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.

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.

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.

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.

Improved experimental model of hepatic cystic hydatid disease resembling natural infection route with stable growing dynamics and immune reaction

AIM To investigate a safer way to set up the disease model of cystic echinococcosis without contamination risk and develop a novel experimental murine model of hepatic cystic echinococcosis. METHODS C57 B/6 mice were injected with human protoscolices of three different concentrations via the portal vein. The mice were followed for 10 mo by ultrasound,gross anatomy,and pathological and immunological examinations. The protoscolex migration in the portal vein,hydatid cyst growth,host immune reaction,and hepatic histopathology were examined periodically.RESULTS The infection rates in the mice in the high,medium,and low concentration groups were 90%,100%,and 63.6%,respectively. The protoscolices migrated in the portal vein with blood flow,settled in the liver,and developed into orthotopic hepatic hydatid cysts,resembling the natural infection route and course.CONCLUSION We have established an improved experimental model of hepatic cystic echinococcosis with low biohazard risk but stable growing dynamics and immune reaction. It is especially useful for new anti-parasite medication trials against hydatid disease.

Hepatitis C Virus Experimental Model Systems and Antiviral drug Research

An estimated 130 million people worldwide are chronically infected with hepatitis C virus (HCV) making it a leading cause of liver disease worldwide. Because the currently available therapy of pegylated interferon-alpha and ribavirin is only effective in a subset of patients, the development of new HCV antivirals is a healthcare imperative. This review discusses the experimental models available for HCV antiviral drug research, recent advances in HCV antiviral drug development, as well as active research being pursued to facilitate development of new HCV-specific therapeutics.

Establishing an experimental model of photodynamic induced anterior ischemic optic neuropathy

BACKGROUND： Scholars have supposed to establish animal models of optic neuropathy by pressing and partially amputating optic nerve, increasing intraocular pressure and injecting vasoconstrictor, etc., but the models are greatly different from anterior ischemia optic neuropathy. Therefore, a more ideal method is needed to establish animal model of anterior ischemic optic neuropathy （AION）. OBJECTIVE ： To establish AION models in rats, observe the functional changes of fundus, fundus fluorescein angiography （FFA）, optical coherence tomography （OCT）, flash visual evoked potential （F-VEP）, and histopathologically confirm its reliability. DESIGN： A randomized control tria SETTINGS ： Department of Ophthalmology, Xi＇an Fourth Hospital; Xi＇an Institute of Ocular Fundus Diseases MATERIALS ： The experiments were carried out in the research room of Xi＇an Institute of Ocular Fundus Diseases from February 2005 to May 2006. Thirty healthy male SD rats of 4-5 weeks old, weighing 140-160 g, were provided by the animal experimental center of the Fourth Military Medical University of Chinese PLA [SCXK （Military）2002-005], and those without eye disease examined by slit lamp and direct ophthalmoscope after mydriasis were enrolled. The conditions for feeding mice without special pathogen were strictly followed. The rats were randomly divided into blank control group （n =5）, laser group （n =5）, hematoporphyrin derivative （HPD） group and AION group （n =15）, each group was numbered randomly. For each rat, the right eye was taken as the experimental eye, and the left one as the control one. METHODS： In the AION group, the rats were injected with HPD （10 mg/kg） via caudal vein, and then the optic discs were exposed to krypton red （647 nm, 80 mV） for 120 s, and the rats were in avoidance of light for 2 weeks postoperatively. Rats in the laser group were only exposed to krypton red （647 rim, 80 mV） for 120 s, and in avoidance of light for 2 weeks postoperatively; Those in the HPD group were only injected with HPD （10 mg/kg） via caudal vein; Those in the blank control group were untouched. （1） Visual electrophysiological test： The F-VEP was used to evaluate the function of visual nerve. （2） FFA： After mydriasis and anesthesia as describe above, the fluorescein sodium parenteral solution （1 mL/kg） was injected v/a caudal vein and finished within about 3 s, the time of FFA was recorded from the beginning of injection, the video sight aimed at the optic disc and the surrounding area. （3） After mydriasis and anesthesia as describe above, the rats were examined with OCT. （4） Histological observation： After hematoxylin and eosin （HE） staining, the optic disc and surrounding blood vessels of retina were observed under light microscope at high power field. MAIN OUTCOME MEASURES： The results of fundus, FFA, visual electrophysiological test and OCT detection within 90 days after model establishment were observed. RESULTS： Of the 30 rats, 1 died after anesthesia in the laser group and 2 died in the AION group respectively, and finally 27 rats were involved in the analysis of results. （1） Changes in fundus： In the AION group, there was edema in upper optic disc and unclear boundary at 1 day after establishment, edema still could be observed at 6 days, and upper optic disc atrophied and appeared as pale at 90 days. （2） FFA results： In the AION group, early ＂low fluorescence＂, middle and late ＂high fluorescence＂ were observed in upper optic disc 1 day after model establishment, and there was ＂low fluorescence＂ at 6 days, and the low fluorescence could be observed all the time at 23 days. （3） Visual electrophysiological changes： In the AION group as compared with the control eyes, the experimental ones had prolonged F-VEP P100 latency [（71.65±8.81）, （57.58±8.38） ms, t =3.148, P =0.012], and decreased wave amplitude [（4.77±1.90）, （10.06±3.66） μV, t =4.082, P =0.003], and these changes lasted to 35 days after model establishment. （4） OCT results： In the AION group, the reflection surface of part nerve fiber layer was higher than the retina plane, the surface was rough and the thickness was increased at 6 days after model establishment. （5） Histopathological results： At 1 day after model establishment, part optic discs had highly edema, edema of nerve fibers, and loose tissue, also accompanied by the displacement of surrounding retina; At 23 days, the optic disc and surrounding nerve fiber layers became thinner, and the numbers of ganglion nuclei in the retina tissue sections were obviously decreased. These changes were not observed in the laser group, HPD group and blank control group. CONCLUSION ： The changes of fundus, FFA, OCT, visual electrophysiology and histopathology confirmed that the krypton red laser irradiation （647 nm） at 2 hours after HPD was injected via caudal vein can establish more ideal animal models of AION.

Experimental Model for Biological Control of Stored Grain Pests

The insecticidal efficacy of the diatomaceous earth against granary weevil, Sitophilus granarius L. （Coleoptera： Curculionidae）, with two essential oils for the degree of repellent activity, was evaluated in an experimental model in laboratory tests. The diatomaceous earth was obtained from three Romanian sources （Patirlagele, Urloaia and Adamclisi） and was applied at four doses of 100, 300, 500 and 900 ppm （5, 15, 25 and 45 mg, respectively） on three replicates each variant. Mortality of S. granarius adults was estimated after 7, 14 and 21 d of exposure on treated grain. The insecticidal efficacy of the examined diatomaceous earth against the granary weevil was highly influenced by exposure time, dose and essential oil type. The longer exposure times increased weevil mortality in the case of low doses （100 ppm and 300 ppm）. After 60 d from the experiment initiation, the exposed grains from each variant were assessed about the progeny production. For the model proposed as bio-experiment, two essential oils in concentration of 80μL/L air and 125μL/L of Thymus vulgaris L. and Satureja hortensis L., respectively, were tested compared with untreated control in laboratory conditions. Both plant species belong to the family Lamiaceae, and the major active insecticidal compound was thymol among other providing to terpenoid class, such as eugenol and linalool. The species S. granarius chosen for experimental model was grown in the Research-Development Institute of Plant Protection （RDIPP） Bucharest bio-base. The results show that mortality induced from diatomaceous earth was at the level between 83.33% and 100% in all variants after 21 d, compared with untreated control and a standard product Silicosec.

Evaluating the Amount of Erodability and Sedimentation by Comparing Sediment Weight Model and PSIAC Experimental Model (Case Study: Lali Water Catchment, Khuzestan, Iran)

The upstream water catchments are the main source providing sediments in rivers and sedimentary basins. The balance between the erosion phenomenon and the amount of sediment entering into the basin relies on the geometrical specifications and the morphology of the river along the water catchment direction and the amount and type of the sediments. The sedimentary feed of rivers and basins are changed for the sake of natural factors or human disturbances. The river and basin react against this change in that their shape, morphology, plan and profile get changed due to the increase or decrease of the input sediment into the basin. It is essential to know the sediment amount produced by erodability and sedimentation of upstream basins and effects of projects and also to evaluate the amount of sedimentary load in base studies, civil projects, optimizing rivers and dam construction studies specially calculating the amount of sediment amount entering into the dams’ reservoirs in order to take engineering decisions and related alternatives. Sediment Weight Model and PSIAC Experimental Model are recognized as two common methods calculating the amount of the produced sediment caused by erosion applied in this research. Holistically, these methods have been used and compared. Although the results are almost close to one another, more sediment load has been produced in PSIAC method. As more affective parameters are used to cause erosion and produce sediment in PSIAC experimental model, it is recommended to refer to the results of this method because they are closer to reality.

Human prostate cancer heterotransplants： a review on this experimental model

A common model used for preclinical research was in vitro human tumor cell culture. An alternative model was the direct implantation of a unique patient＇s tumor biopsy specimens into immunodeficient host mice. Published data from PubMed （http：//www.ncbi.nlm.nih.gov） and Current Contents Connect databases （http：//thomsonreuters.com/ products_services/science/science_roducts/a-z/current_contents_connect） were reviewed. Prostate cancer （PCa） heterotransplantation was evaluated using histopathology, morphology, cell differentiation, DNA content, tumor marker expression, metastases, tumor kinetics, tumor take rate and tumor vasculature in the first tumor heterotransplant. The heterotransplanted tumor retained the biological properties of the original tumor, such as morphology, degree of differentiation, pathology, secretory activity, expression of tumor markers and human vasculature. Human PCa heterotransplants have considerable experimental advantages over cell culture following xenotransplantation.

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.

Deterioration in Hemodynamics Reaction, Baroreflex Sensitivity, Sympathetic Nerve Activity and Redox State of Thoracic Aorta in the Experimental Model of Nitrate Tolerance and Its Pharmacological Correction

Continuous treatment with organic nitrates causes nitrate tolerance and provides evidence for a relationship between mitochondrial complex 1 activity and mitochondrial aldehyde dehydrogenase-2 (ALDH-2) with disturbances of the hemodynamics reaction during nitroglycerin (NTG) tolerance (NTGT). The purpose of this study was the evaluation of efficacy of original oxidized form NAD-containing drug, NADCIN®, on hemodynamic reactions, baroreflex sensitivity (BRS) and reflex control of splanchnic sympathetic nerve activity (SSNA), level of redox-potential, activity of ALDH-2 and superoxide anion generation in aortic tissue in rat model of NTGT. Five groups (7 - 9 each) of male Wistar rats, including control, acute i.v. NTG (150 mcg/kg) administration, NTG tolerance NTGT treatment with NADCIN® 8 mg/kg and methylene blue (MB, 2.5 mg/kg) were used. NTGT in rats was accompanied with the greatly attenuation of hemodynamics reaction, BRS, the decreasing of the ability to reflex control of SSNA without pronounce overexpression of endothelin-1 in vessels (aorta). In NTGT rats i.v. NTG along induced less hypotensive reactions and alterations in heart period vs single NTG treated group, more expressively decreased BRS (-34%) and reflex control of SSNA (-18%). NADCIN® significantly inhibits tolerance-inducing properties of the prolonged nitroglycerin infusion (max decrease of blood pressure response to nitroglycerin injection, % of normal controls: NTGT 51.2%, NADCIN® 91.6%, MB 55.8%). NADCIN® in NTGT rats after NTG i.v. administration increased reduced BRS (+37.8%, p < 0,05), reflex control of SSNA (+29.4%, p < 0.05) and reversed the decreasing of NAD/NADH ratio, ALDH-2 activity and decreasing in superoxide generation in thoracic aortic tissue. Thus, course treatment with NADCIN® of NTGT rats restores hemodynamics changes, BRS and SSNA throughout the increasing of redox-potential NAD/NADH and cessates the NTGT developing.

Establishment of a cerebral schistosomiasis experimental model in rabbits

Objective The present study aimed to establish a cerebral schistosomiasis model in rabbits,to provide a valuable tool for morphological analysis,clinical manifestation observation,as well as investigations into immunological reactions and pathogenesis of focal inflammatory reaction in neuroschistosomiasis（NS）.Methods Sixty New Zealand rabbits were randomly assigned into operation,sham-operation and normal groups.Rabbits in the operation group received direct injection of dead schistosome eggs into the brain,while their counterparts in the sham-operation group received saline injection.Rabbits in the normal group received no treatment.Base on the clinical manifestations,rabbits were sacrificed on days 3,5,7,10,20,and 30 post injection,and brain samples were sectioned and stained with hematoxylin-eosin.Sections were observed under the microscope.Results The rabbits in the operation group exhibited various neurological symptoms,including anorexy,partial and general seizures,and paralysis.The morphological analysis showed several schistosome eggs in the nervous tissue on day 3 post operation,with very mild inflammation.On days 7-10 post operation,several schistosome eggs were localized in proximity to red blood cells with many neutrophilic granulocytes and eosinophilic granulocytes around them.The schistosome eggs developed into the productive granuloma stage on days 14-20 post operation.On day 30,the schistosome eggs were found to be in the healing-by-fibrosis stage,and the granuloma area was replaced by fibrillary glia through astrocytosis.The sham-operation group and the normal group showed negative results.Conclusion This method might be used to establish the cerebral schistosomiasis experimental model.Several factors need to be considered in establishing this model,such as the antigenic property of eggs,the time of scarification,and the clinical manifestations.

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.

Immune Homeostasis: Effects of Chinese Herbal Formulae and Herb-Derived Compounds on Allergic Asthma in Different Experimental Models

Allergic asthma is thought to arise from an imbalance of immune regulation, which is characterized by the production of large quantities of Ig E antibodies by B cells and a decrease of the interferon-γ/interleukin-4(Th1/Th2) ratio. Certain immunomodulatory components and Chinese herbal formulae have been used in traditional herbal medicine for thousands of years. However, there are few studies performing evidence-based Chinese medicine(CM) research on the mechanisms and efficacy of these drugs in allergic asthma. This review aims to explore the roles of Chinese herbal formulae and herb-derived compounds in experimental research models of allergic asthma. We screened published modern CM research results on the experimental effects of Chinese herbal formulae and herb-derived bioactive compounds for allergic asthma and their possible underlying mechanisms in English language articles from the Pub Med and the Google Scholar databases with the keywords allergic asthma, experimental model and Chinese herbal medicine. We found 22 Chinese herb species and 31 herb-derived anti-asthmatic compounds as well as 12 Chinese herbal formulae which showed a reduction of airway hyperresponsiveness, allergen-specific immunoglobulin E, inflammatory cell infiltration and a regulation of Th1 and Th2 cytokines in vivo, in vitro and ex vivo, respectively. Chinese herbal formulae and herbderived bioactive compounds exhibit immunomodulatory, anti-inflammatory and anti-asthma activities in different experimental models and their various mechanisms of action are being investigated in modern CM research with genomics, proteomics and metabolomics technologies, which will lead to a new era in the development of new drug discovery for allergic asthma in CM.

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.

Numerical and Experimental Modelling of Gas Flow and Heat Transfer in the Air Gap of an Electric Machine. Part II: Grooved Surfaces

The study deals with the cooling of a high-speed electric machine through an air gap with numerical and experimental methods.The rotation speed of the test machine is between 5000-4000 r/rain and the machine is cooled by a forced gas flow through the air gap.In the previous part of the research the friction coefficient was measured for smooth and grooved stator cases with a smooth rotor.The heat transfer coefficient was recently calculated by a numerical method and measured for a smooth stator-rotor combination.In this report the cases with axial groove slots at the stator and/or rotor surfaces are studied.Numerical flow simulations and measurements have been done for the test machine dimensions at a large velocity range.At constant mass flow rate the heat transfer coefficients by the numerical method attain bigger values with groove slots on the stator or rotor surfaces.The results by the numerical method have been confirmed with measurements.The RdF-sensor was glued to the stator and rotor surfaces to measure the heat flux through the surface,as well as the temperature.

A new experimental model to study healing process of metaphyseal fracture

Background There are few researches for the healing of metaphyseal fractures; moreover,the animal models to study the metaphyseal fractures are usually made by the oscillating saw osteotomy without reliable fixation,which is not in accordance with our current clinical practice.In this study,we established a new model to observe the healing process of metaphyseal fractures.Methods Eighteen New Zealand rabbits were used in the study.The fracture model was created by splitting the medial tibial plateau in rabbits,then reset,and fixed with compression screws.At 1,2,3,4,6,and 8 weeks postoperatively,the tibial specimens were collected; firstly,a general observation and an X-ray examination of the specimens was done,and then they were embedded in methylmethacrylate and cut into sections with hard tissue slicer.The sections were stained with Giemsa reagent and examined under light microscopy.Results There was no fracture displacement in the tibial specimens of all time points,except for one showing a collapse.No external callus formation could be observed by X-ray and general examination.After 1 week of the operation,the fracture gap was filled by mesenchymal tissue; 2 weeks postoperatively,a large number of woven bones were formed; from the third week onwards,the woven bone began to turn into lamellar bone,and new trabecular structure began to form.In all of the slices,no obvious chondrocytes formed in fracture areas; thus,there was no endochondral ossification.Conclusions This model was an ideal fracture animal model and suitable for the study of metaphyseal fracture healing.The X-ray and histological images demonstrated that metaphyseal fracture healing was a process of direct bone healing through intramembranous bone formation under the conditions of minor trauma,good reduction,and firm fixation.

Experimental modeling of polymer latex spray coating for producing controlled-release urea

Spray coating of polymer latex onto fertilizer particles in a fiuidized bed for producing controlled-release urea is an environment friendly technology as it does not need any toxic organic solvent. Since the spray coating process in a fluidized bed occurs in the presence of particle collisions, the coating of the particles is random, intermittent and multiple, thus making it difficult to investigate the film formation process. In this paper, an experimental model apparatus was designed and used to investigate the effects of the key factors in the spray coating process. This apparatus reasonably simplified the complex process to avoid particle collisions and randomness in the coating. The intermittent coating in the fluidized bed was modeled by periodic coating and dewatering in the experimental apparatus. A large area film was obtained, and the film permeability was measured. The effects of atomizing gas flow rate, spray rate of latex, solid content of latex and gas temperature on film structure and film permeability were investigated. It was found that water transfer played a dominant role in the spray coating process.