The authors employed inappropriate search keywords and strategies in their published bibliometric papers within volume 29 of the World Journal of Gastroenterology.The comment highlights the identified issues,provides ...The authors employed inappropriate search keywords and strategies in their published bibliometric papers within volume 29 of the World Journal of Gastroenterology.The comment highlights the identified issues,provides evidence,and suggests improved study methodologies.Subsequent results with more appro-priate search strategies were presented to address the shortcomings.展开更多
The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,p...The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.展开更多
Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chron...Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).展开更多
Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via...Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via decarboxylation in mitochondria or from ethanolamine via the cytidine diphosphate-ethanolamine pathway in the endoplasmic reticulum,phosphatidylethanolamine that resides in mitochondria is preferentially produced locally and is distinct and separate from the pool of phosphatidylethanolamine made in the endoplasmic reticulum.Mitochondria-derived phosphatidylethanolamine is not only essential for mitochondrial integrity but also is exported to other organelles to fulfill diverse cellular functions.Neurons are highly enriched with phosphatidylethanolamine,and the importance of phosphatidylethanolamine metabolism in neuronal health has recently been recognized following its reported links to Alzheimer’s disease,Parkinson’s disease,and hereditary spastic paraplegia,among other neurological disorders.Indeed,disturbances in mitochondrial function and phosphatidylethanolamine metabolism and the resulting neuronal dysfunction are the common features of individuals suffering from these diseases,highlighting the great importance of maintaining proper phosphatidylethanolamine homeostasis in neurons.In this review,we summarize the current knowledge of phosphatidylethanolamine metabolism and its role in neuronal function with a special emphasis on the phosphatidylethanolamine biosynthetic pathway in mitochondria.We then review findings on how phosphatidylethanolamine biosynthesis is affected in major neurodegenerative diseases.Finally,we highlight promising future research areas that will help advance the understanding of neuronal phosphatidylethanolamine mechanisms and identify phosphatidylethanolamine-targeted therapeutic strategies for combating such brain diseases.展开更多
Using multi-source reanalysis data,this study examines the relationship between the tropical Pacific-Atlantic SST Dipole Mode(TPA-DM)and summer precipitation in North China(NCSP)on the interannual timescale during the...Using multi-source reanalysis data,this study examines the relationship between the tropical Pacific-Atlantic SST Dipole Mode(TPA-DM)and summer precipitation in North China(NCSP)on the interannual timescale during the period of 1979-2022.The results show that the TPA-DM,the dominant pattern of interannual variability in the tropical Pacific and Atlantic regions,exhibits a significant negative correlation with NCSP.The positive phase of TPA-DM induces subsidence over the Maritime Continent through a zonal circulation pattern,which initiates a Pacific-Japan-like wave train along the East Asian coast.The circulation anomalies lead to moisture deficits and convergence subsidence over North China,leading to below-normal rainfall.Further analysis reveals that cooler SST in the Southern Tropical Atlantic facilitates the persistence of the TPA-DM by stimulating the anomalous Walker circulation associated with wind-evaporation-SST-convection feedback.展开更多
Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation ...Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation of water.Here,we found that phytoplankton photosynthesis elevated ambient water δ^(18)O and δD values,a conclusion supported by a large-scale survey across extensive spatiotemporal environmental gradients and further confirmed by a laboratory culture experiment.This biological effect depended on phytoplankton biomass and light utilization efficiency and could result in a deviation of at least 16.7% in the slope of the water δD-δ^(18)O regression line.We termed this phenomenon the“biological evaporation effect”.Given the potential universality of this effect across aquatic ecosystems,our findings challenge the conventional paradigm in isotope hydrology.展开更多
Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SD...Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SDAT)has emerged as a promising area of research.This perspective summarizes the recent NPT-based sonosensitizers in SDAT.Currently,common NPT-based sonosensitizers include curcumin,chlorophyll derivatives,hypericin,and berberine.Compared with other sonosensitizers,natural sources of NPT-based sonosensitizers with reactive oxide species production performance under ultrasound conditions,low biotoxicity,and other additional biological activity make them have application prospects in bacterial removal.Finally,the potential benefits and challenges of NPT-based nanosonosensitizers were also discussed.展开更多
The Pliocene-Pleistocene transition(3.0-2.5 million years ago,Ma)was a critical period during which the Arctic ice sheets expanded extensively and intensified,with the establishment of a permanent ice sheet on Greenla...The Pliocene-Pleistocene transition(3.0-2.5 million years ago,Ma)was a critical period during which the Arctic ice sheets expanded extensively and intensified,with the establishment of a permanent ice sheet on Greenland marking the onset of a bipolar“icehouse”climate state.This interval,characterized by atmospheric CO_(2) concentrations between pre-industrial and modern levels(~280-400 ppmv),provides a critical time window for understanding ice-sheet response to external forcing.Using a high-resolution climate model and a 3D thermomechanical ice sheet model,we simulate the Greenland Ice Sheet(GrIS)volume evolution under different CO_(2) scenarios and analyze its periodic behavior during this period.Our results show that when the GrIS volume was small,its variability was strongly paced by 65°N summer insolation.As the ice sheet grew,its response shifted,becoming increasingly dominated by the obliquity cycle.The GrIS volume reconstruction,consistent with ice-rafted debris records,indicates that after approximately 2.7 Ma,the expanded GrIS exhibited enhanced suborbital to millennial-scale signals and greater ice dynamical variability-a pattern echoing the amplified millennial-scale climate events observed in late Quaternary Greenland ice cores.Furthermore,comparison with deep-sea oxygen isotope records shows that the GrIS began to significantly contribute to the 40,000-year cycle after 2.7 Ma,with its changes slightly leading the signal of the benthic δ^(18)O.This study clarifies the GrIS’s cyclic evolution and constrains its role in the climate system evolution during the Pliocene-Pleistocene transition.展开更多
Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential ...Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential benefits by reducing metabolic demands and protecting organs,but its application in HS is challenged by cooling difficulties and side effects.This study introduces a novel nasal gel formulation of N6-cyclohexyladenosine(CHA),an adenosine A1 receptor agonist,designed to enhance brain delivery while minimizing peripheral side effects.In a mouse model of HS,administration of CHA nasal gel significantly improved survival rates,reduced metabolic rates,and protected major organs without worsening coagulopathy.Metabolomics analysis revealed a shift towards fatty acid oxidation and increased antioxidant capacity.These findings demonstrate that CHA nasal gel effectively induces TH,offering a safe and innovative treatment strategy for HS,particularly in resource-limited environments.展开更多
Undesired ice accumulation on infrastructure and transportation systems leads to catastrophic events and significant economic losses.Although various anti-icing surfaces with photothermal effects can initially prevent...Undesired ice accumulation on infrastructure and transportation systems leads to catastrophic events and significant economic losses.Although various anti-icing surfaces with photothermal effects can initially prevent icing,any thawy droplets remaining on the horizontal surface can quickly re-freezing once the light diminishes.To address these challenges,we have developed a self-draining slippery surface(SDSS)that enables the thawy droplets to self-remove on the horizontal surface,thereby facilitating real-time anti-icing with the aid of sunlight(100 m W cm^(-2)).This is achieved by sandwiching a thin pyroelectric layer between slippery surface and photothermal film.Due to the synergy between the photothermal and pyroelectric layers,the SDSS not only maintains a high surface temperature of 19.8±2.2℃at the low temperature(-20.0±1.0℃),but also generates amount of charge through thermoelectric coupling.Thus,as cold droplets dropped on the SDSS,electrostatic force pushes the droplets off the charged surface because of the charge transfer mechanism.Even if the surface freezes overnight,the ice can melt and drain off the SDSS within 10 min of exposure to sunlight at-20.0±1.0℃,leaving a clean surface.This work provides a new perspective on the anti-icing system in the real-world environments.展开更多
The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technol...The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technolo-gies have been unable to eliminate these pollutants,resulting in their ongoing release into aquatic ecosystems.This study focuses on cloperastine(CPS),a cough suppressant and antihistamine medication.The environmental impact of CPS usage has become a concern,mainly due to its increased detection during the COVID-19 pandemic.CPS has been found in wastewater treatment facilities,effluents from senior living residences,river waters,and sewage sludge.However,the photosensitivity of CPS and its photodegradation profile remain largely unknown.This study investigates the photodegradation process of CPS under simulated tertiary treatment conditions using UV photolysis,a method commonly applied in some wastewater treatment plants.Several transformation prod-ucts were identified,evaluating their kinetic profiles using chemometric approaches(i.e.,curve fitting and the hard-soft multivariate curve resolution-alternating least squares(HS-MCR-ALS)algorithm)and calculating the reaction quantum yield.As a result,three different transformation products have been detected and correctly identified.In addition,a comprehensive description of the kinetic pathway involved in the photodegradation process of the CPS drug has been provided,including observed kinetic rate constants.展开更多
Plants constitute nearly 80%of the planet’s total biomass(Bar-On et al.,2018);however,this vital group is experiencing severe threats,and recent evaluations indicate that approximately 45%of the world's described...Plants constitute nearly 80%of the planet’s total biomass(Bar-On et al.,2018);however,this vital group is experiencing severe threats,and recent evaluations indicate that approximately 45%of the world's described plant species are at risk of extinction(Bachman et al.,2024).The number of plant extinctions has increased by 60%in the last 100 years(Di Marco et al.,2017).Over the past 250 years,571 plant species have gone extinct—more than twice the combined total of extinct birds,mammals,and amphibians(217 species)(Briggs,2019).展开更多
This study explores the motivations,perceived benefits,and challenges associated with the adoption of clearcutfree forestry by early adopters among non-industrial private forest(NIPF)owners in southern-central Sweden....This study explores the motivations,perceived benefits,and challenges associated with the adoption of clearcutfree forestry by early adopters among non-industrial private forest(NIPF)owners in southern-central Sweden.Clearcut-free forestry,characterized by continuous tree cover and an emphasis on biodiversity,structural diversity,and ecosystem services(ES),is increasingly seen as a sustainable alternative to conventional intensive management based on short rotations and clear-cutting practices.Based on qualitative interviews with 22 NIPF owners who have adopted this approach,the study provides insights into how these early adopters perceive the value of clearcut-free forestry.Reported motivations include environmental concerns,such as biodiversity conservation and climate resilience,as well as strong socio-cultural values linked to family traditions,aesthetic preferences,and community wellbeing.In this study,we use the multi-level perspective(MLP)framework to conceptualize NIPF owners who have adopted clearcut-free forestry as niche actors and analyze their potential contribution to the emergence of an alternative forest management regime.The findings highlight that early adopters associate multiple benefits with clearcut-free forestry,encompassing enhanced ecosystem services such as carbon sequestration,water regulation,habitat preservation,and socio-cultural enrichment through recreation and relational values.However,the interviewees identify several interrelated challenges,including knowledge gaps,lack of clear definitions and standardized practices,limited advisory services,underdeveloped value chains for high-quality timber,and market barriers,which hinder more widespread adoption.Within the multi-level perspective,owner perceptions linking clearcut-free management with improved forest multifunctionality serve as a key driver of niche-level experimentation.This suggests an alignment between these owners and evolving societal demands for more inclusive,sustainable,and diversified forest use.Policy recommendations include targeted investments in knowledge co-production,infrastructure,market incentives,and certification schemes to support the economic viability and broader adoption of clearcut-free forestry.展开更多
The multi-principal element characteristic of high-entropy alloys has revolutionized the conventional alloy design concept of single-principal element,endowing them with excellent mechanical properties.However,owing t...The multi-principal element characteristic of high-entropy alloys has revolutionized the conventional alloy design concept of single-principal element,endowing them with excellent mechanical properties.However,owing to this multi-principal element nature,high-entropy alloys exhibit complex deformation behavior dominated by alternating and coupled deformation mechanisms.Therefore,elucidating these intricate deformation mechanisms remains a key challenge in current research.Neutron diffraction(ND)techniques offer distinct advantages over traditional microscopic methods for characterizing such complex deformation behavior.The strong penetration capability of neutrons enables in-situ,real-time,and non-destructive detection of structural evolution in most centimeter-level bulk samples under complex environments,and ND allows precise characterization of lattice site occupations for light elements,such as C and O,and neighboring elements.This review discussed the principles of ND,experiment procedures,and data analysis.Combining with recent advances in the research about face-centered cubic high-entropy alloy,typical examples of using ND to investigate the deformation behavior were summarized,ultimately revealing deformation mechanisms dominated by dislocations,stacking faults,twinning,and phase transformations.展开更多
Carbon(C)sequestered in the mantle andcrust over geological timescales accounts for more than 99% of allcarbon in the bulk silicate Earth and plays a fundamental role in driving surface biogeochemical cycles,which inv...Carbon(C)sequestered in the mantle andcrust over geological timescales accounts for more than 99% of allcarbon in the bulk silicate Earth and plays a fundamental role in driving surface biogeochemical cycles,which involve only a tiny fraction of Earth's total carbon inventory[1].In addition to CO_(2) released through near surface weathering of sedimentary rocks[2],a substantial,butstill poorly quantified,amount of carbon in the deeper crust and mantle(hereafter referred to as deeply-sourced carbon)could be mobilized by magmatism and metamorphism and then outgassed in volcanic and non-volcanic settings.展开更多
Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and ...Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.展开更多
Lightweight nodes are crucial for blockchain scalability,but verifying the availability of complete block data puts significant strain on bandwidth and latency.Existing data availability sampling(DAS)schemes either re...Lightweight nodes are crucial for blockchain scalability,but verifying the availability of complete block data puts significant strain on bandwidth and latency.Existing data availability sampling(DAS)schemes either require trusted setups or suffer from high communication overhead and low verification efficiency.This paper presents ISTIRDA,a DAS scheme that lets light clients certify availability by sampling small random codeword symbols.Built on ISTIR,an improved Reed–Solomon interactive oracle proof of proximity,ISTIRDA combines adaptive folding with dynamic code rate adjustment to preserve soundness while lowering communication.This paper formalizes opening consistency and prove security with bounded error in the random oracle model,giving polylogarithmic verifier queries and no trusted setup.In a prototype compared with FRIDA under equal soundness,ISTIRDA reduces communication by 40.65%to 80%.For data larger than 16 MB,ISTIRDA verifies faster and the advantage widens;at 128 MB,proofs are about 60%smaller and verification time is roughly 25%shorter,while prover overhead remains modest.In peer-to-peer emulation under injected latency and loss,ISTIRDA reaches confidence more quickly and is less sensitive to packet loss and load.These results indicate that ISTIRDA is a scalable and provably secure DAS scheme suitable for high-throughput,large-block public blockchains,substantially easing bandwidth and latency pressure on lightweight nodes.展开更多
Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,d...Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.展开更多
文摘The authors employed inappropriate search keywords and strategies in their published bibliometric papers within volume 29 of the World Journal of Gastroenterology.The comment highlights the identified issues,provides evidence,and suggests improved study methodologies.Subsequent results with more appro-priate search strategies were presented to address the shortcomings.
基金supported by the National Natural Science Foundation of China,No.81971031(to ZL)the National Key Research and Development Program of China,No.2022YFE0210100(to JFC)+7 种基金the National Natural Science Foundation of China(Original Exploration Project),No.82151308(to JFC)the National Natural Science Foundation of China(Research Fund for International Senior Scientists),No.82150710558(to JFC)Science&Technology Initiative STI2030-Major Projects,No.2021ZD0203400(to JFC)Key Research and Development Program of Zhejiang Province,No.2023C03079(to JFC)Scientific Research Starting Foundation of Oujiang Laboratory(Zhejiang Laboratory for Regenerative Medicine,Vision and Brain Health),No.OJQDSP2022007(to JFC)Project of State Key Laboratory of Ophthalmology,Optometry and Visual Science,Wenzhou Medical University,No.J01-20190101(to JFC)Scientific Research Starting Foundation of Wenzhou Medical University,No.QTJ12003(to JFC)Department of Science and Technology of Zhejiang Province,No.2023ZY1011(to JFC)。
文摘The excessive buildup of neurotoxicα-synuclein plays a pivotal role in the pathogenesis of Parkinson's disease,highlighting the urgent need for innovative therapeutic strategies to promoteα-synuclein clearance,particularly given the current lack of disease-modifying treatments.The glymphatic system,a recently identified perivascular fluid transport network,is crucial for clearing neurotoxic proteins.This review aims to synthesize current knowledge on the role of the glymphatic system inα-synuclein clearance and its implications for the pathology of Parkinson's disease while emphasizing potential therapeutic strategies and areas for future research.The review begins with an overview of the glymphatic system and details its anatomical structure and physiological functions that facilitate cerebrospinal fluid circulation and waste clearance.It summarizes emerging evidence from neuroimaging and experimental studies that highlight the close correlation between the glymphatic system and clinical symptom severity in patients with Parkinson's disease,as well as the effect of glymphatic dysfunction onα-synuclein accumulation in Parkinson's disease models.Subsequently,the review summarizes the mechanisms of glymphatic system impairment in Parkinson's disease,including sleep disturbances,aquaporin-4 impairment,and mitochondrial dysfunction,all of which diminish glymphatic system efficiency.This creates a vicious cycle that exacerbatesα-synuclein accumulation and worsens Parkinson's disease.The therapeutic perspectives section outlines strategies for enhancing glymphatic activity,such as improving sleep quality and pharmacologically targeting aquaporin-4 or its subcellular localization.Promising interventions include deep brain stimulation,melatonin supplementation,γ-aminobutyric acid modulation,and non-invasive methods(such as exercise and bright-light therapy),multisensoryγstimulation,and ultrasound therapy.Moreover,identifying neuroimaging biomarkers to assess glymphatic flow as an indicator ofα-synuclein burden could refine Parkinson's disease diagnosis and track disease progression.In conclusion,the review highlights the critical role of the glymphatic system inα-synuclein clearance and its potential as a therapeutic target in Parkinson's disease.It advocates for further research to elucidate the specific mechanisms by which the glymphatic system clears misfoldedα-synuclein and the development of imaging biomarkers to monitor glymphatic activity in patients with Parkinson's disease.Findings from this review suggest that enhancing glymphatic clearance is a promising strategy for reducingα-synuclein deposits and mitigating the progression of Parkinson's disease.
基金supported by the Judith Jane Mason and Harold Stannett Williams Memorial Foundation National Medical Program(#Mason2210)to JX。
文摘Myalgic encephalomyelitis/chronic fatigue syndrome-an insidious disease:The recent COVID-19 pandemic has brought substantial attention to the overlapping symptoms between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome(ME/CFS),a chronic and poorly understood neurological disorder(Shankar et al.,2024).
基金supported by the National Institutes of Health(grant numbers R01NS089737,RF1NS130881,and R21AG089974,to QC).
文摘Phosphatidylethanolamine is a major phospholipid class abundant in the brain,particularly in the inner leaflet of the plasma and mitochondrial membranes.Although it is primarily synthesized from phosphatidylserine via decarboxylation in mitochondria or from ethanolamine via the cytidine diphosphate-ethanolamine pathway in the endoplasmic reticulum,phosphatidylethanolamine that resides in mitochondria is preferentially produced locally and is distinct and separate from the pool of phosphatidylethanolamine made in the endoplasmic reticulum.Mitochondria-derived phosphatidylethanolamine is not only essential for mitochondrial integrity but also is exported to other organelles to fulfill diverse cellular functions.Neurons are highly enriched with phosphatidylethanolamine,and the importance of phosphatidylethanolamine metabolism in neuronal health has recently been recognized following its reported links to Alzheimer’s disease,Parkinson’s disease,and hereditary spastic paraplegia,among other neurological disorders.Indeed,disturbances in mitochondrial function and phosphatidylethanolamine metabolism and the resulting neuronal dysfunction are the common features of individuals suffering from these diseases,highlighting the great importance of maintaining proper phosphatidylethanolamine homeostasis in neurons.In this review,we summarize the current knowledge of phosphatidylethanolamine metabolism and its role in neuronal function with a special emphasis on the phosphatidylethanolamine biosynthetic pathway in mitochondria.We then review findings on how phosphatidylethanolamine biosynthesis is affected in major neurodegenerative diseases.Finally,we highlight promising future research areas that will help advance the understanding of neuronal phosphatidylethanolamine mechanisms and identify phosphatidylethanolamine-targeted therapeutic strategies for combating such brain diseases.
基金jointly supported by the Second Tibetan Plateau Scientific Expedition and Research Program[grant number-ber 2019QZKK0103]the National Natural Science Foundation of China[grant number 42293294]the China Meteorological Admin-istration Climate Change Special Program[grant number QBZ202303]。
文摘Using multi-source reanalysis data,this study examines the relationship between the tropical Pacific-Atlantic SST Dipole Mode(TPA-DM)and summer precipitation in North China(NCSP)on the interannual timescale during the period of 1979-2022.The results show that the TPA-DM,the dominant pattern of interannual variability in the tropical Pacific and Atlantic regions,exhibits a significant negative correlation with NCSP.The positive phase of TPA-DM induces subsidence over the Maritime Continent through a zonal circulation pattern,which initiates a Pacific-Japan-like wave train along the East Asian coast.The circulation anomalies lead to moisture deficits and convergence subsidence over North China,leading to below-normal rainfall.Further analysis reveals that cooler SST in the Southern Tropical Atlantic facilitates the persistence of the TPA-DM by stimulating the anomalous Walker circulation associated with wind-evaporation-SST-convection feedback.
基金financially supported by the National Natural Science Foundation of China(Grant Nos.42293264&42293262)the Postdoctoral Fellowship Program of CPSF(Grant No.GZC20241196).
文摘Stable isotope analysis of water(δD and δ^(18)O)is widely used to trace water cycle processes in aquatic ecosystems,based on the established assumption that biological activity does not cause isotopic fractionation of water.Here,we found that phytoplankton photosynthesis elevated ambient water δ^(18)O and δD values,a conclusion supported by a large-scale survey across extensive spatiotemporal environmental gradients and further confirmed by a laboratory culture experiment.This biological effect depended on phytoplankton biomass and light utilization efficiency and could result in a deviation of at least 16.7% in the slope of the water δD-δ^(18)O regression line.We termed this phenomenon the“biological evaporation effect”.Given the potential universality of this effect across aquatic ecosystems,our findings challenge the conventional paradigm in isotope hydrology.
基金supported by the Innovation and Entrepreneurship Training Program for College Students(X2025102911746,X2025102910483).
文摘Natural product(NPT)derived from traditional Chinese medicine has a rich history as an integral part of Chinese healthcare for thousands of years.Recently,the application of NPT in sonodynamic antibacterial therapy(SDAT)has emerged as a promising area of research.This perspective summarizes the recent NPT-based sonosensitizers in SDAT.Currently,common NPT-based sonosensitizers include curcumin,chlorophyll derivatives,hypericin,and berberine.Compared with other sonosensitizers,natural sources of NPT-based sonosensitizers with reactive oxide species production performance under ultrasound conditions,low biotoxicity,and other additional biological activity make them have application prospects in bacterial removal.Finally,the potential benefits and challenges of NPT-based nanosonosensitizers were also discussed.
基金funded by the Strategy Priority Research Program(Category B)of the Chinese Academy of Sciences(Grant No.XDB0710000)the National Key Research and Development Program(No.2022YFF0801504)+1 种基金the National Natural Science Foundation of China(Nos.42488201,41907371)support from the IGGCAS Key Program(No.IGGCAS-202201).
文摘The Pliocene-Pleistocene transition(3.0-2.5 million years ago,Ma)was a critical period during which the Arctic ice sheets expanded extensively and intensified,with the establishment of a permanent ice sheet on Greenland marking the onset of a bipolar“icehouse”climate state.This interval,characterized by atmospheric CO_(2) concentrations between pre-industrial and modern levels(~280-400 ppmv),provides a critical time window for understanding ice-sheet response to external forcing.Using a high-resolution climate model and a 3D thermomechanical ice sheet model,we simulate the Greenland Ice Sheet(GrIS)volume evolution under different CO_(2) scenarios and analyze its periodic behavior during this period.Our results show that when the GrIS volume was small,its variability was strongly paced by 65°N summer insolation.As the ice sheet grew,its response shifted,becoming increasingly dominated by the obliquity cycle.The GrIS volume reconstruction,consistent with ice-rafted debris records,indicates that after approximately 2.7 Ma,the expanded GrIS exhibited enhanced suborbital to millennial-scale signals and greater ice dynamical variability-a pattern echoing the amplified millennial-scale climate events observed in late Quaternary Greenland ice cores.Furthermore,comparison with deep-sea oxygen isotope records shows that the GrIS began to significantly contribute to the 40,000-year cycle after 2.7 Ma,with its changes slightly leading the signal of the benthic δ^(18)O.This study clarifies the GrIS’s cyclic evolution and constrains its role in the climate system evolution during the Pliocene-Pleistocene transition.
基金supported by grants from the National Natural Science Foundation of China(No.81981340417 to LiSu)Natural Science Foundation of Jiangsu Province Outstanding Youth Fund(No.BK20240134 to Yuanqing Gao).
文摘Hemorrhagic shock(HS)is a leading cause of death worldwide,particularly within the first 24 h post-injury.Current treatments are limited,especially in low-resource settings.Therapeutic hypothermia(TH)offers potential benefits by reducing metabolic demands and protecting organs,but its application in HS is challenged by cooling difficulties and side effects.This study introduces a novel nasal gel formulation of N6-cyclohexyladenosine(CHA),an adenosine A1 receptor agonist,designed to enhance brain delivery while minimizing peripheral side effects.In a mouse model of HS,administration of CHA nasal gel significantly improved survival rates,reduced metabolic rates,and protected major organs without worsening coagulopathy.Metabolomics analysis revealed a shift towards fatty acid oxidation and increased antioxidant capacity.These findings demonstrate that CHA nasal gel effectively induces TH,offering a safe and innovative treatment strategy for HS,particularly in resource-limited environments.
基金supported by the National Natural Science Foundation of China(52273101,51922018,and 21875011)the Fundamental Research Funds for the Central Universities(KG21015201 and KG21020801)China Postdoctoral Science Foundation(2025M77422)。
文摘Undesired ice accumulation on infrastructure and transportation systems leads to catastrophic events and significant economic losses.Although various anti-icing surfaces with photothermal effects can initially prevent icing,any thawy droplets remaining on the horizontal surface can quickly re-freezing once the light diminishes.To address these challenges,we have developed a self-draining slippery surface(SDSS)that enables the thawy droplets to self-remove on the horizontal surface,thereby facilitating real-time anti-icing with the aid of sunlight(100 m W cm^(-2)).This is achieved by sandwiching a thin pyroelectric layer between slippery surface and photothermal film.Due to the synergy between the photothermal and pyroelectric layers,the SDSS not only maintains a high surface temperature of 19.8±2.2℃at the low temperature(-20.0±1.0℃),but also generates amount of charge through thermoelectric coupling.Thus,as cold droplets dropped on the SDSS,electrostatic force pushes the droplets off the charged surface because of the charge transfer mechanism.Even if the surface freezes overnight,the ice can melt and drain off the SDSS within 10 min of exposure to sunlight at-20.0±1.0℃,leaving a clean surface.This work provides a new perspective on the anti-icing system in the real-world environments.
基金supported by the grants PID2020-113371RA-C22 and TED2021-130845A-C32,funded by MCIN/AEI/10.13039/501100011033.M.Marín-García,R.González-OlmosC.Gómez-Canela are members of the GESPA group(Grup d’Enginyeria i Simulacióde Processos Ambientals)at IQS-URL,which has been acknowledged as a Consolidated Research Group by the Government of Catalonia(No.2021-SGR-00321)+1 种基金In addition,M.Marín-García has been awarded a public grant for the Investigo Programme,aimed at hiring young job seekers to undertake research and innovation projects under the Recovery,Transformation,and Resilience Plan(PRTR),European Union Next Generation,for the year 2022,through the Government of Catalonia and the Spanish Ministry for Work and Social Economy(No.100045ID16)Ana Belén Cuenca for her support and expertise,which helped to confirm the proposed reaction mechanism involved in the UV photolysis of cloperastine.
文摘The increasing production and release of synthetic organic chemicals,including pharmaceuticals,into our envi-ronment has allowed these substances to accumulate in our surface water systems.Current purification technolo-gies have been unable to eliminate these pollutants,resulting in their ongoing release into aquatic ecosystems.This study focuses on cloperastine(CPS),a cough suppressant and antihistamine medication.The environmental impact of CPS usage has become a concern,mainly due to its increased detection during the COVID-19 pandemic.CPS has been found in wastewater treatment facilities,effluents from senior living residences,river waters,and sewage sludge.However,the photosensitivity of CPS and its photodegradation profile remain largely unknown.This study investigates the photodegradation process of CPS under simulated tertiary treatment conditions using UV photolysis,a method commonly applied in some wastewater treatment plants.Several transformation prod-ucts were identified,evaluating their kinetic profiles using chemometric approaches(i.e.,curve fitting and the hard-soft multivariate curve resolution-alternating least squares(HS-MCR-ALS)algorithm)and calculating the reaction quantum yield.As a result,three different transformation products have been detected and correctly identified.In addition,a comprehensive description of the kinetic pathway involved in the photodegradation process of the CPS drug has been provided,including observed kinetic rate constants.
基金support of the ORG.one project of Oxford Nanopore Technologies(ONT),the Rufford Grants(45249-1)the Idea Wild Grants(Project ID-KJOSINDI0125-00)the Mohamed Bin Zyed Species Conservation(MBZ)(GEF Grant no-240535253)Funds in our efforts to conserve threatened trees in the Western Ghats Biodiversity Hotspot Forest regions.
文摘Plants constitute nearly 80%of the planet’s total biomass(Bar-On et al.,2018);however,this vital group is experiencing severe threats,and recent evaluations indicate that approximately 45%of the world's described plant species are at risk of extinction(Bachman et al.,2024).The number of plant extinctions has increased by 60%in the last 100 years(Di Marco et al.,2017).Over the past 250 years,571 plant species have gone extinct—more than twice the combined total of extinct birds,mammals,and amphibians(217 species)(Briggs,2019).
基金financed by a grant from Mistra[DIA 2019/28]and from Formas via the National Research Programme on Climate(2021–00416)FORMAS,Grant Nos.2022-02146 and 2021–01067Swedish Environmental Protection Agency Research Grant No.2021–00040。
文摘This study explores the motivations,perceived benefits,and challenges associated with the adoption of clearcutfree forestry by early adopters among non-industrial private forest(NIPF)owners in southern-central Sweden.Clearcut-free forestry,characterized by continuous tree cover and an emphasis on biodiversity,structural diversity,and ecosystem services(ES),is increasingly seen as a sustainable alternative to conventional intensive management based on short rotations and clear-cutting practices.Based on qualitative interviews with 22 NIPF owners who have adopted this approach,the study provides insights into how these early adopters perceive the value of clearcut-free forestry.Reported motivations include environmental concerns,such as biodiversity conservation and climate resilience,as well as strong socio-cultural values linked to family traditions,aesthetic preferences,and community wellbeing.In this study,we use the multi-level perspective(MLP)framework to conceptualize NIPF owners who have adopted clearcut-free forestry as niche actors and analyze their potential contribution to the emergence of an alternative forest management regime.The findings highlight that early adopters associate multiple benefits with clearcut-free forestry,encompassing enhanced ecosystem services such as carbon sequestration,water regulation,habitat preservation,and socio-cultural enrichment through recreation and relational values.However,the interviewees identify several interrelated challenges,including knowledge gaps,lack of clear definitions and standardized practices,limited advisory services,underdeveloped value chains for high-quality timber,and market barriers,which hinder more widespread adoption.Within the multi-level perspective,owner perceptions linking clearcut-free management with improved forest multifunctionality serve as a key driver of niche-level experimentation.This suggests an alignment between these owners and evolving societal demands for more inclusive,sustainable,and diversified forest use.Policy recommendations include targeted investments in knowledge co-production,infrastructure,market incentives,and certification schemes to support the economic viability and broader adoption of clearcut-free forestry.
基金National Key R&D Program of China(2023YFB3711904,2022YFA1603801)National Natural Science Foundation of China(12404230,52471181,52301213,52130108,52471005)+2 种基金National Nature Science Foundation of Zhejiang Province(LY23E010002)Open Fund of the China Spallation Neutron Source,Songshan Lake Science City(KFKT2023B11)Guangdong Basic and Applied Basic Research Foundation(2022A1515110805,2024A1515010878)。
文摘The multi-principal element characteristic of high-entropy alloys has revolutionized the conventional alloy design concept of single-principal element,endowing them with excellent mechanical properties.However,owing to this multi-principal element nature,high-entropy alloys exhibit complex deformation behavior dominated by alternating and coupled deformation mechanisms.Therefore,elucidating these intricate deformation mechanisms remains a key challenge in current research.Neutron diffraction(ND)techniques offer distinct advantages over traditional microscopic methods for characterizing such complex deformation behavior.The strong penetration capability of neutrons enables in-situ,real-time,and non-destructive detection of structural evolution in most centimeter-level bulk samples under complex environments,and ND allows precise characterization of lattice site occupations for light elements,such as C and O,and neighboring elements.This review discussed the principles of ND,experiment procedures,and data analysis.Combining with recent advances in the research about face-centered cubic high-entropy alloy,typical examples of using ND to investigate the deformation behavior were summarized,ultimately revealing deformation mechanisms dominated by dislocations,stacking faults,twinning,and phase transformations.
基金supported by the National Key Research and Development Program of China(2020YFA0607700)the National Natural Science Foundation of China(41930642 and 42522211).
文摘Carbon(C)sequestered in the mantle andcrust over geological timescales accounts for more than 99% of allcarbon in the bulk silicate Earth and plays a fundamental role in driving surface biogeochemical cycles,which involve only a tiny fraction of Earth's total carbon inventory[1].In addition to CO_(2) released through near surface weathering of sedimentary rocks[2],a substantial,butstill poorly quantified,amount of carbon in the deeper crust and mantle(hereafter referred to as deeply-sourced carbon)could be mobilized by magmatism and metamorphism and then outgassed in volcanic and non-volcanic settings.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702704)the National Natural Science Foundation of China(Nos.22376005,22076006 and 82073506).
文摘Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.
基金supported in part by the Research Fund of Key Lab of Education Blockchain and Intelligent Technology,Ministry of Education(EBME25-F-08).
文摘Lightweight nodes are crucial for blockchain scalability,but verifying the availability of complete block data puts significant strain on bandwidth and latency.Existing data availability sampling(DAS)schemes either require trusted setups or suffer from high communication overhead and low verification efficiency.This paper presents ISTIRDA,a DAS scheme that lets light clients certify availability by sampling small random codeword symbols.Built on ISTIR,an improved Reed–Solomon interactive oracle proof of proximity,ISTIRDA combines adaptive folding with dynamic code rate adjustment to preserve soundness while lowering communication.This paper formalizes opening consistency and prove security with bounded error in the random oracle model,giving polylogarithmic verifier queries and no trusted setup.In a prototype compared with FRIDA under equal soundness,ISTIRDA reduces communication by 40.65%to 80%.For data larger than 16 MB,ISTIRDA verifies faster and the advantage widens;at 128 MB,proofs are about 60%smaller and verification time is roughly 25%shorter,while prover overhead remains modest.In peer-to-peer emulation under injected latency and loss,ISTIRDA reaches confidence more quickly and is less sensitive to packet loss and load.These results indicate that ISTIRDA is a scalable and provably secure DAS scheme suitable for high-throughput,large-block public blockchains,substantially easing bandwidth and latency pressure on lightweight nodes.
文摘Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.
