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
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
The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately iden...The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately identifying the rotor unbalance.This paper utilizes a high-frequency composite sensor to monitor the engine’s blade tip clearance(BTC)and extracts unbalanced information from BTC signals for rotor dynamic balancing,while avoiding the need for the once per revolution(OPR)sensor.First,the vibration characteristics of the rotor-blade system under multi-fault conditions are investigated.Then,based on BTC measurement,a none OPR method and an unbalance identification method are proposed,in which the radial vibration of the blade tip in the BTC signals at different speeds is extracted and operated in the time domain to obtain the rotor unbalanced vibration,the signal is reconstructed,and cross-correlation analysis is used to accurately identify the magnitude and phase of the unbalanced signal.Finally,a rotor test bench is utilized for experimental verification.The results reveal that the dynamic balancing method based on the BTC signal can more precisely identify the rotor unbalance than the traditional rotor dynamic balancing method.The application of this technique will effectively improve engine health management and fault prediction.展开更多
BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized th...BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.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
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
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
Mechanical vibration sputum clearance is commonly used for airway clearance.However,existing handheld vibration-assisted expectorators confront several challenges including operator’s hand fatigue and a high risk of ...Mechanical vibration sputum clearance is commonly used for airway clearance.However,existing handheld vibration-assisted expectorators confront several challenges including operator’s hand fatigue and a high risk of cross-infection between medical staff and patients.To address these issues,this study presents a novel design for an intelligent percussion-based sputum clearance robot.The robot is designed to assist medical staff in providing percussion-based sputum clearance nursing for patients.Initially,the structure of the robot is designed based on the environmental conditions in the intensive care unit(ICU).To mitigate the impact of the vibrations generated by the vibration percussion head on the robotic arm operation,a fixture equipped with a vibration damper is designed to ensure that the robot’s standard functionality remains unaffected.Furthermore,a human back detection(HBD)framework constructed from multi-subtask modules is proposed to address the shortcomings of existing robotic systems in terms of human perception capabilities.These modules are designed to accurately identify and map the anatomical features of the human back.This effectively improves the capability of the robot to interact with the human body.Based on this framework,the robotic arm is controlled precisely to emulate the percussion strategies employed by physicians.Finally,extensive experiments are conducted in a real-world setting with multiple participants.The results indicate that the robot could provide percussion-based sputum clearance nursing that is practically equivalent to the operations by medical staff.展开更多
As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canist...As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canister,have grown increasingly complex.However,deficiencies still exist in the current launch modeling theory for BMLRS.In this study,a multi-rigid-flexible-body launch dynamics model coupling the launch platform and rocket was established using the multibody system transfer matrix method and the Newton-Euler formulation.Furthermore,considering the bending of the launch canister,a detection algorithm for slider-guide plane clearance contact was proposed.To quantify the contact force and friction effect between the slider and guide,the contact force model and modified Coulomb model were introduced.Both the modal and launch tests were conducted.Additionally,the modal convergence was verified.By comparing the modal experiments and simulation results,the maximum relative error of the eigenfrequency is 3.29%.thereby verifying the accuracy of the developed BMLRS dynamics model.Furthermore,the launch test validated the proposed plane clearance contact model.Moreover,the study investigated the influence of various model parameters on the dynamic characteristics of BMLRS,including launch canister bending stiffness,slider and guide material,slider-guide clearance,slider length and layout.This analysis of influencing factors provides a foundation for future optimization in BMLRS design.展开更多
This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-ho...This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10, 0.14 and 0.19. At each exit Mach number, experiments are performed at the tip clearance heights of 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of the blade height. The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied. The results show that at a given tip clearance height, generally, total pressure loss rises with exit Mach numbers proportionally. At a fixed exit Mach number, the total pressure loss augments nearly proportionally as the tip clearance height increases. The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade. Compared to the effects of the tip clearance height, the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.展开更多
本文深入剖析了国内外关于电动垂直起降航空器(electric Vertical Take-off and Landing,eVTOL)起降点净空要求的相关规范,通过实例分析,找出适用于不同性能水平的eVTOL的净空需求。研究方法是对现有规范的梳理以及结合具体eVTOL性能水...本文深入剖析了国内外关于电动垂直起降航空器(electric Vertical Take-off and Landing,eVTOL)起降点净空要求的相关规范,通过实例分析,找出适用于不同性能水平的eVTOL的净空需求。研究方法是对现有规范的梳理以及结合具体eVTOL性能水平的实例分析。研究内容涵盖eVTOL起降点的重要术语定义、障碍物限制面要求以及无障碍空域的参数要求等。研究结论表明,中国民用机场协会团体标准在悬停高度≤D值时的净空要求比EASA规章更严格,更适合在净空环境复杂的城市中使用,但在较低的悬停高度时,对于起飞爬升面的下方障碍物要求也会更加严格。未来研究将着重结合国内通过适航审定的机型,进一步细化并提出针对不同构型的eVTOL的精准净空建议。展开更多
Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Alt...Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.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.
基金supported by the Key Program of National Natural Science Foundation of China(No.92160203)National Natural Science Foundation of China(No.92360306).
文摘The existence of the aeroengine casing,limited monitoring points,and multi-fault characteristics make obtaining the rotor’s vibration transmission characteristics challenging,resulting in difficulties accurately identifying the rotor unbalance.This paper utilizes a high-frequency composite sensor to monitor the engine’s blade tip clearance(BTC)and extracts unbalanced information from BTC signals for rotor dynamic balancing,while avoiding the need for the once per revolution(OPR)sensor.First,the vibration characteristics of the rotor-blade system under multi-fault conditions are investigated.Then,based on BTC measurement,a none OPR method and an unbalance identification method are proposed,in which the radial vibration of the blade tip in the BTC signals at different speeds is extracted and operated in the time domain to obtain the rotor unbalanced vibration,the signal is reconstructed,and cross-correlation analysis is used to accurately identify the magnitude and phase of the unbalanced signal.Finally,a rotor test bench is utilized for experimental verification.The results reveal that the dynamic balancing method based on the BTC signal can more precisely identify the rotor unbalance than the traditional rotor dynamic balancing method.The application of this technique will effectively improve engine health management and fault prediction.
基金Supported by the Tianjin Health Research Project(Key Project),No.TJWJ2024ZD004Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-034A.
文摘BACKGROUND Chronic hepatitis B(CHB)patients rarely achieve functional cure with initial pegylated interferon alpha-2b(Peg-IFNα-2b)therapy.Validated tools to guide retreatment candidates are lacking.We hypothesized that clinical indicators predict hepatitis B surface antigen(HBsAg)clearance during retreatment.AIM To develop a prediction model for HBsAg clearance in Peg-IFNα-2b retreatment.METHODS In this retrospective cohort study,we enrolled 135 CHB/compensated cirrhosis patients receiving Peg-IFNα-2b retreatment after initial non-clearance at Tianjin University Central Hospital(2017-2025).Predictors were identified through univariate Cox,least absolute shrinkage and selection operator,and multivariate Cox regression.Model performance was assessed via receiver operating characteristic analysis and Harrell’s C-index,with risk stratification by X-tile optimization.RESULTS HBsAg clearance rate was 20.74%(28/135).Independent predictors included:Combination nucleos(t)ide analogue(NA)therapy during initial treatment[hazard ratio(HR)=0.276,95%confidence interval(CI):0.092-0.833],baseline HBsAg at retreatment(HR=0.571,95%CI:0.410-0.795),HBsAg decline after initial treatment(HR=2.050,95%CI:1.108-3.793),and treatment interval(HR=1.013/week,95%CI:1.008-1.018).The retreatment HBsAg clearance prediction score(RHCP-S)demonstrated area under the curve of 0.920(95%CI:0.863-0.946),sensitivity of 92.3%,specificity of 79.3%.Clearance rates differed significantly:RHCP-S challenge group(≤74 points):3.45%,RHCP-S probable group(74-110 points):29.63%,RHCP-S dominant group(≥110 points):80.95%(P<0.001).CONCLUSION The overall HBsAg clearance rate with Peg-IFNα-2b retreatment was 20.74%(28/135).The RHCP-S model identifies optimal retreatment candidates(≥110 points)with 80.95%clearance probability,associated with the absence of combination NA therapy during initial treatment,greater initial HBsAg decline,longer intervals,and lower retreatment HBsAg.
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.
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.
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 National Key R&D Program of China(Grant No.2021YFC0122700).
文摘Mechanical vibration sputum clearance is commonly used for airway clearance.However,existing handheld vibration-assisted expectorators confront several challenges including operator’s hand fatigue and a high risk of cross-infection between medical staff and patients.To address these issues,this study presents a novel design for an intelligent percussion-based sputum clearance robot.The robot is designed to assist medical staff in providing percussion-based sputum clearance nursing for patients.Initially,the structure of the robot is designed based on the environmental conditions in the intensive care unit(ICU).To mitigate the impact of the vibrations generated by the vibration percussion head on the robotic arm operation,a fixture equipped with a vibration damper is designed to ensure that the robot’s standard functionality remains unaffected.Furthermore,a human back detection(HBD)framework constructed from multi-subtask modules is proposed to address the shortcomings of existing robotic systems in terms of human perception capabilities.These modules are designed to accurately identify and map the anatomical features of the human back.This effectively improves the capability of the robot to interact with the human body.Based on this framework,the robotic arm is controlled precisely to emulate the percussion strategies employed by physicians.Finally,extensive experiments are conducted in a real-world setting with multiple participants.The results indicate that the robot could provide percussion-based sputum clearance nursing that is practically equivalent to the operations by medical staff.
基金supported by National Natural Science Foundation of China(Grant No.92266201).
文摘As the performance of the box-type multiple launch rocket system(BMLRS)improves,its mechanical structures,particularly the plane clearance design between the slider on the rocket and the guide inside the launch canister,have grown increasingly complex.However,deficiencies still exist in the current launch modeling theory for BMLRS.In this study,a multi-rigid-flexible-body launch dynamics model coupling the launch platform and rocket was established using the multibody system transfer matrix method and the Newton-Euler formulation.Furthermore,considering the bending of the launch canister,a detection algorithm for slider-guide plane clearance contact was proposed.To quantify the contact force and friction effect between the slider and guide,the contact force model and modified Coulomb model were introduced.Both the modal and launch tests were conducted.Additionally,the modal convergence was verified.By comparing the modal experiments and simulation results,the maximum relative error of the eigenfrequency is 3.29%.thereby verifying the accuracy of the developed BMLRS dynamics model.Furthermore,the launch test validated the proposed plane clearance contact model.Moreover,the study investigated the influence of various model parameters on the dynamic characteristics of BMLRS,including launch canister bending stiffness,slider and guide material,slider-guide clearance,slider length and layout.This analysis of influencing factors provides a foundation for future optimization in BMLRS design.
基金National Natural Science Foundation of China (10377011)
文摘This article describes the effects of some factors on the tip clearance flow in axial linear turbine cascades. The measurements of the total pressure loss coefficient are made at the cascade outlets by using a five-hole probe at exit Mach numbers of 0.10, 0.14 and 0.19. At each exit Mach number, experiments are performed at the tip clearance heights of 1.0%, 1.5%, 2.0%, 2.5% and 3.0% of the blade height. The effects of the non-uniform tip clearance height of each blade in the pitchwise direction are also studied. The results show that at a given tip clearance height, generally, total pressure loss rises with exit Mach numbers proportionally. At a fixed exit Mach number, the total pressure loss augments nearly proportionally as the tip clearance height increases. The increased tip clearance heights in the tip regions of two adjacent blades are to be blame for the larger clearance loss of the center blade. Compared to the effects of the tip clearance height, the effects of the exit Mach number and the pitchwise variation of the tip clearance height on the cascade total pressure loss are so less significant to be omitted.
文摘本文深入剖析了国内外关于电动垂直起降航空器(electric Vertical Take-off and Landing,eVTOL)起降点净空要求的相关规范,通过实例分析,找出适用于不同性能水平的eVTOL的净空需求。研究方法是对现有规范的梳理以及结合具体eVTOL性能水平的实例分析。研究内容涵盖eVTOL起降点的重要术语定义、障碍物限制面要求以及无障碍空域的参数要求等。研究结论表明,中国民用机场协会团体标准在悬停高度≤D值时的净空要求比EASA规章更严格,更适合在净空环境复杂的城市中使用,但在较低的悬停高度时,对于起飞爬升面的下方障碍物要求也会更加严格。未来研究将着重结合国内通过适航审定的机型,进一步细化并提出针对不同构型的eVTOL的精准净空建议。
文摘Mitochondrial dysfunction has emerged as a critical factor in the etiology of various neurodevelopmental disorders, including autism spectrum disorders, attention-deficit/hyperactivity disorder, and Rett syndrome. Although these conditions differ in clinical presentation, they share fundamental pathological features that may stem from abnormal mitochondrial dynamics and impaired autophagic clearance, which contribute to redox imbalance and oxidative stress in neurons. This review aimed to elucidate the relationship between mitochondrial dynamics dysfunction and neurodevelopmental disorders. Mitochondria are highly dynamic organelles that undergo continuous fusion and fission to meet the substantial energy demands of neural cells. Dysregulation of these processes, as observed in certain neurodevelopmental disorders, causes accumulation of damaged mitochondria, exacerbating oxidative damage and impairing neuronal function. The phosphatase and tensin homolog-induced putative kinase 1/E3 ubiquitin-protein ligase pathway is crucial for mitophagy, the process of selectively removing malfunctioning mitochondria. Mutations in genes encoding mitochondrial fusion proteins have been identified in autism spectrum disorders, linking disruptions in the fusion-fission equilibrium to neurodevelopmental impairments. Additionally, animal models of Rett syndrome have shown pronounced defects in mitophagy, reinforcing the notion that mitochondrial quality control is indispensable for neuronal health. Clinical studies have highlighted the importance of mitochondrial disturbances in neurodevelopmental disorders. In autism spectrum disorders, elevated oxidative stress markers and mitochondrial DNA deletions indicate compromised mitochondrial function. Attention-deficit/hyperactivity disorder has also been associated with cognitive deficits linked to mitochondrial dysfunction and oxidative stress. Moreover, induced pluripotent stem cell models derived from patients with Rett syndrome have shown impaired mitochondrial dynamics and heightened vulnerability to oxidative injury, suggesting the role of defective mitochondrial homeostasis in these disorders. From a translational standpoint, multiple therapeutic approaches targeting mitochondrial pathways show promise. Interventions aimed at preserving normal fusion-fission cycles or enhancing mitophagy can reduce oxidative damage by limiting the accumulation of defective mitochondria. Pharmacological modulation of mitochondrial permeability and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, an essential regulator of mitochondrial biogenesis, may also ameliorate cellular energy deficits. Identifying early biomarkers of mitochondrial impairment is crucial for precision medicine, since it can help clinicians tailor interventions to individual patient profiles and improve prognoses. Furthermore, integrating mitochondria-focused strategies with established therapies, such as antioxidants or behavioral interventions, may enhance treatment efficacy and yield better clinical outcomes. Leveraging these pathways could open avenues for regenerative strategies, given the influence of mitochondria on neuronal repair and plasticity. In conclusion, this review indicates mitochondrial homeostasis as a unifying therapeutic axis within neurodevelopmental pathophysiology. Disruptions in mitochondrial dynamics and autophagic clearance converge on oxidative stress, and researchers should prioritize validating these interventions in clinical settings to advance precision medicine and enhance outcomes for individuals affected by neurodevelopmental disorders.
