percutaneous,minimally invasive,nephron sparing *** patient also had intracollecting system instillations of gemcitabine and *** invasive percutaneous resection of high-grade UTUC is a safe procedure in select *** guidelines may not apply to all patients;unique scenarios with UTUC may require personalized decision-making and treatment at specialized centers.

关键词： Upper tract urothelial cancer Percutaneous resection Horseshoe kidney Nephrolithiasis

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Development of T cell antigen-based human coronavirus vaccinesagainst nAb-escaping SARS-CoV-2 variants

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Science Bulletin 2024年第15期69卷 2456-2470页

作者： Hao Zhou Ping Leng Yang Wang Kaiwen Yang Chen Li david m.Ojcius Pengfei Wang Shibo Jiang College of medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400016China Shanghai Pudong Hospital Fudan University Pudong Medical CenterShanghai Institute of Infectious Disease and BiosecuritySchool of Life SciencesFudan UniversityShanghai 200438China Department of Biomedical Sciences University of the PaciﬁcArthur Dugoni School of DentistrySan FranciscoCA 94115USA Key Laboratory of medical molecular Virology of ministry of Education/ministry of Health/Chinese Academy of medical Sciences Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghai 200032China

Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses;however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus,raising serious concerns about their efficacy. Additionally, while neutralizing antibodies(nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus(HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to n Abs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCo Vs based on different vaccine platforms.

关键词： COVID-19 Immune escape Omicron variant SARS-CoV-2 T cell antigen-based vaccine

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