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.

An experimental investigation on the effect of grain size on oil-well sand production

Sand production in oil wells is closely related to the mechanical behavior and petrographical properties of sandstones reservoir. Grain size is one of the main parameters controlling the phenomenon, which is studied in this paper. Large-scale hollow cylindrical synthetic samples with the same rock strength but different grain sizes were tested by an experimental setup in the laboratory. Different external stresses and fluid flow rates were applied to the samples and produced sand was measured continuously. Results show two different trends between sanding stress level and grain size. For the samples with finer grain size （D50〈0.3 mm）, the required confining stress for different sanding levels decreased with an increase in the grain size and for the samples with the coarser grains （D50〉0.3 mm） the required confining stress for different sanding levels dramatically increased with an increase in the grain size. Those two different trends were discussed and explained. The first one was production of individual grains and the second was bigger chunks in the slab form. In samples with large grains, plastic zones around hole were changed to a completely loose zone including interlocked individual grains or cluster of grains. In these samples after breakage of these interlocked zones sand was produced in the form of individual grains and clusters. Contrary to this, for samples with smaller grain size, shear bands were formed around the plastified hole and sand was produced in the form of big chunks or slabs.

Simulation logging experiment and interpretation model of array production logging measurements in a horizontal well

The distributions of local velocity and local phase holdup along the radial direction of pipes are complicated because of gravity differentiation,and the distribution of fluid velocity fi eld changes along the gravity direction in horizontal wells.Therefore,measuring the mixture flow and water holdup is difficult,resulting in poor interpretation accuracy of the production logging output profile.In this paper,oil–water two-phase flow dynamic simulation logging experiments in horizontal oil–water two-phase fl ow simulation wells were conducted using the Multiple Array Production Suite,which comprises a capacitance array tool(CAT)and a spinner array tool(SAT),and then the response characteristics of SAT and CAT in diff erent fl ow rates and water cut production conditions were studied.According to the response characteristics of CAT in diff erent water holdup ranges,interpolation imaging along the wellbore section determines the water holdup distribution,and then,the oil–water two-phase velocity fi eld in the fl ow section was reconstructed on the basis of the fl ow section water holdup distribution and the logging value of SAT and combined with the rheological equation of viscous fl uid,and the calculation method of the oil–water partial phase fl ow rate in the fl ow section was proposed.This new approach was applied in the experiment data calculations,and the results are basically consistent with the experimental data.The total fl ow rate and water holdup from the calculation are in agreement with the set values in the experiment,suggesting that the method has high accuracy.

An Experimental Study on the Pressure Distribution in Horizontal Gas Wells

Laboratory experiments have been carried out to study the fluid flow in the wellbore of a horizontal gas well during the production process.The related pressure distribution has been determined considering different cases(different inflow media,different perforation opening methods and different liquid holdup).It has been found that the larger the fluid flow rate,the greater the pressure changes in the wellbore under the same hole opening mode.The uniformity of the perforation opening method was also an important factor affecting the magnitude of the wellbore pressure change.The liquid holdup also affected the pressure distribution,especially when the gas volumetric flow rate exceeded 200 m3/h.Comparison of the outcomes of the present experimental study with the predictions of a theoretical model available in the literature has provided a relative error smaller than 20%.

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”.

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.

Effect of stress-dependent microannulus aperture on well leakage

Debonding at the cement-casing interface is recognized as a principal failure mechanism leading to CO_(2) leakage in wells.This detachment gives rise to a microannulus,which notably possesses greater permeability than undamaged cement,undermining its sealing efficacy.Conventionally,the permeability of the microannulus is regarded as a uniform value throughout the well.However,fundamentally,a microannulus is one type of fracture,and its gap or aperture size is affected by the effective stress.In this work,we developed a unique experimental apparatus.This equipment facilitates the curing of cement inside a steel casing,the formation of a microannulus between the casing and the cement,and the investigation of the fluid flow dynamics along the microannulus under laboratory-replicated in situ conditions.The microannulus was formed by injecting fluid from one end of the setup,and receiving similar amount of fluid on the other end signified the development of the leakage channel.Additionally,strain gauges affixed to the casing’s external surface yielded key information on the microannulus’s opening and closure.We observed a noticeable decline in microannulus hydraulic aperture(or permeability)in relation to effective stress and an exponential equation fits their relationship.Our findings also indicate a distinct behavior when comparing liquid CO_(2) with water.Specifically,it is easier for liquid CO_(2) to create the microannulus.However,the hydraulic aperture range for this microannulus(0.7-6 mm)is considerably smaller than that created by water flow(2-17 mm).Finally,we integrated the stressdependent microannulus aperture size into the combined analysis of well mechanical integrity and well leakage.The outcomes consistently demonstrated that when factoring in the stress-dependent aperture sizes,the leakage rates are 3e5 times compared to a fixed aperture model.The traditional assumption of a constant aperture significantly underestimates fluid leakage risks.

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.

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.

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.

Application of Intravenous Indwelling Needle in Undergraduate's Pharmacology Teaching Experiment

In this study,an intravenous indwelling needle was placed in the central artery of rabbit ear for collecting blood.The results show that this method greatly improves the success rate of blood sampling and well controls the experimental time.The students'unanimous feedback was that the method is simple and easy to operate,which is of great help to the stability of the experimental results.

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.

Numerical and Experimental Evaluation of New Coldform Inverted “U” Section in Single or Multiple FamilyDwellings’ Flooring Systems

This article will introduce a new version of the metal deck for building residential flooring with a newly designed cold form U section. This flooring will allow residential structures to be built more quickly while also reducing the necessary thickness of the floor. The level of strength and deflection of this floor will be determined via analysis of a floor bed comprised of cold-formed inverted U sections (IUS) covered by sheathing that is subjected to different loading scenarios. The necessary computational quantities associated with the experiment have been compared to established laboratory values by performing all related and applicable tests. Then, these quantities are compared to different existing flooring techniques to determine the efficacy of this technique. The results show that this flooring technique can be effective and cost-efficient in residential applications.

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.

Multi-environment BSA-seq using large F3 populations is able to achieve reliable QTL mapping with high power and resolution: An experimental demonstration in rice

Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.

Experimental Investigation on Vertical Hydraulic Transport of Ores in Deepsea Mining

Deepsea mining has been proposed since the 1960s to alleviate the lack of resources on land.Vertical hydraulic transport of collected ores from the seabed to the sea surface is considered the most promising method for industrial applications.In the present study,an indoor model test of the vertical hydraulic transport of particles was conducted.A noncontact optical method has been proposed to measure the local characteristics of the particles inside a vertical pipe,including the local concentration and particle velocity.The hydraulic gradient of ore transport was evaluated with various particle size distributions,particle densities,feeding concentrations and mixture flow velocities.During transport,the local concentration is larger than the feeding concentration,whereas the particle velocity is less than the mixture velocity.The qualitative effects of the local concentration and local fluid velocity on the particle velocity and slip velocity were investigated.The local fluid velocity contributes significantly to particle velocity and slip velocity,whereas the effect of the local concentration is marginal.A higher feeding concentration and mixture flow velocity result in an increased hydraulic gradient.The effect of the particle size gradation is slight,whereas the particle density plays a crucial role in the transport.