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Adenosine A1 receptor ligands bind toα-synuclein:implications forα-synuclein misfolding andα-synucleinopathy in Parkinson’s disease

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Translational Neurodegeneration 2022年第1期11卷 809-834页

作者： Elisabet Jakova Mohamed Taha Moutaoufik Jeremy s.Lee Mohan Babu francisco s.cayabyab Department of surgery College of MedicineUniversity of SaskatchewanSaskatoonSKCanada Department of Chemistry and Biochemistry Faculty of ScienceUniversity of ReginaReginaSKCanada Department of Biochemistry Microbiology and ImmunologyCollege of MedicineUniversity of SaskatchewanSaskatoonSKCanada.

Background:Accumulatingα-synuclein(α-syn)aggregates in neurons and glial cells are the staples of many synucleinopathy disorders,such as Parkinson’s disease(PD).since brain adenosine becomes greatly elevated in ageing brains and chronic adenosine A1 receptor(A1R)stimulation leads to neurodegeneration,we determined whether adenosine or A1R receptor ligands mimic the action of known compounds that promoteα-syn aggregation(e.g.,the amphetamine analogue 2-aminoindan)or inhibitα-syn aggregation(e.g.,Rasagiline metabolite 1-aminoindan).In the present study,we determined whether adenosine,A1R receptor agonist N^(6)-Cyclopentyladenosine(CPA)and antago-nist 8-cyclopentyl-1,3-dipropylxanthine(DPCPX)could directly interact withα-syn to modulateα-syn aggregation and neurodegeneration of dopaminergic neurons in the substantia nigra(sN).Methods:Nanopore analysis and molecular docking were used to test the binding properties of CPA and DPCPX withα-syn in ***-Dawley rats were administered with 7-day intraperitoneal injections of the A1R ligands and 1-and 2-aminoindan,and levels ofα-syn aggregation and neurodegeneration were examined in the sN pars compacta and hippocampal regions using confocal imaging and Western ***:Using nanopore analysis,we showed that the A1R agonists(CPA and adenosine)interacted with the N-terminus ofα-syn,similar to 2-aminoindan,which is expected to promote a“knot”conformation andα-syn *** contrast,the A1R antagonist DPCPX interacted with the N-and C-termini ofα-syn,similar to 1-aminoindan,which is expected to promote a“loop”conformation that preventsα-syn *** docking studies revealed that adenosine,CPA and 2-aminoindan interacted with the hydrophobic core ofα-syn N-terminus,whereas DPCPX and 1-aminoindan showed direct binding to the N-and C-terminal hydrophobic *** imaging and Western blot analyses revealed that chronic treatments with CPA alone or in combination with 2-aminoindan increasedα-syn

关键词： Alpha-synucleinopathy Adenosine A1 receptor N6-cyclopentyladenosine 8-cyclopentyl-1 3-dipropylxanthine 1-aminoindan 2-aminoindan Neuroprotection Neurodegeneration Protein misfolding

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Long-term adenosine A1 receptor activation-induced sortilin expression promotes α-synuclein upregulation in dopaminergic neurons

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Neural Regeneration Research 2020年第4期15卷 712-723页

作者： Yun-Cheng Lv An-Bo Gao Jing Yang Li-Yuan Zhong Bo Jia shu-Hui Ouyang Le Gui Tian-Hong Peng sha sun francisco s.cayabyab Clinical Anatomy&Reproductive Medicine Application Institute Hengyang Medical CollegeUniversity of South ChinaHengyangHunan ProvinceChina Department of surgery College of MedicineUniversity of SaskatchewanSaskatoonCanada Institute of Pharmacy and Pharmacology School of Pharmaceutical ScienceUniversity of South ChinaHengyangHunan ProvinceChina Department of Metabolism&Endocrinology the First Affiliated HospitalHengyang Medical CollegeUniversity of South ChinaHengyangHunan ProvinceChina

Prolonged activation of adenosine A1 receptor likely leads to damage of dopaminergic neurons and subsequent development of neurodegenerative ***,the pathogenesis underlying long-term adenosine A1 receptor activation-induced neurodegeneration remains *** this study,rats were intraperitoneally injected with 5 mg/kg of the adenosine A1 receptor agonist N6-cyclopentyladenosine(CPA)for five *** mobility of rats was evaluated by forced swimming test,while their cognitive capabilities were evaluated by Y-maze *** of sortilin,α-synuclein,p-JUN,and c-JUN proteins in the substantia nigra were detected by western blot *** addition,immunofluorescence staining of sortilin andα-synuclein was performed to detect expression in the substantia *** results showed that,compared with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine(5 mg/kg)+CPA co-treated rats,motor and memory abilities were reduced,surface expression of sortin andα-synuclein in dopaminergic neurons was reduced,and total sortilin and totalα-synuclein were increased in CPA-treated ***9D cells were incubated with 500 nM CPA alone or in combination with 10μM sP600125(JNK inhibitor)for 48 *** real-time polymerase chain reaction analysis of sortilin andα-synuclein mRNA levels in MN9D cells revealed upregulated sortilin expression in MN9D cells cultured with CPA alone,but the combination of CPA and sP600125 could inhibit this *** made using Jasper,PROMO,and Alibaba online databases identified a highly conserved sequence in the sortilin promoter that was predicted to bind JUN in both humans and rodents.A luciferase reporter assay of sortilin promoter plasmid-transfected HEK293T cells confirmed this *** sortilin expression was inhibited by sh-sORT1,expression of p-JUN and c-JUN was detected by western blot ***-term adenosine A1 receptor activation levels upregulatedα-synuclein expression at the pos

关键词： cognitive dysfunction dopaminergic neuron dyskinesia JNK/c-JUN pathway long-term adenosine A1 receptor activation neural regeneration neurodegenerative diseases sortilin α-synuclein

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An approximate Kerr-Newman-like metric endowed with a magnetic dipole and mass quadrupole

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Communications in Theoretical Physics 2024年第8期76卷 124-138页

作者： francisco Frutos-Alfaro space Research Center and school of Physics University of Costa RicaSan PedroSan JoseCosta Rica

Approximate all-terrain spacetimes for astrophysical applications are presented. The metrics possess five relativistic multipole moments, namely, mass, rotation, mass quadrupole, charge,and magnetic dipole moment. All these spacetimes approximately satisfy the Einstein-Maxwell field equations. The first metric is generated using the Hoenselaers-Perjés method from given relativistic multipoles. The second metric is a perturbation of the Kerr-Newman metric, which makes it a relevant approximation for astrophysical calculations. The last metric is an extension of the Hartle-Thorne metric that is important for obtaining internal models of compact objects perturbatively. The electromagnetic field is calculated using Cartan forms for locally non-rotating observers. These spacetimes are relevant for inferring properties of compact objects from astrophysical observations. Furthermore, the numerical implementations of these metrics are straightforward, making them versatile for simulating potential astrophysical applications.

关键词： Gravitation Einstein-Maxwell equations Compact objects

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Hydrochar and synthetic natural gas co-production for a full circular economy implementation via hydrothermal carbonization and methanation:An economic approach

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Journal of Environmental sciences 2024年第6期140卷 69-78页

作者： Judith González-Arias Guillermo Torres-sempere Miriam González-Castaño francisco MBaena-Moreno Tomás RReina Inorganic Chemistry Department and Materials sciences Institute University of Seville-CSICSevilleSpain Materials sciences Institute(ICMsE) CSIC-University of SevilleSevilleSpain Department of Chemistry and Chemical Engineering Chalmers University of TechnologyGothenburgSE 41296Sweden

Herein we study the economic performance of hydrochar and synthetic natural gas coproduction from olive tree *** process entails a combination of hydrothermal carbonization and *** a previous work,we evidenced that standalone hydrochar production via HTC results ***,we propose a step forward on the process design by implementing a methanation,adding value to the gas effluent in an attempt to boost the overall process techno-economic *** different plant capacities were analyzed(312.5,625 and 1250 kg/hr).The baseline scenarios showed that,under the current circumstances,our circular economy strategy in *** analysis of the revenues shows that hydrochar selling price have a high impact on NPV and subsidies for renewable coal production could help to boost the profitability of the *** the contrary,the analysis for natural gas prices reveals that prices 8 times higher than the current ones in spain must be achieved to reach *** seems unlikely even under the presence of a strong subsidy *** costs analysis suggests that a remarkable electricity cost reduction or electricity consumption of the HTC stage could be a potential strategy to reach profitability ***,significant reduction of green hydrogen production costs is deemed instrumental to improve the economic performance of the *** results show the formidable techno-economic challenge that our society faces in the path towards circular economy societies.

关键词： Hydrothermal carbonization CO_(2)waste valorization Methanation Profitability analysis

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Towards efficient strain engineering of 2D materials:A four-points bending approach for compressive strain

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Nano Research 2024年第6期17卷 5317-5325页

作者： Hao Li Félix Carrascoso Ana Borrás Gloria P.Moreno francisco J.Aparicio Ángel Barranco Andrés Castellanos Gómez Campus de Cantoblanco Instituto de Ciencia de Materiales de MadridC.Sor Juana Inés de la Cruz328049 MadridSpain Nanotechnology on surfaces and Plasma Lab Instituto de Ciencia de Materiales de Sevilla(CSIC-Universidad de Sevilla).C/Americo Vespucio 49E-41092 SevilleSpain Departamento de Física Aplicada I Escuela Politécnica SuperiorUniversidad de Sevillac/Virgen deÁfrica 7E-41011 SevilleSpain

strain engineering,as a powerful strategy to tune the optical and electrical properties of two-dimensional(2D)materials by deforming their crystal lattice,has attracted significant interest in recent years.2D materials can sustain ultra-high strains,even up to 10%,due to the lack of dangling bonds on their surface,making them ideal brittle *** remarkable mechanical resilience,together with a strong strain-tunable band structure,endows 2D materials with a broad optical and electrical response upon ***,strain engineering based on 2D materials is restricted by their nanoscale and strain quantification *** this study,we have modified a homebuilt three-points bending apparatus to transform it into a four-points bending apparatus that allows for the application of both compressive and tensile strains on 2D *** approach allows for the efficient and reproducible construction of a strain system and minimizes the buckling effect caused by the van der Waals interaction by adamantane encapsulation *** results demonstrate the feasibility of introducing compressive strain on 2D materials and the potential for tuning their optical and physical properties through this approach.

关键词： uniaxial compressive strain polymer encapsulation differential reflectance spectroscopy exciton tunability

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social networks of reintroduced Przewalski's horses in the Great Gobi B strictly Protected Area (Mongolia)

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Current Zoology 2024年第2期70卷 182-194页

作者： Anna Bernatkova Ganbaatar Oyunsaikhan Jaroslav simek Martina Komarkova francisco Ceacero Faculty of Tropical Agrisciences Czech University of Life Sciences PragueCzech Republic Great Gobi B strictly Protected Area Takhin TalMongolia Zoo Praha U Trojského zamku 120/3PragueCzech Republic

Analyzing social networks is a powerful tool for understanding the ecology of social *** most studies focus on the role of each group member,few compare groups with different *** current population of Przewalski's horses Equus ferus przewalskii at the Great Gobi B strictly Protected Area(Mongolia)includes groups of wild-born and captive-bred individuals with different experiences with the area(acclimatizing,long-term reintroduced,and wild-born),therefore serving as an ideal natural behavioral *** filmed 11 groups for 141.5 hours in summer 2018(July),late spring 2019(May,June),and autumn 2019(september,October).Affiliative and agonistic interactions were recorded,and social networks were *** tested the influence of origin,experience,season,sex,age,relative time belonging to the group,relat-edness,and dominance rank on different network indices at the individual and group *** found that groups with greater experience in the area are generally better connected than members of the newly formed ***,these strong networks were created by wild-born individuals with very low interaction *** the contrary,inexperienced groups composed of captive-bred individuals displayed many inter actions but created weak social *** results show a trend of behavioral transition from acclimatizing through long-term reintroduced to wild-born groups,supporting that the newly formed groups of released Przewalski's horses need time to display the typical social behavior patterns of wild-born ***-term monitoring of released Przewalski's horses is recommended to promote the success of this reintroduction program.

关键词： Przewalski's horses reintroduction social behavior soft-release.

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Bias-Free solar-to-Hydrogen Conversion in a BiVO4/PM6:Y6 Compact Tandem with Optically Balanced Light Absorption

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Energy & Environmental Materials 2024年第4期7卷 231-238页

作者： Catarina G.Ferreira Constanza sansierra francisco Bernal-Texca Mingyu Zhang Carles Ros Jordi Martorell ICFO–Institut de Ciències Fotòniques The Barcelona Institute of Science and Technology Departament de Física Universitat Politècnica de Catalunya

The high voltage required to overcome the thermodynamic threshold and the complicated kinetics of the water splitting reaction limit the efficiency of single semiconductor-based photoelectrochemistry.A semiconductor/solar cell tandem structure has been theoretically demonstrated as a viable path to achieve an efficient direct transformation of sunlight into chemical energy.

关键词： bismuth vanadate compact tandem organic solar cells photonic multilayers solar-to-hydrogen conversion

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Protein glycation:a wolf in sweet sheep’s clothing behind neurodegeneration

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Neural Regeneration Research 2024年第5期19卷 975-976页

作者： Ana B.Uceda francisco Leal-Pérez Miquel Adrover Institut Universitari d’Investigacióen Ciències de la salut(IUNICs) Institut d’Investigaciósanitària Illes Balears(IdIsBa) Departament de Química Universitat de les Illes BalearsCtraPalma de MallorcaSpain

At the beginning of the 16th century,Paracelsus coined the maxim:“the dose makes the poison”.This principle can be applied to all living organisms,including organs and *** brain and its glial and neuronal cells are ... 详细信息

关键词： organs sheep sweet

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Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1578-1595页

作者： Eric Toshiyuki Nakamura Amanda Park Marina Alessandra Pereira Daniel Kikawa francisco Tustumi Department of Gastroenterology Instituto do CâncerHospital das Clínicas da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of scientific Initiation Universidade Mogi das CruzesSão Paulo 08780911Brazil Department of Evidence-Based Medicine Centro Universitário LusíadaCentre for Evidence-Based MedicineCentro Universitário Lusíada(UNILUS)SantosBrazil Department of surgery Hospital Israelita Albert EinsteinSão Paulo 05652900Brazil

BACKGROUND Heat shock proteins(HsPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many *** prognostic significance of HsPs and their regulatory factors,such as heat shock factor 1(HsF1)and CHIP,are poorly *** To investigate the relationship between HsP expression and prognosis in esophageal and esophagogastric *** A systematic review was conducted in accordance with PRIsMA recommend-ations(PROsPERO:CRD42022370653),on Embase,PubMed,Cochrane,and ***,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were ***-positive patients were compared with HsP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(Os).HsPs were stratified according to the HsP family,and the summary risk difference(RD)was calculated using a random-effect *** The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 ***40 and 60 were associated with a higher 3-year Os[HsP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HsP60:RD=0.33;95%CI:0.17-0.50],while HsF1 was associated with a poor 3-year Os(RD=-0.22;95%CI:-0.32 to-0.12).The other HsP families were not associated with long-term ***1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HsP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HsP families was not significantly related to tumor depth and lymph node or distant *** The expression levels of certain families of HsP,such as HsP40 and 60 and HsF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

关键词： Heat-shock proteins Heat-shock response Prognosis Esophageal neoplasms Meta-analysis

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Latest developments in early diagnosis and specific treatment of severe influenza infection

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Journal of Intensive Medicine 2024年第2期4卷 160-174页

作者： francisco Valenzuela-sánchez Blanca Valenzuela-Méndez Juan francisco Rodríguez-Gutiérrez Ángel Estella Intensive Care Unit University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Haematology Department University Hospital of JerezRonda de Circunvalación s/nJerez de la FronteraSpain Centro de Investigación Biomédica en Red Enfermedades respiratoriasCIBERESInstituto de Salud Carlos IIIAv.de Monforte de LemosMadridSpain Department of Oncological surgery Institut du Cancer de Montpellier(ICM)Parc Euromédecine208 Av.des ApothicairesMontpellierFrance Department of Medicine Faculty of MedicineUniversity of CádizCalle Doctor MarañónCádizSpain Instituto de Investigación e Innovación Biomédica de Cádiz(INIBiCA) Avenida Ana de Viya 21CádizSpain

Influenza pandemics are unpredictable recurrent events with global health,economic,and social *** objective of this review is to provide an update on the latest developments in early diagnosis and specific treatment of the disease and its complications,particularly with regard to respiratory organ *** advances in treatment,the rate of mortality in the intensive care unit remains approximately 30%.Therefore,early identification of potentially severe viral pneumonia is extremely important to optimize treatment in these *** pathogenesis of influenza virus infection depends on viral virulence and host ***,in some patients,it is associated with an excessive systemic response mediated by an authentic cytokine *** process leads to severe primary pneumonia and acute respiratory distress *** prognostication in the emergency department based on comorbidities,vital signs,and biomarkers(e.g.,procalcitonin,ferritin,human leukocyte antigen-DR,mid-regional proadrenomedullin,and lactate)is *** of these biomarkers on admission may facilitate clinical decision-making to determine early admission to the hospital or the intensive care *** decisions are reached considering pathophysiological circumstances that are associated with a poor prognosis(e.g.,bacterial co-infection,hyperinflammation,immune paralysis,severe endothelial damage,organ dysfunction,and septic shock).Moreover,early implementation is important to increase treatment *** on a limited level of evidence,all current guidelines recommend using oseltamivir in this *** possibility of drug resistance should also be *** options include other antiviral drugs and combination therapies with monoclonal ***,it is not recommended to use corticosteroids in the initial treatment of these ***,the implementation of supportive measures for respiratory failure is ***

关键词： Influenza Pandemic Respiratory failure Acute respiratory distress syndrome Intensive care unit admission

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