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.

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.

Classic mechanisms and experimental models for the anti-inflammatory effect of traditional Chinese medicine

Inflammation is a common disease involved in the pathogenesis,complications,and sequelae of a large number of related diseases,and therefore considerable research has been directed toward developing anti-inflammatory drugs for the prevention and treatment of these diseases.Traditional Chinese medicine(TCM)has been used to treat inflammatory and related diseases since ancient times.According to the re-view of abundant modern scientific researches,it is suggested that TCM exhibit anti-inflammatory effects at different levels,and via multiple pathways with various targets,and recently a series of in vitro and in vivo anti-inflammatory models have been developed for anti-inflammation research in TCM.Currently,the reported classic mechanisms of TCM and experimental models of its anti-inflammatory effects pro-vide reference points and guidance for further research and development of TCM.Importantly,the research clearly confirms that TCM is now and will continue to be an effective form of treatment for many types of inflammation and inflammation-related diseases.

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.

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.

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.

Numerical Study on the Effect of Gap Diffraction on the Hydrodynamic Performance of A Floating Breakwater

Two-dimensional(2D)flume experiments are useful in investigating the performances of floating breakwaters(FBs),including hydrodynamic performances,motion responses,and mooring forces.Designing a reasonable gap between the flume wall and the FBs is a critical step in 2D flume tests.However,research on the effect of the gap on the accuracy of 2D FB experimental results is scarce.To address this issue,a numerical wave tank is developed using CFD to estimate the wave-FB interaction of a moored dual-cylindrical FB,and the results are compared to experimental data from a previously published work.There is good agreement between them,indicating that the numerical model is sufficiently accurate.The numerical model is then applied to explore the effect of gap diffraction on the performance of FBs in2D experiments.It was discovered that the nondimensional gap length L_(Gap)/W_(Pool)should be smaller than 7.5%to ensure that the relative error of the transmission coefficient is smaller than 3%.The influence of the gap is also related to the entering wave properties,such as the wave height and period.

Maximum initial primary wave model for low-Froude-number reservoir landslides based on wave theory

The impulse waves induced by large-reservoir landslides can be characterized by a low Froude number.However,systematic research on predictive models specifically targeting the initial primary wave is lacking.Taking the Shuipingzi 1#landslide that occurred in the Baihetan Reservoir area of the Jinsha River in China as an engineering example,this study established a large-scale physical model(with dimensions of 30 m×29 m×3.5 m at a scale of 1:150)and conducted scaled experiments on 3D landslide-induced impulse waves.During the process in which a sliding mass displaced and compressed a body of water to generate waves,the maximum initial wave amplitude was found to be positively correlated with the sliding velocity and the volume of the landslide.With the increase in the water depth,the wave amplitude initially increased and then decreased.The duration of pressure exertion by the sliding mass at its maximum velocity directly correlated with an elevated wave amplitude.Based on the theories of low-amplitude waves and energy conservation,while considering the energy conversion efficiency,a predictive model for the initial wave amplitude was derived.This model could fit and validate the functions of wavelength and wave velocity.The accuracy of the initial wave amplitude was verified using physical experiment data,with a prediction accuracy for the maximum initial wave amplitude reaching 90%.The conversion efficiency(η)directly determined the accuracy of the estimation formula.Under clear conditions for landslide-induced impulse wave generation,estimating the value ofηthrough analogy cases was feasible.This study has derived the landslide-induced impulse waves amplitude prediction formula from the standpoints of wave theory and energy conservation,with greater consideration given to the intrinsic characteristics in the formation process of landslide-induced impulse waves,thereby enhancing the applicability and extensibility of the formula.This can facilitate the development of empirical estimation methods for landslide-induced impulse waves toward universality.

Calculating the number of radial cracks around a wellbore fractured by liquid CO2 phase transition blasting technology

Integrating liquid CO_(2)phase transition blasting(LCPTB)technology with hydraulic fracturing(HF)methods can help reduce wellbore damage,create multiple radial fractures,and establish a complex fracture network.This approach significantly increases the recovery efficiency of low-permeability oil and gas fields.Accurately calculating the number of fractures caused by LCPTB is necessary to predict production enhancement effects and optimize subsequent HF designs.However,few studies are reported on large-scale physical model experiments in terms of a method for calculating the fracture number.This study analyzed the initiation and propagation of cracks under LCPTB,derived a calculation formula for crack propagation radius under stress waves,and then proposed a new,fast,and accurate method for calculating the fracture number using the principle of mass conservation.Through ten rock-breaking tests using LCPTB,the study confirmed the effectiveness of the proposed calculation approach and elucidated the variation rule of explosion pressure,rock-breaking scenario,and the impact of varying parameters on fracture number.The results show that the new calculation method is suitable for fracturing technologies with high pressure rates.Recommendations include enlarging the diameter of the fracturing tube and increasing the liquid CO2 mass in the tube to enhance fracture effectiveness.Moreover,the method can be applied to other fracturing technologies,such as explosive fracturing(EF)within HF formations,indicating its broader applicability and potential impact on optimizing unconventional resource extraction technologies.

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.

Structure and kinematic analysis of the deepwater area of the Qiongdongnan Basin through a seismic interpretation and analogue modeling experiments

Located at the northwest continental slope of the South China Sea, the Qiongdongnan Basin bears valley-shaped bathymetry deepening toward east. It is separated from the Yinggehai Basin through NW-trending Indo-China-Red River shear zone, and connected with NW subsea basin through the Xisha Trough. Along with the rapid progress of the deepwater exploration, large amounts of high resolution geophysical and geological data were accumulated. Scientific researches about deepwater basins kept revealing brand new tectonic and sedimentary discoveries. In order to summarize the structural features and main controlling factors of the deepwater Qiongdongnan Basin, a series of researches on basin architecture, fault activities, tectonic deformation and evolution were carried out. In reference to analogue modeling experiments, a tectonic situation and a basin formation mechanism were discussed. The researches indicate that：the northern boundary of the Qiongdongnan Basin is strongly controlled by No. 2 fault. The overlapping control of two stress fields from the east and the west made the central depression zone extremely thinned. Combined with the changed stress field, the segmentation of a preexisting weakness zone made the sags in the east experiencing different rifting histories from the west ones. The NE-trending west segment of the Qiongdongnan Basin experienced strong rifting during Eocene, while the roughly EW-trending sags in the east segment show strong rifting during late Eocene and early Oligocene. Local structures such as NW-trending basal fault and inherited uplifts controlled the lateral segmentation. So first order factors such as regional stress field and preexisting weakness zone controlled the basin zonation, while the second order factors determined the segmentation from east to west.

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.

Experimental Study on Free Spanning Submarine Pipeline Under Dynamic Excitation

Seismic load has a significant effect on the response of a free spanning submarine pipeline when the pipeline is constructed in a seismically active region. The model experiment is performed on an underwater shaking table to simulate the response of submarine pipelines under dynamic input. In consideration of the effects of the terrestrial and submarine pipeline, water depth, support condition, distance from seabed, empty and full pipeline, and span on dynamic response, 120 groups of experiments are conducted. Affecting factors are analyzed and conclusions are drawn for reference. For the control of dynamic response, the span of a submarine pipeline is by far more important than the other factors. Meanwhile, the rosponse difference between a submarine pipeline under sine excitation and that under random excitation exists in experiments.

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.