Amyloidosis is a group of diseases caused by the abnormal accumulation of amyloid fibrils(misfolded protein aggregates)in various human tissues.These amyloid deposits can interfere with normal organ function and lead ...Amyloidosis is a group of diseases caused by the abnormal accumulation of amyloid fibrils(misfolded protein aggregates)in various human tissues.These amyloid deposits can interfere with normal organ function and lead to severe health issues.Amyloid plaque formation in the brain is linked to neurodegenerative diseases,including Tau and Aβplaques in Alzheimer’s disease,α-synuclein plaques in Parkinson’s disease,and huntingtin plaques in Huntington’s disease.Although this condition is typically associated with aging,certain mutations in amyloid-forming proteins can trigger early-onset amyloidosis(Hatami et al.,2017).Given its progressive and life-threatening nature,early detection and treatment are crucial.展开更多
Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted th...Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.展开更多
Towards the development of highly efficient electrochromic coatings,the crystallinity,morphology(e.g.size and shape)of electrochromic nanomaterials,and their charge insertion capacities play a significant role.Herein,...Towards the development of highly efficient electrochromic coatings,the crystallinity,morphology(e.g.size and shape)of electrochromic nanomaterials,and their charge insertion capacities play a significant role.Herein,we report the structure-dependent colouration effciency in electrochromic coatings based on the use of 0D,1D and 2D tungsten trioxide(WO_(3))nanostructures.A series of WO_(3)with different nanostructures were prepared and used as working electrodes to fabricate electrochromic devices for smart windows applications.Facile spray coating was applied on fluorine-doped tin oxide(FTO)substrate to make~70%transparent working electrodes to investigate their charge insertion capacities,electrochromic active surface area,and colouration efficiency.Results showed that the 2D WO_(3)nanoflakes displayed the highest diffusion coefficient for the intercalation of 1.52×10^(-10)cm^(2)/s with an increased electrochemical active surface area of 25.10 mF/cm^(2),a large modulation of optical reflectance(42.63%)with 3.79 s shorter response time for bleaching and a greater colouration efficiency(CE)value(89.29 cm^(2)/C)at 700 nm compared to the CE value for 1D WO_(3)(of 22 cm^(2)/C)and 0D WO_(3)(8 cm^(2)/C).The outcome of this study provides a new insight and valuable contribution to design an efficient electrochromic coating by controlling and optimising the nanostructures of selective electrochromic materials.展开更多
Among various advanced oxidation processes(AOPs),heterogeneous catalytic ozonation has garnered extensive attention in wastewater treatment owing to its broad pH range applicability and the elimination of the need for...Among various advanced oxidation processes(AOPs),heterogeneous catalytic ozonation has garnered extensive attention in wastewater treatment owing to its broad pH range applicability and the elimination of the need for additional energy input.Enhancing catalyst activity by introducing oxygen vacancies has been used extensively in heterogeneous catalytic ozonation.This paper reviews prevalent methods for the construction and characterization of oxygen vacancies.Based on a thorough examination of existing research,the role of oxygen vacancies is categorized according to their primary mechanisms of action in heterogeneous catalytic ozonation.For example,modulation of the catalyst electronic structure to enhance electron transfer;participation in the reaction as an active site to generate radicals and non-radicals;and exposure of more metal sites to enhance the reaction.Lastly,the paper delineates the limitations and future research directions concerning the role of oxygen vacancies in catalytic ozonation.This review addresses the gap in existing literature concerning the role of oxygen vacancies in catalytic ozone systems,establishes a comprehensive theoretical framework to aid in the design of efficient ozone catalysts,and delves into the functionality of oxygen vacancies in heterogeneous catalytic ozone reactions.展开更多
In this study,a facile method was employed to synthesize strong,yet highly elastic polyurethane-urea(PUU)with typical characteristics and 94% optical transmittance.Graphene platelets(GNPs)were prepared and modified vi...In this study,a facile method was employed to synthesize strong,yet highly elastic polyurethane-urea(PUU)with typical characteristics and 94% optical transmittance.Graphene platelets(GNPs)were prepared and modified via a scalable and eco-friendly mechanochemical approach.The produced GNPs is at 1.6-nm thickness with high electrical conductivity of~950 S/m.The structure-property relations of PUU/GNP nanocomposites were comprehensively investigated through morphology and mechanical properties measurements.The strong interface and high-density hydrogen bonds between modified GNPs(M-GNPs)and PUU significantly enhanced the mechanical properties of the PUU nanocomposite.The PUU composite showed 66.7%and 36.2%increments in tensile and impact strengths,respectively,at 0.2 wt% M-GNPs.The reversible hydrogen bond between M-GNPs and PUU endowed the nanocomposite with self-healing properties achieving 97.8% healing efficiency of the strength after 5 h at 120℃.This study demonstrates the importance of surface modification and provides a simple yet robust approach for preparing high-performance and functional PUU/graphene composites.展开更多
Biochar has been widely recognized as a promising solid CO_(2)adsorbent with economic and ecological benefits.Industrial CO_(2)emissions originate from diverse sources,while the pore structure and chemical functional ...Biochar has been widely recognized as a promising solid CO_(2)adsorbent with economic and ecological benefits.Industrial CO_(2)emissions originate from diverse sources,while the pore structure and chemical functional groups of biochar exhibit varying degrees of influence on CO_(2)adsorption and separation performance under different adsorption conditions.Therefore,exploring the matching relationship between the physicochemical properties of biochar and its adsorption and separation performance at different adsorption conditions is essential for the development and optimization of carbon-based adsorbents.This study selected the high-performance extreme gradient boosting(XGB)algorithm from various algorithms and utilized it to develop CO_(2),N_(2),CH_(4)adsorption prediction models.Based on this,coupled prediction models were developed for CO_(2)/N_(2)and CO_(2)/CH_(4)adsorption selectivity.Furthermore,feature importance and partial dependence analysis were performed using SHAP values.The results indicate that during CO_(2)adsorption,the influence of the pore structure of biochar outweighs that of its chemical composition.Specifically,the pore structure of 0.4–0.6 nm is the most important property influencing CO_(2)adsorption at low and medium pressure(0–0.6 bar),and the pore structure of 0.6–0.8 nm,as well as the specific surface area contribute the most at high pressure(0.6–1 bar).During CO_(2)selective separation,the CO_(2)/N_(2)mixture is primarily separated through the selective adsorption of CO_(2)by nitrogen functional groups.In contrast,for CO_(2)/CH_(4)mixtures,pore structure<1 nm plays a more critical role in determining adsorption selectivity.In addition,molecular simulation studies further revealed the adsorption filling mechanisms of CO_(2)molecules within different pore sizes and functional groups.Finally,nitrogen-doped biochar was synthesized using de-alkalize lignin as the precursor,KOH as the activating agent,and urea as the nitrogen dopant.CO_(2),N_(2),and CH_(4)isothermal adsorption experiments were conducted,and the experimental results confirmed that the developed prediction models exhibit high accuracy(R^(2)>0.9).展开更多
Groundwater level(GWL)is a key indicator used to accurately assess groundwater resources and form the foundation for ef-fective groundwater management.This paper integrates a Gate Recurrent Unit(GRU)model with a Multi...Groundwater level(GWL)is a key indicator used to accurately assess groundwater resources and form the foundation for ef-fective groundwater management.This paper integrates a Gate Recurrent Unit(GRU)model with a Multi-head Self-attention mechan-ism(MSAM-GRU)to simulate GWLs in both confined and unconfined aquifers simultaneously.The model innovatively captures the lag times between GWLs in the unconfined aquifer and precipitation,as well as between GWLs in the confined aquifer and the upper aquifer.We have assessed the effectiveness of the proposed model using a case study in the Beijing Plain,China from January 2005 to December 2020.With the consideration of lag times,the results indicated that the MSAM-GRU model exhibits a maximum 67%and 73%reduction in RMSE compared to the Attention mechanism-GRU(AM-GRU)and GRU model,respectively.MSAM-GRU model exhibited a 31%reduction in RMSE and a 0.12 increase in R^(2) compared to the same model that do not account for lag time.In Region I,the shortest lag time of GWL in the unconfined aquifer was two months,while that in the confined aquifer was three months,indicating a longer delayed response in the confined aquifer.MSAM-GRU model considering lag time,was then applied to simulate the GWLs in the unconfined aquifer under different scenarios and to analyze whether GWL fluctuations affect subway operations.The simulation res-ults showed that under the scenario 1,the GWL in the unconfined aquifer would rise above the depth of subway station floor,threaten-ing the operation of subways.This study can provide reliable technical support for the accurate simulation of GWLs in multi-aquifer systems.展开更多
Central venous catheters(CVCs),which play a vital role in medical care and are widely utilized in intensive care units,are h ighly susceptible to microbial colonization,thus leading to serious catheter-related bloodst...Central venous catheters(CVCs),which play a vital role in medical care and are widely utilized in intensive care units,are h ighly susceptible to microbial colonization,thus leading to serious catheter-related bloodstream infections and greatly increasing morbidity,mortality,and healthcare costs,accounting for 12%-25%of annual mortality in the USA.The corre sponding preventive measures include the use of antibiotic and antiseptic coatings,impregnated catheters,and maximally sterile barrier techniques,but they are often ineffective,particularly against biofilm formation and antibiotic-resistant bacteria.This review focuses on strategies for fabricating antimicrobial CVCs,e.g.,the use of antifouling materials,antimicrobial nanoparti cles(NPs),and surface functionalization,covering both commercially available solutions and those investigated.Additionally,w e explore the materials and processing technologies used to fabricate antimicrobial CVCs,emphasizing their advantages and challenges in industrial and clinical applications.Finally,we discuss the potential of inorganic NPs and the origin of their antimicrobial activity,providing insights for future advances in infection prevention that will help improve the patients’life quality.展开更多
Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyp...Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.展开更多
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Althoug...Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.展开更多
In floodplain wetlands,alterations in hydrological patterns resulting from climate change and human activities could potentially diminish the carbon sequestration capacity of the soils,thereby having a negative impact...In floodplain wetlands,alterations in hydrological patterns resulting from climate change and human activities could potentially diminish the carbon sequestration capacity of the soils,thereby having a negative impact on global climate change.However,the magnitude of the influence of hydrological regime change on soil carbon remains inadequately monitored.To address this research gap,we collected 306 upper layer(0–20 cm)soil samples from the Dongting Lake floodplain between 2013 and 2022.The random forest(RF)algorithm was used to analyze the spatial distribution of soil organic carbon(SOC)in the upper soil layer of Dongting Lake floodplain and the impact of climate and hydrological changes in the past decade on surface SOC in the East Dongting Lake area was studied.In 2022,the SOC concentration of the Dongting Lake floodplain upper layer soil ranged from 3.34 to 17.67 g kg^(-1),averaging 10.43 g kg^(-1),with a corresponding SOC density of(2.65±0.49)kg m^(-2) and total SOC stock of 6.82 Tg C(2.87–13.48 Tg C).From 2013 to 2022,the SOC concentration of the upper soil layer of the East Dongting Lake area decreased from 18.37 to 10.82 g kg^(-1).This reduction could be attributed to climate and hydrological changes which reduce SOC input by reducing vegetation growth and accelerating SOC decomposition.Above 21.4 m elevation,the amount of SOC loss increased with elevation,the loss being related to the decline in Miscanthus community biomass and greater susceptibility of higher altitude areas to climate and hydrological changes.Our results highlight the need for strengthening wetland SOC management to increase SOC in the soils to help combat climate change.展开更多
Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continu...Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continuous bout.Methods:PA was assessed using accelerometery in UK Biobank participants.The intensity of the most active continuous(MXCONT)and accumulated(MX)X min of the day,and their ratio(MXRATIO=MXCONT/MX),were determined.MXRATIO indicates how the most active minutes of the day are accumulated,ranging from a single continuous bout through to sporadic accumulation spread across the day.Durations(X)considered ranged from 1 to 20 min.The outcome was mortality.Results:In total,94,541 participants(56.5% female)were included.Over a median(interquartile range)follow-up of 6.9(6.3,7.4)years,2649(2.8%)deaths occurred.Intensity moderated the association between how the most active minutes of the day were accumulated and mortality risk,expressed relative to sporadically accumulated moderate PA.If the most active minutes were of moderate intensity,the risk of mortality was halved for continuous compared to sporadic accumulation,irrespective of duration;if the most active minutes were of vigorous intensity,a continuous bout was associated with the lowest risk for durations under 5 min(e.g.,3 min:hazard ratio(HR)=0.27,95% confidence interval(95%CI):0.21-0.34),while sporadic accumulation was associated with the lowest risk for durations beyond 5 min(HR=0.11,95%CI:0.08-0.15 for the most active 20 min).Conclusion:Optimal PA patterns for reducing mortality differ by intensity and duration.For moderate-intensity PA,a lower mortality risk may be optimized by prioritizing continuous PA for up to 20 min.However,for vigorous-intensity PA,multiple short bouts(<5 min)may be optimal.This suggests tailored PA recommendations may enhance longevity benefits.展开更多
Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focu...Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focus on their effects on recovery metrics,particularly how they influence sleep quality,perceived wellness,and athletic performance.Despite anecdotal evidence of its efficacy,rigorous comparative studies are scarce.Objective:This study aimed to evaluates and compare the effects of WCT and DCT on endurance,perceived wellness,exertion levels,and sleep quality among young,active males,addressing the gap in the literature regarding CT's efficacy in sports performance and recovery.Methods:Thirty-two amateur runners were randomly divided into two groups:one followed WCT sessions and the other followed DCT sessions.The study assessed the interventions'impacts on endurance performance(Yo-Yo intermittent recovery test),sleep quality(Pittsburgh Sleep Quality Index),and perceived exertion(Borg CR10 Scale).Heart rate was measured using a Polar H10 sensor to gauge physiological responses during physical tests.Results:Significant improvements were observed in the WCT group for sleep latency(%change=-82.31%;interaction group×time p=0.006;Cohen's d=0.74)and sleep disturbance(%change=-68.70%;interaction group×time p<0.001;Cohen's d=1.09),suggesting enhanced sleep quality(global score;%change=-52.81;interaction group×time p=0.004;Cohen's d=0.77).However,no significant differences were found in direct performance metrics(distance,maximal heart rate,maximal oxygen uptake)between WCT and DCT groups.These findings highlight WCT's potential as a recovery aid,particularly through improved sleep,without directly influencing endurance performance outcomes.Conclusion:WCT may serve as an effective ergogenic aid for athletes by potentially improving sleep quality and reducing perceived exertion,thus contributing indirectly to performance through enhanced recovery.展开更多
In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflamma...In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.展开更多
基金supported in part by a CIFRE PhD fellowship through the“Association Nationale de la Recherche et de la Technologie”(ANRT)program,in collaboration between PROTERA and“Center National de la Recherche Scientifique”(CNRS)to VGby EU COST Action ML4NGP CA21160 to VG and AVK+1 种基金the Fondation pour la Recherche Médicale(grant MND202310017898)to AVKthe AFM-Téléthon(grant n°28988)to AVK.
文摘Amyloidosis is a group of diseases caused by the abnormal accumulation of amyloid fibrils(misfolded protein aggregates)in various human tissues.These amyloid deposits can interfere with normal organ function and lead to severe health issues.Amyloid plaque formation in the brain is linked to neurodegenerative diseases,including Tau and Aβplaques in Alzheimer’s disease,α-synuclein plaques in Parkinson’s disease,and huntingtin plaques in Huntington’s disease.Although this condition is typically associated with aging,certain mutations in amyloid-forming proteins can trigger early-onset amyloidosis(Hatami et al.,2017).Given its progressive and life-threatening nature,early detection and treatment are crucial.
基金supported by Porsolt SAS,https://www.porsolt.com/.
文摘Objectives:The five-year survival rate for pancreatic cancer is notably low,posing a significant challenge to patient health.The primary treatments are radiotherapy and chemotherapy,sometimes combined with targeted therapy;however,their clinical benefits are limited.Therefore,developing new models to evaluate the therapeutic potential of novel molecules is essential.Fingolimod and Dimethyl Fumarate(DMF),currently used to treat multiple sclerosis,have recently been shown to have anti-cancer effects in several preclinical tumor models.This study aims to evaluate the therapeutic potential of Fingolimod and DMF in pancreatic cancer by investigating their respective in vitro cytotoxicity and in vivo antitumor effects.Methods:In this study,we evaluated for the first time these two drugs in pancreatic preclinical models in vitro using 3D spheroid tumor models and in vivo,which are compared to two standard-of-care consisting of Gemcitabine and Erlotinib.Results:In vitro,both Fingolimod and DMF induced cytotoxicity in spheroids from two pancreatic cell lines.Additionally,Fingolimod and DMF displayed anticancer effects in two subcutaneous xenograft models using PANC-1 and CFPAC-1 cells.Conclusions:Although the responses observed with Fingolimod and DMF were similar to those of Gemcitabine and Erlotinib,these findings indicate a potential emerging interest in Fingolimod and DMF for the treatment of pancreatic cancer.However,further work is still necessary to fully characterize how these drugs affect tumor progression.
基金the funding by the ARC Research Hub for Advanced Manufacturing with 2D Materials(ARC IH210100025)。
文摘Towards the development of highly efficient electrochromic coatings,the crystallinity,morphology(e.g.size and shape)of electrochromic nanomaterials,and their charge insertion capacities play a significant role.Herein,we report the structure-dependent colouration effciency in electrochromic coatings based on the use of 0D,1D and 2D tungsten trioxide(WO_(3))nanostructures.A series of WO_(3)with different nanostructures were prepared and used as working electrodes to fabricate electrochromic devices for smart windows applications.Facile spray coating was applied on fluorine-doped tin oxide(FTO)substrate to make~70%transparent working electrodes to investigate their charge insertion capacities,electrochromic active surface area,and colouration efficiency.Results showed that the 2D WO_(3)nanoflakes displayed the highest diffusion coefficient for the intercalation of 1.52×10^(-10)cm^(2)/s with an increased electrochemical active surface area of 25.10 mF/cm^(2),a large modulation of optical reflectance(42.63%)with 3.79 s shorter response time for bleaching and a greater colouration efficiency(CE)value(89.29 cm^(2)/C)at 700 nm compared to the CE value for 1D WO_(3)(of 22 cm^(2)/C)and 0D WO_(3)(8 cm^(2)/C).The outcome of this study provides a new insight and valuable contribution to design an efficient electrochromic coating by controlling and optimising the nanostructures of selective electrochromic materials.
基金support from the Key R&D Program of Zhejiang province(No.2024C03136).
文摘Among various advanced oxidation processes(AOPs),heterogeneous catalytic ozonation has garnered extensive attention in wastewater treatment owing to its broad pH range applicability and the elimination of the need for additional energy input.Enhancing catalyst activity by introducing oxygen vacancies has been used extensively in heterogeneous catalytic ozonation.This paper reviews prevalent methods for the construction and characterization of oxygen vacancies.Based on a thorough examination of existing research,the role of oxygen vacancies is categorized according to their primary mechanisms of action in heterogeneous catalytic ozonation.For example,modulation of the catalyst electronic structure to enhance electron transfer;participation in the reaction as an active site to generate radicals and non-radicals;and exposure of more metal sites to enhance the reaction.Lastly,the paper delineates the limitations and future research directions concerning the role of oxygen vacancies in catalytic ozonation.This review addresses the gap in existing literature concerning the role of oxygen vacancies in catalytic ozone systems,establishes a comprehensive theoretical framework to aid in the design of efficient ozone catalysts,and delves into the functionality of oxygen vacancies in heterogeneous catalytic ozone reactions.
基金The National Natural Science Foundation of China(No.52173077)the Liaoning Provincial Department of Education Series Project(No.LJKZ0187)+1 种基金Natural Science Foundation of Liaoning Province(No.2023-MS-239)Liaoning BaiQianWan Talents Program(No.2021921081)。
文摘In this study,a facile method was employed to synthesize strong,yet highly elastic polyurethane-urea(PUU)with typical characteristics and 94% optical transmittance.Graphene platelets(GNPs)were prepared and modified via a scalable and eco-friendly mechanochemical approach.The produced GNPs is at 1.6-nm thickness with high electrical conductivity of~950 S/m.The structure-property relations of PUU/GNP nanocomposites were comprehensively investigated through morphology and mechanical properties measurements.The strong interface and high-density hydrogen bonds between modified GNPs(M-GNPs)and PUU significantly enhanced the mechanical properties of the PUU nanocomposite.The PUU composite showed 66.7%and 36.2%increments in tensile and impact strengths,respectively,at 0.2 wt% M-GNPs.The reversible hydrogen bond between M-GNPs and PUU endowed the nanocomposite with self-healing properties achieving 97.8% healing efficiency of the strength after 5 h at 120℃.This study demonstrates the importance of surface modification and provides a simple yet robust approach for preparing high-performance and functional PUU/graphene composites.
基金supported by the Fundamental Research Funds for the Central Universities(No.2025JC008)the National Natural Science Foundation of China(grant number 52176105)+2 种基金the Science and Technology Project of Hebei Education Department-China(BJK2022063)the Hebei Natural Science Foundation-China(grant number E2025502038)the Funding Program for Cultivating Innovative Abilities of Graduate Students in Hebei Province of China(CXZZBS2025184).
文摘Biochar has been widely recognized as a promising solid CO_(2)adsorbent with economic and ecological benefits.Industrial CO_(2)emissions originate from diverse sources,while the pore structure and chemical functional groups of biochar exhibit varying degrees of influence on CO_(2)adsorption and separation performance under different adsorption conditions.Therefore,exploring the matching relationship between the physicochemical properties of biochar and its adsorption and separation performance at different adsorption conditions is essential for the development and optimization of carbon-based adsorbents.This study selected the high-performance extreme gradient boosting(XGB)algorithm from various algorithms and utilized it to develop CO_(2),N_(2),CH_(4)adsorption prediction models.Based on this,coupled prediction models were developed for CO_(2)/N_(2)and CO_(2)/CH_(4)adsorption selectivity.Furthermore,feature importance and partial dependence analysis were performed using SHAP values.The results indicate that during CO_(2)adsorption,the influence of the pore structure of biochar outweighs that of its chemical composition.Specifically,the pore structure of 0.4–0.6 nm is the most important property influencing CO_(2)adsorption at low and medium pressure(0–0.6 bar),and the pore structure of 0.6–0.8 nm,as well as the specific surface area contribute the most at high pressure(0.6–1 bar).During CO_(2)selective separation,the CO_(2)/N_(2)mixture is primarily separated through the selective adsorption of CO_(2)by nitrogen functional groups.In contrast,for CO_(2)/CH_(4)mixtures,pore structure<1 nm plays a more critical role in determining adsorption selectivity.In addition,molecular simulation studies further revealed the adsorption filling mechanisms of CO_(2)molecules within different pore sizes and functional groups.Finally,nitrogen-doped biochar was synthesized using de-alkalize lignin as the precursor,KOH as the activating agent,and urea as the nitrogen dopant.CO_(2),N_(2),and CH_(4)isothermal adsorption experiments were conducted,and the experimental results confirmed that the developed prediction models exhibit high accuracy(R^(2)>0.9).
基金Under the auspices of the National Key Research and Development Program of China(No.2024YFC3713102)。
文摘Groundwater level(GWL)is a key indicator used to accurately assess groundwater resources and form the foundation for ef-fective groundwater management.This paper integrates a Gate Recurrent Unit(GRU)model with a Multi-head Self-attention mechan-ism(MSAM-GRU)to simulate GWLs in both confined and unconfined aquifers simultaneously.The model innovatively captures the lag times between GWLs in the unconfined aquifer and precipitation,as well as between GWLs in the confined aquifer and the upper aquifer.We have assessed the effectiveness of the proposed model using a case study in the Beijing Plain,China from January 2005 to December 2020.With the consideration of lag times,the results indicated that the MSAM-GRU model exhibits a maximum 67%and 73%reduction in RMSE compared to the Attention mechanism-GRU(AM-GRU)and GRU model,respectively.MSAM-GRU model exhibited a 31%reduction in RMSE and a 0.12 increase in R^(2) compared to the same model that do not account for lag time.In Region I,the shortest lag time of GWL in the unconfined aquifer was two months,while that in the confined aquifer was three months,indicating a longer delayed response in the confined aquifer.MSAM-GRU model considering lag time,was then applied to simulate the GWLs in the unconfined aquifer under different scenarios and to analyze whether GWL fluctuations affect subway operations.The simulation res-ults showed that under the scenario 1,the GWL in the unconfined aquifer would rise above the depth of subway station floor,threaten-ing the operation of subways.This study can provide reliable technical support for the accurate simulation of GWLs in multi-aquifer systems.
基金supported by the Foundation for Science and Technology(FCT)under the project CDRSP funding(DOI:10.54499/UID/04044/2025 and ARISE funding(DOI:1054499/LA/P/0112/2020)the grant awarded to TP(10.54499/2020.09198.BD)+3 种基金the funding to JRD(10.54499/CEECINST/00060/2021/CP2902/CT0005)supported by INOV.AM-Inovação em Fabricação Aditiva,02-C05-i01.01-2022Nanofilm(CENTRO 2030-FEDER-01469100)Open access funding provided by FCT|FCCN (b-on).
文摘Central venous catheters(CVCs),which play a vital role in medical care and are widely utilized in intensive care units,are h ighly susceptible to microbial colonization,thus leading to serious catheter-related bloodstream infections and greatly increasing morbidity,mortality,and healthcare costs,accounting for 12%-25%of annual mortality in the USA.The corre sponding preventive measures include the use of antibiotic and antiseptic coatings,impregnated catheters,and maximally sterile barrier techniques,but they are often ineffective,particularly against biofilm formation and antibiotic-resistant bacteria.This review focuses on strategies for fabricating antimicrobial CVCs,e.g.,the use of antifouling materials,antimicrobial nanoparti cles(NPs),and surface functionalization,covering both commercially available solutions and those investigated.Additionally,w e explore the materials and processing technologies used to fabricate antimicrobial CVCs,emphasizing their advantages and challenges in industrial and clinical applications.Finally,we discuss the potential of inorganic NPs and the origin of their antimicrobial activity,providing insights for future advances in infection prevention that will help improve the patients’life quality.
基金supported by the National Natural Science Foundation of China(No.82204610)Qihang Talent Program(L2022046)+1 种基金the Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences(CI2021A04013)Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:Cyperi Rhizoma,derived from Cyperus rotundus L.,is a widely used medicinal herb in traditional Chinese medicine(TCM),with Shandong Province recognized as its geo-authentic habitat.However,the quality of Cyperi Rhizoma varies significantly across different regions,potentially influencing its therapeutic efficacy.This study investigates the influence of geographic origin on the chemical composition and overall quality of Cyperi Rhizoma.Methods:A comprehensive approach,including traditional quality assessment,GC-MS(g as c hromatography-m ass s pectrometry),RP-HPLC(r everse p hase h igh-p erformance l iquid c hromatography),and FT-IR(f ourier t ransform i nfrared s pectroscopy)techniques,was employed to analyze Cyperi Rhizoma samples from Shandong Province.These methods examined the physical appearance,chemical profile,and content variations,particularly focusing onα-cyperone.Results:Traditional quality assessments revealed noticeable differences in the external characteristics of the samples.GC-MS analysis identified a variety of unique chemical constituents,while RP-HPLC and FT-IR showed significant variations inα-cyperone content,with higher levels found in Shandong samples.Conclusion:These results demonstrate that geographic origin is a critical determinant of Cyperi Rhizoma quality,with Shandong specimens exhibiting superiorα-cyperone levels and characteristic phytochemical profiles.This validates the geo-authenticity concept in TCM and provides actionable data for developing evidence-based quality standards,suggesting that provenance should be prioritized in medicinal material selection and pharmacopeial specifications.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金National Research,Development and Innovation Fund of the Ministry of Culture and Innovation under the National Laboratories Program(National Tumor Biology Laboratory,Grant/Award Number:2022-2.1.1-NL-2022-00010)Senior Research Fellowship from National Health and Medical Research Council of Australia,Grant/Award Number:1156693+1 种基金Hungarian Thematic Excellence Program,Grant/Award Number:TKP2021-EGA-44Tour de Cure,Pioneering Grant,Grant/Award Number:RSP-253-18/19。
文摘Realistic models for cancer research representing disease progression that commensurately respond to therapeutics consistent with clinical observation are the holy grail for pre-clinical research and screening.Although such an ideal is elusive,well-characterized in vivo models facilitate our understanding of disease,progression,and therapeutic opportunities.Here,we characterize a commonly used syngeneic BALB/c mouse model of triple negative breast cancer(4T1)after establishing tumors in their flanks.Tumors developed at the subcutaneous injection site for all experimental mice and their volumes were monitored.We quantified a rare subset of breast cancer stemlike cells(CSCs),classified as CD44^(+)/CD24^(−)phenotypes in in vitro and ex vivo cell populations.Chromosome numbers in ex vivo metaphase cells were greater than cells cultured in vitro(89.4±3.4,range of 70-132 and 82.6±1.1,range of 70-128;respectively).Further,we observed different types of chromosome aberrations,including gap,deletion,exchange,interstitial deletion,terminal deletion,ring,dicentric,and Robertsonian translocations.For both sources of cells,the number of aberrations was dominated by deletions,terminal deletions,and Robertsonian translocations.Ex vivo cells exhibited greater prevalence of deletions and terminal deletions,whereas in vitro cells displayed more ring aberrations and Robertsonian translocations.In conclusion,we successfully characterized cancer cells from a syngeneic mouse model of breast cancer in terms of rare CSC proportion and a variety of chromosomal aberrations,which is useful for understanding tumor traits associated with cancer development and therapeutic action.The data act as a valuable resource for other studies using the 4T1 BALB/c model.
基金supported by the National Key Research and Development Program of China(2022YFC3204101 and 2023YFF0807202)the National Natural Science Foundation of China(U22A20570 and U2444221)+4 种基金the Youth Promotion Association of the Chinese Academy of Sciences(2021365)the Changsha Outstanding Innovative Youth Project,China(kq2305035)the Science,Technology and Innovation Platform Plan of Hunan Province,China(2022PT1010)the Major Scientific and Technological Projects of the Ministry of Water Resources,China(SKS-2022081)the Comprehensive Investigation and Potential Evaluation of Natural Resources Carbon Sink in Southern Hilly Region,China(DD20220880)。
文摘In floodplain wetlands,alterations in hydrological patterns resulting from climate change and human activities could potentially diminish the carbon sequestration capacity of the soils,thereby having a negative impact on global climate change.However,the magnitude of the influence of hydrological regime change on soil carbon remains inadequately monitored.To address this research gap,we collected 306 upper layer(0–20 cm)soil samples from the Dongting Lake floodplain between 2013 and 2022.The random forest(RF)algorithm was used to analyze the spatial distribution of soil organic carbon(SOC)in the upper soil layer of Dongting Lake floodplain and the impact of climate and hydrological changes in the past decade on surface SOC in the East Dongting Lake area was studied.In 2022,the SOC concentration of the Dongting Lake floodplain upper layer soil ranged from 3.34 to 17.67 g kg^(-1),averaging 10.43 g kg^(-1),with a corresponding SOC density of(2.65±0.49)kg m^(-2) and total SOC stock of 6.82 Tg C(2.87–13.48 Tg C).From 2013 to 2022,the SOC concentration of the upper soil layer of the East Dongting Lake area decreased from 18.37 to 10.82 g kg^(-1).This reduction could be attributed to climate and hydrological changes which reduce SOC input by reducing vegetation growth and accelerating SOC decomposition.Above 21.4 m elevation,the amount of SOC loss increased with elevation,the loss being related to the decline in Miscanthus community biomass and greater susceptibility of higher altitude areas to climate and hydrological changes.Our results highlight the need for strengthening wetland SOC management to increase SOC in the soils to help combat climate change.
基金funded by UK Research and Innovation(research which commenced between October 1,2020-March 31,2021,Grant ref MC_PC_20029April 1,2021-September 31,2022,Grant ref MC_PC_20058)supported by the National Institute for Health Research(NIHR)Leicester Biomedical Research Centre and NIHR Applied Research CollaborationEast Midlands(ARC-EM)。
文摘Background:Recent evidence suggests continuous bouts of physical activity(PA)are associated with longevity.We hypothesized the risk of mortality would be lower when the most active minutes of the day were in a continuous bout.Methods:PA was assessed using accelerometery in UK Biobank participants.The intensity of the most active continuous(MXCONT)and accumulated(MX)X min of the day,and their ratio(MXRATIO=MXCONT/MX),were determined.MXRATIO indicates how the most active minutes of the day are accumulated,ranging from a single continuous bout through to sporadic accumulation spread across the day.Durations(X)considered ranged from 1 to 20 min.The outcome was mortality.Results:In total,94,541 participants(56.5% female)were included.Over a median(interquartile range)follow-up of 6.9(6.3,7.4)years,2649(2.8%)deaths occurred.Intensity moderated the association between how the most active minutes of the day were accumulated and mortality risk,expressed relative to sporadically accumulated moderate PA.If the most active minutes were of moderate intensity,the risk of mortality was halved for continuous compared to sporadic accumulation,irrespective of duration;if the most active minutes were of vigorous intensity,a continuous bout was associated with the lowest risk for durations under 5 min(e.g.,3 min:hazard ratio(HR)=0.27,95% confidence interval(95%CI):0.21-0.34),while sporadic accumulation was associated with the lowest risk for durations beyond 5 min(HR=0.11,95%CI:0.08-0.15 for the most active 20 min).Conclusion:Optimal PA patterns for reducing mortality differ by intensity and duration.For moderate-intensity PA,a lower mortality risk may be optimized by prioritizing continuous PA for up to 20 min.However,for vigorous-intensity PA,multiple short bouts(<5 min)may be optimal.This suggests tailored PA recommendations may enhance longevity benefits.
文摘Background:Cupping therapy(CT),an ancient practice revived in modern sports medicine,offers potential benefits for athlete recovery and performance.Distinctions between wet CT(WCT)and dry CT(DCT)in sports science focus on their effects on recovery metrics,particularly how they influence sleep quality,perceived wellness,and athletic performance.Despite anecdotal evidence of its efficacy,rigorous comparative studies are scarce.Objective:This study aimed to evaluates and compare the effects of WCT and DCT on endurance,perceived wellness,exertion levels,and sleep quality among young,active males,addressing the gap in the literature regarding CT's efficacy in sports performance and recovery.Methods:Thirty-two amateur runners were randomly divided into two groups:one followed WCT sessions and the other followed DCT sessions.The study assessed the interventions'impacts on endurance performance(Yo-Yo intermittent recovery test),sleep quality(Pittsburgh Sleep Quality Index),and perceived exertion(Borg CR10 Scale).Heart rate was measured using a Polar H10 sensor to gauge physiological responses during physical tests.Results:Significant improvements were observed in the WCT group for sleep latency(%change=-82.31%;interaction group×time p=0.006;Cohen's d=0.74)and sleep disturbance(%change=-68.70%;interaction group×time p<0.001;Cohen's d=1.09),suggesting enhanced sleep quality(global score;%change=-52.81;interaction group×time p=0.004;Cohen's d=0.77).However,no significant differences were found in direct performance metrics(distance,maximal heart rate,maximal oxygen uptake)between WCT and DCT groups.These findings highlight WCT's potential as a recovery aid,particularly through improved sleep,without directly influencing endurance performance outcomes.Conclusion:WCT may serve as an effective ergogenic aid for athletes by potentially improving sleep quality and reducing perceived exertion,thus contributing indirectly to performance through enhanced recovery.
基金part of the EU consortium DCog Plast ‘Diet Cognition and Plasticity” funded by the Joint Programming Initiative “A Health Diet for a Healthy Life”(JPI-HDHL) via the BMWFW (BMWFW-10.420/0009-WF/V/3c/2015 and the Medical Research Council UK:MR/N030087/1)(to LA and ST)supported by the PMU-FFF Research Fund (A-16/01/019-AIG)+9 种基金BA by the PMU-Research and Innovation Fund (PMU-RIF)(project 2023-PRE-008-Altendorfer)supported by the Center for Urban Mental Healthby Alzheimer Nederlandthe Zon MW Program Mechanisms Of DEMentia (MODEM)by the Gravitation program iCNS of the Dutch Research Council (NWO)supported by Grant PID2020-114921RB-C21Maria de Maeztu Unit of Excellence grant CEX2021-001234-M funded by MCIU/AEI/and CIBERFESCB16/10/00269, from the Instituto de Salud Carlos III all of them by “ERDF A way of making Europe”the Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687ICREA Award
文摘In Alzheimer’s disease,microglial phagocytosis is engaged in the pathogenesis as it clears abnormal protein accumulations,debris,and apoptotic cells in the early stages of Alzheimer’s disease,but fuels neuroinflammation and accelerates disease progression in later stages.In vivo parabiosis experiments in aged animals have demonstrated that blood-born factors modulate synaptic plasticity,neurogenesis,and microglial responses.We hypothesize that peripheral factors can modulate microglial function and thereby possibly influence Alzheimer’s disease pathology.The objective of this study is to investigate the effects of Alzheimer’s disease serum on microglial phagocytosis.Here,we use an immortalized human microglial cell line in an in vitro parabiosis assay to investigate the impact of the serum from individuals diagnosed with Alzheimer’s disease(n=30)and age-matched controls(n=30)(PRODEM study)on microglial phagocytosis.Exposure to Alzheimer’s disease serum increased microglial phagocytic uptake of pH-sensitive fluorescent particles and downregulated expression of the lysosomal master regulator transcription factor EB(TFEB)and of ATPase H^(+)transporting lysosomal V1 subunit B2(ATP6V1B2),a component of the vacuolar ATPase.To identify serum components that may relate to changes in phagocytosis,serum samples of the Three-City Study(3C Study)were used.In the 3C Study,blood samples were collected up to 12 years before the onset of cognitive decline or dementia and their serum metabolome is well-defined.Microglia exposed to the serum of future Alzheimer’s disease patients from the 3C Study displayed an increased phagocytic uptake compared with the serum of matched controls,depending on the presence of the apolipoprotein Eε4 allele in the Alzheimer’s disease patients.Furthermore,microglial phagocytosis correlated inversely with serum levels of the omega-3 fatty acid eicosapentaenoic acid.We confirmed this inverse correlation between eicosapentaenoic acid and phagocytosis in the serum samples of the PRODEM cohort.In addition,in vitro testing of eicosapentaenoic acid on microglial phagocytosis showed a concentration-dependent decrease in phagocytic uptake.In conclusion,following incubation with Alzheimer’s disease blood serum,we observed increased microglial phagocytic uptake and the downregulation of TFEB and ATP6V1B2,possibly indicating lysosomal dysfunction.Furthermore,microglial phagocytosis was inversely correlated with serum eicosapentaenoic acid levels,suggesting an important role for dietary eicosapentaenoic acid in microglial function.
