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
Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynam...Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.展开更多
Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities ofte...Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities often result in the deprioritization of standardized management practices,as they do not yield immediate benefits.The implementation of such systems typically encompasses the integrated phases of "development,construction,utiliz ation,and operation and maintenance".To enhance the overall delivery quality of these systems,it is imperative to dismantle the management barriers among these phases and adopt a holistic approach to standardized management.This paper takes a specific system project as a research object to identify common challenges,and proposes improvement strategies in the implementation of standar dized management.Empirical results indicate a substantial reduction in the system s full-lifecycle costs.展开更多
Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to t...Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.展开更多
This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the ...This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the design process,we transform the studied system into the form of a fully actuated system through a state transformation.Then,to address the unknown nonlinear functions and actuator fault parameters,we employ neural networks and adaptive estimation techniques,respectively.Moreover,to reduce the control cost and improve the control efficiency,we introduce event-triggered inputs into the control strategy.It is proved by the Lyapunov stability analysis that all signals of the closed-loop system are bounded and the output of system eventually converge to a bounded region.The efficacy of the control approach is ultimately demonstrated via the simulation of an actual machine feeding system.展开更多
1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Int...1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Intergovernmental Panel on Climate Change(IPCC)—consistently predict the widespread implementation of CO_(2)geological storage on a global scale.展开更多
The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,...The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,in combination with numerical simulation,was conducted to investigate the influence of ground fissures on a metro shield tunnel.The results indicate that the lining contact pressure at the vault increases in the hanging wall while decreases in the footwall,resulting in a two-dimensional stress state of vertical shear and axial tension-compression,and simultaneous vertical dislocation and axial tilt for the segments around the ground fissure.In addition,the damage to curved bolts includes tensile yield,flexural yield,and shear twist,leading to obvious concrete lining damage,particularly at the vault,arch bottom,and hance,indicating that the joints in these positions are weak areas.The shield tunnel orthogonal to the ground fissure ultimately experiences shear failure,suggesting that the maximum actual dislocation of ground fissure that the structure can withstand is approximately 20 cm,and five segment rings in the hanging wall and six segment rings in the footwall also need to be reinforced.This study could provide a reference for metro design in ground fissure sites.展开更多
Based on the analysis of typical lacustrine shale oil zones in China and their geological characteristics,this study elucidates the fundamental differences between the enrichment patterns of shale oil sweet spots and ...Based on the analysis of typical lacustrine shale oil zones in China and their geological characteristics,this study elucidates the fundamental differences between the enrichment patterns of shale oil sweet spots and conventional oil and gas.The key parameters and evaluation methods for assessing the large-scale production potential of lacustrine shale oil are proposed.The results show that shale oil is a petroleum resource that exists in organic-rich shale formations,in other words,it is preserved in its source bed,following a different process of generation-accumulation-enrichment from conventional oil and gas.Thus,the concept of“reservoir”seems to be inapplicable to shale oil.In China,lacustrine shale oil is distributed widely,but the geological characteristics and sweet spots enrichment patterns of shale oil vary significantly in lacustrine basins where the water environment and the tectonic evolution and diagenetic transformation frameworks are distinct.The core of the evaluation of lacustrine shale oil is“sweet spot volume”.The key factors for evaluating the large-scale production of continental shale oil are the oil storage capacity,oil-bearing capacity and oil producing capacity.The key parameters for evaluating these capacities are total porosity,oil content,and free oil content,respectively.It is recommended to determine the total porosity of shale by combining helium porosity measurement with nuclear magnetic resonance(NMR)method,the oil content of key layers by using organic solvent extraction,NMR method and high pressure mercury intrusion methods,and the free oil content by using NMR fluid distribution secondary spectral stripping decomposition and logging.The research results contribute supplemental insights on continental shale oil deliverability in China,and provide a scientific basis for the rapid exploration and large-scale production of lacustrine shale oil.展开更多
The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the...The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the forging process.Using the previously optimized shape and initial position of preform,the influence of the friction condition(friction factor m=0.1–0.3)on material flow and cavity filling was studied by numerical method with a shear friction model.A novel filling index was defined to reflect material flow into left and right flashes and zoom in on friction-induced results.The results indicate that the workpiece moves rigidly to the right direction,with the displacement decreasing as m increases.When m<0.18,the underfilling defect will occur in the left side of strut forging,while overflow occurs in the right forging die cavity.By combining the filling index and analyses of material flow and filling status,a reasonable friction factor interval of m=0.21–0.24 can be determined.Within this interval,the cavity filling behavior demonstrates robustness,with friction fluctuations exerting minimal influence.展开更多
Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primar...Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.展开更多
Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configura...Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configuration transformation is prominent feature of the metamorphic mechanism. The number of constraints or properties of the kinematic pairs provided by the metamorphic kinematic pairs will change under certain conditions, its dynamic performance is much more complex than that of traditional kinematic pairs with immutable constraints. However, the clearance model about traditional kinematic pairs with immutable constraints established by long-term research is difficult to be directly applied to the metachromatic kinematic pairs. Referring to the experience of the traditional kinematic pairs with immutable constraints, the continuous contact model of Metamorphic Groove pin pair with clearance is established. According to the traditional continuous contact model of the kinematic pairs with immutable constraints, the forces between the elements of kinematic pair of the mechanism with clearance and the ideal mechanism without clearance are regarded as the same, and the inertia force and inertia moment of the components are also calculated according to the acceleration of the ideal mechanism. The clearance is regarded as a massless virtual bar with length r. For the rotating pair part, the massless virtual bar length r is the difference between the radius of the shaft and the hole, and for the sliding pair part, the massless virtual bar length r is half of the difference between the height of the slider and the guide groove. According to the new mechanism without gap after adding the imaginary bar, kinetic energy and potential energy of the system are calculated for the two configurations of mechanism with metamorphic Groove pin pair with clearance. The kinetic energy and potential energy of the system are calculated according to the new mechanism without clearance after adding the massless virtual bar. The kinetic energy, potential energy and generalized force are substituted into the Lagrangian equation to obtain the motion equation of the metamorphic mechanism, which lays the foundation for the dynamic performance study of the mechanism with metamorphic groove pin pair with clearance.展开更多
Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical...Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical frameworks to systematically examine the evolution,performance,and influencing factors of governance mechanisms within these organizations.Using both quantitative and inductive analytical methods,the paper proposes innovative designs and supporting measures for improving governance mechanisms.The findings reveal that,amid large-scale farmland circulation,the governance mechanisms of agricultural production organizations in Daqing City are evolving from traditional to modern structures.However,challenges remain in areas such as decision-making efficiency,benefit distribution,and supervision mechanisms.In response,this study proposes innovative governance designs focusing on decision-making processes,profit-sharing mechanisms,and risk prevention.Corresponding policy recommendations are also provided to support the sustainable development of agricultural modernization in China.展开更多
Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overa...Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy.In this study,we have designed an organic PS(Nc PB)with an excellent near-infrared light absorption through a refined molecular strategy.Meanwhile,Nc PB was assembled into nanoparticles with different sizes(Nano Nc PB-1 and Nano Nc PB-0)by a supramolecular modulation strategy.As the results,the nanoparticle with an ultra-small size(Nano Nc PB-1)generated a large number of superoxide anion(O_(2)^(·-))in a low-O_(2)-dependent manner and release plenty of heat.Furthermore,the results of in vivo experiments demonstrated that Nano Nc PB-1 actively accumulated in tumor tissues and showed a 92%tumor inhibition after photodynamic and photothermal combination therapy.More importantly,Nano Nc PB-1 could be rapidly cleared from the body of mice via the renal pathway,which alleviates potential side effects of prolonged retention of PS in the circulation.展开更多
Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale opti...Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale optimization problems are solved using computing machines,leading to an enormous computational time being required,which may delay deriving timely solutions.Decomposition methods,which partition a large-scale optimization problem into lower-dimensional subproblems,represent a key approach to addressing time-efficiency issues.There has been significant progress in both applied mathematics and emerging artificial intelligence approaches on this front.This work aims at providing an overview of the decomposition methods from both the mathematics and computer science points of view.We also remark on the state-of-the-art developments and recent applications of the decomposition methods,and discuss the future research and development perspectives.展开更多
This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management m...This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management measures.Through practical observation and logical analysis,this article elaborates on the management connotations of large-scale machinery and equipment in highway construction,affirming its management value from different perspectives.On this basis,it carefully analyzes the problems existing in the management of large-scale machinery and equipment,providing a detailed interpretation of issues such as the weak foundation of the equipment management system and the disconnection between equipment selection and configuration from reality.Combining the manifestations of related problems,this article proposes strategies such as strengthening the institutional foundation of equipment management,selecting and configuring equipment based on actual conditions,aiming to provide references for large-scale machinery and equipment management to relevant enterprises.展开更多
Bulb-type hydro turbines are commonly used in small-to medium-scale hydropower stations due to their compact design and adaptability to low-head conditions.However,long-termoperation often results in wear at the runne...Bulb-type hydro turbines are commonly used in small-to medium-scale hydropower stations due to their compact design and adaptability to low-head conditions.However,long-termoperation often results in wear at the runner rim,increasing tip clearance and triggering leakage flow and cavitation.These effects reduce hydraulic efficiency and accelerate blade surface erosion,posing serious risks to unit safety and operational stability.This study investigates the influence of tip clearance on cavitation performance in a 24 MW prototype bulb turbine.A three-dimensional numericalmodel is developed to simulate various operating conditions with different tip clearance values(3.0,4.5,and 6.0 mm)and cavitation numbers(σ=1.20–1.33).Internal flow characteristics—including pressure distribution,velocity fields,hydraulic efficiency,and pressure pulsation—are analyzed to elucidate the impact of tip clearance on cavitation development.Results show that underσ=1.2 and a 4.5 mm tip clearance,the pressure pulsation amplitude at the blade tip reaches 4870 Pa—approximately 1.5 times higher than that near the hub.At partial flowconditions,turbine efficiency decreases by up to 6.8%compared to the rated condition.Increasing the tip clearance from 1.5 to 6.0 mm expands the low-pressure area near the blade tip by around 32%,significantly intensifying cavitation.Frequency domain analysis reveals dominant pulsation frequencies between 10–20Hz,characterized by blade-passing features and a wave-clipping effect.These findings provide theoretical insight and quantitative evidence to support the optimization of tip clearance design and cavitation mitigation strategies in bulb turbines,aiming to improve both efficiency and operational stability.展开更多
Offshore wind power plays a crucial role in energy strategies.The results of traditional small-scale physical models may be unreliable when extrapolated to large field scales.This study addressed this limitation by co...Offshore wind power plays a crucial role in energy strategies.The results of traditional small-scale physical models may be unreliable when extrapolated to large field scales.This study addressed this limitation by conducting large-scale(1:13)experiments to investigate the scour hole pattern and equilibrium scour depth around both slender and large monopiles under irregular waves.The experiments adopted KeuleganeCarpenter number(NKC)values from 1.01 to 8.89 and diffraction parameter(D/L,where D is the diameter of the monopile,and L is the wave length)values from 0.016 to 0.056.The results showed that changes in the maximum scour location and scour hole shape around a slender monopile were associated with NKC,with differences observed between irregular and regular waves.Improving the calculation of NKC enhanced the accuracy of existing scour formulae under irregular waves.The maximum scour locations around a large monopile were consistently found on both sides,regardless of NKC and D/L,but the scour hole topography was influenced by both parameters.Notably,the scour range around a large monopile was at least as large as the monopile diameter.展开更多
It has been argued that the human brain,as an information-processing machine,operates near a phase transition point in a non-equilibrium state,where it violates detailed balance leading to entropy production.Thus,the ...It has been argued that the human brain,as an information-processing machine,operates near a phase transition point in a non-equilibrium state,where it violates detailed balance leading to entropy production.Thus,the assessment of irreversibility in brain networks can provide valuable insights into their non-equilibrium properties.In this study,we utilized an open-source whole-brain functional magnetic resonance imaging(fMRI)dataset from both resting and task states to evaluate the irreversibility of large-scale human brain networks.Our analysis revealed that the brain networks exhibited significant irreversibility,violating detailed balance,and generating entropy.Notably,both physical and cognitive tasks increased the extent of this violation compared to the resting state.Regardless of the state(rest or task),interactions between pairs of brain regions were the primary contributors to this irreversibility.Moreover,we observed that as global synchrony increased within brain networks,so did irreversibility.The first derivative of irreversibility with respect to synchronization peaked near the phase transition point,characterized by the moderate mean synchronization and maximized synchronization entropy of blood oxygenation level-dependent(BOLD)signals.These findings deepen our understanding of the non-equilibrium dynamics of large-scale brain networks,particularly in relation to their phase transition behaviors,and may have potential clinical applications for brain disorders.展开更多
Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the p...Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the project, a comparison of design options for insufficient clearance in interchanges, and the main design strategies for reconstruction and expansion. It is hoped that this analysis can provide a reference for the design of such road reconstruction and expansion projects.展开更多
In 2022, South China(SC) experienced record-breaking rainfall during its first rainy season, causing severe socioeconomic losses. This study examines the large-scale circulation anomalies responsible for this extreme ...In 2022, South China(SC) experienced record-breaking rainfall during its first rainy season, causing severe socioeconomic losses. This study examines the large-scale circulation anomalies responsible for this extreme event.Analysis reveals that the lower-tropospheric cyclonic anomaly over SC plays a crucial role. This cyclonic anomaly consists of extratropical northeasterly anomalies to the north of SC and tropical southwesterly anomalies to the south. Both components were particularly intense during the 2022 first rainy season, contributing to the heavy rainfall in SC. Moreover,the lower-tropospheric cyclonic anomaly is enhanced by its counterpart in the upper troposphere, which is associated with a wave train propagating from the North Atlantic to East Asia across the mid-high latitudes of the Eurasian continent.Further analysis indicates that the extratropical wave train correlates with sea surface temperature anomalies(SSTAs) in the North Atlantic. Additionally, the SSTAs over the North Indian Ocean also play a role in enhancing the tropical southwesterlies in the lower troposphere. This study highlights the combined influence of tropical and extratropical circulation anomalies, offering a comprehensive understanding of the record-breaking rainfall.展开更多
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 National Natural Science Foundation of China(Nos.52293472,22473096 and 22471164)。
文摘Among various architectures of polymers,end-group-free rings have attracted growing interests due to their distinct physicochemical performances over the linear counterparts which are exemplified by reduced hydrodynamic size and slower degradation.It is key to develop facile methods to large-scale synthesis of polymer rings with tunable compositions and microstructures.Recent progresses in large-scale synthesis of polymer rings against single-chain dynamic nanoparticles,and the example applications in synchronous enhancing toughness and strength of polymer nanocomposites are summarized.Once there is the breakthrough in rational design and effective large-scale synthesis of polymer rings and their functional derivatives,a family of cyclic functional hybrids would be available,thus providing a new paradigm in developing polymer science and engineering.
文摘Large-scale complex systems are integral to the functioning of various organizations within the national economy.Despite their significance,the lengthy construction cycles and the involvement of multiple entities often result in the deprioritization of standardized management practices,as they do not yield immediate benefits.The implementation of such systems typically encompasses the integrated phases of "development,construction,utiliz ation,and operation and maintenance".To enhance the overall delivery quality of these systems,it is imperative to dismantle the management barriers among these phases and adopt a holistic approach to standardized management.This paper takes a specific system project as a research object to identify common challenges,and proposes improvement strategies in the implementation of standar dized management.Empirical results indicate a substantial reduction in the system s full-lifecycle costs.
基金supported by the National Natural Science Foundation of China(Grant No.42275041)the Hainan Province Science and Technology Special Fund(Grant No.SOLZSKY2025006).
文摘Summer rainfall in the Yangtze River basin(YRB)is favored by two key factors in the lower troposphere:the tropical anticyclonic anomaly over the western North Pacific and the extratropical northeasterly anomalies to the north of the YRB.This study,however,found that approximately 46%of heavy rainfall events in the YRB occur when only one factor appears and the other is opposite signed.Accordingly,these heavy rainfall events can be categorized into two types:the extratropical northeasterly anomalies but tropical cyclonic anomaly(first unconventional type),and the tropical anticyclonic anomaly but extratropical southwesterly anomalies(second unconventional type).Anomalous water vapor convergence and upward motion exists for both types,but through different mechanisms.For the first type,the moisture convergence and upward motion are induced by a cyclonic anomaly over the YRB,which appears in the mid and lower troposphere and originates from the upstream region.For the second type,a mid-tropospheric cyclonic anomaly over Lake Baikal extends southward and results in southwesterly anomalies over the YRB,in conjunction with the tropical anticyclonic anomaly.The southwesterly anomalies transport water vapor to the YRB and lead to upward motion through warm advection.This study emphasizes the role of mid-tropospheric circulations in inducing heavy rainfall in the YRB.
基金supported by the Science Center Program of National Natural Science Foundation of China under Grant 62188101the National Natural Science Foundation of China under Grant 62573265.
文摘This study develops an event-triggered control strategy utilizing the fully actuated system approach for nonlinear interconnected large-scale systems containing actuator failures.First,to reduce the complexity of the design process,we transform the studied system into the form of a fully actuated system through a state transformation.Then,to address the unknown nonlinear functions and actuator fault parameters,we employ neural networks and adaptive estimation techniques,respectively.Moreover,to reduce the control cost and improve the control efficiency,we introduce event-triggered inputs into the control strategy.It is proved by the Lyapunov stability analysis that all signals of the closed-loop system are bounded and the output of system eventually converge to a bounded region.The efficacy of the control approach is ultimately demonstrated via the simulation of an actual machine feeding system.
基金supported by the National Key Research and Development Program of China(2022YFE0206700)。
文摘1.Introduction Climate change mitigation pathways aimed at limiting global anthropogenic carbon dioxide(CO_(2))emissions while striving to constrain the global temperature increase to below 2℃—as outlined by the Intergovernmental Panel on Climate Change(IPCC)—consistently predict the widespread implementation of CO_(2)geological storage on a global scale.
基金supported by the National Key Research&Development Program of China(Grant No.2023YFC3008404)the Key Laboratory of Earth Fissures Geological Disaster,Ministry of Natural Resources,China(Grant Nos.EFGD20240609 and EFGD20240610).
文摘The recent upsurge in metro construction emphasizes the necessity of understanding the mechanical performance of metro shield tunnel subjected to the influence of ground fissures.In this study,a largescale experiment,in combination with numerical simulation,was conducted to investigate the influence of ground fissures on a metro shield tunnel.The results indicate that the lining contact pressure at the vault increases in the hanging wall while decreases in the footwall,resulting in a two-dimensional stress state of vertical shear and axial tension-compression,and simultaneous vertical dislocation and axial tilt for the segments around the ground fissure.In addition,the damage to curved bolts includes tensile yield,flexural yield,and shear twist,leading to obvious concrete lining damage,particularly at the vault,arch bottom,and hance,indicating that the joints in these positions are weak areas.The shield tunnel orthogonal to the ground fissure ultimately experiences shear failure,suggesting that the maximum actual dislocation of ground fissure that the structure can withstand is approximately 20 cm,and five segment rings in the hanging wall and six segment rings in the footwall also need to be reinforced.This study could provide a reference for metro design in ground fissure sites.
基金Supported by the National Key R&D Program of China(2024YFE0114000)Science and Technology Project of China National Petroleum Corporation(2024DJ8702).
文摘Based on the analysis of typical lacustrine shale oil zones in China and their geological characteristics,this study elucidates the fundamental differences between the enrichment patterns of shale oil sweet spots and conventional oil and gas.The key parameters and evaluation methods for assessing the large-scale production potential of lacustrine shale oil are proposed.The results show that shale oil is a petroleum resource that exists in organic-rich shale formations,in other words,it is preserved in its source bed,following a different process of generation-accumulation-enrichment from conventional oil and gas.Thus,the concept of“reservoir”seems to be inapplicable to shale oil.In China,lacustrine shale oil is distributed widely,but the geological characteristics and sweet spots enrichment patterns of shale oil vary significantly in lacustrine basins where the water environment and the tectonic evolution and diagenetic transformation frameworks are distinct.The core of the evaluation of lacustrine shale oil is“sweet spot volume”.The key factors for evaluating the large-scale production of continental shale oil are the oil storage capacity,oil-bearing capacity and oil producing capacity.The key parameters for evaluating these capacities are total porosity,oil content,and free oil content,respectively.It is recommended to determine the total porosity of shale by combining helium porosity measurement with nuclear magnetic resonance(NMR)method,the oil content of key layers by using organic solvent extraction,NMR method and high pressure mercury intrusion methods,and the free oil content by using NMR fluid distribution secondary spectral stripping decomposition and logging.The research results contribute supplemental insights on continental shale oil deliverability in China,and provide a scientific basis for the rapid exploration and large-scale production of lacustrine shale oil.
基金National Natural Science Foundation of China(52375378)National Key Laboratory of Metal Forming Technology and Heavy Equipment(S2308100.W12)Huxiang High-Level Talent Gathering Project of Hunan Province(2021RC5001)。
文摘The titanium alloy strut serves as a key load-bearing component of aircraft landing gear,typically manufactured via forging.The friction condition has important influence on material flow and cavity filling during the forging process.Using the previously optimized shape and initial position of preform,the influence of the friction condition(friction factor m=0.1–0.3)on material flow and cavity filling was studied by numerical method with a shear friction model.A novel filling index was defined to reflect material flow into left and right flashes and zoom in on friction-induced results.The results indicate that the workpiece moves rigidly to the right direction,with the displacement decreasing as m increases.When m<0.18,the underfilling defect will occur in the left side of strut forging,while overflow occurs in the right forging die cavity.By combining the filling index and analyses of material flow and filling status,a reasonable friction factor interval of m=0.21–0.24 can be determined.Within this interval,the cavity filling behavior demonstrates robustness,with friction fluctuations exerting minimal influence.
基金financially supported by the Science and Technology Innovation Program of Hunan Province,No.2022RC1220(to WP)China Postdoctoral Science Foundation,No.2022M711733(to ZZ)+2 种基金the National Natural Science Foundation of China,No.82160920(to ZZ)Hebei Postdoctoral Scientific Research Project,No.B2022003040(to ZZ)Hunan Flagship Department of Integrated Traditional Chinese and Western Medicine(to WP)。
文摘Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.
文摘Metamorphic mechanism has the advantages of variable topology and variable degrees of freedom, which can realize the requirements of multi-conditions and multi-tasks, and has a good application prospect. The configuration transformation is prominent feature of the metamorphic mechanism. The number of constraints or properties of the kinematic pairs provided by the metamorphic kinematic pairs will change under certain conditions, its dynamic performance is much more complex than that of traditional kinematic pairs with immutable constraints. However, the clearance model about traditional kinematic pairs with immutable constraints established by long-term research is difficult to be directly applied to the metachromatic kinematic pairs. Referring to the experience of the traditional kinematic pairs with immutable constraints, the continuous contact model of Metamorphic Groove pin pair with clearance is established. According to the traditional continuous contact model of the kinematic pairs with immutable constraints, the forces between the elements of kinematic pair of the mechanism with clearance and the ideal mechanism without clearance are regarded as the same, and the inertia force and inertia moment of the components are also calculated according to the acceleration of the ideal mechanism. The clearance is regarded as a massless virtual bar with length r. For the rotating pair part, the massless virtual bar length r is the difference between the radius of the shaft and the hole, and for the sliding pair part, the massless virtual bar length r is half of the difference between the height of the slider and the guide groove. According to the new mechanism without gap after adding the imaginary bar, kinetic energy and potential energy of the system are calculated for the two configurations of mechanism with metamorphic Groove pin pair with clearance. The kinetic energy and potential energy of the system are calculated according to the new mechanism without clearance after adding the massless virtual bar. The kinetic energy, potential energy and generalized force are substituted into the Lagrangian equation to obtain the motion equation of the metamorphic mechanism, which lays the foundation for the dynamic performance study of the mechanism with metamorphic groove pin pair with clearance.
基金Supported by Daqing City Philosophy and Social Sciences Planning Research Project(DSGB 2025011)the Heilongjiang Province Education Science Planning Key Project(GJB1320229).
文摘Based on questionnaire surveys and field interviews conducted with various types of agricultural production organizations across five districts and four counties in Daqing City,this study combines relevant theoretical frameworks to systematically examine the evolution,performance,and influencing factors of governance mechanisms within these organizations.Using both quantitative and inductive analytical methods,the paper proposes innovative designs and supporting measures for improving governance mechanisms.The findings reveal that,amid large-scale farmland circulation,the governance mechanisms of agricultural production organizations in Daqing City are evolving from traditional to modern structures.However,challenges remain in areas such as decision-making efficiency,benefit distribution,and supervision mechanisms.In response,this study proposes innovative governance designs focusing on decision-making processes,profit-sharing mechanisms,and risk prevention.Corresponding policy recommendations are also provided to support the sustainable development of agricultural modernization in China.
基金the National Natural Science Foundation of China(Nos.T2322004 and 22078066)。
文摘Currently,it is still a challenge to develop an organic photosensitizer(PS)with outstanding near-infrared absorption,low O2dependence,precise tumor targeting and rapid clearance through the kidney to improve the overall outcome of phototherapy.In this study,we have designed an organic PS(Nc PB)with an excellent near-infrared light absorption through a refined molecular strategy.Meanwhile,Nc PB was assembled into nanoparticles with different sizes(Nano Nc PB-1 and Nano Nc PB-0)by a supramolecular modulation strategy.As the results,the nanoparticle with an ultra-small size(Nano Nc PB-1)generated a large number of superoxide anion(O_(2)^(·-))in a low-O_(2)-dependent manner and release plenty of heat.Furthermore,the results of in vivo experiments demonstrated that Nano Nc PB-1 actively accumulated in tumor tissues and showed a 92%tumor inhibition after photodynamic and photothermal combination therapy.More importantly,Nano Nc PB-1 could be rapidly cleared from the body of mice via the renal pathway,which alleviates potential side effects of prolonged retention of PS in the circulation.
基金The Australian Research Council(DP200101197,DP230101107).
文摘Formalizing complex processes and phenomena of a real-world problem may require a large number of variables and constraints,resulting in what is termed a large-scale optimization problem.Nowadays,such large-scale optimization problems are solved using computing machines,leading to an enormous computational time being required,which may delay deriving timely solutions.Decomposition methods,which partition a large-scale optimization problem into lower-dimensional subproblems,represent a key approach to addressing time-efficiency issues.There has been significant progress in both applied mathematics and emerging artificial intelligence approaches on this front.This work aims at providing an overview of the decomposition methods from both the mathematics and computer science points of view.We also remark on the state-of-the-art developments and recent applications of the decomposition methods,and discuss the future research and development perspectives.
文摘This article focuses on the management of large-scale machinery and equipment in highway construction,with the research objective of identifying issues at the management level and exploring more effective management measures.Through practical observation and logical analysis,this article elaborates on the management connotations of large-scale machinery and equipment in highway construction,affirming its management value from different perspectives.On this basis,it carefully analyzes the problems existing in the management of large-scale machinery and equipment,providing a detailed interpretation of issues such as the weak foundation of the equipment management system and the disconnection between equipment selection and configuration from reality.Combining the manifestations of related problems,this article proposes strategies such as strengthening the institutional foundation of equipment management,selecting and configuring equipment based on actual conditions,aiming to provide references for large-scale machinery and equipment management to relevant enterprises.
基金Funded by the National Natural Science Foundation of China(52066011)Jiuquan Science and Technology Plan Project University-Level Key Project(2024XJKXM03)Foundation of Key Laboratory of Solar Power System(Grant No.2024SPKL03).
文摘Bulb-type hydro turbines are commonly used in small-to medium-scale hydropower stations due to their compact design and adaptability to low-head conditions.However,long-termoperation often results in wear at the runner rim,increasing tip clearance and triggering leakage flow and cavitation.These effects reduce hydraulic efficiency and accelerate blade surface erosion,posing serious risks to unit safety and operational stability.This study investigates the influence of tip clearance on cavitation performance in a 24 MW prototype bulb turbine.A three-dimensional numericalmodel is developed to simulate various operating conditions with different tip clearance values(3.0,4.5,and 6.0 mm)and cavitation numbers(σ=1.20–1.33).Internal flow characteristics—including pressure distribution,velocity fields,hydraulic efficiency,and pressure pulsation—are analyzed to elucidate the impact of tip clearance on cavitation development.Results show that underσ=1.2 and a 4.5 mm tip clearance,the pressure pulsation amplitude at the blade tip reaches 4870 Pa—approximately 1.5 times higher than that near the hub.At partial flowconditions,turbine efficiency decreases by up to 6.8%compared to the rated condition.Increasing the tip clearance from 1.5 to 6.0 mm expands the low-pressure area near the blade tip by around 32%,significantly intensifying cavitation.Frequency domain analysis reveals dominant pulsation frequencies between 10–20Hz,characterized by blade-passing features and a wave-clipping effect.These findings provide theoretical insight and quantitative evidence to support the optimization of tip clearance design and cavitation mitigation strategies in bulb turbines,aiming to improve both efficiency and operational stability.
基金supported by the National Nature Science Foundation of China National Outstanding Youth Science Fund Project(Grant No.52122109)the National Natural Science Foundation of China(Grants No.51861165102 and 52039005).
文摘Offshore wind power plays a crucial role in energy strategies.The results of traditional small-scale physical models may be unreliable when extrapolated to large field scales.This study addressed this limitation by conducting large-scale(1:13)experiments to investigate the scour hole pattern and equilibrium scour depth around both slender and large monopiles under irregular waves.The experiments adopted KeuleganeCarpenter number(NKC)values from 1.01 to 8.89 and diffraction parameter(D/L,where D is the diameter of the monopile,and L is the wave length)values from 0.016 to 0.056.The results showed that changes in the maximum scour location and scour hole shape around a slender monopile were associated with NKC,with differences observed between irregular and regular waves.Improving the calculation of NKC enhanced the accuracy of existing scour formulae under irregular waves.The maximum scour locations around a large monopile were consistently found on both sides,regardless of NKC and D/L,but the scour hole topography was influenced by both parameters.Notably,the scour range around a large monopile was at least as large as the monopile diameter.
基金supported by the Fundamental Research Funds for the Central Universities(Grant Nos.lzujbky-2021-62 and lzujbky-2024-jdzx06)the National Natural Science Foundation of China(Grant No.12247101)+1 种基金the Natural Science Foundation of Gansu Province,China(Grant Nos.22JR5RA389 and 23JRRA1740)the‘111 Center’Fund(Grant No.B20063).
文摘It has been argued that the human brain,as an information-processing machine,operates near a phase transition point in a non-equilibrium state,where it violates detailed balance leading to entropy production.Thus,the assessment of irreversibility in brain networks can provide valuable insights into their non-equilibrium properties.In this study,we utilized an open-source whole-brain functional magnetic resonance imaging(fMRI)dataset from both resting and task states to evaluate the irreversibility of large-scale human brain networks.Our analysis revealed that the brain networks exhibited significant irreversibility,violating detailed balance,and generating entropy.Notably,both physical and cognitive tasks increased the extent of this violation compared to the resting state.Regardless of the state(rest or task),interactions between pairs of brain regions were the primary contributors to this irreversibility.Moreover,we observed that as global synchrony increased within brain networks,so did irreversibility.The first derivative of irreversibility with respect to synchronization peaked near the phase transition point,characterized by the moderate mean synchronization and maximized synchronization entropy of blood oxygenation level-dependent(BOLD)signals.These findings deepen our understanding of the non-equilibrium dynamics of large-scale brain networks,particularly in relation to their phase transition behaviors,and may have potential clinical applications for brain disorders.
文摘Combining practical engineering projects, this article analyzes the design strategies for the reconstruction and expansion of insufficient clearance sections in highway interchanges. This includes an overview of the project, a comparison of design options for insufficient clearance in interchanges, and the main design strategies for reconstruction and expansion. It is hoped that this analysis can provide a reference for the design of such road reconstruction and expansion projects.
基金Guangdong Major Project of Basic and Applied Basic Research (2020B0301030004)National Natural Science Foundation of China (42275041)Hainan Province Science and Technology Special Fund (SOLZSKY2025006)。
文摘In 2022, South China(SC) experienced record-breaking rainfall during its first rainy season, causing severe socioeconomic losses. This study examines the large-scale circulation anomalies responsible for this extreme event.Analysis reveals that the lower-tropospheric cyclonic anomaly over SC plays a crucial role. This cyclonic anomaly consists of extratropical northeasterly anomalies to the north of SC and tropical southwesterly anomalies to the south. Both components were particularly intense during the 2022 first rainy season, contributing to the heavy rainfall in SC. Moreover,the lower-tropospheric cyclonic anomaly is enhanced by its counterpart in the upper troposphere, which is associated with a wave train propagating from the North Atlantic to East Asia across the mid-high latitudes of the Eurasian continent.Further analysis indicates that the extratropical wave train correlates with sea surface temperature anomalies(SSTAs) in the North Atlantic. Additionally, the SSTAs over the North Indian Ocean also play a role in enhancing the tropical southwesterlies in the lower troposphere. This study highlights the combined influence of tropical and extratropical circulation anomalies, offering a comprehensive understanding of the record-breaking rainfall.
