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.

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.

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.

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 investigation on the permeability of gap-graded soil due to horizontal suffusion considering boundary effect

The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundary effect is conducted,where the hydraulic head difference(DH)varies,and the boundary includes non-loss and soil-loss conditions.Soil samples are filled into seven soil storerooms connected in turn.After evaluation,the variation in content of fine sand(ΔR_(f))and the hydraulic conductivity of soils in each storeroom(C_(i))are analyzed.In the non-loss test,the soil sample filling area is divided into runoff,transited,and accumulated areas according to the negative or positive ΔR_(f) values.ΔR_(f) increases from negative to positive along the seepage path,and Ci decreases from runoff area to transited area and then rebounds in accumulated area.In the soil-loss test,all soil sample filling areas belong to the runoff area,where the gentle-loss,strengthened-loss,and alleviated-loss parts are further divided.ΔR_(f) decreases from the gentle-loss part to the strengthened-loss part and then rebounds in the alleviated-loss part,and C_(i) increases and then decreases along the seepage path.The relationship between ΔR_(f) and Ci is different with the boundary condition.Ci exponentially decreases with ΔR_(f) in the non-loss test and increases with ΔR_(f) generally in the soil-loss test.

Theoretical and Experimental Study on the Performance of Hermetic Diaphragm Squeeze Film Dampers for Gas-Lubricated Bearings

Low damping characteristics have always been a key sticking points in the development of gas bearings.The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearings.This paper proposed a novel hermetic diaphragm squeeze film damper(HDSFD)for oil-free turbomachinery supported by gas lubricated bearings.Several types of HDSFDs with symmetrical structure were proposed for good damping performance.By considering the compressibility of the damper fluid,based on hydraulic fluid mechanics theory,a dynamic model of HDSFDs under medium is proposed,which successfully reflects the frequency dependence of force coefficients.Based on the dynamic model,the effects of damper fluid viscosity,bulk modulus of damper fluid,thickness of damper fluid film and plunger thickness on the dynamic stiffness and damping of HDSFDs were analyzed.An experimental test rig was assembled and series of experimental studies on HDSFDs were conducted.The damper fluid transverse flow is added to the existing HDSFD concept,which aims to make the dynamic force coefficients independent of frequency.Although the force coefficient is still frequency dependent,the damping coefficient at high frequency excitation with damper fluid supply twice as that without damper fluid supply.The results serve as a benchmark for the calibration of analytical tools under development.

Experimental investigation of dynamic characteristics of leaching tubing for solution mining of salt cavern carbon and energy storage

Salt caverns are extensively utilized for storing various substances such as fossil energy,hydrogen,compressed air,nuclear waste,and industrial solid waste.In China,when the salt cavern is leached through single-well water solution mining with oil as a cushion,engineering challenges arise with the leaching tubing,leading to issues like damage and instability.These problems significantly hinder the progress of cavern construction and the control of cavern shape.The primary cause of this is the flowinduced vibration instability of leaching tubing within a confined space,which results in severe bending or damage to the tubing.This study presents a model experimental investigation on the dynamic characteristics of leaching tubing using a self-developed liquid-solid coupling physical model experiment apparatus.The experiment utilizes a silicone-rubber pipe(SRP)and a polycarbonate pipe(PCP)to examine the effects of various factors on the dynamic stability of cantilevered pipes conveying fluid.These factors include external space constraint,flexural rigidity,medium outside the pipe,overhanging length,and end conditions.The experiments reveal four dynamic response phenomena:water hammer,static buckling,chaotic motion,and flutter instability.The study further demonstrates that the length of the external space constraint has a direct impact on the flutter critical flow velocity of the cantilevered pipe conveying fluid.Additionally,the flutter critical flow velocity is influenced by the end conditions and different external media.

Analytical and Experimental Research on Wave Scattering by an Open-Type Rectangular Breakwater with Horizontal Perforated Plates

This study proposes a novel open-type rectangular breakwater combined with horizontal perforated plates on both sides to enhance the sheltering effect of the rectangular box-type breakwaters against longer waves.The hydrodynamic characteristics of this breakwater are analyzed through analytical potential solutions and experimental tests.The quadratic pressure drop conditions are exerted on the horizontal perforated plates to facilitate assessing the effect of wave height on the dissipated wave energy of breakwater through the analytical solution.The hydrodynamic quantities of the breakwater,including the reflection,transmission,and energyloss coefficients,together with vertical and horizontal wave forces,are calculated using the velocity potential decomposition method as well as an iterative algorithm.Furthermore,the reflection and transmission coefficients of the breakwater are measured by conducting experimental tests at various wave periods,wave heights,and both porosities and widths of the horizontal perforated plates.The analytical predicted results demonstrate good agreement with the iterative boundary element method solution and measured data.The influences of variable incident waves and structure parameters on the hydrodynamic characteristics of the breakwater are investigated through further calculations based on analytical solutions.Results indicate that horizontal perforated plates placed on the water surface for both sides of the rectangular breakwater can enhance the wave dissipation ability of the breakwater while effectively decreasing the transmission and reflection coefficients.

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.

An internal ballistic model of electromagnetic railgun based on PFN coupled with multi-physical field and experimental validation

To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dimensional numerical model of the augmented railgun with four parallel unconventional rails is introduced to simulate the internal ballistic process and realize the multi-physics field coupling calculation of the rail gun,and a test experiment of a medium-caliber electromagnetic launcher powered by pulse formation network(PFN)is carried out.Various test methods such as spectrometer,fiber grating and high-speed camera are used to test several parameters such as muzzle initial velocity,transient magnetic field strength and stress-strain of rail.Combining the simulation results and experimental data,the damage condition of the contact surface is analyzed.

Experimental Analysis of Radial Centrifugal Pump Shutdown

Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency and frequency conversion modes,experiments were carried to determine the characteristic evolution of parameters such as speed,inlet and outlet pressure,head,flow rate and shaft power.A quasi-steady-state method was also used to further investigate these transient behaviors.The results show that,compared to the power frequency input,the performance parameter curves for the frequency conversion input are less volatile and smoother.The characteristic time is longer and the response to shutdown is slower.The quasi-steady-state theoretical head-flow curves match the experimental head-flow curves more closely at low flow rates when the frequency conversion input is considered.Moreover,in this case,the similarity law predicts the hydraulic performance more accurately.

Experimental and Three-Dimensional Numerical Simulation of Phenomena Induced by Submerged Oblique Jet Scouring

Scouring experiments were conducted using a three-dimensional laser scanning technology for angles of the jet spanning the interval from 0°to 30°,and the characteristics of the scour hole in equilibrium conditions were investigated accordingly.The results indicate that the optimal scouring effects occur when the jet angle is in the ranges between 15°and 20°.Moreover,the dimensionless profiles of the scour hole exhibit a high degree of similarity at different jet angles.Numerical simulations conducted using the Flow-3D software to investigate the bed shear stress along the jet impingement surface have shown that this stress is influenced by both the resultant force and the jet impingement surface area.It reaches its maximum value when the jet is vertical,decreases rapidly as the jet starts to tilt,then increases slightly,and decreases again significantly when the angle exceeds 20°.

Exploring Xiaojianzhong decoction's potential in gastric cancer treatment:Integrative insights and experimental validation

Gastric cancer(GC)remains a formidable global health concern with significant morbidity and mortality rates,despite the fact that numerous advances have been made to improve conventional therapies.Xiaojianzhong decoction(XJZ),a traditional Chinese medicine,has garnered academic attention as a multicomponent,multitarget approach to managing GC.The present editorial explores the potential of XJZ in the treatment of GC through a comprehensive analysis of network pharmacology and experimental validation.Network pharmacology was used to identify key molecular targets of XJZ,including interleukin 6,prostaglandin-endoperoxide synthase 2,and matrix metalloproteinase 9,and in vitro experiments were used to confirm the efficacy of XJZ in inhibiting cell proliferation,inducing apoptosis,and modulating gene expression associated with GC progression.This editorial highlights XJZ as a promising therapeutic strategy for GC and indicates a need for further clinical exploration and validation of its efficacy.

Design and verification of an improved experimental platform for stray current in urban rail transit

With the rapid development of urban rail transit,there have been an urgent problem of excessive stray current.Because the stray current distribution is random and difficult to verify in the field,we designed an improved stray current experimental platform by replacing the simulated aqueous solution with a real soil environment and by calculating the transition resistance by measuring the soil resistivity,which makes up for the defects in the previous references.Firstly,the mathematical models of rail-drainage net and rail-drainage netground were established,and the analytical expressions of current and voltage of rail,drainage net and other structures were derived.In addition,the simulation model was built,and the mathematical analysis results were compared with the simulation results.Secondly,the accuracy of the improved stray current experimental platform was verified by comparing the measured and simulation results.Finally,based on the experimental results,the influence factors of stray current were analyzed.The relevant conclusions provide experimental data and theoretical reference for the study of stray current in urban rail transit.

Optimization of Center of Gravity Position and Anti-Wave Plate Angle of Amphibious Unmanned Vehicle Based on Orthogonal Experimental Method

When the amphibious vehicle navigates in water,the angle of the anti-wave plate and the position of the center of gravity greatly influence the navigation characteristics.In the relevant research on reducing the navigation resistance of amphibious vehicles by adjusting the angle of the anti-wave plate,there is a lack of scientific selection of parameters and reasonable research of simulation results by using mathematical methods,and the influence of the center of gravity position on navigation characteristics is not considered at the same time.To study the influence of the combinations of the angle of the anti-wave plate and the position of the center of gravity on the resistance reduction characteristics,a numerical calculation model of the amphibious unmanned vehicle was established by using the theory of computational fluid dynamics,and the experimental data verified the correctness of the numerical model.Based on this numerical model,the navigation characteristics of the amphibious unmanned vehicle were studied when the center of gravity was located at different positions,and the orthogonal experimental design method was used to optimize the parameters of the angle of the anti-wave plate and the position of the center of gravity.The results show that through the parameter optimization analysis based on the orthogonal experimental method,the combination of the optimal angle of the anti-wave plate and the position of the center of gravity is obtained.And the numerical simulation result of resistance is consistent with the predicted optimal solution.Compared with the maximum navigational resistance,the parameter optimization reduces the navigational resistance of the amphibious unmanned vehicle by 24%.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Potential-dependent insights into the origin of high ammonia yield rate on copper surface via nitrate reduction:A computational and experimental study

Focusing on revealing the origin of high ammonia yield rate on Cu via nitrate reduction(NO3RR),we herein applied constant potential method via grand-canonical density functional theory(GC-DFT)with implicit continuum solvation model to predict the reaction energetics of NO3RR on pure copper surface in alkaline media.The potential-dependent mechanism on the most prevailing Cu(111)and the minor(100)and(110)facets were established,in consideration of NO_(2)_(−),NO,NH_(3),NH_(2)OH,N_(2),and N_(2)O as the main products.The computational results show that the major Cu(111)is the ideal surface to produce ammonia with the highest onset potential at 0.06 V(until−0.37 V)and the highest optimal potential at−0.31 V for ammonia production without kinetic obstacles in activation energies at critical steps.For other minor facets,the secondary Cu(100)shows activity to ammonia from−0.03 to−0.54 V with the ideal potential at−0.50 V,which requires larger overpotential to overcome kinetic activation energy barriers.The least Cu(110)possesses the longest potential range for ammonia yield from−0.27 to−1.12 V due to the higher adsorption coverage of nitrate,but also with higher tendency to generate di-nitrogen species.Experimental evaluations on commercial Cu/C electrocatalyst validated the accuracy of our proposed mechanism.The most influential(111)surface with highest percentage in electrocatalyst determined the trend of ammonia production.In specific,the onset potential of ammonia production at 0.1 V and emergence of yield rate peak at−0.3 V in experiments precisely located in the predicted potentials on Cu(111).Four critical factors for the high ammonia yield and selectivity on Cu surface via NO3RR are summarized,including high NO3RR activity towards ammonia on the dominant Cu(111)facet,more possibilities to produce ammonia along different pathways on each facet,excellent ability for HER inhibition and suitable surface size to suppress di-nitrogen species formation at high nitrate coverage.Overall,our work provides comprehensive potential-dependent insights into the reaction details of NO3RR to ammonia,which can serve as references for the future development of NO3RR electrocatalysts,achieving higher activity and selectivity by maximizing these characteristics of copper-based materials.