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Nanomaterials-mediated lysosomal regulation:a robust protein-clearance approach for the treatment of Alzheimer’s disease

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Neural Regeneration Research 2025年第2期20卷 424-439页

作者： Mengqi Hao Jianjian Chu Tinglin Zhang Tong Yin Yuankai Gu Wendanqi Liang Wenbo Ji Jianhua Zhuang Yan Liu Jie Gao You Yin Department of Neurology Second Affiliated Hospital of Naval Medical University(Shanghai Changzheng Hospital)ShanghaiChina school of Health Science and Engineering University of Shanghai for Science and TechnologyShanghaiChina Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghaiChina Department of Clinical Pharmacy Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Neurology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the ***,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular *** studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s *** the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s ***,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and ***,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical *** review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s *** review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal *** conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s *** application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.

关键词： Alzheimer’s disease autophagy dysfunction lysosomal acidification lysosomal system nanomaterials neurodegenerative diseases

Evaluation of Haney-Type Surface ThermalBoundary Conditions Using a CoupledAtmosphere and Ocean Model

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Advances in Atmospheric Sciences 2001年第3期18卷 355-375页

作者： Peter C. Chu 陈玉春吕世华 Department of Oceanography Naval Postgraduate School

A coupled atmosphere-ocean model developed at the Institute for Space Studies at NASA Goddard Space Flight Center (Russell et al., 1995) was used to verify the validity of Haney-type surface thermal boundary condition, which linearly connects net downward surface heat fluxQ to air/sea temperature difference ΔT by a relaxation coefficientk. The model was initiated from the National Centers for Environmental Prediction (NCEP) atmospheric observations for 1 December 1977, and from the National Ocean Data Center (NODC) global climatological mean December temperature and salinity fields at 1°x 1° resolution. The time step is 7.5 minutes. We integrated the model for 450 days and obtained a complete model-generated global data set of daily mean downward net surface fluxQ, surface air temperatureT A, and sea surface temperatureT O. Then, we calculated the cross-correlation coefficients (CCC) betweenQ and ΔT. The ensemble mean CCC fields show (a) no correlation betweenQ and ΔT in the equatiorial regions, and (b) evident correlation (CCC≥0.7) betweenQ and ΔT in the middle and high latitudes. Additionally, we did the variance analysis and found that whenk=120 W m?2K?1, the two standard deviations, σQ and σκδT , are quite close in the middle and high latitudes. These results agree quite well with a previous research (Chu et al., 1998) on analyzing the NCEP re-analyzed surface data, except that a smaller value ofk (80 W m?2K?1) was found in the previous study. Key words Air-sea coupled system - Ocean surface fluxes - Surface thermal boundary condition

关键词： Air-sea coupled system Ocean surface fluxes Surface thermal boundary condition

Improvement of tree-like network constructal method for heat conduction optimization

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Science China(Technological Sciences) 2006年第3期49卷 332-341页

作者： WU Wenjun CHEN Lingen SUN Fengrui postgraduate school Naval University of Engineering Wuhan 430033 China Postgraduate School Naval University of Engineering Wuhan 430033 China Postgraduate School Naval University of Engineering Wuhan 430033 China

The analysis of the “tree-like network” construct method has been repeated. The high effective conduction channel distribution has been optimized again, without the premise that the new order assembly construct must be assembled by the optimized last order construct. It is proved that the “tree-like network” construct method is faultiness. A more optimal construct is obtained,; when the thermal conductivity; the proportion of the two heat conduction materials are constant, the limit of the minimum heat resistance is derived. All these conclusions can be used to guide the engineering application.

关键词： constructal theory, 'tree-like network' construct method, high effective conduction channel distribution, generalized thermodynamic optimization.

Thermal fronts and cross-frontal heat flux in the southern Huanghai Sea and the East China Sea

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Acta Oceanologica Sinica 2008年第5期27卷 1-20页

作者： PARK Sunghyea CHU Peter C Department of Oceanography Naval Postgraduate School

Synoptic features in/around thermal fronts and cross-frontal heat fluxes in the southern Huanghai./Yellow Sea and East China Sea （HES） were examined using the data collected from four airborne expendable bathythermograph surveys with horizontal approxmately 35 km and vertical 1 m（from the surface to 400 m deep） spacings. Since the fronts are strongly affected by HES current system, the synoptic thermal features in/around them represent the interaction of currents with surrounding water masses. These features can not be obtained from climatological data. The identified thermal features are listed as follows ：（ 1 ） multiple boundaries of cold water, asymmetric thermocline intrusion, locally-split front by homogeneous water of approxmately 18 ℃, and mergence of the front by the Taiwan Warm Current in/around summertime southern Cheju - Changjiang/Yangtze front and Tsushima front; （2） springtime frontal eddy-like feature around Tsushima front; （3） year-round cyclonic meandering and summertime temperature-inversion at the bottom of the surface mixed layer in Cheju - Tsushima front; and （4） multistructure of Kuroshio front. In the Kuroshio front the mean variance of vertical temperature gradient is an order of degree smaller than that in other HES fronts. The southern Cheju- Changjiang front and Cheju -Tsushima front are connected with each other in the summer with comparable cross-frontal temperature gradient. However, cross-frontal heat flux and lateral eddy diffusivity are stronger in the southern Cheju - Changjiang front. The cross-frontal heat exchange is the largest in the mixing zone between the modified Huanghai Sea bottom cold water and the Tsushima Warm Current, which is attributable to enhanced thermocline intrusions.

关键词： southern Huanghai Sea and East China Sea AXBT synoptic thermal front cross-frontal heat flux lateral eddy diffusivity

Constructal optimization of twice Y-shaped assemblies of fins by taking maximum thermal resistance minimization as objective

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Science China(Technological Sciences) 2010年第10期53卷 2756-2764页

作者： XIE ZhiHui, CHEN LinGen & SUN FengRui postgraduate school, naval University of Engineering, Wuhan 430033, China postgraduate school Naval University of Engineering Wuhan China

In this paper,constructal optimization of the twice Y-shaped assemblies of fins with six freedom degrees (characteristic parameters of geometry) is performed by employing finite element method and taking dimensionless maximum thermal resistance as a performance index,and the heat transfer performance of the twice Y-shaped assemblies of fins under various conditions with different freedom degrees are analyzed. The results show that the twice assemblies can improve the heat transfer performance of Y-shaped fin remarkably,and the minimum maximum thermal resistance of the twice Y-shaped assemblies of fins decreases by 36.37% compared with that of once Y-shaped assembly of fins. It is also proved again that the larger the number of freedom degrees for evolving is,the more perfect the system performance is. The effects of different characteristic parameters of geometry on the performance of the twice Y-shaped assemblies of fins are different,one should pay different attention to these parameters in practical engineering designs. The effects of two angles on the maximum thermal resistance are larger,but the optima of the two angles are robust. The effects of two height ratios on the maximum thermal resistance are more remarkable than those of two thickness ratios.

关键词： constructal theory fin multi-scale enhanced heat transfer generalized thermodynamic optimization

Thermodynamic characteristics of a Brownian heat pump in a spatially periodic temperature field

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Science China(Physics,Mechanics & Astronomy) 2010年第5期53卷 876-885页

作者： DING ZeMin,CHEN LinGen & SUN FengRui postgraduate school,naval University of Engineering,Wuhan 430033,China postgraduate school Naval University of Engineering Wuhan China

This paper has studied the thermodynamic performance of a thermal Brownian heat pump,which consists of Brownian particles moving at a periodic sawtooth potential with external forces and contacting with the alternating hot and cold reservoirs along the space *** heat flows driven by both potential and kinetic energies are taken into *** analytical expressions for the heating load,coefficient of performance(COP) and power input of the Brownian heat pump are derived and the performance characteristics are obtained by numerical *** is shown that due to the heat flow via the change of kinetic energy of the particles,the Brownian heat pump is always irreversible and the COP can never attain the Carnot *** study has also investigated the influences of the operating parameters,*** external force,barrier height of the potential,asymmetry of the sawtooth potential and temperature ratio of the heat reservoirs,on the performance of the Brownian heat *** effective regions of external force and barrier height of the potential in which the Brownian motor can operates as a heat pump are *** results show that the performance of the Brownian heat pump greatly depends on the parameters;if the parameters are properly chosen,the Brownian heat pump may be controlled to operate in the optimal regimes.

关键词： Brownian heat pump COP heating load heat flow performance characteristics finite time thermodynamics

Optimal paths for a light-driven engine with a linear phenomenological heat transfer law

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Science China Chemistry 2010年第4期53卷 917-926页

作者： MA Kang, CHEN LinGen & SUN FengRui postgraduate school, naval University of Engineering, Wuhan 430033, China postgraduate school Naval University of Engineering Wuhan China

An irreversible light-driven engine is described in this paper, in which the heat transfer between the working fluid and the environment obeys a linear phenomenological heat transfer law [ q ∝Δ(T -1)], with a working fluid composed of the bimolecular reacting system 2SO 3 F■S 2 O 6 F2. Piston trajectories maximizing work output and minimizing entropy generation are determined for such an engine with rate-dependent loss mechanisms of friction and heat leakage. The optimal control theory is applied to determine the optimal configurations of the piston motion trajectory and the fluid temperature. Numerical examples for the optimal configuration are provided, and the obtained results are compared with those derived with Newtonian heat transfer law [ q ∝Δ(T )].

关键词： linear phenomenological heat transfer law maximum work output minimum entropy generation irreversible lightdriven engine optimal control finite time thermodynamics

Constructal optimization of discrete and continuous-variable cross-section conducting path based on entransy dissipation rate minimization

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Science China(Technological Sciences) 2010年第6期53卷 1666-1677页

作者： WEI ShuHuan,CHEN LinGen & SUN FengRui postgraduate school,naval University of Engineering,Wuhan 430033,China postgraduate school Naval University of Engineering Wuhan China

Using constructal entransy dissipation rate minimization method based on discrete variable cross-section conducting path,constructal optimizations of elemental area with variable cross-section conducting path are performed,and the results are compared with the optimization results of elemental area with the constant cross-section conducting *** comparison shows that the minimum mean temperature difference based on elemental area with variable cross-section conducting path increases and approaches a constant as the assembly's order increases,but the minimum mean temperature difference based on elemental area with constant cross-section conducting path decreases and approaches a constant as the assembly's order *** difference between them is caused by the different dimensionless mean temperature difference of the first order assembly.A universal constructal optimization method by self similar organization to improve heat transfer ability and its corresponding rule are *** the constructal optimization method by self similar organization based on entransy dissipation rate minimization objective,the mean temperature difference approaches a constant as the assembly's order increases.

关键词： constructal theory entransy entransy dissipation area-point conduction generalized thermodynamic optimization

“Volume-Point” heat conduction constructal optimization with entransy dissipation minimization objective based on rectangular element

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Science China(Technological Sciences) 2008年第8期51卷 1283-1295页

作者： WEI ShuHuan, CHEN LinGen & SUN FengRui postgraduate school, naval University of Engineering, Wuhan 430033, China postgraduate school Naval University of Engineering Wuhan China

By taking equivalent thermal resistance, which reflects the average heat conduc- tion effect and is defined based on entransy dissipation, as optimization objective, the "volume to point" constructal problem of how to discharge the heat generated in a fixed volume to a heat sink on the border through relatively high conductive link is re-analyzed and re-optimized in this paper. The constructal shape of the control volume with the best average heat conduction effect is deduced. For the elemental area and the first order construct assembly, when the thermal current density in the high conductive link is linear with the length, the optimized shapes of assemble based on the minimization of entransy dissipation are the same as those based on minimization of maximum temperature difference, and the mean tem- perature difference is 2/3 of the maximum temperature difference. For the second and higher order construct assemblies, the thermal current densities in the high conductive link are not linear with the length, and the optimized shapes of assem- ble based on the minimization of entransy dissipation are different from those based on minimization of maximum temperature difference. For the same parame- ters, the constructs based on minimization of entransy dissipation and the con- structs based on minimization of maximum temperature difference are compared, and the results show that the constructs based on entransy dissipation can de- crease the mean temperature difference better than the constructs based on mini- mization of maximum temperature difference. But with the increase of the number of the order, the mean temperature difference does not always decrease, and there exist some fluctuations. Because the idea of entransy describes the heat transfer ability more suitably, all of the heat conduction constructal problems may be re-optimized based on it.

关键词： constructal theory entransy dissipation volume-point heat conduction generalized thermodynamic optimi- zation