不同强度运动抑制糖尿病大鼠肾脏PI3K/AKT/mTOR信号通路改善自噬的比较

背景:2型糖尿病损害肾功能。研究表明运动干预可以保护肾脏;鸢尾素可以通过抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路恢复自噬,保护糖尿病肾病患者的肾功能。目的:探讨运动能否通过抑制肾脏磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活来恢复自噬,改善肾损伤,以及分析不同方式运动产生影响的差异。方法:将6周龄的SD大鼠随机分为空白对照组(正常大鼠)和糖尿病组,其中糖尿病组大鼠经过高脂高糖喂养加腹腔注射低剂量1%链脲佐菌素(30 mg/kg)建立2型糖尿病模型。造模成功后再将糖尿病组大鼠随机分成糖尿病模型组、中强度持续运动组和高强度间歇运动组。两个运动组大鼠分别进行8周不同强度运动干预。取材后采用葡萄糖氧化酶法检测大鼠空腹血糖,使用试剂盒检测糖化血红蛋白水平,Elisa法检测血清胰岛素浓度,计算胰岛素抵抗指数,RT-PCR检测肾组织磷脂酰肌醇3-激酶、蛋白激酶B、雷帕霉素靶蛋白、Beclin-1、podocin、nephrin的基因表达量,Western Blot检测肾组织雷帕霉素靶蛋白及自噬标记蛋白LC3-1、LC3-2、Beclin-1的蛋白表达量。结果与结论:①2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著性升高,胰岛素抵抗水平显著上升,胰岛素水平显著下降;两种运动均能使2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著下降,胰岛素抵抗水平显著下降,胰岛素水平显著上升;与中强度持续运动组相比,高强度间歇运动组胰岛素水平显著上升。②2型糖尿病大鼠podocin、nephrin基因表达量显著降低;两种不同形式运动均能显著提高其表达;与高强度间歇运动组相比,中等强度持续性运动组足细胞相关蛋白基因表达有进一步上升趋势,但无显著性差异。③2型糖尿病大鼠肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及蛋白的表达量显著增加,自噬标志蛋白Beclin-1、LC3-2表达量以及LC3-2/LC3-1显著降低;两种不同形式运动均能使肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白蛋白的表达量显著降低,自噬标志蛋白Beclin-1、LC3-2以及LC3-2/LC3-1显著升高;与中等强度持续性运动组相比,高强度间歇运动的磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白的蛋白表达量有进一步下降的趋势,Beclin-1、LC3-2以及LC3-2/LC3-1有进一步升高的趋势,但仅Beclin-1有显著性差异。④结果说明2型糖尿病肾脏足细胞损伤,自噬受到抑制,与磷脂酰肌醇3-激酶/蛋白激酶B/mTORC1信号通路被异常激活密切相关。高强度间歇运动和中等强度持续性运动可以保护糖尿病肾脏,减少足细胞损伤,促进自噬恢复,这可能与运动抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活有关。与中等强度持续性运动相比,高强度间歇运动恢复自噬的效果呈更优趋势,但足细胞蛋白表达稍有下降。

Drilling-based measuring method for the c-φ parameter of rock and its field application

The technology of drilling tests makes it possible to obtain the strength parameter of rock accurately in situ. In this paper, a new rock cutting analysis model that considers the influence of the rock crushing zone(RCZ) is built. The formula for an ultimate cutting force is established based on the limit equilibrium principle. The relationship between digital drilling parameters(DDP) and the c-φ parameter(DDP-cφ formula, where c refers to the cohesion and φ refers to the internal friction angle) is derived, and the response of drilling parameters and cutting ratio to the strength parameters is analyzed. The drillingbased measuring method for the c-φ parameter of rock is constructed. The laboratory verification test is then completed, and the difference in results between the drilling test and the compression test is less than 6%. On this basis, in-situ rock drilling tests in a traffic tunnel and a coal mine roadway are carried out, and the strength parameters of the surrounding rock are effectively tested. The average difference ratio of the results is less than 11%, which verifies the effectiveness of the proposed method for obtaining the strength parameters based on digital drilling. This study provides methodological support for field testing of rock strength parameters.

A comparison study on structure-function relationship of polysaccharides obtained from sea buckthorn berries using different methods:antioxidant and bile acid-binding capacity

In this study,the structural characters,antioxidant activities and bile acid-binding ability of sea buckthorn polysaccharides(HRPs)obtained by the commonly used hot water(HRP-W),pressurized hot water(HRP-H),ultrasonic(HRP-U),acid(HRP-C)and alkali(HRP-A)assisted extraction methods were investigated.The results demonstrated that extraction methods had significant effects on extraction yield,monosaccharide composition,molecular weight,particle size,triple-helical structure,and surface morphology of HRPs except for the major linkage bands.Thermogravimetric analysis showed that HRP-U with filamentous reticular microstructure exhibited better thermal stability.The HRP-A with the lowest molecular weight and highest arabinose content possessed the best antioxidant activities.Moreover,the rheological analysis indicated that HRPs with higher galacturonic acid content and molecular weight showed higher viscosity and stronger crosslinking network(HRP-C,HRP-W and HRP-U),which exhibited stronger bile acid binding capacity.The present findings provide scientific evidence in the preparation technology of sea buckthorn polysaccharides with good antioxidant and bile acid binding capacity which are related to the structure affected by the extraction methods.

Numerical manifold method for thermo-mechanical coupling simulation of fractured rock mass

As a calculation method based on the Galerkin variation,the numerical manifold method(NMM)adopts a double covering system,which can easily deal with discontinuous deformation problems and has a high calculation accuracy.Aiming at the thermo-mechanical(TM)coupling problem of fractured rock masses,this study uses the NMM to simulate the processes of crack initiation and propagation in a rock mass under the influence of temperature field,deduces related system equations,and proposes a penalty function method to deal with boundary conditions.Numerical examples are employed to confirm the effectiveness and high accuracy of this method.By the thermal stress analysis of a thick-walled cylinder(TWC),the simulation of cracking in the TWC under heating and cooling conditions,and the simulation of thermal cracking of the SwedishÄspöPillar Stability Experiment(APSE)rock column,the thermal stress,and TM coupling are obtained.The numerical simulation results are in good agreement with the test data and other numerical results,thus verifying the effectiveness of the NMM in dealing with thermal stress and crack propagation problems of fractured rock masses.

Cascading multi-segment rupture process of the 2023 Turkish earthquake doublet on a complex fault system revealed by teleseismic P wave back projection method

In this study,the vertical components of broadband teleseismic P wave data recorded by China Earthquake Network are used to image the rupture processes of the February 6th,2023 Turkish earthquake doublet via back projection analysis.Data in two frequency bands(0.5-2 Hz and 1-3 Hz)are used in the imaging processes.The results show that the rupture of the first event extends about 200 km to the northeast and about 150 km to the southwest,lasting~90 s in total.The southwestern rupture is triggered by the northeastern rupture,demonstrating a sequential bidirectional unilateral rupture pattern.The rupture of the second event extends approximately 80 km in both northeast and west directions,lasting~35 s in total and demonstrates a typical bilateral rupture feature.The cascading ruptures on both sides also reflect the occurrence of selective rupture behaviors on bifurcated faults.In addition,we observe super-shear ruptures on certain fault sections with relatively straight fault structures and sparse aftershocks.

Stability Analysis and Performance Evaluation of Additive Mixed-Precision Runge-Kutta Methods

Additive Runge-Kutta methods designed for preserving highly accurate solutions in mixed-precision computation were previously proposed and analyzed.These specially designed methods use reduced precision for the implicit computations and full precision for the explicit computations.In this work,we analyze the stability properties of these methods and their sensitivity to the low-precision rounding errors,and demonstrate their performance in terms of accuracy and efficiency.We develop codes in FORTRAN and Julia to solve nonlinear systems of ODEs and PDEs using the mixed-precision additive Runge-Kutta(MP-ARK)methods.The convergence,accuracy,and runtime of these methods are explored.We show that for a given level of accuracy,suitably chosen MP-ARK methods may provide significant reductions in runtime.

High-Order Decoupled and Bound Preserving Local Discontinuous Galerkin Methods for a Class of Chemotaxis Models

In this paper,we explore bound preserving and high-order accurate local discontinuous Galerkin(LDG)schemes to solve a class of chemotaxis models,including the classical Keller-Segel(KS)model and two other density-dependent problems.We use the convex splitting method,the variant energy quadratization method,and the scalar auxiliary variable method coupled with the LDG method to construct first-order temporal accurate schemes based on the gradient flow structure of the models.These semi-implicit schemes are decoupled,energy stable,and can be extended to high accuracy schemes using the semi-implicit spectral deferred correction method.Many bound preserving DG discretizations are only worked on explicit time integration methods and are difficult to get high-order accuracy.To overcome these difficulties,we use the Lagrange multipliers to enforce the implicit or semi-implicit LDG schemes to satisfy the bound constraints at each time step.This bound preserving limiter results in the Karush-Kuhn-Tucker condition,which can be solved by an efficient active set semi-smooth Newton method.Various numerical experiments illustrate the high-order accuracy and the effect of bound preserving.

The Adjustment Analysis Method of the Active Surface Antenna Based on Convolutional Neural Network

Active surface technique is one of the key technologies to ensure the reflector accuracy of the millimeter/submillimeter wave large reflector antenna.The antenna is complex,large-scale,and high-precision equipment,and its active surfaces are affected by various factors that are difficult to comprehensively deal with.In this paper,based on the advantage of the deep learning method that can be improved through data learning,we propose the active adjustment value analysis method of large reflector antenna based on deep learning.This method constructs a neural network model for antenna active adjustment analysis in view of the fact that a large reflector antenna consists of multiple panels spliced together.Based on the constraint that a single actuator has to support multiple panels(usually 4),an autonomously learned neural network emphasis layer module is designed to enhance the adaptability of the active adjustment neural network model.The classical 8-meter antenna is used as a case study,the actuators have a mean adjustment error of 0.00252 mm,and the corresponding antenna surface error is0.00523 mm.This active adjustment result shows the effectiveness of the method in this paper.

An Evidence-Based CoCoSo Framework with Double Hierarchy Linguistic Data for Viable Selection of Hydrogen Storage Methods

Hydrogen is the new age alternative energy source to combat energy demand and climate change.Storage of hydrogen is vital for a nation’s growth.Works of literature provide different methods for storing the produced hydrogen,and the rational selection of a viable method is crucial for promoting sustainability and green practices.Typically,hydrogen storage is associated with diverse sustainable and circular economy(SCE)criteria.As a result,the authors consider the situation a multi-criteria decision-making(MCDM)problem.Studies infer that previous models for hydrogen storage method(HSM)selection(i)do not consider preferences in the natural language form;(ii)weights of experts are not methodically determined;(iii)hesitation of experts during criteria weight assessment is not effectively explored;and(iv)three-stage solution of a suitable selection of HSM is unexplored.Driven by these gaps,in this paper,authors put forward a new integrated framework,which considers double hierarchy linguistic information for rating,criteria importance through inter-criteria correlation(CRITIC)for expert weight calculation,evidence-based Bayesian method for criteria weight estimation,and combined compromise solution(CoCoSo)for ranking HSMs.The applicability of the developed framework is testified by using a case example of HSM selection in India.Sensitivity and comparative analysis reveal the merits and limitations of the developed framework.

A Localization Method of High Energy Transients for All-sky Gamma-ray Monitor

Fast and reliable localization of high-energy transients is crucial for characterizing the burst properties and guiding the follow-up observations.Localization based on the relative counts of different detectors has been widely used for all-sky gamma-ray monitors.There are two major methods for this count distribution localization:χ^(2)minimization method and the Bayesian method.Here we propose a modified Bayesian method that could take advantage of both the accuracy of the Bayesian method and the simplicity of the χ^(2)method.With comprehensive simulations,we find that our Bayesian method with Poisson likelihood is generally more applicable for various bursts than the χ^(2)method,especially for weak bursts.We further proposed a location-spectrum iteration approach based on the Bayesian inference,which could alleviate the problems caused by the spectral difference between the burst and location templates.Our method is very suitable for scenarios with limited computation resources or timesensitive applications,such as in-flight localization software,and low-latency localization for rapidly follow-up observations.

Research on the Extraction of OLR Anomaly Prior to Ms 7.5 Sand Point,Alaska Earthquake based on IPI Method

Based on the understanding that the seismic fault system is a nonlinear complex system,Rundle(1995)introduced the nonlinear threshold system used in meteorology to analyze the ocean-atmosphere interface and the El Ni?o Southern Oscillation into the study of seismic activity changes,and then proposed the PI method(Rundle et al.,2000a,b).Wu et al.(2011)modified the Pattern Informatics Method named MPI to extract the ionospheric anomaly by using data from DEMETER satellites which is suitable for 1–3 months short-term prediction.

Bound-Preserving Discontinuous Galerkin Methods with Modified Patankar Time Integrations for Chemical Reacting Flows

In this paper,we develop bound-preserving discontinuous Galerkin(DG)methods for chemical reactive flows.There are several difficulties in constructing suitable numerical schemes.First of all,the density and internal energy are positive,and the mass fraction of each species is between 0 and 1.Second,due to the rapid reaction rate,the system may contain stiff sources,and the strong-stability-preserving explicit Runge-Kutta method may result in limited time-step sizes.To obtain physically relevant numerical approximations,we apply the bound-preserving technique to the DG methods.Though traditional positivity-preserving techniques can successfully yield positive density,internal energy,and mass fractions,they may not enforce the upper bound 1 of the mass fractions.To solve this problem,we need to(i)make sure the numerical fluxes in the equations of the mass fractions are consistent with that in the equation of the density;(ii)choose conservative time integrations,such that the summation of the mass fractions is preserved.With the above two conditions,the positive mass fractions have summation 1,and then,they are all between 0 and 1.For time discretization,we apply the modified Runge-Kutta/multi-step Patankar methods,which are explicit for the flux while implicit for the source.Such methods can handle stiff sources with relatively large time steps,preserve the positivity of the target variables,and keep the summation of the mass fractions to be 1.Finally,it is not straightforward to combine the bound-preserving DG methods and the Patankar time integrations.The positivity-preserving technique for DG methods requires positive numerical approximations at the cell interfaces,while Patankar methods can keep the positivity of the pre-selected point values of the target variables.To match the degree of freedom,we use polynomials on rectangular meshes for problems in two space dimensions.To evolve in time,we first read the polynomials at the Gaussian points.Then,suitable slope limiters can be applied to enforce the positivity of the solutions at those points,which can be preserved by the Patankar methods,leading to positive updated numerical cell averages.In addition,we use another slope limiter to get positive solutions used for the bound-preserving technique for the flux.Numerical examples are given to demonstrate the good performance of the proposed schemes.

Numerical Investigations on the Resonance Errors of Multiscale Discontinuous Galerkin Methods for One-Dimensional Stationary Schrödinger Equation

In this paper,numerical experiments are carried out to investigate the impact of penalty parameters in the numerical traces on the resonance errors of high-order multiscale discontinuous Galerkin(DG)methods(Dong et al.in J Sci Comput 66:321–345,2016;Dong and Wang in J Comput Appl Math 380:1–11,2020)for a one-dimensional stationary Schrödinger equation.Previous work showed that penalty parameters were required to be positive in error analysis,but the methods with zero penalty parameters worked fine in numerical simulations on coarse meshes.In this work,by performing extensive numerical experiments,we discover that zero penalty parameters lead to resonance errors in the multiscale DG methods,and taking positive penalty parameters can effectively reduce resonance errors and make the matrix in the global linear system have better condition numbers.

Analytical Method for the Wave Diffraction of Asymmetrically Arranged Breakwaters

The layout forms of several breakwater structures can be generalized as asymmetrical arrangements in actual engineering.However,the problem of wave diffraction around asymmetrically arranged breakwaters has not been adequately investigated.In this study,we propose an analytical method of wave diffraction for regular waves passing through asymmetrically arranged breakwaters,and we use the Nyström method to obtain the analytical solution numerically.We compared the results of this method with those of previous analytical solutions and with numerical results to demonstrate the validity of our approach.We also provided diffraction coefficient diagrams of breakwaters with different layout forms.Moreover,we described the analytical expression for the problem of diffraction through long-wave incident breakwaters and presented an analysis of the relationship between the diffraction coefficients and the widths of breakwater gates.The analytical method presented in this study contributes to the limited literature on the theory of wave diffraction through asymmetrically arranged breakwaters.

Superconvergence of Direct Discontinuous Galerkin Methods:Eigen-structure Analysis Based on Fourier Approach

This paper investigates superconvergence properties of the direct discontinuous Galerkin(DDG)method with interface corrections and the symmetric DDG method for diffusion equations.We apply the Fourier analysis technique to symbolically compute eigenvalues and eigenvectors of the amplification matrices for both DDG methods with different coefficient settings in the numerical fluxes.Based on the eigen-structure analysis,we carry out error estimates of the DDG solutions,which can be decomposed into three parts:(i)dissipation errors of the physically relevant eigenvalue,which grow linearly with the time and are of order 2k for P^(k)(k=2,3)approximations;(ii)projection error from a special projection of the exact solution,which is decreasing over the time and is related to the eigenvector corresponding to the physically relevant eigenvalue;(iii)dissipative errors of non-physically relevant eigenvalues,which decay exponentially with respect to the spatial mesh sizeΔx.We observe that the errors are sensitive to the choice of the numerical flux coefficient for even degree P^(2)approximations,but are not for odd degree P^(3)approximations.Numerical experiments are provided to verify the theoretical results.

AHermitian C^(2) Differential Reproducing Kernel Interpolation Meshless Method for the 3D Microstructure-Dependent Static Flexural Analysis of Simply Supported and Functionally Graded Microplates

This work develops a Hermitian C^(2) differential reproducing kernel interpolation meshless(DRKIM)method within the consistent couple stress theory(CCST)framework to study the three-dimensional(3D)microstructuredependent static flexural behavior of a functionally graded(FG)microplate subjected to mechanical loads and placed under full simple supports.In the formulation,we select the transverse stress and displacement components and their first-and second-order derivatives as primary variables.Then,we set up the differential reproducing conditions(DRCs)to obtain the shape functions of the Hermitian C^(2) differential reproducing kernel(DRK)interpolant’s derivatives without using direct differentiation.The interpolant’s shape function is combined with a primitive function that possesses Kronecker delta properties and an enrichment function that constituents DRCs.As a result,the primary variables and their first-and second-order derivatives satisfy the nodal interpolation properties.Subsequently,incorporating ourHermitianC^(2)DRKinterpolant intothe strong formof the3DCCST,we develop a DRKIM method to analyze the FG microplate’s 3D microstructure-dependent static flexural behavior.The Hermitian C^(2) DRKIM method is confirmed to be accurate and fast in its convergence rate by comparing the solutions it produces with the relevant 3D solutions available in the literature.Finally,the impact of essential factors on the transverse stresses,in-plane stresses,displacements,and couple stresses that are induced in the loaded microplate is examined.These factors include the length-to-thickness ratio,the material length-scale parameter,and the inhomogeneity index,which appear to be significant.

Efficient method to calculate the eigenvalues of the Zakharov–Shabat system

A numerical method is proposed to calculate the eigenvalues of the Zakharov–Shabat system based on Chebyshev polynomials. A mapping in the form of tanh(ax) is constructed according to the asymptotic of the potential function for the Zakharov–Shabat eigenvalue problem. The mapping can distribute Chebyshev nodes very well considering the gradient for the potential function. Using Chebyshev polynomials, tanh(ax) mapping, and Chebyshev nodes, the Zakharov–Shabat eigenvalue problem is transformed into a matrix eigenvalue problem. This method has good convergence for the Satsuma–Yajima potential and the convergence rate is faster than the Fourier collocation method. This method is not only suitable for simple potential functions but also converges quickly for a complex Y-shape potential. It can also be further extended to other linear eigenvalue problems.

Noise-induced phase transition in the Vicsek model through eigen microstate methodology

This paper presents a comprehensive framework for analyzing phase transitions in collective models such as theVicsek model under various noise types. The Vicsek model, focusing on understanding the collective behaviors of socialanimals, is known due to its discontinuous phase transitions under vector noise. However, its behavior under scalar noiseremains less conclusive. Renowned for its efficacy in the analysis of complex systems under both equilibrium and nonequilibriumstates, the eigen microstate method is employed here for a quantitative examination of the phase transitions inthe Vicsek model under both vector and scalar noises. The study finds that the Vicsek model exhibits discontinuous phasetransitions regardless of noise type. Furthermore, the dichotomy method is utilized to identify the critical points for thesephase transitions. A significant finding is the observed increase in the critical point for discontinuous phase transitions withescalation of population density.

Application of the Electrical Resistivity Method in Precision Agriculture of Coffee Cultivation, in the Kabiri Area, Ícolo e Bengo Township, Luanda, Angola

The electrical resistivity method is a geophysical tool used to characterize the subsoil and can provide an important information for precision agriculture. The lack of knowledge about agronomic properties of the soil tends to affect the agricultural coffee production system. Therefore, research related to geoelectrical properties of soil such as resistivity for characterization the region of the study for coffee cultivation purposes can improve and optimize the production. This resistivity method allows to investigate the subsurface through different techniques: 1D vertical electrical sounding and electrical imaging. The acquisition of data using these techniques permitted the creation of 2D resistivity cross section from the study area. The geoelectrical data was acquired by using a resistivity meter equipment and was processed in different softwares. The results of the geoelectrical characterization from 1D resistivity model and 2D resistivity electrical sections show that in the study area of Kabiri, there are 8 varieties of geoelectrical layers with different resistivity or conductivity. Near survey in the study area, the lowest resistivity is around 0.322 Ω·m, while the highest is about 92.1 Ω·m. These values illustrated where is possible to plant coffee for suggestion of specific fertilization plan for some area to improve the cultivation.

THE SUPERCLOSENESS OF THE FINITE ELEMENT METHOD FOR A SINGULARLY PERTURBED CONVECTION-DIFFUSION PROBLEM ON A BAKHVALOV-TYPE MESH IN 2D

For singularly perturbed convection-diffusion problems,supercloseness analysis of the finite element method is still open on Bakhvalov-type meshes,especially in the case of 2D.The difficulties arise from the width of the mesh in the layer adjacent to the transition point,resulting in a suboptimal estimate for convergence.Existing analysis techniques cannot handle these difficulties well.To fill this gap,here a novel interpolation is designed delicately for the smooth part of the solution,bringing about the optimal supercloseness result of almost order 2 under an energy norm for the finite element method.Our theoretical result is uniform in the singular perturbation parameterεand is supported by the numerical experiments.