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 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.

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.

Auto-parametric resonance of a continuous-beam-bridge model under two-point periodic excitation:an experimental investigation and stability analysis

The auto-parametric resonance of a continuous-beam bridge model subjected to a two-point periodic excitation is experimentally and numerically investigated in this study.An auto-parametric resonance experiment of the test model is conducted to observe and measure the auto-parametric resonance of a continuous beam under a two-point excitation on columns.The parametric vibration equation is established for the test model using the finite-element method.The auto-parametric resonance stability of the structure is analyzed by using Newmark's method and the energy-growth exponent method.The effects of the phase difference of the two-point excitation on the stability boundaries of auto-parametric resonance are studied for the test model.Compared with the experiment,the numerical instability predictions of auto-parametric resonance are consistent with the test phenomena,and the numerical stability boundaries of auto-parametric resonance agree with the experimental ones.For a continuous beam bridge,when the ratio of multipoint excitation frequency(applied to the columns)to natural frequency of the continuous girder is approximately equal to 2,the continuous beam may undergo a strong auto-parametric resonance.Combined with the present experiment and analysis,a hypothesis of Volgograd Bridge's serpentine vibration is discussed.

Modular Extremely Large-Scale Array Communication:Near-Field Modelling and Performance Analysis

This paper investigates the wireless communication with a novel architecture of antenna arrays,termed modular extremely large-scale array(XLarray),where array elements of an extremely large number/size are regularly mounted on a shared platform with both horizontally and vertically interlaced modules.Each module consists of a moderate/flexible number of array elements with the inter-element distance typically in the order of the signal wavelength,while different modules are separated by the relatively large inter-module distance for convenience of practical deployment.By accurately modelling the signal amplitudes and phases,as well as projected apertures across all modular elements,we analyse the near-field signal-to-noise ratio(SNR)performance for modular XL-array communications.Based on the non-uniform spherical wave(NUSW)modelling,the closed-form SNR expression is derived in terms of key system parameters,such as the overall modular array size,distances of adjacent modules along all dimensions,and the user's three-dimensional(3D)location.In addition,with the number of modules in different dimensions increasing infinitely,the asymptotic SNR scaling laws are revealed.Furthermore,we show that our proposed near-field modelling and performance analysis include the results for existing array architectures/modelling as special cases,e.g.,the collocated XL-array architecture,the uniform plane wave(UPW)based far-field modelling,and the modular extremely large-scale uniform linear array(XL-ULA)of onedimension.Extensive simulation results are presented to validate our findings.

Experimental models of high-risk bowel anastomosis in rats:A systematic review

BACKGROUND Anastomotic leaks remain one of the most dreaded complications in gastrointestinal surgery causing significant morbidity,that negatively affect the patients’quality of life.Experimental studies play an important role in understanding the pathophysiological background of anastomotic healing and there are still many fields that require further investigation.Knowledge drawn from these studies can lead to interventions or techniques that can reduce the risk of anastomotic leak in patients with high-risk features.Despite the advances in experimental protocols and techniques,designing a high-quality study is still challenging for the investigators as there is a plethora of different models used.AIM To review current state of the art for experimental protocols in high-risk anastomosis in rats.METHODS This systematic review was performed according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.To identify eligible studies,a comprehensive literature search was performed in the electronic databases PubMed(MEDLINE)and Scopus,covering the period from conception until 18 October 2023.RESULTS From our search strategy 102 studies were included and were categorized based on the mechanism used to create a high-risk anastomosis.Methods of assessing anastomotic healing were extracted and were individually appraised.CONCLUSION Anastomotic healing studies have evolved over the last decades,but the findings are yet to be translated into human studies.There is a need for high-quality,well-designed studies that will help to the better understanding of the pathophysiology of anastomotic healing and the effects of various interventions.

Comparison of Pile-Soil-Structure Interaction Modeling Techniques for A 10-MW Large-Scale Monopile Wind Turbine Model Under Wind and Wave Conditions

Considering the large diameter effect of piles,the influence of different pile-soil analysis methods on the design of monopile foundations for offshore wind turbines has become an urgent problem to be solved.Three different pile-soil models were used to study a large 10 MW monopile wind turbine.By modeling the three models in the SACS software,this paper analyzed the motion response of the overall structure under the conditions of wind and waves.According to the given working conditions,this paper concludes that under the condition of independent wind,the average value of the tower top x-displacement of the rigid connection method is the smalle st,and the standard deviation is the smallest under the condition of independent wave.The results obtained by the p-y curve method are the most conservative.

Some results of modeling D-D seismogenic pattern by the fracture model experiment of large-scale rock samples(I)

sing the natural limestone samples taken from the field with dimension of 500 mm×500 mm×1 000 mm, the D-D (dilatancy-diffusion) seismogeny pattern was modeled under the condition of water injection, which observes the time-space evolutionary features about the relative physics fields of the loaded samples from deformation, formation of microcracks to the occurrence of main rupture. The results of observed apparent resistivity show: ① The process of the deformation from microcrack to main rupture on the loaded rock sample could be characterized by the precursory spatial-temporal changes in the observation of apparent resistivity; ② The precursory temporal changes of observation in apparent resistivity could be divided into several stages, and its spatial distribution shows the difference in different parts of the rock sample; ③ Before the main rupture of the rock sample the obvious ″tendency anomaly′ and ′short-term anomaly″ were observed, and some of them could be likely considered as the ″impending earthquake ″anomaly precursor of apparent resistivity. The changes and distribution features of apparent resistivity show that they are intrinsically related to the dilatancy phenomenon of the loaded rock sample. Finally, this paper discusses the mechanism of resistivity change of loaded rock sample theoretically.

MicroRNAs in mouse and rat models of experimental epilepsy and potential therapeutic targets

Epilepsy is a common and serious neurological disease that causes recurrent seizures. The brain damage caused by seizures can lead to depression, anxiety, cognitive impairment, or disability. In almost all cases chronic seizures are difficult to cure. MicroRNAs are widely expressed in the central nervous system and play important roles in the pathogenesis of several neurological disorders, including epilepsy. A variety of animals(mostly mice and rats) have been used to induce experimental epilepsy using different protocols and miRNA profiling performed. Most of the recent studies reviewed had performed miRNA profiling in hippocampal tissues and a large number of microRNAs were dysregulated when compared to controls. Most notably, miR-132-3p,-146a-5p,-10a-5p,-21a-3p,-27a-3p,-142a-5p,-212-3p,-431-5p, and-155 were upregulated in both the mouse and rat studies. Overexpression of miR-137 and miR-219 decreased seizure severity in a mouse epileptic model, and suppression of miR-451,-10a-5p,-21a-5p,-27a-5p,-142a-5p,-431-5p,-155, and-134 had a positive influence on seizure behavior. In the rat studies, overexpression of miR-139-5p decreased neuronal damage in drug-resistant rats and inhibition of miR-129-2-3p,-27a-3p,-155,-134,-181a, and-146a had a positive effect on seizure behavior and/or reduced the loss of neuronal cells. Further studies are warranted using adult female and immature male and female animals. It would also be helpful to test the ability of specific agomirs and antagomirs to control seizure activity in a subhuman primate model of epilepsy such as adult marmosets injected intraperitoneally with pilocarpine or cynomolgus monkeys given intrahippocampal injections of kainic acid.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Long Short-Term Memory Recurrent Neural Network-Based Acoustic Model Using Connectionist Temporal Classification on a Large-Scale Training Corpus

A Long Short-Term Memory(LSTM) Recurrent Neural Network(RNN) has driven tremendous improvements on an acoustic model based on Gaussian Mixture Model(GMM). However, these models based on a hybrid method require a forced aligned Hidden Markov Model(HMM) state sequence obtained from the GMM-based acoustic model. Therefore, it requires a long computation time for training both the GMM-based acoustic model and a deep learning-based acoustic model. In order to solve this problem, an acoustic model using CTC algorithm is proposed. CTC algorithm does not require the GMM-based acoustic model because it does not use the forced aligned HMM state sequence. However, previous works on a LSTM RNN-based acoustic model using CTC used a small-scale training corpus. In this paper, the LSTM RNN-based acoustic model using CTC is trained on a large-scale training corpus and its performance is evaluated. The implemented acoustic model has a performance of 6.18% and 15.01% in terms of Word Error Rate(WER) for clean speech and noisy speech, respectively. This is similar to a performance of the acoustic model based on the hybrid method.

Validating the Runoff from the PRECIS Model Using a Large-Scale Routing Model

The streamflow over the Yellow River basin is simulated using the PRECIS （Providing REgional Climates for Impacts Studies） regional climate model driven by 15-year （1979-1993） ECMWF reanalysis data as the initial and lateral boundary conditions and an off-line large-scale routing model （LRM）. The LRM uses physical catchment and river channel information and allows streamflow to be predicted for large continental rivers with a 1°×1° spatial resolution. The results show that the PRECIS model can reproduce the general southeast to northwest gradient distribution of the precipitation over the Yellow River basin, The PRECIS- LRM model combination has the capability to simulate the seasonal and annual streamflow over the Yellow River basin. The simulated streamflow is generally coincident with the naturalized streamflow both in timing and in magnitude.

Micro sliding friction model considering periodic variation stress distribution of contact surface and experimental verification

Micro sliding phenomenon widely exists in the operation process of mechanical systems,and the micro sliding friction mechanism is always a research hotspot.In this work,based on the total reflection method,a measuring device for interface contact behavior under two-dimensional(2D)vibration is built.The stress distribution is characterized by the light intensity distribution of the contact image,and the interface contact behavior in the 2D vibration process is studied.It is found that the vibration angle of the normal direction of the contact surface and its fluctuation affect the interface friction coefficient,the tangential stiffness,and the fluctuation amplitude of the stress distribution.Then they will affect the change of friction state and energy dissipation in the process of micro sliding.Further,an improved micro sliding friction model is proposed based on the experimental analysis,with the nonlinear change of contact parameters caused by the normal contact stress distribution fluctuation taken into account.This model considers the interface tangential stiffness fluctuation,friction coefficient hysteresis,and stress distribution fluctuation,whose simulation results are consistent well with the experimental results.It is found that considering the nonlinear effect of a certain contact parameter alone may bring a greater error to the prediction of friction behavior.Only by integrating multiple contact parameters can the accuracy of friction prediction is improved.

Experimental investigation and analytically modeling of hysteretic behavior of rigid bus-flexible connectors of 220 kV electrical substations

This paper describes the quasi-static testing and analytical modelling of the hysteretic behavior of aluminum alloy rigid bus-flexible connectors of 220 kV electrical substations.The main objective of the study is to experimentally investigate the hysteretic behavior of six different types of rigid bus-flexible connectors 220 kV electrical substations when subjected to cyclic loading.Another objective is to theoretically study the flexibility and effectiveness of a previously proposed analytical model in fitting the experimental hysteresis loops of the tested rigid bus-flexible connectors.The experimental investigation indicates that the tested rigid bus-flexible connectors exhibit highly asymmetric hysteresis behavior along with tension stiffening effect.The theoretical study demonstrates that the generalized Bouc-Wen model has high flexibility and is effective in fitting the experimental hysteresis resisting force-displacement curves of the six tested rigid bus-flexible connectors.

Numerical experimental study on the potential climatic impacts oflarge-scale wind farms in China

Wind energy has been rapidly developed in China during the past decades and the installed capacity has been the largest in the world. In the future, utilization of wind power is still expected to carry out in China mainly with a large-scale centralized layout. Here, we examine the potential climatic impacts of large-scale windfarms associated with deployment scale in China using numerical experiments, in which four deployment scenarios were designed. These four scenarios represented relatively small- (484 GW), medium- (2165 GW) and large-scale (3490 GW and 5412 GW) installed wind power capacities, respectively. Results showed that turbulent kinetic energy, wind velocity, and air temperature varied consistently within those windfarms with the largest changes in turbine hub heights. Moreover, the above relatively large- scale windfarms could induce regional wanning with a maximum of above 0.8 °C in North China. This regional warming may be linked to an anomalous circulation pattern with a negative pressure anomaly center in Northeast China and a positive pressure anomaly center in the middle and lower reaches of the Yangtze-Huaihe River Basin.

The Study of Optimizing Reservoir Model Using Experimental Design in Stochastic Models

In response to the main problems in commonly used model selection methods,a method was proposed to apply the concept of experimental design to the optimization of uncertain reservoir models.Firstly,based on the actual situation of the oil field,the uncertain variables were determined that affect the geological reserves of the model and their possible range of variation,and experimental design was used to determine the modeling plan.Then,multiple geological models were established and reserves were calculated,and multiple regression was performed between uncertain variables and the corresponding geological reserves of the model.Finally,Monte Carlo simulation technology was applied to determine the parameters of the P10,P50,and P90 models for probabilistic reserves,and P10,P50,and P90 models were established.This method is not only more objective and time-saving in the application process,but also can determine the main geological variables that affect geological reserves,providing a new idea for evaluating the uncertainty of geological reserves.

Experimentation and thermodynamic modelling on SrZrO_3

Experimental data for the perovskite phase SrZrO3 were subjected to a critical thermodynamic assessment using the CALPHAD approach. Special attention was paid to the structural behavior of SrZrO3 to illustrate, how to select an appropriate thermodynamic model based on crystal structure and chemistry information, how to identify and resolve the inconsistency between various kinds of experimental data, and how to use thermodynamic modeling as a basic tool in the development and optimization of materials and process. Our assessment results in a Gibbs energy function covering the temperature range between 300 K and the melting point, which explains the experimental data within the experimental uncertainty.

Comparison of nonlinear modeling methods for the composite rubber clamp

The cubic stiffness force model(CSFM)and Bouc-Wen model(BWM)are introduced and compared innovatively.The unknown coefficients of the nonlinear models are identified by the genetic algorithm combined with experiments.By fitting the identified nonlinear coefficients under different excitation amplitudes,the nonlinear vibration responses of the system are predicted.The results show that the accuracy of the BWM is higher than that of the CSFM,especially in the non-resonant region.However,the optimization time of the BWM is longer than that of the CSFM.

Improved Diurnal Cycle of Precipitation on Land in a Global Non-Hydrostatic Model Using a Revised NSAS Deep Convective Scheme

In relatively coarse-resolution atmospheric models,cumulus parameterization helps account for the effect of subgridscale convection,which produces supplemental rainfall to the grid-scale precipitation and impacts the diurnal cycle of precipitation.In this study,the diurnal cycle of precipitation was studied using the new simplified Arakawa-Schubert scheme in a global non-hydrostatic atmospheric model,i.e.,the Yin-Yang-grid Unified Model for the Atmosphere.Two new diagnostic closures and a convective trigger function were suggested to emphasize the job of the cloud work function corresponding to the free tropospheric large-scale forcing.Numerical results of the 0.25-degree model in 3-month batched real-case simulations revealed an improvement in the diurnal precipitation variation by using a revised trigger function with an enhanced dynamical constraint on the convective initiation and a suitable threshold of the trigger.By reducing the occurrence of convection during peak solar radiation hours,the revised scheme was shown to be effective in delaying the appearance of early-afternoon rainfall peaks over most land areas and accentuating the nocturnal peaks that were wrongly concealed by the more substantial afternoon peak.In addition,the revised scheme enhanced the simulation capability of the precipitation probability density function,such as increasing the extremely low-and high-intensity precipitation events and decreasing small and moderate rainfall events,which contributed to the reduction of precipitation bias over mid-latitude and tropical land areas.