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.

Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals

Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.

Experimental and Numerical Study of Bonding Capacity of Interface between Ultra-High Performance Concrete and Steel Tube

This study investigates the bond performance at the interfacial region shared by Ultra-High Performance Concrete(UHPC)and steel tubes through push-out tests.This study examines how changes in steel fiber volumetric ratio and thickness of steel tube influence the bond strength characteristics.The results show that as the enhancement of the steel tube wall thickness,the ultimate bond strength at the interface improves significantly,whereas the initial bond strength exhibits only slight variations.The influence of steel fiber volumetric ratio presents a nonlinear trend,with initial bond strength decreasing at low fiber content and increasing significantly as fiber content rises.Additionally,finite element(FE)simulations were applied to replicate the experimental conditions,and the outcomes showed strong correlation with the experimental data,confirming the exactitude of the FE model in predicting the bond behavior at the UHPC-Steel interface.These findings provide valuable insights for optimizing the design of UHPC-Filled steel tubes in high-performance structure.

Experimental analysis of the slip sinkage effect based on real vehicle test

To improve the semi-empirical model, the slip sinkage effect is analyzed based on the real vehicle test. A dynamic testing system is used to gain the dynamic responses of wheel-soil interactions, The Gauss-Newton algorithm is adopted to estimate the undetermined parameters involved in the slip sinkage models. Wong＇s original model is compared with three typical slip sinkage models on the prediction performance of a drawbar pull. The maximum error rate, root mean squared error and correlation coefficient are utilized to evaluate the performance. The results indicate that the slip sinkage models outperform Wong＇s model and greatly improve the prediction accuracy. Lyasko＇s model is confirmed as an outstanding one for its comprehensive performance. Hence, the existence of the slip sinkage effect is validated. Lyasko＇s model is selected as an optimal one for the practical evaluation of military vehicle trafficability.

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.

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.

Design and Experimental Investigation for Subsea Control Module Test System

As a core part of subsea production systems,subsea control modules(SCMs)are costly,difficult,and expensive to install and inconvenient to use in underwater maintenance.Therefore,performance and function tests must be carried out before launching SCMs.This study developed a testing device and an SCM test by investigating SCMs and their underwater.The testing device includes four parts:a hydraulic station,an SCM test stand,a signal generating device,and an electronic test unit.First,the basic indices of the testing device were determined from the performance and working parameters of the SCM.Second,the design scheme of the testing device for the SCM was tentatively proposed,and each testing device was designed.Finally,a practical measurement of the SCM,in combination with the hydraulic station,SCM test stand,signal generator,electronic unit,and highpressure water tank,was carried out according to the test requirements.The measurement mainly involved equipment inspection before testing and an experimental test for the SCM.The validity and feasibility of the testing device and method were simultaneously verified through an association test.

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.

Experimental Investigations on the Roll Motion Characteristics of Multi-Fishing Boats Anchored Side by Side

Fishing boats are usually anchored side by side in the harbor because of the small structural size and poor resistance to wind and waves.A series of physical model experiments are conducted to investigate the motion characteristics of multiple fishing boats that are moored together.A decay test in calm water is conducted to study the natural period and damping coefficients.Regular wave experiments are performed to analyze the roll motion response of each boat for four modes(different numbers of boats side-by-side).The results indicate that the“natural period”of each boat for the mode of multi-boats especially three or four boats,is slightly smaller than that of a single boat,whereas the damping coefficient is visibly larger than that of a single boat.The maximum roll angle of each boat does not appear at the same time under a 90°incident wave.Small roll motion energy is generated at low frequencies and high frequencies when multiple boats are moored together.The energy decreases with the increasing wave period.The roll motion responses of each boat in four modes exhibit different trends with the increasing wave frequency.The number of boats and boat position have significant effects on roll motion.

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.

Antioxidants in experimental ischemia-reperfusion injury of the testis: Where are we heading towards?

Testicular torsion(TT) is a medical emergency that primary affects newborns and young adolescents.It causes testicular injury due to the torsion of the spermatic cord and its components, initially in the venous blood flow and finally in the arterial blood flow.Prompt diagnosis and early surgical management are necessary in managing this urgent situation.The process of the pathophysiological events in ischemia-reperfusion is multifactorial and deals with the perception of the oxidative stress responsible for the consequences of ischemia/reperfusion(I/R) stress following TT.Duration and severity of torsion also play a significant role in the oxidative stress.A detrimental result of the defense system of the testes takes place resulting finally in testicular atrophy and impaired function.Antioxidant factors have been experimentally studied in an effort to front this state.They have been classified as endogenous or exogenous antioxidants.Endogenous antioxidants comprise a structure of enzymic enzymatic and nonenzymic enzymatic particles presented within cytoplasm and numerous other subunits in the cells.Exogenous antioxidants include a variety of natural and pharmaceutical agents that may prevent or ameliorate the harmful effects of I/R injury.In this study we review those factors and their ability to enhance the oxidative status of the testis.A feature insight into where we are heading is attempted.

Effects of Intestinal Trefoil Factor on Colonic Mucosa in Experimental Colitis of Rats

In order to investigate the protective effects of intestinal trefoil factor (ITF) on colonic mucosa in experimental colitis of rats, ITF was detected by RT-PCR and immunohistochemistry at different time points. Three days after colitis induction, rats were treated with either 0.9 % saline solution or rhITF. Pathological changes and the expression of iNOS mRNA, NO, MDA and SOD were measured respectively. It was found that ITF was mainly located in goblet cells, significantly higher in model group than in normal group (P<0.05). rhITF could increase the iNOS mRNA expression and NO contents, and there was statistically significant difference between rhITF group and model group (P<0.05). rhITF also caused an increase of MDA and a decrease of SOD, but there was no significant difference between two groups. These results indicated that ITF has apparent therapeutic effects in ulcerative colitis, which may be associated with iNOS and NO.

A case study of excessive vibrations inside buildings due to an underground railway:Experimental tests and theoretical analysis

Excessive vibrations inside buildings in the Lihu New Village caused by the Shenzhen Metro Line 2 underground railway were investigated by conducting analyses of the tunnel,the track irregularities,the stiffness of the fastening system,and the vibrations of the track system and the building at different speeds.A numerical simulation based on the dynamic coupling theory of the vehicle-track system was used to verify the experimental results.Suitable countermeasures were investigated.The results show that rail corrugation is the primary reason for the excessive vibration,and an increase in the stiffness of the vertical fastening system is the secondary reason.The solution was to eliminate the rail corrugation using rail grinding and decrease the vertical stiffness by changing the fastening system.The results of this study provide references for solving vibration problems caused by rail lines.

Experimental investigation on flow properties of cemented paste backfill through L-pipe and loop-pipe tests

With the gradual depletion of available ore at shallow depth,deep mines have been widely operated around the world and therefore need a longer distance to transport the backfill to the underground stope.In this case,the determination of pressure drop is more important in the pipeline transportation system design.As the pilot loop systems require a large amount of capital and manual investment,even its results are reliable,there is an urgent need to find an alternative simple and cost-saving method to determine the pressure drop.Hence,laboratory L-pipe and a pilot-loop tests were employed to study the flow properties of cemented paste backfill cured at various solid and binder content.The results indicate that the L-pipe test presented a similar trend to the loop test,but the L-pipe was characterized by higher pressure drop values for various solid and cement contents.As cement content increased beyond 0%,the paste in the L-pipe showed a slighter difference in pressure drop evolution compared to the paste in the loop-pipe.These results suggest that the simple L-pipe is a workable substitute for semi-industrial loop tests and can provide guidance for designing practical CPB pipeline systems in deep mines.

Message from animal models and experimental medicine for 2024-Persevering in its mission to be at the heart of laboratory animal science

In recent years,new technologies have enabled a steady stream of novel theoretical approaches to understanding the mechanisms of disease occurrence and development.The emergence of these new technologies has provided the pharmaceutical industry with a huge amount of data that can be utilized,such as brain-computer inter-faces,artificial intelligence(AI)doctors,wearable medical testing de-vices,etc.

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.

Drag pick cutting tests: A comparison between experimental and theoretical results

This paper aims at reporting the results of a number of drag pick cutting tests on selected igneous rock samples to compare the experimentally determined maximum cutting force （FC） values with theoreti- cally estimated ones. First, a review on theoretical rock cutting models proposed for both chisel and conical picks was presented in detail. Experimental study consists of both chisel and conical pick cutting tests in unrelieved （single-pick） cutting mode with varying cutting depths. FC＇ values were determined from experimental results, and theoretical models were utilized to compute FC for all cutting conditions. Computed and experimentally determined F（ data were then compared for a referenced cutting depth. It is shown that the theoretical models might overestimate or underestimate FC＇ and cannot give reliable results. Finally, explanations for these mismatches were presented.