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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： Ana M.López-Estévez Y.Zhang mar.a Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia mar.a j.Vicent defang Ouyang Dolores Torres mar.a josé Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(HANAs)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).HANAs composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed HANAs’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of HANAs technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Reuse of port industrial heritage in tourist cities:Shipyards as case studies

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Frontiers of Architectural Research 2024年第1期13卷 164-183页

作者： mar.a j.Andrade Eduardo jiménez-Morales Rachel Rodríguez-Ramos Pablo martínez-Ramírez department of Art and Architecture School of ArchitectureMalaga UniversityMalaga 29013Spain

The progressive deindustrialisation of many western cities since the 1980s has led to many industrial zones linked to port activities being abandoned or falling into *** such as Barcelona,Naples,Lisbon,Amsterdam,and Hamburg have port industrial complexes of high tangible and intangible heritage value that could totally or partially disappear,resulting in an irreparable loss of their scientific,architectural,social,technological,and historical *** that in mind,Adaptive Reuse(AR)of the built heritage allows the industrial memory of the ports to be preserved by turning them into new functional centres within the existing urban *** occurs in the context of the contemporary challenges of those cities,such as touristification,the circular economy and climate change,while guaranteeing the life cycle of those *** article analyses two case studies—the Nederlandsche Scheepsbouw Maatschappij(NDSM)and the Rotterdamsche Droogdok Maatschappij(RDM)shipyards,both in the Netherlands—in order to contribute to the knowledge of AR of Port Industrial *** are two examples of good practices in port industrial heritage interventions,where the factors behind their acclaim can be easily highlighted.A multi-scale methodology is therefore used and tailored to the case of port industrial heritage,based on analysing previous studies of the heritage in different spheres and on different scales.A relationship matrix tool is thus *** enables a comparative study to be conducted,using key variables and indicators,and considering qualitative and quantitative *** provides extensive output information for each case study,which is summarised in the most favourable factors for the success of the AR of this port industrial heritage.

关键词： Industrial heritage Port-city Adaptive reuse Best practices Circular economy HUL Touristification

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Intestinal anti-inflammatory effect of a plant sterol food supplement in experimental murine colitis and cell co-culture models

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Food Science and Human Wellness 2024年

作者： Mussa Makran Antonio Cilla Rosa mar.a Giner mar.a Carmen Recio Luisa Tesoriere Alessandro Attanzio Guadalupe Garcia-Llatas Nutrition and Food Science Area， Faculty of Pharmacy and Food Sciences， University of Valencia.Av.Vicente Andrés Estellés s/n department of Pharmacology， Faculty of Pharmacy and Food Sciences， University of Valencia.Av.Vicente Andrés Estellés s/n department of Biological， Chemical and Pharmaceutical Sciences and Technologies， University of Palermo

The potential of a plant sterol food supplement （PS-FS） in addressing intestinal inflammation in vivo and in vitro was evaluated. As in vivo model， C57BL/6j mice were exposed to 1.5% dextran sulfate sodium in three 5-day periods， with 10-day rest intervals in between， daily reciving PS-FS （35 mg PS/kg）. The in vitro approach involved a bi-cameral system with 8-day-differentiated Caco-2 （apical） and RAW264.7 cells （basolateral）. The bioaccessible fraction of PS-FS， obtained after INFOGEST 2.0 simulated gastrointestinal digestion， was added to the apical part （90 min）， followed by stimulation with lipopolysaccharide （1 μg/mL， 24 h）. PS-FS alleviated rectal bleeding and rebalanced pro- (tumor necrosis factor α， interleukin （IL）-6， and IL-8) and anti-inflammatory cytokines （IL-10）. Additionally， PS-FS ameliorated histopathological damage and enhancing occludin expression. A reduction in oxidative stress was evidenced by decreased myeloperoxidase activity and reactive oxygen species production. The anti-inflammatory mechanism included suppressing cyclooxygenase 2 expression， reducing prostaglandin E2production， and inhibiting the phosphorylation and nuclear translocation of the nuclear factor κB p65 subunit. This study reveals the potential of PS-FS as a therapeutic intervention for colitis. The alignment between in vivo and in vitro outcomes substantiates the appropriateness of the co-culture model to evaluate the anti-inflammatory activity of foods.

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Single atom Cu-N-C catalysts for the electro-reduction of CO_(2) to CO assessed by rotating ring-disc electrode

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journal of Energy Chemistry 2024年第1期88卷 169-182,I0004页

作者： S.Pérez-Rodríguez M.Gutiérrez-Roa C.Giménez-Rubio D.Ríos-Ruiz P.Arévalo-Cid M.V.martínez-Huerta A.Zitolo M.j.Lázaro D.Sebastián Instituto de Carboquímica(CSIC) Miguel Luesma Castán 450018 ZaragozaSpain Instituto de Catálisis y Petroleoquímica(CSIC) Marie Curie 228049 MadridSpain Synchrotron SOLEIL L’Orme des MerisiersDépartementale 12891190France

The electrochemical CO_(2) reduction reaction(CO_(2)RR) to controllable chemicals is considered as a promising pathway to store intermittent renewable energy. Herein, a set of catalysts based on copper-nitrogendoped carbon xerogel(Cu-N-C) are successfully developed varying the copper amount and the nature of the copper precursor, for the efficient CO_(2)RR. The electrocatalytic performance of Cu-N-C materials is assessed by a rotating ring-disc electrode(RRde), technique still rarely explored for CO_(2)RR. For comparison, products are also characterized by online gas chromatography in a H-cell. The as-synthesized Cu-NC catalysts are found to be active and highly CO selective at low overpotentials(from -0.6 to -0.8 V ***) in 0.1 M KHCO_(3), while H_(2) from the competitive water reduction appears at larger overpotentials(-0.9 V vs. RHE). The optimum copper acetate-derived catalyst containing Cu-N_(4) moieties exhibits a CO_(2)-to-CO turnover frequency of 997 h^(-1) at -0.9 V vs. RHE with a H_(2)/CO ratio of 1.8. These results demonstrate that RRde configuration can be used as a feasible approach for identifying electrolysis products from CO_(2)RR.

关键词： Cu-N-C Carbon xerogel Rotating ring disc electrode Carbon dioxide reduction reaction Carbon monoxide

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Anatomical characterization of central, apical and minimal corneal thickness

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International journal of Ophthalmology(English edition) 2014年第4期7卷 668-672页

作者： Federico Saenz-Frances martha Cecilia Bermúdez-Vallecilla lara Borrego-Sanz Luis jaez j osé mar.a martinez-de-la-casa laura Morales-Fernandez Enrique Santos-Bueso julián Garcia-Sanchez julián Garcia-Feijoo department of Ophthalmology Hospital Clínico San CarlosUniversidad Complutense de Madrid Instituto de Tecnologìa del Conocimiento Universidad Complutense de Madrid

·AIM: To anatomically locate the points of minimum corneal thickness and central corneal thickness(pupil center) in relation to the corneal apex.·METHODS: Observational, cross-sectional study, 299 healthy volunteers. Thickness at the corneal apex(AT),minimum corneal thickness(MT) and corneal thickness at the pupil center(PT) were determined using the pentacam. Distances from the corneal apex to MT(MD)and PT(PD) were calculated and their quadrant position(taking the corneal apex as the reference) determined:point of minimum thickness(MC) and point of central thickness(PC) depending on the quadrant position. Two multivariate linear regression models were constructed to examine the influence of age, gender, power of the flattest and steepest corneal axes, position of the flattest axis, corneal volume(determined using the Pentacam)and PT on MD and PD. The effects of these variables on MC and PC were also determined in two multinomial regression models.·RESULTS: MT was located at a mean distance of 0.909 mm from the apex(79.4% in the inferior-temporal quadrant). PT was located at a mean distance of 0.156 mm from the apex. The linear regression model for MD indicated it was significantly influenced by corneal volume(B =-0.024; 95% CI:-0.043 to-0.004). No significant relations were identified in the linear regression model for PD or the multinomial logisticregressions for MC and PC.·CONCLUSION: MT was typically located at the inferiortemporal quadrant of the cornea and its distance to the corneal apex tended to decrease with the increment of corneal volume.

关键词： cornealthickness anatomy glaucoma

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Rainfall Sensitivity to Microphysics and Planetary Boundary layer Parameterizations in Convection-Permitting Simulations over Northwestern South America

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journal of Meteorological Research 2024年第4期38卷 805-825页

作者： K.Santiago HERNANdeZ Sebastian GOMEZ-RIos juan j.HENAO Vanessa ROBLEDO Alvaro RAMiREZ-CARDONA Angela M.RENDON Geolimna Escuela AmbientalFacultad de IngenieriaUniversidad de AntioquiaMedellin 050010Colombia Grupo de Ingenieria y Gestion Ambiental(GIGA) Escuela AmbientalFacultad de IngenieriaUniversidad de AntioquiaMedellin 050010Colombia Division of Atmospheric Sciences Desert Research InstituteRenoNV 89512USA

Convection-permitting modeling allows us to understand mechanisms that influence rainfall in specific ***,microphysics parameterization(MP) and planetary boundary layer(PBL) schemes remain an important source of uncertainty,affecting rainfall intensity,occurrence,duration,and ***,we study the sensitivity of rainfall to three MP [Weather Research and Forecasting(WRF) Single-Moment 6-class(WSM6),Thompson,and Morrison] and two PBL [the Yonsei University(YSU) and Mellor–Yamada Nakanishi Niino(MYNN)] schemes with a convection-permitting resolution(4 km) over northwestern South America(NWSA).Simulations were performed by using the WRF model and the results were evaluated against soundings,rain gauges,and satellite data,considering the spatio-temporal variability of rainfall over diverse regions prone to deep convection in *** and PBL schemes largely influenced simulated rainfall,with better results for the less computationally expensive WSM6 MP and YSU PBL *** rain gauges and satellite estimates,simulations with Morrison MP overestimated rainfall,especially westward of the Andes,whereas the MYNN PBL underestimated precipitation in the Amazon–Savannas *** found that the uncertainty in the rainfall representation is highly dependent on the region,with a higher influence of MP in the Colombian Pacific and PBL in the Amazon–Savannas *** analyzing rainfall-related processes,the selection of both MP and PBL parameterizations exerted a large influence on the simulated lower tropospheric moisture flux and moisture *** schemes significantly influenced the downward shortwave radiation,with MYNN simulating a greater amount of low clouds,which decreased the radiation ***,latent heat fluxes were greater for YSU,favoring moist convection and *** schemes had a marked impact on vertical ***,Morrison MP showed stronger convection and higher precipitation rates,which is assoc

关键词： sensitivity microphysics planetary boundary layer(PBL) Weather Research and Forecasting(WRF) processes

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Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

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journal of Tuberculosis Research 2024年第2期12卷 91-104页

作者： júlia Malache António Domingas Pacala Isabelle Munyangaju Isaías Benzana Claudia Mutaquiha Dulce osório Benedita josé Edy Nacarapa Pereira Zindoga Faculdade de Cincias de Sade Universidade Catlica de Moambique Beira Moambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Moambique ISGlobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique

Introduction: Tuberculosis is closely linked to poverty, with patients facing significant indirect treatment costs. Treating drug-resistant tuberculosis further increases these expenses. Notably, there is a lack of published data on the indirect costs incurred by patients with drug-resistant tuberculosis in Mozambique. Objective: To assess the indirect costs, income reduction, and work productivity incurred by patients undergoing diagnosis and treatment for Drug-Resistant Tuberculosis (DRTB) in Mozambique during their TB treatment. Methods: As part of a comprehensive mixed-methods study conducted from january 2021 to April 2023, this research utilized a descriptive cross-sectional approach, incorporating both quantitative and qualitative methods. The primary goal was to evaluate the costs incurred by the national health system due to drug-resistant TB. Additionally, to explore the indirect costs experienced by patients and their families during treatment, semi-structured interviews were conducted with 27 individuals who had been undergoing treatment for over six months. Results: All survey participants unanimously reported a significant decline in labour productivity, with 70.3% experiencing a reduction in their monthly income. Before falling ill, the majority of respondents (33.3%) earned up to $76.92 monthly, representing the minimum earnings range, while 29.2% had a monthly income above $230.77, the maximum earnings range. Among those who experienced income loss, the majority (22.2%) reported a decrease of up to $76.92 per month, and 18.5% cited a loss exceeding $230.77 per month. Notably, patients with Drug-Resistant Tuberculosis (DRTB) have not incurred the direct costs of the disease, as these are covered by the government. Conclusion: The financial burden of treating Drug-Resistant Tuberculosis (DRTB), along with the income reduction it causes, is substantial. Implementing a patient-centred, multidisciplinary, and multisector approach, coupled with strong psy

关键词： Economic Costs Drug Resistance Tuberculosis Catastrophic Costs

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An Analysis of the Accounting Costs Associated with 20-Month DR TB Regimens in Maputo City, Mozambique

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journal of Tuberculosis Research 2024年第2期12卷 73-90页

作者： júlia Malache António Isaías Benzana Isabelle Munyangaju Benedita josé Dulce osório Edy Nacarapa Claudia Mutaquiha Simeão Nhabinde Pereira Zindoga Universidade Catlica de Moambique Beira Moambique Centro de Estudos e Apoio Psicolgico (CEAP) Universidade Eduardo Mondlane Maputo Moambique ISGlobal Hospital Clnic Universitat de Barcelona Barcelona Spain Tinpswalo Association Vincentian Association to Fight AIDS and TB Chokwe Mozambique Programa Nacional de Controlo da Tuberculose Ministrio da Sade de Moambique Maputo Mozambique Faculdade de Economia Universidade Eduardo Mondlane Maputo Moambique

Introduction: Socioeconomic and demographic conditions in a country can influence tuberculosis incidence and mortality, with nearly 95% of tuberculosis-related deaths occurring in poorer countries. Mozambique is among the 30 countries with the highest TB burden. Objective: The study aimed to estimate the average direct medical cost of treating drug-resistant tuberculosis in 19 health centers in Maputo City, Mozambique. Methods: A retrospective analysis of direct medical costs was conducted on patients aged 18 and older who completed 20-month drug-resistant tuberculosis treatment regimens in Maputo City in 2019. Results: This analysis covered 140 patients who completed a 20-month treatment regimen, with 64.3% (78) being male and 35.7% (62) female. Approximately 50% of the participants were aged between 29 and 47. The average direct medical cost of DRTB treatment was $4789.43, reaching up to $6568.00, with a standard deviation of $753.26, including clinical interventions and treatment. Conclusion: The direct medical costs for a basic treatment package for a patient with drug-resistant TB in Mozambique equal 36 minimum wages. developing alternative and innovative funding mechanisms and identifying ways to mitigate costs through the use of generic medicines would be beneficial.

关键词： Antitubercular Agents Multidrug-Resistant Healthcare Costs Tuberculosis Mozambique

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Multi-environment BSA-seq using large F3 populations is able to achieve reliable QTL mapping with high power and resolution: An experimental demonstration in rice

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The Crop journal 2024年第2期12卷 549-557页

作者： Yan Zheng Ei Ei Khine Khin mar Thi Ei Ei Nyein Likun Huang Lihui Lin Xiaofang Xie Min Htay Wai Lin Khin Than Oo Myat Myat Moe San San Aye Weiren Wu College of Life Sciences Fujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Fujian Provincial Key laboratory of Crop Breeding by design Fujian Agriculture and Forestry UniversityFuzhou 350002FujianChina Key laboratory of Genetics Breeding and Multiple Utilization of CropsMinistry of EducationFujian Agriculture and Forestry UniversityFuzhou 350002FujianChina department of Botany Mawlamyine UniversityMon StateMawlamyineMyanmar department of Botany Dagon UniversityNorth DagonYangonMyanmar

Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.

关键词： BSA-seq QTL mapping large F3 population Multi-environment experiment Cross-validation

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Physical activity and amyloid beta in middle-aged and older adults:A systematic review and meta-analysis

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journal of Sport and Health Science 2024年第2期13卷 133-144页

作者： mar.a Rodriguez-Ayllon Patricio Solis-Urra Cristina Arroyo-ávila Miriam álvarez-Ortega Pablo Molina-García Cristina Molina-Hidalgo Manuel Gómez-Río Belinda Brown Kirk I.Erickson Irene Esteban-Cornejo department of Epidemiology Erasmus University Medical Center RotterdamRotterdamGD 3015the Netherlands department of Physical Education and Sports Faculty of Sport SciencesSport and Health University Research Institute(iMUDS)University of GranadaGranada 18071Spain Faculty of Education and Social Sciences Universidad Andres BelloVina del Mar 2531015Chile department of Nuclear Medicine Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain Physical Medicine and Rehabilitation Service Virgen de las Nieves University HospitalInstitute of Biosanitary Research of Granada(IBS)Granada 18014Spain department of Psychology University of PittsburghPittsburghPA 15260USA Centre for Healthy Ageing Health Futures InstituteMurdoch UniversityMurdochWA 6150Australia School of Medical and Health Sciences Edith Cowan UniversityJoondalupWA 6027Australia Advent Health Research Institute Neuroscience Institute OrlandoOrlandoFL 32803USA Physiopathology of Obesity and Nutrition Research Center(CIBERobn) Institute of Health Carlos Ⅲ(ISCⅢ)Madrid 28029Spain

Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels *** aimed to explore the relationship between physical activity and Aβin middle-aged and older ***:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,*** were eligible if they included physical activity and Aβdata in adults aged 45 years or ***-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβ***:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and *** physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older ***,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included *** observational studies,higher levels of physical activity were positively associated with Aβonly in ***,further research is needed t

关键词： Aging Cognitive impairment dementia Exercise PET

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