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.

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.

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.

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.

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.

Animal models for anti-neutrophil cytoplasmic antibody-associated vasculitis:Are current models good enough?

Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.

FLOW STRESS MODELING FOR AERONAUTICAL ALUMINUM ALLOY 7050-T7451 IN HIGH-SPEED CUTTING

The high temperature split Hopkinson pressure bar （SHPB） compression experiment is conducted to obtain the data relationship among strain, strain rate and flow stress from room temperature to 550 C for aeronautical aluminum alloy 7050-T7451. Combined high-speed orthogonal cutting experiments with the cutting process simulations, the data relationship of high temperature, high strain rate and large strain in high-speed cutting is modified. The Johnson-Cook empirical model considering the effects of strain hardening, strain rate hardening and thermal softening is selected to describe the data relationship in high-speed cutting, and the material constants of flow stress constitutive model for aluminum alloy 7050-T7451 are determined. Finally, the constitutive model of aluminum alloy 7050-T7451 is established through experiment and simulation verification in high-speed cutting. The model is proved to be reasonable by matching the measured values of the cutting force with the estimated results from FEM simulations.

Experimental verification of mathematical model for multiphase flow in air-agitated seed precipitation tank

In order to check the validity of the mathematical model for analyzing the flow field in the air-agitated seed precipitation tank,a scaled down experimental apparatus was designed and the colored tracer and KCl tracer were added in the apparatus to follow the real flow line.Virtue tracers were considered in the mathematical model and the algorithm of tracers was built.The comparison of the results between the experiment and numerical calculation shows that the time of the tracer flows out of stirring tube are 40 s in the experiment and 42 s in numerical calculated result.The transient diffusion process and the solution residence time of the numerical calculation are in good agreement with the experimental results,which indicates that the mathematical model is reliable and can be used to predict the flow field of the air-agitated seed precipitation tank.

The influence of inter-band rock on rib spalling in longwall panel with large mining height

In order to improve rib stability,failure criteria and instability mode of a thick coal seam with inter-band rock layer are analysed in this study.A three-dimensional mechanical model is established for the rib by considering the rock layer.A safety factor is defined foy the rib,and it is observed that the safety factor exhibits a positive correlation with the thickness and strength of the inter-band rock.A calculation method for determining critical parameters of the rock layer is presented to ensure the rib stability.It is revealed that incomplete propagation of the fracture at the hard rock constitutes a fundamental prerequisite for ensuring the rib stability.The influence of the position of the inter-band rock in the coal seam on failure mechanism of the rib was thoroughly investigated by developing a series of physical models for the rib at the face area.The best position for the inter-band rock in the coal seam is at a height of 1.5 m away from the roof line,which tends to provide a good stability state for the rib.For different inter-band rock positions,two ways of controlling rib by increasing supports stiffness and flexible grouting reinforcement are proposed.

Wide angle reflections in OBC seismic physical model experiment

Wide angle acquisition has been taken as a significant measure to obtain high quality seismic data and is getting greater attention, In this paper, we discuss ocean bottom cable （OBC） seismic wide angle reflections on the basis of a layered model experiment. Some experiment results don＇t support theoretical conclusions. The main experimental conclusions are： 1. Wide angle reflection energies are stronger than non-wide-angle reflections （up to twice as strong） but there is a big difference between observations and theoretical calculations that suggest the wide angle reflection energies are 15 times the non- wide-angle reflection energy. The reflection energy increases gradually rather than sharply as the theoretical calculations suggest. 2. The reflection events remain hyperbolic when the offset increases. 3. Wide angle reflection dominant frequency is about 20-30% less than non- wide-angle reflections and decreases as the offset increases. The non-wide-angle reflection dominant frequency shows no obvious variation for small offsets. 4. There is no wave shape mutation or polarity reversal near the critical angle. 5. The reflection event group features are the same for both cases of incidence angle greater and less than the critical angle. 6. Direct arrivals, multiples, and water bottom refractions influence the wide angle reflections of the sea floor.

Advances in cytokine-mediated mechanisms for cardiac regeneration and repair post-myocardial infarction:a comprehensive review

Cardiovascular disease(CVD)has become the leading cause of death globally,imposing significant health and economic burdens.Among these,myocardial infarction(MI)is a predominant cause of mortality.Several animal studies have shown that cytokines participate in cardiac regeneration and repair by modulating cellular proliferation,differentiation,and apoptosis post-MI.Here,we explored the crucial role of cytokines in cardiac regeneration and repair processes in experimental animal models,detailing how cytokines modulate cellular mechanisms involved in repairing cardiac tissue post myocardial infarction(MI).Specifically,it highlights the activation of cardiac stem cells and progenitors,the regulation of inflammatory responses to prevent excessive damage,and the involvement in matrix remodeling to ensure functional integrity of the heart.This comprehensive examination underscores the therapeutic potential of enhancing cytokine secretion to mitigate adverse effects and promote recovery following MI,offering insights into possible interventions that could improve patient outcomes in clinical settings.

Water Modeling of Optimizing Tundish Flow Field

In the water modeling experiments, three cases were considered, i. e, , a bare tundish, a tundish equipped with a turbulence inhibitor, and a rectangular tundish equipped with weirs （dams） and a turbulence inhibitor. Comparing the RTD curves, inclusion separation, and the result of the streamline experiment, it can be found that the tundish equipped with weirs （dams） and a turbulence inhibitor has a great effect on the flow field and the inclusion separation when compared with the sole use or no use of the turbulent inhibitor or weirs （dams）. In addition, the enlargement of the distance between the weir and dam will result in a better effect when the tundish equipped with weirs （dam） and a turbulence inhibitor was used.

Bearing capacity of foundation on slope determined by energy dissipation method and model experiments

To determine the ultimate bearing capacity of foundations on sloping ground surface in practice, energy dissipation method was used to formulate the beating capacity as programming problem, and full-scale model experiments were investigated to analyze the performance of the soil slopes loaded by a strip footing in laboratory. The soil failure is governed by a linear Mohr-Coulomb yield criterion, and soil deformation follows an associated flow rule. Based on the energy dissipation method of plastic mechanics, a multi-wedge translational failure mechanism was employed to obtain the three bearing capacity factors related to cohesion, equivalent surcharge load and the unit gravity for various slope inclination angles. Numerical results were compared with those of the published solutions using finite element method and those of model experiments. The bearing capacity factors were presented in the form of design charts for practical use in engineering. The results show that limit analysis solutions approximate to those of model tests, and that the energy dissipation method is effective to estimate bearing capacity of soil slope.

Spatiotemporal evolution rule of rocks fracture surrounding gob-side roadway with model experiments

A series of plane-strain physical model experiments are carried out to study the spatiotemporal evolution rule of rocks fracture surrounding gob-side roadway, which is subjected to the pressure induced by the mining process. The digital photogrammetry technology and large deformation analysis method are applied to measure the deformation and fracture of surrounding rocks. The experimental results indicate that the deformation and fracture of coal pillars are the cause to the instability and failure of the surrounding rocks. The spatiotemporal evolution rule of the rock deformation and fracture surrounding gob-side roadway is obtained. The coal pillar and the roof near coal pillar should be strengthened in support design. The engineering application results also can provide a useful guide that the combined support with wire meshes, beam, anchor bolt and cable is an effective method.

Model experiment of rock blasting with single borehole and double free-surface

In order to improve the quality of laneways and tunnel excavation by drilling and blasting and by making effective use of explosive energy, a model experiment of rock blasting with a single borehole and a double free-surface was performed with the objective of studying the effect of parameters such as charge structure, free-surface and rock compressive strength on rock blasting.The model experiments indicate that:1) the smaller the rock compressive strength and density, the more distinctive the cavity expanding action by blasting;2) the powder factor in an air-decoupling charge structure is larger than that in a coupling charge structure, i.e., the explosive energy in an air-decoupling charge structure transferred to the rocks is less than that in a coupling charge structure;3) a free-surface improves the utilizations of explosive energy;4) an air-decoupling charge structure helps to maintain the integrity and stability of wall rock in controlled perimeter blasting, such as in roadways and tunnel excavation by drilling and blasting.

Mechanism of progressive failure of a slope with a steep joint under the action of freezing and thawing:model test

The stability of slope rock masses is influenced by freeze-thaw cycles in cold region,and the mechanism of stability deterioration is not clear.In order to understand the damage and progressive failure characteristics of rock masses under the action of freezing and thawing,a model test was conducted on slope with steep joint in this study.The temperature,frost heaving pressure and deformation of slope rock mass were monitored in real-time during the test and the progressive failure mode was studied.The experimental results show that the temperature variations of cracking and the rock mass of a slope are different.There are obvious latent heat stages in the temperature-change plot in the crack,but not in the slope rock masses.The frost heaving effect in the fracture is closely related to the constraint conditions,which change with the deformation of the fracture.The frost heaving pressure fluctuates periodically during freezing and continues to decrease during thawing.The surface deformation of the rock mass increases during freezing,and the deformation is restored when it thaws.Freeze-thaw cycling results in residual deformation of the rock mass which cannot be fully restored.Analysis shows that the rock mass at the free side of the steep-dip joint rotates slightly under the frost heaving effect,causing fracture propagation.The fracture propagation pattern is a circular arc at the beginning,then extends to the possible sliding direction of the rock mass.Frost heaving force and fracture water pressure are the key factors for the failure of the slope,which can cause the crack to penetrate the rock mass,and a landslide ensues when the overall anti-sliding resistance of the rock mass is overcome.

The Selection and Breeding of a Novel Microorganism Strain I and Investigation of Core Model Experiment for MEOR

This paper introduces the results of selecting and breeding a micro-organism, Strain I, and its core model experiment investigation for microbial enhanced oil recovery (MEOR). Strain I was separated from the formation water of the Dagang oil field, with analytical results showing that Strain I is a gram-positive bacillus. A further study revealed that this strain has an excellent tolerance of environmental stresses: It can survive in conditions of 70℃, 30 wt% salinity and pH3.5-9.4. Strain I can metabolize biosurfactants that could increase the oil recovery ratio, use crude oil as the single carbon source, and decompose long-chain paraffin with a large molecular weight into short-chain paraffin with a small molecular weight. The core model experiment shows that Strain I enhances oil recovery well. Using 2 vol% of the fermentation solution of Strain I to displace the crude oil in the synthetic plastic bonding core could increase the recovery ratio by 21.6%.

EMD Based Multi-scale Model for High Resolution Image Fusion

High resolution image fusion is a significant focus in the field of image processing. A new image fusion model is presented based on the characteristic level of empirical mode decomposition （EMD）. The intensity hue saturation （IHS） transform of the multi-spectral image first gives the intensity image. Thereafter, the 2D EMD in terms of row-column extension of the 1D EMD model is used to decompose the detailed scale image and coarse scale image from the high-resolution band image and the intensity image. Finally, a fused intensity image is obtained by reconstruction with high frequency of the high-resolution image and low frequency of the intensity image and IHS inverse transform result in the fused image. After presenting the EMD principle, a multi-scale decomposition and reconstruction algorithm of 2D EMD is defined and a fusion technique scheme is advanced based on EMD. Panchromatic band and multi-spectral band 3,2,1 of Quickbird are used to assess the quality of the fusion algorithm. After selecting the appropriate intrinsic mode function （IMF） for the merger on the basis of EMD analysis on specific row （column） pixel gray value series, the fusion scheme gives a fused image, which is compared with generally used fusion algorithms （wavelet, IHS, Brovey）. The objectives of image fusion include enhancing the visibility of the image and improving the spatial resolution and the spectral information of the original images. To assess quality of an image after fusion, information entropy and standard deviation are applied to assess spatial details of the fused images and correlation coefficient, bias index and warping degree for measuring distortion between the original image and fused image in terms of spectral information. For the proposed fusion algorithm, better results are obtained when EMD algorithm is used to perform the fusion experience.

Early warning model for slope debris flow initiation

Early warning model of debris flow is important for providing local residents with reliable and accurate warning information to escape from debris flow hazards. This research studied the debris flow initiation in the Yindongzi gully in Dujiangyan City, Sichuan province, China with scaled-down model experiments. We set rainfall intensity and slope angle as dominating parameters and carried out 20 scaled-down model tests under artificial rainfall conditions. The experiments set four slope angles(32°, 34°, 37°, 42°) and five rainfall intensities(60 mm/h, 90 mm/h, 120 mm/h, 150 mm/h, and 180 mm/h) treatments. The characteristic variables in the experiments, such as, rainfall duration, pore water pressure, moisture content, surface inclination, and volume were monitored. The experimental results revealed the failure mode of loose slope material and the process of slope debris flow initiation, as well as the relationship between the surface deformation and the physical parameters of experimental model. A traditional rainfall intensity-duration early warning model(I-D model) was firstly established by using a mathematical regression analysis, and it was then improved into ISD model and ISM model(Here, I is rainfall Intensity, S is Slope angle, D is rainfall Duration, and M is Moisture content). The warning model can provide reliable early warning of slope debris flow initiation.

Introduction of CMIP5 Experiments Carried out with the Climate System Models of Beijing Climate Center

The climate system models from Beijing Climate Center, BCC_CSM1.1 and BCC_CSM1.1-M, are used to carry out most of the CMIP5 experiments. This study gives a general introduction of these two models, and provides main information on the experiments including the experiment purpose, design, and the external forcings. The transient climate responses to the CO2 concentration increase at 1% per year are presented in the simulation of the two models. The BCC_CSM1.1-M result is closer to the CMIP5 multiple models ensemble. The two models perform well in simulating the historical evolution of the surface air temperature, globally and averaged for China. Both models overestimate the global warming and underestimate the warming over China in the 20th century. With higher horizontal resolution, the BCC_CSM1.1-M has a better capability in reproducing the annual evolution of surface air temperature over China.