Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellul...Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.展开更多
Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson...Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.展开更多
Date palm(Phoenix dactylifera L.)seeds,often discarded as by-products during date fruit processing,represent approximately 6-20%of the fruit’s mass depending on cultivar and maturity stage.Although traditionally used...Date palm(Phoenix dactylifera L.)seeds,often discarded as by-products during date fruit processing,represent approximately 6-20%of the fruit’s mass depending on cultivar and maturity stage.Although traditionally used for producing activated charcoal and in environmental remediation,their pharmacological potential remains underexplored.This study aimed to evaluate the chemical composition,biological activity,and potential commercial value of seeds from four widely consumed Saharan cultivars(Assiane,Boufegouss,Aziza,and Majhoul)collected in the Figuig region.Soxhlet extraction was employed to obtain seed extracts,which were subsequently characterized by qualitative and quantitative phytochemical screening.The analyses revealed the presence of polyphenols,flavonoids,terpenoids,steroids,alkaloids,and other secondary metabolites.The Aziza and Boufegouss varieties were particularly rich in flavonoids(82.09-139.61 mg quercetin equivalents/100 g dry matter)and total polyphenols(69.81-1183.96 mg gallic acid equivalents/100 g dry matter).Mineral profiling confirmed the occurrence of essential trace elements,including Zn,Cu,Fe,and Co.To investigate their antidiabetic potential,in vitro assays ofα-glucosidase andα-amylase inhibition were performed.Acetone extracts demonstrated significant inhibitory activity against both enzymes,suggesting a promising role of P.dactylifera seed extracts as natural agents for the management of type 2 diabetes mellitus.展开更多
The effects of initial spin orientation on the final electron beam polarization in laser wakefield acceleration in a pre-polarized plasma are investigated theoretically and numerically.From the results of variation of...The effects of initial spin orientation on the final electron beam polarization in laser wakefield acceleration in a pre-polarized plasma are investigated theoretically and numerically.From the results of variation of the initial spin direction,the spin dynamics of the electron beam are found to depend on the self-injection mechanism.The effects of wakefields and laser fields are studied using test particle dynamics and particle-in-cell simulations based on the Thomas-Bargmann-Michel-Telegdi equation.Compared with transverse injection,longitudinal injection is found to be preferable for obtaining a highly polarized electron beam.展开更多
The research findings on the ground motion and liquefaction potential analyses during the 2018 Great Indonesia Earthquake(M_(w)7.5)are significant and crucial.The earthquake triggered soil-structure damage due to liqu...The research findings on the ground motion and liquefaction potential analyses during the 2018 Great Indonesia Earthquake(M_(w)7.5)are significant and crucial.The earthquake triggered soil-structure damage due to liquefaction.This study,which thoroughly investigated four sites at Palu,was conducted by performing a comprehensive ground motion parameter analysis.The ground motion characteristics were presented and justified,particularly for the most impacted direction.Ground motion predictions were analysed to define the spectral accelerations,and matching spectral accelerations were conducted to produce ground motions for each site.Non-linear seismic ground response analysis based on the hyperbolic model of pressure pressure-dependent was performed to investigate cyclic soil behaviour.The results revealed that ground motion is crucial in significant soil damage,and the earthquake energy could trigger deep liquefaction.As the most significant ground motion,the vertical ground motion is essential in determining deep liquefaction.The discussion on the impact of liquefaction based on the results of the numerical analysis is presented.Significant ground motion with a longer duration could have a substantial impact on deep liquefaction in the study area.These findings depict how the 2018 Indonesia Earthquake(M_(w)7.5)triggered a mega-liquefaction in Palu City.The results could enhance the understanding of the importance of seismic hazard assessment.It is recommended that site investigation and soil improvement should be planned to counteract liquefaction damage before construction.This study also suggests conducting seismic hazard assessments for city development to minimise the potential disaster impact in the study area.展开更多
Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely us...Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely used in fields such as injection molding,die casting,and stamping dies.Adding reinforcing particles into steel is an effective means to improve its performance.Nb/18Ni300 composites were fabricated by LPBF using two kinds of Nb powders with different particle sizes,and their microstructures and properties were studied.The results show that the unmelted Nb particles are uniformly distributed in the 18Ni300 matrix and the grains are refined,which is particularly pronounced with fine Nb particles.In addition,element diffusion occurs between the particles and the matrix.The main phases of the base alloy are α-Fe and a small amount of γ-Fe.With the addition of Nb,part of the α-Fe is transformed into γ-Fe,and unmelted Nb phases appear.The addition of Nb also enhances the hardness and wear resistance of the composites but slightly reduces their tensile properties.After aging treatment,the molten pools and grain boundaries become blurred,grains are further refined,and the interfaces around the particles are thinned.The aging treatment also promotes the formation of reverted austenite.The hardness,ultimate tensile strength,and volumetric wear rate of the base alloy reach 51.9 HRC,1704 MPa,and 17.8×10^(-6) mm^(3)/(N·m),respectively.In contrast,the sample added with fine Nb particles has the highest hardness(56.1 HRC),ultimate tensile strength(1892 MPa)and yield strength(1842 MPa),and the volume wear rate of the sample added with coarse Nb particles is reduced by 90%to 1.7×10^(-6) mm^(3)/(N·m).展开更多
After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the tim...After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.展开更多
Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewa...Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at...Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.展开更多
With the increasing complexity of malware attack techniques,traditional detection methods face significant challenges,such as privacy preservation,data heterogeneity,and lacking category information.To address these i...With the increasing complexity of malware attack techniques,traditional detection methods face significant challenges,such as privacy preservation,data heterogeneity,and lacking category information.To address these issues,we propose Federated Dynamic Prototype Learning(FedDPL)for malware classification by integrating Federated Learning with a specifically designed K-means.Under the Federated Learning framework,model training occurs locally without data sharing,effectively protecting user data privacy and preventing the leakage of sensitive information.Furthermore,to tackle the challenges of data heterogeneity and the lack of category information,FedDPL introduces a dynamic prototype learning mechanism,which adaptively adjusts the clustering prototypes in terms of position and number.Thus,the dependency on predefined category numbers in typical K-means and its variants can be significantly reduced,resulting in improved clustering performance.Theoretically,it provides a more accurate detection of malicious behavior.Experimental results confirm that FedDPL excels in handling malware classification tasks,demonstrating superior accuracy,robustness,and privacy protection.展开更多
Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contribu...Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].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
The thermal conductivity of nanofluids is an important property that influences the heat transfer capabilities of nanofluids.Researchers rely on experimental investigations to explore nanofluid properties,as it is a n...The thermal conductivity of nanofluids is an important property that influences the heat transfer capabilities of nanofluids.Researchers rely on experimental investigations to explore nanofluid properties,as it is a necessary step before their practical application.As these investigations are time and resource-consuming undertakings,an effective prediction model can significantly improve the efficiency of research operations.In this work,an Artificial Neural Network(ANN)model is developed to predict the thermal conductivity of metal oxide water-based nanofluid.For this,a comprehensive set of 691 data points was collected from the literature.This dataset is split into training(70%),validation(15%),and testing(15%)and used to train the ANN model.The developed model is a backpropagation artificial neural network with a 4–12–1 architecture.The performance of the developed model shows high accuracy with R values above 0.90 and rapid convergence.It shows that the developed ANN model accurately predicts the thermal conductivity of nanofluids.展开更多
This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a ...This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.展开更多
Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-...Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.展开更多
Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended...Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended conjugation is designed and synthesized,named NaPh-4PACz.Compared to Ph-4PACz,NaPh-4PACz exhibits a larger adsorption energy with the ITO substrate,enabling the formation of a more uniform and dense film,thereby preventing direct contact between the perovskite and ITO.Additionally,NaPh-4PACz also has a stronger interaction with the perovskite,which can reduce buried interface defects and suppress non-radiative recombination.Consequently,NaPh-4PACz-based devices achieved a power conversion efficiency of 25.48%due to their interfacial“adhesive”ability.Importantly,the stability of the NaPh-4PACz-based devices was significantly improved.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
文摘Alzheimer’s disease(AD)is a complex,progressive neurodegenerative disorder and the leading cause of dementia worldwide.It is characterized by the accumulation of extracellular amyloid-beta(Aβ)plaques and intracellular tau neurofibrillary tangles,leading to synaptic dysfunction,neuronal loss,and cognitive decline.These pathological changes can begin decades before clinical symptoms emerge,highlighting the critical need for early,accessible,and accurate diagnostic tools.
基金supported by the Spanish Ministry of Science and Innovation via a doctoral grant[FPU22/03656].supported by the Spanish Ministry of Science and Innovation(PID2022-137963OB-I00)Generalitat de Catalunya(2021-SGR-00635 AGAUR)+1 种基金CERCA Programme(Generalitat de Catalunya)by ICREA,ICREA-Academia 2020(to SV)。
文摘Alpha-synuclein and Parkinson's disease:Neuronal damage and inflammation caused by the aggregation of alpha-synuclein(α-syn)are central to a group of disorders known as synucleopathies,which includes Parkinson's disease(PD),dementia with Lewy bodies,and multiple system atrophy,among others.PD,the most common synucleinopathy,is the second most prevalent neurodegenerative disease after Alzheimer's disease,and it is the fastest growing.Its primary hallmark is the degeneration of dopaminergic neurons in the substantia nigra pars compacta,disrupting the communication with the striatum.
文摘Date palm(Phoenix dactylifera L.)seeds,often discarded as by-products during date fruit processing,represent approximately 6-20%of the fruit’s mass depending on cultivar and maturity stage.Although traditionally used for producing activated charcoal and in environmental remediation,their pharmacological potential remains underexplored.This study aimed to evaluate the chemical composition,biological activity,and potential commercial value of seeds from four widely consumed Saharan cultivars(Assiane,Boufegouss,Aziza,and Majhoul)collected in the Figuig region.Soxhlet extraction was employed to obtain seed extracts,which were subsequently characterized by qualitative and quantitative phytochemical screening.The analyses revealed the presence of polyphenols,flavonoids,terpenoids,steroids,alkaloids,and other secondary metabolites.The Aziza and Boufegouss varieties were particularly rich in flavonoids(82.09-139.61 mg quercetin equivalents/100 g dry matter)and total polyphenols(69.81-1183.96 mg gallic acid equivalents/100 g dry matter).Mineral profiling confirmed the occurrence of essential trace elements,including Zn,Cu,Fe,and Co.To investigate their antidiabetic potential,in vitro assays ofα-glucosidase andα-amylase inhibition were performed.Acetone extracts demonstrated significant inhibitory activity against both enzymes,suggesting a promising role of P.dactylifera seed extracts as natural agents for the management of type 2 diabetes mellitus.
基金supported by the National Natural Science Foundation of China(Grant Nos.11804348,11775056,11975154,12225505,and 12405281)the Science Challenge(Project No.TZ2018005)+2 种基金supported by the Shanghai Pujiang Program(Grant No.23PJ1414600)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB0890203)supported by the Accelerator Technology Helmholtz Infrastructure consortium ATHENA.
文摘The effects of initial spin orientation on the final electron beam polarization in laser wakefield acceleration in a pre-polarized plasma are investigated theoretically and numerically.From the results of variation of the initial spin direction,the spin dynamics of the electron beam are found to depend on the self-injection mechanism.The effects of wakefields and laser fields are studied using test particle dynamics and particle-in-cell simulations based on the Thomas-Bargmann-Michel-Telegdi equation.Compared with transverse injection,longitudinal injection is found to be preferable for obtaining a highly polarized electron beam.
基金The World Class Professor(WCP)Program of the Directorate of Resources,Directorate General of Higher Education,Ministry of Education and Culture in 2023 supports this studythe JAPAN-ASEAN Science and Technology Innovation Platform(JASTIP-WP4)+3 种基金the University of Bengkulu's International Collaboration Research Fund(2183/UN30.15/LT/2019)for partial fundingthe C2F Fund for Postdoctoral Fellowship from Chulalongkorn Universitythe Thailand Science Research and Innovation Fund Chulalongkorn University(DISF68210001)the National Research Council of Thailand(N42A670572)。
文摘The research findings on the ground motion and liquefaction potential analyses during the 2018 Great Indonesia Earthquake(M_(w)7.5)are significant and crucial.The earthquake triggered soil-structure damage due to liquefaction.This study,which thoroughly investigated four sites at Palu,was conducted by performing a comprehensive ground motion parameter analysis.The ground motion characteristics were presented and justified,particularly for the most impacted direction.Ground motion predictions were analysed to define the spectral accelerations,and matching spectral accelerations were conducted to produce ground motions for each site.Non-linear seismic ground response analysis based on the hyperbolic model of pressure pressure-dependent was performed to investigate cyclic soil behaviour.The results revealed that ground motion is crucial in significant soil damage,and the earthquake energy could trigger deep liquefaction.As the most significant ground motion,the vertical ground motion is essential in determining deep liquefaction.The discussion on the impact of liquefaction based on the results of the numerical analysis is presented.Significant ground motion with a longer duration could have a substantial impact on deep liquefaction in the study area.These findings depict how the 2018 Indonesia Earthquake(M_(w)7.5)triggered a mega-liquefaction in Palu City.The results could enhance the understanding of the importance of seismic hazard assessment.It is recommended that site investigation and soil improvement should be planned to counteract liquefaction damage before construction.This study also suggests conducting seismic hazard assessments for city development to minimise the potential disaster impact in the study area.
基金Key-Area Research and Development Program of Guangdong Province(2023B0909020004)Project of Innovation Research Team in Zhongshan(CXTD2023006)+1 种基金Natural Science Foundation of Guangdong Province(2023A1515011573)Zhongshan Social Welfare Science and Technology Research Project(2024B2022)。
文摘Laser powder bed fusion(LPBF)is highly suitable for forming 18Ni300 mold steel,thanks to its excellent capability in manufacturing complex shapes and outstanding capacity for regulating microstructures.It is widely used in fields such as injection molding,die casting,and stamping dies.Adding reinforcing particles into steel is an effective means to improve its performance.Nb/18Ni300 composites were fabricated by LPBF using two kinds of Nb powders with different particle sizes,and their microstructures and properties were studied.The results show that the unmelted Nb particles are uniformly distributed in the 18Ni300 matrix and the grains are refined,which is particularly pronounced with fine Nb particles.In addition,element diffusion occurs between the particles and the matrix.The main phases of the base alloy are α-Fe and a small amount of γ-Fe.With the addition of Nb,part of the α-Fe is transformed into γ-Fe,and unmelted Nb phases appear.The addition of Nb also enhances the hardness and wear resistance of the composites but slightly reduces their tensile properties.After aging treatment,the molten pools and grain boundaries become blurred,grains are further refined,and the interfaces around the particles are thinned.The aging treatment also promotes the formation of reverted austenite.The hardness,ultimate tensile strength,and volumetric wear rate of the base alloy reach 51.9 HRC,1704 MPa,and 17.8×10^(-6) mm^(3)/(N·m),respectively.In contrast,the sample added with fine Nb particles has the highest hardness(56.1 HRC),ultimate tensile strength(1892 MPa)and yield strength(1842 MPa),and the volume wear rate of the sample added with coarse Nb particles is reduced by 90%to 1.7×10^(-6) mm^(3)/(N·m).
基金supported by the National Key Research and Development Program of China,No.2023YFC3603705(to DX)the National Natural Science Foundation of China,No.82302866(to YZ).
文摘After spinal cord injury,impairment of the sensorimotor circuit can lead to dysfunction in the motor,sensory,proprioceptive,and autonomic nervous systems.Functional recovery is often hindered by constraints on the timing of interventions,combined with the limitations of current methods.To address these challenges,various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.Notably,neuromodulation has garnered considerable attention for its potential to enhance nerve regeneration,provide neuroprotection,restore neurons,and regulate the neural reorganization of circuits within the cerebral cortex and corticospinal tract.To improve the effectiveness of these interventions,the implementation of multitarget early interventional neuromodulation strategies,such as electrical and magnetic stimulation,is recommended to enhance functional recovery across different phases of nerve injury.This review concisely outlines the challenges encountered following spinal cord injury,synthesizes existing neurostimulation techniques while emphasizing neuroprotection,repair,and regeneration of impaired connections,and advocates for multi-targeted,task-oriented,and timely interventions.
基金supported by the Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences(CI2021A04013)the National Natural Science Foundation of China(82204610)+1 种基金the Qihang Talent Program(L2022046)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ15-YQ-041 and L2021029).
文摘Background:The medicinal material known as Os Draconis(Longgu)originates from fossilized remains of ancient mammals and is widely used in treating emotional and mental conditions.However,fossil resources are nonrenewable,and clinical demand is increasingly difficult to meet,leading to a proliferation of counterfeit products.During prolonged geological burial,static pressure from the surrounding strata severely compromises the microstructural integrity of osteons in Os Draconis,but Os Draconis still largely retains the structural features of mammalian bone.Methods:Using verified authentic Os Draconis samples over 10,000 years old as a baseline,this study summarizes the ultrastructural characteristics of genuine Os Draconis.Employing electron probe microanalysis and optical polarized light microscopy,we examined 28 batches of authentic Os Draconis and 31 batches of counterfeits to identify their ultrastructural differences.Key points for ultrastructural identification of Os Draconis were compiled,and a new identification approach was proposed based on these differences.Results:Authentic Os Draconis exhibited distinct ultrastructural markers:irregularly shaped osteons with traversing fissures,deformed/displaced Haversian canals,and secondary mineral infill(predominantly calcium carbonate).Counterfeits showed regular osteon arrangements,absent traversal fissures,and homogeneous hydroxyapatite composition.Lab-simulated samples lacked structural degradation features.EPMA confirmed calcium carbonate infill in fossilized Haversian canals,while elemental profiles differentiated lacunae types(void vs.mineral-packed).Conclusion:The study established ultrastructural criteria for authentic Os Draconis identification:osteon deformation,geological fissures penetrating bone units,and heterogenous mineral deposition.These features,unattainable in counterfeits or modern processed bones,provide a cost-effective,accurate identification method.This approach bridges gaps in TCM material standardization and supports quality control for clinical applications.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金supported by Postdoc Fellowship from the Foundation for Angelman Syndrome Therapeutics(FT2022-005 to JM,PD2023-001 to XY,and FT2024-001 to YAH)STTR R41 MH118747(to JM)。
文摘Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.
基金supported by the National Natural Science Foundation of China under Grant No.62162009the Key Technologies R&D Program of He’nan Province under Grant No.242102211065+2 种基金the Postgraduate Education Reform and Quality Improvement Project of Henan Province under Grant Nos.YJS2025GZZ36,YJS2024AL112,and YJS2024JD38the Innovation Scientists and Technicians Troop Construction Projects of Henan Province under Grant No.CXTD2017099the Scientific Research Innovation Team of Xuchang University under Grant No.2022CXTD003.
文摘With the increasing complexity of malware attack techniques,traditional detection methods face significant challenges,such as privacy preservation,data heterogeneity,and lacking category information.To address these issues,we propose Federated Dynamic Prototype Learning(FedDPL)for malware classification by integrating Federated Learning with a specifically designed K-means.Under the Federated Learning framework,model training occurs locally without data sharing,effectively protecting user data privacy and preventing the leakage of sensitive information.Furthermore,to tackle the challenges of data heterogeneity and the lack of category information,FedDPL introduces a dynamic prototype learning mechanism,which adaptively adjusts the clustering prototypes in terms of position and number.Thus,the dependency on predefined category numbers in typical K-means and its variants can be significantly reduced,resulting in improved clustering performance.Theoretically,it provides a more accurate detection of malicious behavior.Experimental results confirm that FedDPL excels in handling malware classification tasks,demonstrating superior accuracy,robustness,and privacy protection.
基金supported by the Ministry of Science and Technology of the People’s Republic of China(2022YFD1800400).
文摘Staphylococcus aureus(S.aureus)is the third most common pathogen causing 10.6%of bacterial foodborne illnesses in China in 2021[1].Heat-stable Staphylococcal Enterotoxins(SEs)produced by S.aureus are the main contributors to staphylococcal food poisoning(SFP),causing vomiting,diarrhea,abdominal pain,headache,muscle cramps,and other acute gastroenteritis symptoms.More than 25 SEs and staphylococcal enterotoxin-like toxins(SE/s)have been described and which together comprise a superfamily of pyrogenic toxin superantigens(SAgs)[2].
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.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2021R1A6A1A10044950).
文摘The thermal conductivity of nanofluids is an important property that influences the heat transfer capabilities of nanofluids.Researchers rely on experimental investigations to explore nanofluid properties,as it is a necessary step before their practical application.As these investigations are time and resource-consuming undertakings,an effective prediction model can significantly improve the efficiency of research operations.In this work,an Artificial Neural Network(ANN)model is developed to predict the thermal conductivity of metal oxide water-based nanofluid.For this,a comprehensive set of 691 data points was collected from the literature.This dataset is split into training(70%),validation(15%),and testing(15%)and used to train the ANN model.The developed model is a backpropagation artificial neural network with a 4–12–1 architecture.The performance of the developed model shows high accuracy with R values above 0.90 and rapid convergence.It shows that the developed ANN model accurately predicts the thermal conductivity of nanofluids.
文摘This review is composed of three main parts each of which is written by well-known top specialists that have been,in a way or other,also the main participants of the majority of the developments reported.Thus,after a general part covering the grand lines and more in-depth views of more recent tannin,lignin,carbohydrate and soy bioadhesives,somemix of the other bio raw materials with soy protein and soy flour and some other differently sourced bioadhesives for wood,this review presents a more in-depth part on starch-based wood adhesives and a more indepth part covering plant protein-based adhesives.It must be kept in mind that the review is focused on completely or almost completely biosourced adhesives,the fashionable adhesives derived from mixes of biosourced materials with synthetic resins having been intentionally excluded.This choice was made as the latter constitute only an intermediate interval,possibly temporary if even for a somewhat long times,towards a final full bioeconomy of scale in this field.This review also focuses on more recent results,mainly obtained in the last 10–20 years,thus on adhesive formulations really innovative and sometimes even non-traditional.In all these fields there is still a lot of possibility of innovation for relevant formulation as this field is still in rapid growth.
文摘Objective:Artemether is a semi-synthetic derivative of artemisinin and is widely used in the treatment of Plasmodium(P.)falciparum malaria.This study aimed to characterize the safety profile of artemether based on 15-year data retrived from FDA adverse event reporting system(FAERS).Methods:This is a retrospective analysis on 15-year data of artemether-related adverse effects(AEs)retrieved from the FAERS.AEs were classified according to System Organ Class(SOC)and Preferred Terms(PT).Signal detection was performed using Reporting Odds Ratios(ROR),Proportional Reporting Ratios(PRR),and Empirical Bayes Geometric Mean(EBGM).Stratified analyses examined the impact of demographic factors such as sex,age,and time-to-onset.Temporal patterns and associated risk factors were also investigated.Results:Haemolytic anaemia and haemolysis emerged as the most frequently reported AEs,exhibiting significantly elevated RORs(males:ROR 381.36,95%CI 247.06-588.60;females:ROR 455.11,95%CI 286.43-723.12).Sex-specific differences were evident,with females showing a higher incidence of reproductive-related AEs,including spontaneous abortion and premature labour.Temporal trend analysis revealed that the majority of AEs occurred within the first 30 days after the initiation of artemether administration,indicating a rapid onset.The most affected SOCs were blood and lymphatic system disorders and hepatobiliary disorders.Conclusions:Artemether is associated with a notable frequency of early-onset AEs,particularly hematological and hepatobiliary disorders.The observed sex-specific vulnerability to reproductive AEs highlights the need for sex-conscious clinical approaches.Enhanced post-treatment monitoring and further investigations into the drug’s pharmacokinetics and mechanistic pathways are recommended.
基金supported by the National Natural Science Foundation of China(61904053,22279033)the National Key Research and Development Program of China(2023YFB4204502)+2 种基金the 111 Project(B16016)the Fundamental Research Funds for the Central Universities(2025MS043)the Special Foundation for Carbon Peak Carbon Neutralization Technology Innovation Program of Jiangsu Province(BE2022026).
文摘Molecular tailoring of self-assembled hole-transporting monolayers(SAMs)has been proven as an efficient approach for improving the device performance of inverted perovskite solar cells.Herein,a novel SAM with extended conjugation is designed and synthesized,named NaPh-4PACz.Compared to Ph-4PACz,NaPh-4PACz exhibits a larger adsorption energy with the ITO substrate,enabling the formation of a more uniform and dense film,thereby preventing direct contact between the perovskite and ITO.Additionally,NaPh-4PACz also has a stronger interaction with the perovskite,which can reduce buried interface defects and suppress non-radiative recombination.Consequently,NaPh-4PACz-based devices achieved a power conversion efficiency of 25.48%due to their interfacial“adhesive”ability.Importantly,the stability of the NaPh-4PACz-based devices was significantly improved.
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.
