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.

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.

Characterization of the adsorption behavior of aqueous cadmium on nanozero-valent iron based on orthogonal experiment and surface complexation modeling

Polyvinylpyrrolidone K-30(PVP) was introduced into the preparation of nanozero-valent iron(n ZVI) and the traditional liquid-phase reduction was improved. The introduction of PVP simplified the traditional method.The n ZVI prepared with this new approach showed excellent surface characters and high performance on the removal of cadmium. TEM results showed that the aggregates of n ZVI can reach to several micrometers in length but less than 100 nm in diameter. The iron particles that were enclosed by a layer of oxide film that is less than10 nm, demonstrated that the n ZVI possesses a core–shell structure. BET results indicate that the specific surface area of the n ZVI was 20.3159 m^2g^(-1). A three factor and three level orthogonal experiment was employed to find out the dominant factor that affects the removal rate of cadmium by n ZVI. Based on the range values, the prominence order of each factor was: initial p H of the solution N initial concentration of cadmium N dosage of n ZVI, the range was 96.453, 3.294 and 1.747, respectively. A simulation was performed under the same condition and a same conclusion was derived, this consistence confirmed the validity of the conclusion that p H is the most significant factor that affects the adsorption efficiency.

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.

Factors Controlling Deoxygenation of "Floodwater" Overlying an Acid Sulfate Soil: Experimental Modeling

An incubation experiment was conducted to simulate the effect of flooding onwater deoxygenation in acid sulfate soil floodplain systems. The originally oxygenated 'floodwater'could be deoxygenated immediately following 'flooding' and it is likelythat this was caused mainlyby decomposition of organic debris from the inundated plants. Deoxygenation eventually led to thedepletion of dissolved oxygen (DO) in the 'floodwater' and it is highly possible that this resultedin the transformations of ferric Fe to ferrous Fe, sulfate to hydrogen sulfide. and organic nitrogento ammonia (ammonification). The accumulation of these reduced substances allows the 'floodwater'to develop DO-consuming capacity (DOCC). When the 'floodwater' is mixed with the introducedoxygenated water, apart from the dilution effects, the reduced substances contained in the'floodwater' oxidize to further consume DO carried by the introduced water. However, it appears thatthe DO drop in the mixed water can only last for a few hours if no additional DO-depleted'floodwater' is added. Entry of atmospheric oxygen into the water can raise the DO level of themixed water arid lower water pH through the oxidation of the reduced substances.

EXPERIMENTAL MODELING OF MIDDLE-RISE BUILDING VIA AMBIENT MODAL IDENTIFICATION

Experimental modeling of a middle-rise office building via ambient modal identification is presented. A 200-DOF (Dimension of freedom) test model is designed to correlate with finite element mode. A newly developed frequency-spatial domain decomposition ( FSDD ) technique is used to identify modal characteristics of the full-size building by using ambient response measurements. In the interested frequency ranges of 0～4.5 Hz and 0～ 6.5 Hz altogether 9 bending and torsion modes are identified. As one of the major focuses of the project, the accurate damping estimation is conducted based on FSDD. The identified modal frequencies and mode shapes are utilized for finite element model tuning. Excellent agreement has been achieved with respect to the final tuned finite element (FE) model up to 9 modes.

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.

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.

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.

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.

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.

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.

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.