Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Moment Redistribution Effect of the Continuous Glass Fiber Reinforced Polymer-Concrete Composite Slabs Based on Static Loading Experiment

This study aimed to investigate the moment redistribution in continuous glass fiber reinforced polymer(GFRP)-concrete composite slabs caused by concrete cracking and steel bar yielding in the negative bending moment zone.An experimental bending moment redistribution test was conducted on continuous GFRP-concrete composite slabs,and a calculation method based on the conjugate beam method was proposed.The composite slabs were formed by combining GFRP profiles with a concrete layer and supported on steel beams to create two-span continuous composite slab specimens.Two methods,epoxy resin bonding,and stud connection,were used to connect the composite slabs with the steel beams.The experimental findings showed that the specimen connected with epoxy resin exhibited two moments redistribution phenomena during the loading process:concrete cracking and steel bar yielding at the internal support.In contrast,the composite slab connected with steel beams by studs exhibited only one-moment redistribution phenomenon throughout the loading process.As the concrete at the internal support cracked,the bending moment decreased in the internal support section and increased in the midspan section.When the steel bars yielded,the bending moment further decreased in the internal support section and increased in the mid-span section.Since GFRP profiles do not experience cracking,there was no significant decrease in the bending moment of the mid-span section.All test specimens experienced compressive failure of concrete at the mid-span section.Calculation results showed good agreement between the calculated and experimental values of bending moments in the mid-span section and internal support section.The proposed model can effectively predict the moment redistribution behavior of continuous GFRP-concrete composite slabs.

Computational Experiments for Complex Social Systems:Experiment Design and Generative Explanation

Powered by advanced information technology,more and more complex systems are exhibiting characteristics of the cyber-physical-social systems(CPSS).In this context,computational experiments method has emerged as a novel approach for the design,analysis,management,control,and integration of CPSS,which can realize the causal analysis of complex systems by means of“algorithmization”of“counterfactuals”.However,because CPSS involve human and social factors(e.g.,autonomy,initiative,and sociality),it is difficult for traditional design of experiment(DOE)methods to achieve the generative explanation of system emergence.To address this challenge,this paper proposes an integrated approach to the design of computational experiments,incorporating three key modules:1)Descriptive module:Determining the influencing factors and response variables of the system by means of the modeling of an artificial society;2)Interpretative module:Selecting factorial experimental design solution to identify the relationship between influencing factors and macro phenomena;3)Predictive module:Building a meta-model that is equivalent to artificial society to explore its operating laws.Finally,a case study of crowd-sourcing platforms is presented to illustrate the application process and effectiveness of the proposed approach,which can reveal the social impact of algorithmic behavior on“rider race”.

Experimental studies and failure mechanisms of strain andfault-slip rockburst:A review

In recent years,rockburst have gained significant attention as a crucial topic in rock engineering.Strain andfault-slip rockburst are two common types that occur frequently and cause substantial damage.The objective of thisreview is to conduct a comprehensive study on the experiments and failure mechanisms of strain and fault-slip rockburst.Firstly,the article analyzes the evolving trends in experimental research on rockburst in the past decade,highlightingmechanical properties and failure modes as the primary research focuses in understanding rockburst mechanisms.Subsequently,it provides an overview of the experimental techniques and methods employed for studying both types ofrockburst.Then,with a focus on the mechanical properties and failure modes,the article conducts an extensive analysisof the failure mechanisms associated with strain and fault-slip rockburst.By analyzing experimental data and observingthe failure characteristics of samples,it discusses the variations and common features exhibited by these two types ofrockburst under various test conditions.This analysis is of paramount importance in revealing the causes of rockburstformation and development,as well as in predicting rockburst trends and assessing associated risks.Lastly,thelimitations of current rockburst experiments and future research directions are discussed,followed by a comprehensivesummary of the entire article.

Reduction of uncertainties in rice yield response to elevated CO_(2) by experiment-model integration:A case study in East China

Accurate prediction of future rice yield needs the precise estimations of rice yield response to climate change factors,of which the most important one is the increasing carbon dioxide(CO_(2))concentrations.Estimates of CO_(2) fertilization effect(CFE)on rice,however,still had large uncertainties.Therefore,using the rice planting areas in East China as the study area,we firstly compared the rice yields and CFE predicted by four state-of-the-art crop models,and found that the CFE predicted by these models had significant differences.We then quantified the CFE on rice yield using the field-controlled experiment conducted at Danyang site at Jiangsu province.Using CFE measurements from a field experiment as benchmark,we have developed an experiment–model integration approach aiming to reduce this variation.This study thus highlights the large CFE uncertainties of current crop models and provides us with a method to reduce this uncertainty,which is beneficial for the accurate prediction of future global rice yield in the context of climate change.

Application and Practice of Knowledge Graph in Experimental Teaching in Colleges and Universities

With the reform of experimental teaching in colleges and universities,the teaching mode of"experimental students as the main body,experimental teachers as the guide"needs to constantly explore new experimental teaching methods.In this paper,knowledge graph is integrated into the experiment of mechanical principle to guide undergraduates to use knowledge graph to analyze and summarize independently in experimental teaching activities,aiming at cultivating undergraduates interest in learning and innovative thinking,so as to improve the quality of experimental teaching.This study has a certain reference significance for experimental teaching in colleges and universities.

Undergraduate Experimental Teaching Platform for Intelligent Limb Rehabilitation Training Based on "Medical-Engineering Interdisciplinary Crossing"

In view of the key role of undergraduate experimental teaching reform in cultivating high-quality talents with both innovative spirit and practical ability,this paper deeply discusses multi-dimensional reform strategies.Specifically,the teaching mode of"double teachers for every student"is innovatively introduced,and scientific research projects are deeply integrated into undergraduate experimental teaching,aiming at realizing the modern development of teaching content and the diversified expansion of teaching methods.By designing and applying the undergraduate experimental teaching platform for intelligent limb rehabilitation training based on the concept of"medical-engineering interdisciplinary crossing",it not only builds a bridge for students to contact cutting-edge scientific research and strengthen practical skills,but also provides valuable ideas and practical models for the innovation of undergraduate experimental teaching.In the future,with the continuous optimization and upgrading of platform functions,it is expected to provide students with a richer and richer learning experience and comprehensively promote students'overall quality.

Recent progresses in the development of tubular segmented-in-series solid oxide fuel cells:Experimental and numerical study

Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs suffer from having a higher volume,current leakage,complex connections,and difficulty in gas sealing.To solve these problems,Rolls-Royce has fabricated a simple design by stacking cells in series on an insulating porous support,resulting in the tubular segmented-in-series solid oxide fuel cells(SIS-SOFCs),which achieved higher output voltage.This work systematically reviews recent advances in the structures,preparation methods,perform-ances,and stability of tubular SIS-SOFCs in experimental and numerical studies.Finally,the challenges and future development of tubular SIS-SOFCs are also discussed.The findings of this work can help guide the direction and inspire innovation of future development in this field.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

Predicting the probability distribution of Martian rocks mechanical property based on microscale rock mechanical experiments and accurate grain-based modeling

The exploration of Mars would heavily rely on Martian rocks mechanics and engineering technology.As the mechanical property of Martian rocks is uncertain,it is of utmost importance to predict the probability distribution of Martian rocks mechanical property for the success of Mars exploration.In this paper,a fast and accurate probability distribution method for predicting the macroscale elastic modulus of Martian rocks was proposed by integrating the microscale rock mechanical experiments(micro-RME),accurate grain-based modeling(AGBM)and upscaling methods based on reliability principles.Firstly,the microstructure of NWA12564 Martian sample and elastic modulus of each mineral were obtained by micro-RME with TESCAN integrated mineral analyzer(TIMA)and nanoindentation.The best probability distribution function of the minerals was determined by Kolmogorov-Smirnov(K-S)test.Secondly,based on best distribution function of each mineral,the Monte Carlo simulations(MCS)and upscaling methods were implemented to obtain the probability distribution of upscaled elastic modulus.Thirdly,the correlation between the upscaled elastic modulus and macroscale elastic modulus obtained by AGBM was established.The accurate probability distribution of the macroscale elastic modulus was obtained by this correlation relationship.The proposed method can predict the probability distribution of Martian rocks mechanical property with any size and shape samples.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.

Experimental investigation on coal pore-fracture variation and fractal characteristics synergistically affected by solvents for improving clean gas extraction

Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal synergistically affected by solvents have not been fully understood.Ultrasonic testing,nuclear magnetic resonance analysis,liquid phase mass spectrometry was adopted to comprehensively analyze pore-fracture change characteristics of lean coal treated by combined solvent(NMP and CS_(2)).Meanwhile,quantitative characterization of above changing properties was conducted using geometric fractal theory.Relationship model between permeability,fractal dimension and porosity were established.Results indicate that the end face fractures of coal are well developed after CS2and combined solvent treatments,of which,end face box-counting fractal dimensions range from 1.1227 to 1.4767.Maximum decreases in ultrasonic longitudinal wave velocity of coal affected by NMP,CS_(2)and combined solvent are 2.700%,20.521%,22.454%,respectively.Solvent treatments could lead to increasing amount of both mesopores and macropores.Decrease ratio of fractal dimension Dsis 0.259%–2.159%,while permeability increases ratio of NMR ranges from 0.1904 to 6.4486.Meanwhile,combined solvent could dissolve coal polar and non-polar small molecules and expand flow space.Results could provide reference for solvent selection and parameter optimization of permeability-enhancement technology.

Adaptive Robust Servo Control for Vertical Electric Stabilization System of Tank and Experimental Validation

A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevarying but bounded uncertainty within the vertical electric stabilization system:model parameter uncertainty and uncertain nonlinearity.First,the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system.Second,the dynamical equation in the form of state space is established by designing the angular tracking error.Third,the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty.Finally,an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed.The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform.This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem,and validates the advanced servo control strategy through experiment for the first time.

Experimental and simulation research on hollow AZ31 magnesium alloy three-channel joint by hot extrusion forming with sand mandrel

Magnesium alloy is one of the lightest metal structural materials.The weight is further reduced through the hollow structure.However,the hollow structure is easily damaged during processing.In order to maintain the hollow structure and to transfer the stresses during the high temperature deformation,the sand mandrel is proposed.In this paper,the hollow AZ31 magnesium alloy three-channel joint is studied by hot extrusion forming.Sand as one of solid granule medium is used to fill the hollow magnesium alloy.The extrusion temperatures are 230℃ and 300℃,respectively.The process parameters(die angle,temperature,bottom thickness,sidewall thickness,edge-to-middle ratio in bottom,bottom shape)of the hollow magnesium alloy are analyzed based on the results of experiments and the finite element method.The results are shown that the formability of the hollow magnesium alloy will be much better when the ratio of sidewall thickness to the bottom thickness is 1:1.5.Also when edge-to-middle ratio in bottom is about 1:1.5,a better forming product can be received.The best bottom shape in these experiments will be convex based on the forming results.The grain will be refined obviously after the extrusion.Also the microstructures will be shown as streamlines.And these lines will be well agreement with the mold in the corner.

Computer Management of Quantitative Analysis Chemistry Experiment

The application of computer in the quantitative analysis chemistry experiment is a chemistry experiment teaching applications software, developed by Visual Basic （6.0）, based on the content of quantitative analysis chemistry experiment of chemistry major in higher institute. This software has the function of the automatic processing the experimental data, the automatic generation of test report copies, and the automatic evaluation of students＇ experimental results, which solve the reliability, objectivity and accuracy problems of the students＇ experiment data processing and evaluation, and avoid interference with human factors. The software has the characteristic of the easy installation, the easy operation, the strong practicability, pertinence, the systematicness and the running stability, so it provides a platform in the quantitative analysis chemistry experiment for the students＇ assessment system of automatic processing, and it has a high popularization value. The project＇s technical route design is reasonable, the research method is correct, and the experimental data processing results are reliable, which has reached the leading domestic level in the quantitative analysis chemistry experiment teaching field of computer data processing. And this project has been through the achievements appraisal of Gansu Provincial Sci. ＆ Tech. Department.

Design and analysis of an advanced thermal management system for the solar close observations and proximity experiments spacecraft

In this paper,the mission and the thermal environment of the Solar Close Observations and Proximity Experiments(SCOPE)spacecraft are analyzed,and an advanced thermal management system(ATMS)is designed for it.The relationship and functions of the integrated database,the intelligent thermal control system and the efficient liquid cooling system in the ATMS are elaborated upon.For the complex thermal field regulation system and extreme space thermal environment,a modular simulation and thermal field planning method are proposed,and the feasibility of the planning algorithm is verified by numerical simulation.A solar array liquid cooling system is developed,and the system simulation results indicate that the temperatures of the solar arrays meet the requirements as the spacecraft flies by perihelion and aphelion.The advanced thermal management study supports the development of the SCOPE program and provides a reference for the thermal management in other deep-space exploration programs.

Analysis and experimental study on resistance-increasing behavior of composite high efficiency autonomous inflow control device

Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks through to the wellbore. Autonomous inflow control device(AICD) is an important instrument maintain normal production after bottom water coning, however, the resistance increasing ability of the swirl type AICD is insufficient at present, which seriously affects the water control effect. Aiming this problem, this paper designs a multi-stage resistance-increasing and composite type AICD. The separation mechanism of oil-water two phases in this structure, the resistance form of oil-water single phase and the resistance-increasing principle of water phase are analyzed. Establishing the dual-phase multi-stage separation and resistance-increasing model, and verified by measuring the throttling pressure drop and oil-water volume fraction of the AICD, it is found that the composite type AICD has the effect of ICD and AICD at the same time, which can balance the production rate of each well section at the initial stage of production, delay the occurrence of bottom water coning. In the middle and later stages of production, water-blocking can be effectively increased to achieve water control and stable production.After structural sensitivity analysis, the influence law of various structural parameters on the water control performance of composite AICD was obtained. The simulation calculation results show that,compared with the existing swirl type AICD, composite AICD has higher sensitivity to moisture content,the water phase throttling pressure drop is increased by 4.5 times on average. The composite AICD is suitable for the entire stage of horizontal well production.

Mechanical heterogeneity characterization of coal materials based on nano-indentation experiments

To investigate the complex macro-mechanical properties of coal from a micro-mechanical perspective,we have conducted a series of micro-mechanical experiments on coal using a nano-indentation instrument.These experiments were conducted under both dynamic and static loading conditions,allowing us to gather the micro-mechanical parameters of coal for further analysis of its micro-mechanical heterogeneity using the box counting statistical method and the Weibull model.The research findings indicate that the load–displacement curves of the coal mass under the two different loading modes exhibit noticeable discreteness.This can be attributed to the stress concentration phenomenon caused by variations in the mechanical properties of the micro-units during the loading process of the coal mass.Consequently,there are significant fluctuations in the micro-mechanical parameters of the coal mass.Moreover,the mechanical heterogeneity of the coal at the nanoscale was confirmed based on the calculation results of the standard deviation coefficient and Weibull modulus of the coal body’s micromechanical parameters.These results reveal the influence of microstructural defects and minerals on the uniformity of the stress field distribution within the loaded coal body,as well as on the ductility characteristics of the micro-defect structure.Furthermore,there is a pronounced heterogeneity in the micromechanical parameters.Furthermore,we have established a relationship between the macro and micro elastic modulus of coal by applying the Mori-Tanaka homogenization method.This relationship holds great significance for revealing the micro-mechanical failure mechanism of coal.

Experimental and numerical study of buckling-restrained braces configured with out-of-plane eccentricity under cyclic loading

This study focuses on variations in the hysteretic behavior of buckling-restrained braces(BRBs)configured with or without out-of-plane eccentricity under cyclic loading.Quasi-static experiments and numerical simulations were carried out on concentrically and eccentrically loaded BRB specimens to investigate the mechanical properties,energy dissipation performance,stress distribution,and high-order deformation pattern.The experimental and numerical results showed that compared to the concentrically loaded BRBs,the stiffness,yield force,cumulated plastic ductility(CPD)coefficient,equivalent viscous damping coefficient and energy dissipation decreased,and the yield displacement and compression strength adjustment factor increased for the eccentrically loaded BRBs.With the existence of the out-of-plane eccentricity,the initial yield position changes from the yield segment to the junction between the yield segment and transition segment under a tensile load,while the initial high-order buckling pattern changes from a first-order C-shape to a secondorder S-shape under a compressive load.

Optical design of the time-resolved ARPES beamline of the new material spectroscopy experimental station for the update of CAEP THz-FEL facility

The Chinese Academy of Engineering Physics Terahertz Free Electron Laser Facility(CAEP THz FEL,CTFEL)is the only high-average power free electron laser terahertz source based on superconducting accelerators in China.The update of the CTFEL is now undergoing and will expand the frequency range from 0.1–4.2 THz to 0.1–125 THz.Two experimental stations for material spectroscopy and biomedicine will be built.A high harmonic generation(HHG)lightsource based beamline at the material spectroscopy experimental station for time-resolved angle-resolved photoemission spectroscopy(ARPES)research will be constructed and the optical design is presented.The HHG lightsource covers the extreme ultraviolet(XUV)photon energy range of 20–50 eV.A Czerny–Turner monochromator with two plane gratings worked in conical diffraction configuration is employed to maintain the transmission efficiency and preserve the pulse time duration.The calculated beamline transmission efficiency is better than 5%in the whole photon energy range.To our knowledge,this is the first time in China to combine THz-infrared FEL with HHG light source,and this experimental station will be a powerful and effective instrument that will give new research opportunities in the future for users doing research on the dynamic evolution of the excited electron band structure of a material’s surface.