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CD137 agonist potentiates the abscopal efficacy of nanoparticle-based photothermal therapy for melanoma

Nano Research 2022年第3期15卷 2300-2314页

作者： Preethi Bala Balakrishnan Debbie KLedezma Juliana Cano-Mejia Jaclyn Andricovich Erica Palmer Vishal APatel Patricia SLatham Eric SYvon alejandro villagra Rohan Fernandes Elizabeth E.Sweeney GW Cancer Center Department of MedicineSchool of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA The Institute for Biomedical Sciences School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA GW Cancer Center Department of Biochemistry and Molecular MedicineSchool of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20052USA Department of Dermatology&Oncology School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20037USA Department of Pathology School of Medicine and Health SciencesGeorge Washington UniversityWashingtonDC 20037USA ImmunoBlue BethesdaMD 20817USA

Despite the promise of immunotherapy such as the immune checkpoint inhibitors(ICIs)anti-PD-1 and anti-CTLA-4 for advanced melanoma,only 26%–52%of patients respond,and many experience grade III/IV immune-related adverse events.Motivated by the need for an effective therapy for patients non-responsive to clinically approved ICIs,we have developed a novel nanoimmunotherapy that combines locally administered Prussian blue nanoparticle-based photothermal therapy(PBNP-PTT)with systemically administered agonistic anti-CD137 monoclonal antibody therapy(aCD137).PBNP-PTT was administered at various thermal doses to melanoma cells in vitro,and was combined with aCD137 in vivo to test treatment effects on melanoma tumor progression,animal survival,immunological protection against tumor rechallenge,and hepatotoxicity.When administered at a melanoma-specific thermal dose,PBNP-PTT elicits immunogenic cell death(ICD)in melanoma cells and upregulates markers associated with antigen presentation and immune cell co-stimulation in vitro.Consequently,PBNP-PTT eliminates primary melanoma tumors in vivo,yielding long-term tumor-free survival.However,the antitumor immune effects generated by PBNP-PTT cannot eliminate secondary tumors,despite significantly slowing their growth.The addition of aCD137 enables significant abscopal efficacy and improvement of survival,functioning through activated dendritic cells and tumor-infiltrating CD8^(+)T cells,and generates CD4^(+)and CD8^(+)T cell memory that manifests in the rejection of tumor rechallenge,with no long-term hepatotoxicity.This study describes for the first time a novel and effective nanoimmunotherapy combination of PBNP-PTT with aCD137 mAb therapy for melanoma.

关键词： photothermal therapy Prussian blue nanoparticles anti-CD137 melanoma nanoimmunotherapy

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Targeting autophagy by polyphenols to prevent glycative stress-toxicity in the brain

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Neural Regeneration Research 2024年第5期19卷 941-942页

作者： alejandro Ponce-Mora Eloy Bejarano Department of Biomedical Sciences School of Health Sciences and Veterinary SchoolUniversidad Cardenal Herrera-CEUCEU UniversitiesValenciaSpain

Glycative stress-a pathological hub in brain dysfunction:The nervous system is an intricate network that requires precise and complex maintenance.In recent years,growing evidence highlights the detrimental impact of glycative stress on brain homeostasis,which disables a network of vital processes,necessary for optimal function(Gómez et al.,2021).

关键词： homeostasis stress

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Anticancer effects of exercise:Insights from single-cell analysis

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Journal of Sport and Health Science 2024年第5期13卷 676-678页

作者： Abel Plaza-Florido alejandro Lucia Shlomit Radom-Aizik Carmen Fiuza-Luces Pediatric Exercise and Genomics Research Center Department of PediatricsSchool of MedicineUniversity of California IrvineIrvineCA 92617USA Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Physical Activity and Health Research Group(“PaHerg”) Research Institute of the Hospital 12 de Octubre(“imas12”)Madrid 28041Spain

A recent special topic in the Journal of Sport and Health Science reported the health benefits conferred by traditional and innovative m-health exercise and multimodal programs with respect to several types of cancer.... 详细信息

关键词： protective exercise modal

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Toward sustainable waste management in small islands developing states: integrated waste-to-energy solutions in Maldives context

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Frontiers of Environmental Science & Engineering 2024年第2期18卷 133-148页

作者： Yao Wang alejandro Ruiz-Acevedo Eemaan Rameez Vijaya Raghavan Abid Hussain Xunchang Fei School of Civil and Environmental Engineering Nanyang Technological University50 Nanyang AvenueSingapore 639798Singapore United Nations Office for Project Services(UNOPS) United Nations BuildingBuruzu MaguMale’20184Maldives Department of Bioresource Engineering McGill UniversitySte-Anne-De-BellevueQuebec H9X 3V9Canada Department of Civil and Environmental Engineering Carleton UniversityOttawaOntario K1S 5B6H9X 3V9Canada

Effective waste management is a major challenge for Small Island Developing States (SIDS) like Maldives due to limited land availability. Maldives exemplifies these issues as one of the most geographically dispersed countries, with a population unevenly distributed across numerous islands varying greatly in size and population density. This study provides an in-depth analysis of the unique waste management practices across different regions of Maldives in relation to its natural and socioeconomic context. Data shows Maldives has one of the highest population density and per capita waste generation among SIDS, despite its small land area and medium GDP per capita. Large disparities exist between the densely populated capital Male’ with only 5.8 km2 area generating 63% of waste and the ~194 scattered outer islands with ad hoc waste management practices. Given Male’s dense population and high calorific waste, incineration could generate up to ~30 GW/a energy and even increase Maldives’ renewable energy supply by 200%. In contrast, decentralized anaerobic digestion presents an optimal solution for outer islands to reduce waste volume while providing over 40%–100% energy supply for daily cooking in local families. This timely study delivers valuable insights into designing context-specific waste-to-energy systems and integrated waste policies tailored to Maldives’ distinct regions. The framework presented can also guide other SIDS facing similar challenges as Maldives in establishing sustainable, ecologically sound waste management strategies.

关键词： Anaerobic digestion Waste incineration Waste management Maldives Small Island Developing States Waste-to-energy

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Brent vs.West Texas Intermediate in the US petro derivatives price formation

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Petroleum Science 2024年第1期21卷 729-739页

作者： alejandro Almeida Antonio A.Golpe Juan Manuel Martín-Alvarez Jose Carlos Vides Universidad Internacional de La Rioja Department of Quantitative Methods for Economics and BusinessLa RiojaSpain University of Huelva Department of Economics and Centro de Estudios Avanzados en FisicaMatematicas y Computacion and ICEIHuelvaSpain Complutense University of Madrid Department of Applied and Structural Economics and History and ICEIMadridSpain

In this paper,we apply the spatial panel model to explore the relationship between the dynamic of two types of crude oil prices(WTI and Brent crude oil)and their refined products over time.Considering the turbulent months of 2011,when Cushing Oklahoma had reached capacity and the crude oil export ban removal in 2015 as breakpoints,we apply this method both in the full sample and the three resultant regimes.First,results suggest our results show that both WTI and Brent display very similar behaviour with the refined products.Second,when attending to each regime,results derived from the first and third regimes are quite similar to the full sample results.Therefore,during the second regime,Brent crude oil became the benchmark in the petrol market,and it influenced the distillate products.Furthermore,our model can let us determine the price-setters and price-followers in the price formation mechanism through refined products.These results possess important considerations to policymakers and the market participants and the price formation.

关键词： Crude oil prices Spatial panel model Refined products Price formation

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Weather influenced nestling growth of an insectivorous but not a granivorous grassland passerine in Argentina

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Avian Research 2024年第2期15卷 156-162页

作者： Martín alejandro Colombo Adrian Jauregui Luciano N.Segura Laboratorio de Ecología de Aves.Institute“Dr.Raúl A.Ringuelet”(ILPLA)-UNLP/CONICET Boulevard 1201437La PlataB1900Buenos AiresArgentina

Nestling growth of birds can be affected by weather fluctuations.In general,it is expected that higher temper-atures favor growth by improving food availability and nestling metabolism,while rain hinders it by reducing foraging efficiency.However,most of these patterns have been described in insectivorous cavity-nesting birds in temperate forests.We tested these predictions in two neotropical grassland ground-nesting birds with contrasting nestling diets and therefore potentially different responses to weather.We measured nestlings of the Hellmayr’s Pipit(Anthus hellmayri,an insectivorous passerine)and the Grassland Yellow-Finch(Sicalis luteola,which feeds its nestlings exclusively with seeds)during three breeding seasons(2017-2020)in central-eastern Argentina.We took measurements of tarsus and body mass,modeled growth curves using nonlinear mixed-effects models,and evaluated the effects of minimum daily temperature and precipitation during the growth period and the 30 days prior to hatching.For pipits(60 nestlings from 21 nests),minimum temperatures during the growth period were positively associated with tarsus and body mass asymptotes.Also,there was a positive association between precipitation during the pre-hatching period and tarsus asymptote.Conversely,none of the weather variables analyzed had significant effects on nestling growth of finches(131 nestlings from 35 nests).Dietary contrast between species may explain the different results.Arthropod activity and abundance can be affected by weather variations within the span of a breeding season,whereas seeds may depend on conditions from previous years,making the effects harder to detect.Fledglings with reduced asymptotic size can have reduced chances of sur-vival.Hence,pipit populations could be impacted if they experience cold and dry conditions during their breeding season,which is of major relevance in the current context of climate change.

关键词： Finches Grassland birds Neotropical birds Pipits Precipitation Temperature

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Characteristics and trends of pediatric firepit burns: insights for prevention and safety

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World Journal of Pediatric Surgery 2024年第1期7卷 54-58页

作者： Maria Fazal Charbel Chidiac Raheel Ahmad Oussama Issa Erica Hodgman alejandro V Garcia Johns Hopkins School of Medicine BaltimoreMarylandUSA Department of Surgery Division of Pediatric SurgeryJohns Hopkins School of MedicineBaltimoreMarylandUSA Division of the Biological Sciences University of ChicagoChicagoIlinoisUSA School of Medicine American University of BeirutBeirutLebanon

Introduction As fire pits grow in popularity,so do the associated burn injuries.Our study examines pediatric fire pit burns characteristics to raise awareness and promote safety precautions.Methods We conducted a retrospective review of pediatric patients(<21 years)with firepit burns at a tertiary care hospital from 2016 to 2021.Results Eighty-four patients were identified,of whom 70.2%were male,with a median age of 62 months.The median percent total body surface area burned was 2%(interquartile range(IQR)=1-4).Thirty-five(41.7%)patients were admitted and 7(8.3%)underwent grafting.Neck and trunk burns had the highest grafting rates(66%and 33%,respectively).The hands(41.7%)and the lower extremities(27.4%)were the most frequently burned body areas.The leading causes of burns were ashes/hot coals(34.5%),flames(31.0%),and direct contact(25.0%),often resulting from falling into the fire(59.5%)or running or playing in activities near it(26.2%).Thirty-five(41.7%)were admitted for inpatient management,while 49(58.3%)were treated as outpatient.Eleven(13.2%)underwent at least one reconstructive surgery,7(8.4%)had at least one rehabilitation visit,and 65(77.4%)had follow-up clinic visits.The median length of stay was 2 days(IQR=1.0-3.5).The peak months for burns were from August through October(n=40,46.0%),with an increase observed from 10 cases in 2016to 20 cases in 2020.Conclusions Given the significant proportion of firepit burns resulting from unsafe fire behaviors,it is crucial that caretakers are aware of proper firepit safety precautions.Level ofevidence Il.

关键词： burns admitted prevention

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Exercise benefits meet the esophagus

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Journal of Sport and Health Science 2024年第5期13卷 685-686页

作者： alejandro Santos-Lozano Pedro L.Valenzuela Carmen Fiuza-Luces alejandro Lucia i+HeALTH European University Miguel de CervantesValladolid 47012Spain Research Institute of the Hospital 12 de Octubre(“imas12”) Madrid 28041Spain Department of Systems Biology University of AlcalaAlcala de Heranes 28801Spain Faculty of Sport Sciences Universidad Europea de MadridVillaviciosa de Odon(Madrid)28670Spain

Gastroesophageal reflux disease(GERD)is defined by recurrent and troublesome heartburn and effortless regurgitation or by the specific complications of this condition—that is,esophagitis,esophageal peptic strictures,and Barrett esophagus.1Although GERD is caused by gastric contents'reaching the esophagus,gastric juices can also reach other anatomical locations(pharynx,mouth,larynx,and airways),leading to(or worsening)extra-esophageal conditions(notably asthma)or symptoms(e.g.,wheezing,cough).1 Together with obesity,GERD is the main risk factor for gastroesophageal malignancies.

关键词： esophagus esophageal Barrett

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A new oxidative pathway of nitric oxide production from oximes in plants

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Molecular Plant 2024年第1期17卷 178-198页

作者： Pedro Lopez-Gomez Javier Buezo Marina Urra Alfonso Cornejo Raquel Esteban Jorge Fernandez de los Reyes Estibaliz Urarte Estefania Rodriguez-Dobreva alejandro Chamizo-Ampudia alejandro Eguaras Sebastian Wolf Daniel Marino Victor Martinez-Merino Jose F.Moran Institute for Multidisciplinary Research in Applied Biology(IMAB) Department of SciencesPublic University of Navarre(UPNA)Avda.de Pamplona 12331192 MutilvaSpain Institute for Advanced Materials and Mathematics(INAMAT2) Department of SciencesPublic University of Navarre(UPNA)Campus de Arosadia31006 PamplonaSpain Department of Plant Biology and Ecology University of the Basque Country(UPV/EHU)Sarriena s/nApdo.64448080 BilbaoSpain Center for Plant Molecular Biology(ZMBP) University of TubingenGeschwister-Scholl-Platz72074 TubingenGermany Institute of Natural Resources and Agrobiology of Salamanca(IRNASA) Department of Plant-Microorganism InteractionsSpanish National Research Council(CSIC)Cordel de Merinas40-5237008SalamancaSpain Department of Biochemistry Area of Molecular BiologyVeterinary FacultyUniversity of LeonCampus de Vegazanas/n.24071 LeonSpain

Nitric oxide(NO)is an essential reactive oxygen species and a signal molecule in plants.Although several studies have proposed the occurrence of oxidative NO production,only reductive routes for NO production,such as the nitrate(NO_(3)^(-))-upper-reductase pathway,have been evidenced to date in land plants.However,plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3−,evidencing the existence of a metabolic pathway for oxidative production of NO.We hypothesized that oximes,such as indole-3-acetaldoxime(IAOx),a precursor to indole-3-acetic acid,are intermediate oxidation products in NO synthesis.We detected the production of NO from IAOx and other oximes catalyzed by peroxidase(POD)enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and chemiluminescence.Flavins stimulated the reaction,while superoxide dismutase inhibited it.Interestingly,mouse NO synthase can also use IAOx to produce NO at a lower rate than POD.We provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory calculations.We showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO,while in vivo supplementation of IAOx and other oximes increased the number of lateral roots,as shown for NO donors,and a more than 10-fold increase in IAOx dehydratase expression.Furthermore,we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants,while prx33-34 mutant plants,defective in POD33-34,had reduced production.Our data show that the release of NO by IAOx,as well as its auxinic effect,explain the superroot phenotype.Collectively,our study reveals that plants produce NO utilizing diverse molecules such as oximes,POD,and flavins,which are widely distributed in the plant kingdom,thus introducing a long-awaited oxidative pathway to NO production in plants.This knowledge has essential implications for und

关键词： ammonium oxidation auxin nitric oxide oxime peroxidase root phenotype

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Advancing pediatric exercise research:A focus on immunomics and cutting-edge technologies

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Journal of Sport and Health Science 2024年第5期13卷 679-681页

作者： Abel Plaza-Florido alejandro Lucia Shlomit Radom-Aizik Pediatric Exercise and Genomics Research Center Department of PediatricsSchool of MedicineUniversity of California at IrvineIrvineCA 92617USA Faculty of Sport Sciences Universidad Europea de MadridMadrid 28670Spain Physical Activity Health Research Group(“PaHerg”) Research Institute of Hospital 12 de Octubre(“imas12”)Madrid 28041Spain

1.The importance of immunomics in pediatric exercise research The profound effect that"acute"or"regular"exercise(i.e.,a single exercise session or repeated sessions over time,respectively)exerts on the immune system has been widely recognized.1 Acute exercise is largely"immuno-enhancing"(e.g.,it may even improve vaccine responses in"at-risk"patients),whereas regular exercise reduces the risk of chronic conditions(not only obesity,diabetes,or cardiovascular diseases,but also several types of cancer)partly due to its anti-inflammatory effects.

关键词： pediatric Acute vaccine

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