Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-b...In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-based alloy(typically pure lead or lead-bismuth eutectic(LBE))is used as the coolant.To clarify the pressure build-up characteristics under water-jet injection,this study conducted several experiments by injecting pressurized water into a molten LBE pool at Sun Yat-sen University.To obtain a further understanding,several new experimental parameters were adopted,including the melt temperature,water subcooling,injection pressure,injection duration,and nozzle diameter.Through detailed analyses,it was found that the pressure and temperature during the water-melt interaction exhibited a consistent variation trend with our previous water-droplet injection mode LBE experiment.Similarly,the existence of a steam explosion was confirmed,which typically results in a much stronger pressure build-up.For the non-explosion cases,increasing the injection pressure,melt-pool temperature,nozzle diameter,and water subcooling promoted pressure build-up in the melt pool.However,a limited enhancement effect was observed when increasing the injection duration,which may be owing to the continually rising pressure in the interaction vessel or the isolation effect of the generated steam cavity.Regardless of whether a steam explosion occurred,the calculated mechanical and kinetic energy conversion efficiencies of the melt were relatively small(not exceeding 4.1%and 0.7%,respectively).Moreover,the range of the conversion efficiency was similar to that of previous water-droplet experiments,although the upper limit of the jet mode was slightly lower.展开更多
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 rem...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.展开更多
Airfoil structures play a crucial role across numerous scientific and technological disciplines,with the transition to turbulence and stall onset remaining key challenges in aerodynamic research.While experimental tec...Airfoil structures play a crucial role across numerous scientific and technological disciplines,with the transition to turbulence and stall onset remaining key challenges in aerodynamic research.While experimental techniques often surpass numerical simulations in accuracy,they still present notable limitations.This paper begins by elucidating the fundamental principles of transition,dynamic stall,and airfoil behavior.It then provides a systematic reviewof six major experimentalmethodologies and examines the emerging role of artificial intelligence in this domain.By identifying key challenges and limitations,the study proposes strategic advancements to address these issues,offering a foundational framework to guide future research in airfoil structures and related fields.展开更多
BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventio...BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.展开更多
A new experimental method is developed to investigate the effect of dissolved substances on the evaporation rate of small water droplets suspended in the atmosphere.The laboratory setup is based on converting a genera...A new experimental method is developed to investigate the effect of dissolved substances on the evaporation rate of small water droplets suspended in the atmosphere.The laboratory setup is based on converting a generated droplet jet of complex structure into a directed flow of evaporating droplets falling in a vertical tube.Images of falling droplets captured by a high-speed camera through a window in the vertical channel wall are used to determine the sizes and velocities of individual droplets.The computational modeling of droplet motion and evaporation proved useful at all stages of the experimental work:from selecting the position of the vertical channel to processing the experimental data.It was found that even a 0.1%mass concentration of the dissolved ionic salt KCl has a considerable effect on decreasing the evaporation rate of the droplets.In contrast,a typical fungicide with a mass concentration of 2.5%has only a slight impact on the evaporation rate.The laboratory results enabled the authors to refine the evaporation model of water droplets to account for the presence of dissolved substances.Modified models of this type are expected to be useful in controling crop spraying and also in other potential applications.展开更多
Floating breakwaters(FBs)are commonly employed for the protection of coastal installations.In this work,a convextype floating breakwater(FB)is proposed,and its hydrodynamic characteristics are studied through systemat...Floating breakwaters(FBs)are commonly employed for the protection of coastal installations.In this work,a convextype floating breakwater(FB)is proposed,and its hydrodynamic characteristics are studied through systematic laboratory experiments.Two different deck widths and two different mooring systems are set in the experiment.The transmission coefficients,reflection coefficients,motion responses and mooring forces of convex-type FBs are obtained in experiments.The influences of the deck width and mooring system on the hydrodynamic characteristics of the proposed FB are analyzed and compared.The experimental results show that the reflection coefficient and mooring force of the convex-type FB with a cross-mooring system are significantly larger than those of the convextype FB with a parallel-mooring system.A convex-type FB with a larger deck width has a higher reflection coefficient.The convex-type FBs with cross-and parallel-mooring systems have similar surge and heave motions,but the cross-mooring results in small roll motion.In addition,reliable prediction formulas for the transmission coefficient of convex-type FBs with different mooring systems have been developed,which are important for engineering design.展开更多
Helium sorption cooler technology is a key means to realize highly reliable low-vibration very lowtemperature environments,which have important applications in fields such as quantum computing and space exploration.Th...Helium sorption cooler technology is a key means to realize highly reliable low-vibration very lowtemperature environments,which have important applications in fields such as quantum computing and space exploration.The laboratory designed a superfluid suppression small hole and a multi-ribbed condenser,developed a reliable-performance helium sorption cooler(HSC),and conducted experimental studies.Experimental results show that the prototype can achieve the lowest cooling temperature of 873 mK without load by filling 6MPa helium at room temperature.The low-temperature hold time is 26 h,and the temperature fluctuation is within 0.8 mK.The cooling power of the helium sorption cooler is 1 mW@0.98 K@3.5 h.Experimental results indicate that when the charging pressure is reduced to 4MPa,theminimum temperature decreases to 836mK,and the hold time shortens to 16 h.When the pre-cooling temperature increases from 3.9 to 4.9 K,the hold time is reduced to 3 h.展开更多
The detonation of fuel-rich explosives yields combustible products that persistently burn upon mixing with ambient oxygen,releasing additional energy through a phenomenon known as the afterburning effect.This process ...The detonation of fuel-rich explosives yields combustible products that persistently burn upon mixing with ambient oxygen,releasing additional energy through a phenomenon known as the afterburning effect.This process greatly influences the evolution of confined blast loading and the subsequent structural response,which is crucial in confined blast scenarios.Given the complex nature of the reaction process,accurate analysis of the afterburning effect remains challenging.Previous studies have either overlooked the mechanisms of detonation product combustion or failed to provide experimental validation.This study introduces a three-dimensional model to effectively characterize the combustion of detonation products.The model integrates chemical reaction source terms into the governing equations to consider the combustion processes.Numerical simulations and experimental tests were conducted to analyze the combustion and energy release from the detonation products of fuel-rich explosives in confined spaces.Approximately 50%of the energy was released during the combustion of detonation products in a confined TNT explosion.Although the combustion of these products was much slower than the detonation process,it aligned with the dynamic response of the structure,which enhanced the explosive yield.Excluding afterburning from the analysis reduced the center-point deformation of the structure by 30%.Following the inclusion of afterburning,the simulated quasistatic pressure increased by approximately 45%.Subsequent comparisons highlighted the merits of the proposed approach over conventional methods.This approach eliminates the reliance on empirical parameters,such as the amount and rate of energy release during afterburning,thereby laying the foundation for understanding load evolution in more complex environments,such as ships,buildings,and underground tunnels.展开更多
BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increas...BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.展开更多
This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%...This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%),is mixed with CuO and Al2O3 nanoparticles at volume fractions of 0.5%and 1.5%,respectively.The research is conducted through the conjugate usage of experimental and theoretical models to represent more realistic properties of the non-Newtonian nanofluid.Three types of microchannels including straight,divergent,and convergent are considered,all having the same length and identical inlet cross-sectional area.Using ANSYS FLUENT software,Navier-Stokes equations are solved for the laminar flow of the non-Newtonian nanofluid.The study examines the effects of Reynolds number,nanoparticle concentration and type,and microchannel geometry on flow and heat transfer.The results prove that the alumina nanoparticles outperform copper oxide in increasing the Nusselt number at a 0.5% volume fraction,while copper oxide nanoparticles excel at a 1.5%volume fraction.Moreover,in the selected case study,as the Reynolds number increases from 100 to 500,the Nusselt number rises by 56.26% in straight geometry,52.93% in divergent geometry,and 59.10%in convergent geometry.Besides,the Nusselt number enhances by 18.75% when transitioning from straight to convergent geometry at a Reynolds number of 500,and by 19.81%at a Reynolds number of 1000.Finally,the results of the research depict that the use of thermophysical properties derived from the experimental achievements,despite creating complexity in the modeling and the solution method,leads to more accurate and realistic outputs.展开更多
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.展开更多
Stripping injection overcomes the limitations of Liouville's theorem and is widely used for beam injection and accumulation in high-intensity synchrotrons.The interaction between the stripping foil and beam is cru...Stripping injection overcomes the limitations of Liouville's theorem and is widely used for beam injection and accumulation in high-intensity synchrotrons.The interaction between the stripping foil and beam is crucial in the study of stripping injection,particularly in low-energy stripping injection synchrotrons,such as the XiPAF synchrotron.The foil thickness is the main parameter that affects the properties of the beam after injection.The thin stripping foil is reinforced with collodion during its installation.However,the collodion on the foil surface makes it difficult to determine its equivalent thickness,because the mechanical measurements are not sufficiently reliable or convenient for continuously determining foil thickness.We propose an online stripping foil thickness measurement method based on the ionization energy loss effect,which is suitable for any foil thickness and does not require additional equipment.Experimental studies were conducted using the XiPAF synchrotron.The limitation of this method was examined,and the results were verified by comparing the experimentally obtained beam current accumulation curves with the simulation results.This confirms the accuracy and reliability of the proposed method for measuring the stripping foil thickness.展开更多
Laminated elastomeric bearings used in seismic isolation rely on the mechanical properties of their constituent elastomers to ensure effective performance.However,despite their resistance to temperature fluctuations a...Laminated elastomeric bearings used in seismic isolation rely on the mechanical properties of their constituent elastomers to ensure effective performance.However,despite their resistance to temperature fluctuations and environmental aggressors,silicone elastomers exhibit relatively low stiffness,limiting their direct applicability in seismic isolation.This study investigates the effect of fumed silica as a reinforcing filler to enhance the mechanical properties of laminated silicone elastomeric bearings.Elastomeric samples were fabricated with varying fumed silica proportions and subjected to Shore A hardness,uniaxial tensile,and lap shear tests to assess the influence of filler content.Additionally,quasi-static tests were conducted on reduced-scale bearing prototypes under combined vertical compression and cyclic horizontal shear to evaluate their seismic isolation performance.The results demonstrate that fumed silica reinforcement significantly increases stiffness,as evidenced by higher Shore A hardness values.However,a trade-off was observed in tensile properties,with reductions in tensile strength and elongation at break.Despite this,the equivalent elastic modulus did not show substantial variation up to large deformations,indicating that stiffness is preserved under most working conditions.Lap shear tests showed that fumed silica improves shear resistance,while quasi-static tests revealed inelastic behavior with small increases in equivalent shear coefficients but no substantial loss in damping ratios.These findings suggest that fumed silica reinforcement enhances silicone elastomers’stiffness and shear resistance while maintaining moderate damping properties,making it a promising approach for improving the mechanical performance of elastomeric bearings in seismic isolation applications.展开更多
In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly effi...In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly efficacious approach to enhance the teaching level of experimental courses in medicinal botany.The implementation of a digital microscope mutual system in experimental teaching not only enhances students practical skills in laboratory operations but also increases classroom efficiency.Furthermore,it supports personalized development among students while fostering innovative thinking,independent learning capabilities,and analysis and problem-solving skills.Additionally,this approach contributes to the enhancement of students scientific literacy.展开更多
Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent charac...Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent characteristics of these materials is essential for their effective use in various construction applications.This study presents an experimental evaluation of the compressive and bending properties of the UHPC incorporating polypropylene,steel,and glass fibers.Based on ACI-211 guidelines,the UHPC mix was designed by using three types of aggregates:limestone,andesite,and quartzite,along with 5%fiber content(at varying percentages of 0,5%,10%,15%,and 20%)relative to the cementitious materials,and three different water-to-cement(w/c)ratios(0.24,0.3,and 0.4)were used.In this research,the compressive and flexural strength tests were conducted.The results show that increasing the values of the fibers significantly enhances the compressive strength of the studied samples.Furthermore,the utilization of fibers markedly improves the bending strength of the samples,demonstrating a strong correlation with the yield resistance of the material.Also,findings show that using steel fibers increases the compressive and bending strength of the tested samples more than polypropylene and glass fibers.For instance,in UHPC samples with 0.4 w/c,the average compressive strength values are 82.2 MPa,70.3 MPa,and 67.1 MPa for steel,polypropylene,and glass fibers,respectively.Also,in the flexural strength test,the modulus of rupture is obtained as an average of 6.24 MPa,5.24 MPa and 4.83 MPa for UHPC samples with steel,polypropylene and glass fibers,respectively.展开更多
Graphene,a two-dimensional material with atomic thickness,holds significant importance in advancing the existing theories of solid mechanics.However,as an intersection of multiple scales,it poses challenges to experim...Graphene,a two-dimensional material with atomic thickness,holds significant importance in advancing the existing theories of solid mechanics.However,as an intersection of multiple scales,it poses challenges to experimental measurements of its mechanical behaviors.This review comprehensively discusses the recent achievements in experimental studies on the mechanics of graphene,focusing on sample preparation,loading design,and measurement techniques.Moreover,personal perspectives on the future development in this field are presented,aiming to provide insights and inspiration for researchers engaged in related studies.展开更多
Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pa...Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.展开更多
This paper proposes a modification of the Forrestal-Warren perforation model aimed at extending its applicability range to intermediately-thick high-hardness armor steel plates.When impacted by armorpiercing projectil...This paper proposes a modification of the Forrestal-Warren perforation model aimed at extending its applicability range to intermediately-thick high-hardness armor steel plates.When impacted by armorpiercing projectiles,these plates tend to fail through adiabatic shear plugging which significantly reduces their ballistic resistance.To address this effect,an approach for determining effective thickness was defined and incorporated into the predictive model.Ballistic impact tests were performed to assess the modification's validity,in which ARMOX 500T steel plates were subjected to perpendicular impacts from 7.62×39 mm steel-cored rounds under various velocities.Frequent target failure by soft plugging was observed,as well as the brittle shatter of the hard steel core.Key properties of the recovered plugs including their mass,length and diameter were measured and reported along with the projectiles'residual velocities.Additionally,independent data from the open literature were included in the analysis for further validation.The original Forrestal-Warren model and the novel effective thickness modification were then used to establish the relationship between impact and residual velocities,as well as to determine the ballistic limit velocity.The comparison revealed that the proposed approach significantly improves the model's accuracy,showing a strong correlation with experimental data and reducing deviations to within a few percent.This enhancement highlights the potential of the effective thickness term,which could also be applied to other predictive models to extend their applicability range.Further exploration into other armor steels and impact conditions is recommended to assess the method's versatility.展开更多
Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experim...Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experimental assessment,we examined the key targets,bioactive components,and mechanisms of QSYQ against IS.Results:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform predicted a total number of 254 targets that were potentially related to QSYQ,whereas 699 targets associated with IS were gathered from Therapeutic Target Database,Comparative Toxicogenomics Database,Gene Cards,Online Mendelian Inheritance in Man,and National Center for Biotechnology Information databases,and 83 of these targets overlap with QSYQ-related targets.Importantly,through the analysis of Gene Ontology functional annotation,Kyoto Encyclopedia of Genes and Genomes pathway enrichment,and protein-protein interaction network,we identified 20 related signaling pathways along with 4 hub genes.Subsequently,our molecular docking results revealed that QSYQ might interact with PTGS2,PTGS1,SCN5A,and HSP90AB1.We observed dose-dependent beneficial effects of QSYQ in significantly improving neurological function and alleviating histopathological damage in middle cerebral artery occlusion model,while decreasing infarct volume.Notablely,QSYQ markedly downregulates tumor necrosis factor-α,interleukin-6,and interleukin-1 beta.Overall,this study demonstrates the synergetic effects of QSYQ on regulating multi-targets in IS through inhibiting inflammatory processes and neuronal apoptosis,these findings may expand the understanding of QSYQ and provide guidance for its clinical application in treating IS.Conclusion:Current study reveals the protective roles of QSYQ against IS through modulating PTGS2/PTGS1/SCN5A/HSP90AB1 and TNF signaling pathways.展开更多
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
基金supported by Basic and Applied Basic research foundation of Guangdong province(Nos.2021A1515010343 and 2022A1515011582)the Science and Technology Program of Guangdong Province(Nos.2021A0505030026 and 2022A0505050029).
文摘In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-based alloy(typically pure lead or lead-bismuth eutectic(LBE))is used as the coolant.To clarify the pressure build-up characteristics under water-jet injection,this study conducted several experiments by injecting pressurized water into a molten LBE pool at Sun Yat-sen University.To obtain a further understanding,several new experimental parameters were adopted,including the melt temperature,water subcooling,injection pressure,injection duration,and nozzle diameter.Through detailed analyses,it was found that the pressure and temperature during the water-melt interaction exhibited a consistent variation trend with our previous water-droplet injection mode LBE experiment.Similarly,the existence of a steam explosion was confirmed,which typically results in a much stronger pressure build-up.For the non-explosion cases,increasing the injection pressure,melt-pool temperature,nozzle diameter,and water subcooling promoted pressure build-up in the melt pool.However,a limited enhancement effect was observed when increasing the injection duration,which may be owing to the continually rising pressure in the interaction vessel or the isolation effect of the generated steam cavity.Regardless of whether a steam explosion occurred,the calculated mechanical and kinetic energy conversion efficiencies of the melt were relatively small(not exceeding 4.1%and 0.7%,respectively).Moreover,the range of the conversion efficiency was similar to that of previous water-droplet experiments,although the upper limit of the jet mode was slightly lower.
文摘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.
基金funded by Programfor Scientific Research Start-up Funds of Guangdong Ocean University,grant number 060302072101Zhanjiang Marine Youth Talent Project Comparative Study and Optimization of Horizontal Lifting of Subsea Pipeline,grant number 2021E5011.
文摘Airfoil structures play a crucial role across numerous scientific and technological disciplines,with the transition to turbulence and stall onset remaining key challenges in aerodynamic research.While experimental techniques often surpass numerical simulations in accuracy,they still present notable limitations.This paper begins by elucidating the fundamental principles of transition,dynamic stall,and airfoil behavior.It then provides a systematic reviewof six major experimentalmethodologies and examines the emerging role of artificial intelligence in this domain.By identifying key challenges and limitations,the study proposes strategic advancements to address these issues,offering a foundational framework to guide future research in airfoil structures and related fields.
文摘BACKGROUND IgE plays a critical role in allergic inflammation and asthma pathogenesis.This study investigates the involvement of IgE cells in asthma exacerbation and evaluates the effectiveness of targeted interventions.AIM To evaluate the role of IgE in the exacerbation of allergic asthma and to determine the clinical efficacy of anti-IgE therapy in improving disease outcomes.Specifically,the study investigates changes in serum IgE levels,lung function,asthma control scores,and the frequency of acute exacerbations among patients receiving standard therapy with or without anti-IgE intervention.METHODS A total of 200 patients diagnosed with moderate to severe asthma were enrolled in this experimental study conducted from April 2024 to April 2025.Participants were randomized to receive either standard asthma therapy or therapy combined with anti-IgE agents.IgE levels and asthma control parameters were monitored.RESULTS Participants receiving anti-IgE treatment demonstrated a significant reduction in serum IgE levels(P<0.001),improved Forced expiratory volume in one second scores,and fewer exacerbation episodes compared to the control group.CONCLUSION IgE cells significantly contribute to asthma severity,and targeted therapy against IgE can improve disease outcomes.These findings underscore the importance of immunomodulatory strategies in asthma management.
基金financially supported by the Russian Science Foundation(project No.24-29-00303:https://rscf.ru/project/24-29-00303/,accessed on 01 July 2025).
文摘A new experimental method is developed to investigate the effect of dissolved substances on the evaporation rate of small water droplets suspended in the atmosphere.The laboratory setup is based on converting a generated droplet jet of complex structure into a directed flow of evaporating droplets falling in a vertical tube.Images of falling droplets captured by a high-speed camera through a window in the vertical channel wall are used to determine the sizes and velocities of individual droplets.The computational modeling of droplet motion and evaporation proved useful at all stages of the experimental work:from selecting the position of the vertical channel to processing the experimental data.It was found that even a 0.1%mass concentration of the dissolved ionic salt KCl has a considerable effect on decreasing the evaporation rate of the droplets.In contrast,a typical fungicide with a mass concentration of 2.5%has only a slight impact on the evaporation rate.The laboratory results enabled the authors to refine the evaporation model of water droplets to account for the presence of dissolved substances.Modified models of this type are expected to be useful in controling crop spraying and also in other potential applications.
基金financially supported by the National Natural Science Foundation of China(Grant No.52088102)New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘Floating breakwaters(FBs)are commonly employed for the protection of coastal installations.In this work,a convextype floating breakwater(FB)is proposed,and its hydrodynamic characteristics are studied through systematic laboratory experiments.Two different deck widths and two different mooring systems are set in the experiment.The transmission coefficients,reflection coefficients,motion responses and mooring forces of convex-type FBs are obtained in experiments.The influences of the deck width and mooring system on the hydrodynamic characteristics of the proposed FB are analyzed and compared.The experimental results show that the reflection coefficient and mooring force of the convex-type FB with a cross-mooring system are significantly larger than those of the convextype FB with a parallel-mooring system.A convex-type FB with a larger deck width has a higher reflection coefficient.The convex-type FBs with cross-and parallel-mooring systems have similar surge and heave motions,but the cross-mooring results in small roll motion.In addition,reliable prediction formulas for the transmission coefficient of convex-type FBs with different mooring systems have been developed,which are important for engineering design.
基金supported by the Hundred Talents Programof the Chinese Academy of Sciences,the Pre-Research Project JZX7Y20220414101801the Strategic Priority Research Program of Chinese Academy of Sciences(No.XDB35000000)the National Natural Science Foundation Projects(No.51806231).
文摘Helium sorption cooler technology is a key means to realize highly reliable low-vibration very lowtemperature environments,which have important applications in fields such as quantum computing and space exploration.The laboratory designed a superfluid suppression small hole and a multi-ribbed condenser,developed a reliable-performance helium sorption cooler(HSC),and conducted experimental studies.Experimental results show that the prototype can achieve the lowest cooling temperature of 873 mK without load by filling 6MPa helium at room temperature.The low-temperature hold time is 26 h,and the temperature fluctuation is within 0.8 mK.The cooling power of the helium sorption cooler is 1 mW@0.98 K@3.5 h.Experimental results indicate that when the charging pressure is reduced to 4MPa,theminimum temperature decreases to 836mK,and the hold time shortens to 16 h.When the pre-cooling temperature increases from 3.9 to 4.9 K,the hold time is reduced to 3 h.
基金supported by the National Natural Science Foundation of China(Grant Nos.52171318 and 12202329)Joint Foundation of the Ministry of Education(Grant No.8091B022105)。
文摘The detonation of fuel-rich explosives yields combustible products that persistently burn upon mixing with ambient oxygen,releasing additional energy through a phenomenon known as the afterburning effect.This process greatly influences the evolution of confined blast loading and the subsequent structural response,which is crucial in confined blast scenarios.Given the complex nature of the reaction process,accurate analysis of the afterburning effect remains challenging.Previous studies have either overlooked the mechanisms of detonation product combustion or failed to provide experimental validation.This study introduces a three-dimensional model to effectively characterize the combustion of detonation products.The model integrates chemical reaction source terms into the governing equations to consider the combustion processes.Numerical simulations and experimental tests were conducted to analyze the combustion and energy release from the detonation products of fuel-rich explosives in confined spaces.Approximately 50%of the energy was released during the combustion of detonation products in a confined TNT explosion.Although the combustion of these products was much slower than the detonation process,it aligned with the dynamic response of the structure,which enhanced the explosive yield.Excluding afterburning from the analysis reduced the center-point deformation of the structure by 30%.Following the inclusion of afterburning,the simulated quasistatic pressure increased by approximately 45%.Subsequent comparisons highlighted the merits of the proposed approach over conventional methods.This approach eliminates the reliance on empirical parameters,such as the amount and rate of energy release during afterburning,thereby laying the foundation for understanding load evolution in more complex environments,such as ships,buildings,and underground tunnels.
基金thank the staff of the accredited animal facility of the laboratory of anatomy,Histology and Embryology of Aristotle University of Thessaloniki’s veterinary school for their assistance in animal handling and care.
文摘BACKGROUND Massive rotator cuff tears(RCTs)result in impaired shoulder function and quality of life.These tears lead to structural changes in the rotator cuff muscles,which compromise recovery after repair and increase re-tear rates.AIM To investigate the potential inhibitory effects of alpha-tocopherol(vitamin E)and OTR-4131 on muscle atrophy,fatty infiltration,and fibrosis in rotator cuff muscles following a massive RCT using a Wistar rat model,and establish a standardized methodology for evaluating potential therapeutic agents.METHODS This protocol outlines a controlled animal study using 40 male Wistar rats,randomized into five groups.The experimental groups will receive either systemic administration of alpha-tocopherol or local administration of OTR-4131 via intramuscular injection into the supraspinatus and infraspinatus muscles.Two sham groups will receive systemic and local saline injections respectively,while a control group will undergo no intervention.The interventions will be administered after surgical transection of the supraspinatus and infraspinatus tendons.Outcomes will be assessed via wet muscle weight measurements,muscle fiber diameter,fatty infiltration percentage,and fibrosis evaluation using histological methods.RESULTS The study anticipates that alpha-tocopherol and OTR-4131 will reduce muscle atrophy,fatty infiltration,and fibrosis compared to control and sham groups,supporting their potential protective role in rotator cuff muscle degeneration.CONCLUSION The results are expected to improve the understanding on the role of alpha-tocopherol and OTR-4131 in rotator cuff muscle protection after massive RCT and may serve as a foundation for further preclinical and clinical research aimed at improving rotator cuff repair outcomes.
文摘This article aims tomodel and analyze the heat and fluid flow characteristics of a carboxymethyl cellulose(CMC)nanofluid within a convergent-divergent shaped microchannel(Two-dimensional).The base fluid,water+CMC(0.5%),is mixed with CuO and Al2O3 nanoparticles at volume fractions of 0.5%and 1.5%,respectively.The research is conducted through the conjugate usage of experimental and theoretical models to represent more realistic properties of the non-Newtonian nanofluid.Three types of microchannels including straight,divergent,and convergent are considered,all having the same length and identical inlet cross-sectional area.Using ANSYS FLUENT software,Navier-Stokes equations are solved for the laminar flow of the non-Newtonian nanofluid.The study examines the effects of Reynolds number,nanoparticle concentration and type,and microchannel geometry on flow and heat transfer.The results prove that the alumina nanoparticles outperform copper oxide in increasing the Nusselt number at a 0.5% volume fraction,while copper oxide nanoparticles excel at a 1.5%volume fraction.Moreover,in the selected case study,as the Reynolds number increases from 100 to 500,the Nusselt number rises by 56.26% in straight geometry,52.93% in divergent geometry,and 59.10%in convergent geometry.Besides,the Nusselt number enhances by 18.75% when transitioning from straight to convergent geometry at a Reynolds number of 500,and by 19.81%at a Reynolds number of 1000.Finally,the results of the research depict that the use of thermophysical properties derived from the experimental achievements,despite creating complexity in the modeling and the solution method,leads to more accurate and realistic outputs.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
文摘Stripping injection overcomes the limitations of Liouville's theorem and is widely used for beam injection and accumulation in high-intensity synchrotrons.The interaction between the stripping foil and beam is crucial in the study of stripping injection,particularly in low-energy stripping injection synchrotrons,such as the XiPAF synchrotron.The foil thickness is the main parameter that affects the properties of the beam after injection.The thin stripping foil is reinforced with collodion during its installation.However,the collodion on the foil surface makes it difficult to determine its equivalent thickness,because the mechanical measurements are not sufficiently reliable or convenient for continuously determining foil thickness.We propose an online stripping foil thickness measurement method based on the ionization energy loss effect,which is suitable for any foil thickness and does not require additional equipment.Experimental studies were conducted using the XiPAF synchrotron.The limitation of this method was examined,and the results were verified by comparing the experimentally obtained beam current accumulation curves with the simulation results.This confirms the accuracy and reliability of the proposed method for measuring the stripping foil thickness.
文摘Laminated elastomeric bearings used in seismic isolation rely on the mechanical properties of their constituent elastomers to ensure effective performance.However,despite their resistance to temperature fluctuations and environmental aggressors,silicone elastomers exhibit relatively low stiffness,limiting their direct applicability in seismic isolation.This study investigates the effect of fumed silica as a reinforcing filler to enhance the mechanical properties of laminated silicone elastomeric bearings.Elastomeric samples were fabricated with varying fumed silica proportions and subjected to Shore A hardness,uniaxial tensile,and lap shear tests to assess the influence of filler content.Additionally,quasi-static tests were conducted on reduced-scale bearing prototypes under combined vertical compression and cyclic horizontal shear to evaluate their seismic isolation performance.The results demonstrate that fumed silica reinforcement significantly increases stiffness,as evidenced by higher Shore A hardness values.However,a trade-off was observed in tensile properties,with reductions in tensile strength and elongation at break.Despite this,the equivalent elastic modulus did not show substantial variation up to large deformations,indicating that stiffness is preserved under most working conditions.Lap shear tests showed that fumed silica improves shear resistance,while quasi-static tests revealed inelastic behavior with small increases in equivalent shear coefficients but no substantial loss in damping ratios.These findings suggest that fumed silica reinforcement enhances silicone elastomers’stiffness and shear resistance while maintaining moderate damping properties,making it a promising approach for improving the mechanical performance of elastomeric bearings in seismic isolation applications.
基金Supported by Major Project of School-level Teaching Reform and Research of Guangxi University of Chinese Medicine(2022A006)。
文摘In comparison with conventional experimental teaching methods,the implementation of the Motic digital microscope mutual system in the experimental teaching of medicinal botany has been demonstrated to be a highly efficacious approach to enhance the teaching level of experimental courses in medicinal botany.The implementation of a digital microscope mutual system in experimental teaching not only enhances students practical skills in laboratory operations but also increases classroom efficiency.Furthermore,it supports personalized development among students while fostering innovative thinking,independent learning capabilities,and analysis and problem-solving skills.Additionally,this approach contributes to the enhancement of students scientific literacy.
文摘Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent characteristics of these materials is essential for their effective use in various construction applications.This study presents an experimental evaluation of the compressive and bending properties of the UHPC incorporating polypropylene,steel,and glass fibers.Based on ACI-211 guidelines,the UHPC mix was designed by using three types of aggregates:limestone,andesite,and quartzite,along with 5%fiber content(at varying percentages of 0,5%,10%,15%,and 20%)relative to the cementitious materials,and three different water-to-cement(w/c)ratios(0.24,0.3,and 0.4)were used.In this research,the compressive and flexural strength tests were conducted.The results show that increasing the values of the fibers significantly enhances the compressive strength of the studied samples.Furthermore,the utilization of fibers markedly improves the bending strength of the samples,demonstrating a strong correlation with the yield resistance of the material.Also,findings show that using steel fibers increases the compressive and bending strength of the tested samples more than polypropylene and glass fibers.For instance,in UHPC samples with 0.4 w/c,the average compressive strength values are 82.2 MPa,70.3 MPa,and 67.1 MPa for steel,polypropylene,and glass fibers,respectively.Also,in the flexural strength test,the modulus of rupture is obtained as an average of 6.24 MPa,5.24 MPa and 4.83 MPa for UHPC samples with steel,polypropylene and glass fibers,respectively.
基金supported by the specialized research projects of Huanjiang Laboratory.
文摘Graphene,a two-dimensional material with atomic thickness,holds significant importance in advancing the existing theories of solid mechanics.However,as an intersection of multiple scales,it poses challenges to experimental measurements of its mechanical behaviors.This review comprehensively discusses the recent achievements in experimental studies on the mechanics of graphene,focusing on sample preparation,loading design,and measurement techniques.Moreover,personal perspectives on the future development in this field are presented,aiming to provide insights and inspiration for researchers engaged in related studies.
基金Private DonationLa Trobe Research Focus AreasMultiple Sclerosis Australia,Grant/Award Number:20-032。
文摘Background:Multiple sclerosis(MS)is a chronic disease of the central nervous system(CNS),exhibiting hallmarks of both inflammation and neurodegeneration and with limited treatment options.The intricate nature of MS pathophysiology and its variable progression pose severe challenges for the development of effective therapies.The experimental autoimmune encephalomyelitis(EAE)MS model,in its most common form,is an aggressive disease,which is not representative of the MS course and offers a limited time window for drug evaluation.This study aimed to generate an attenuated EAE variant,which extends the clinical testing window while preserving the high incidence of the standard EAE model.Methods:Components of the EAE induction protocol were titrated to develop a milder disease profile.In a subsequent drug trial using the MS medication fingolimod hydrochloride(FTY,Gilenya),the new variant was validated under prophylactic and therapeutic treatment regimens.Results:The attenuated EAE variant retains the standard hallmarks of neuroinflammation and,crucially,significantly extends the time frame for clinical drug testing.Unlike the standard variant,where FTY efficacy could only be demonstrated by prophylactic treatment,the attenuated variant facilitated differentiation of drug effects by therapeutic treatment initiated early in the acute phase of disease.Conclusion:The new EAE variant is suitable for use in preclinical assessment of candidate therapeutics and the identification of targetable molecular mechanisms underpinning disease development and progression.This study illustrates the importance of optimizing and refining the experimental tool to enhance the translational success of the candidate therapeutics for MS.
基金supported by the Ministry of Science,Technological Development and Innovation of the Republic of Serbia,through the Contract no.451-03-65/2024-03/200105
文摘This paper proposes a modification of the Forrestal-Warren perforation model aimed at extending its applicability range to intermediately-thick high-hardness armor steel plates.When impacted by armorpiercing projectiles,these plates tend to fail through adiabatic shear plugging which significantly reduces their ballistic resistance.To address this effect,an approach for determining effective thickness was defined and incorporated into the predictive model.Ballistic impact tests were performed to assess the modification's validity,in which ARMOX 500T steel plates were subjected to perpendicular impacts from 7.62×39 mm steel-cored rounds under various velocities.Frequent target failure by soft plugging was observed,as well as the brittle shatter of the hard steel core.Key properties of the recovered plugs including their mass,length and diameter were measured and reported along with the projectiles'residual velocities.Additionally,independent data from the open literature were included in the analysis for further validation.The original Forrestal-Warren model and the novel effective thickness modification were then used to establish the relationship between impact and residual velocities,as well as to determine the ballistic limit velocity.The comparison revealed that the proposed approach significantly improves the model's accuracy,showing a strong correlation with experimental data and reducing deviations to within a few percent.This enhancement highlights the potential of the effective thickness term,which could also be applied to other predictive models to extend their applicability range.Further exploration into other armor steels and impact conditions is recommended to assess the method's versatility.
基金supported by the National Natural Science Foundation of China(No.82274313)Projects of Shaanxi Administration of Traditional Chinese Medicine(2022-SLRH-YQ-010)Key Laboratory of Traditional Chinese Medicine and Pharmacology.
文摘Background:QiShenYiQi(QSYQ)is commonly accepted to treat ischemic stroke(IS)in clinical settings,yet the underlying mechanism of action of QSYQ is largely unknown.Methods:By combining systems pharmacology with experimental assessment,we examined the key targets,bioactive components,and mechanisms of QSYQ against IS.Results:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform predicted a total number of 254 targets that were potentially related to QSYQ,whereas 699 targets associated with IS were gathered from Therapeutic Target Database,Comparative Toxicogenomics Database,Gene Cards,Online Mendelian Inheritance in Man,and National Center for Biotechnology Information databases,and 83 of these targets overlap with QSYQ-related targets.Importantly,through the analysis of Gene Ontology functional annotation,Kyoto Encyclopedia of Genes and Genomes pathway enrichment,and protein-protein interaction network,we identified 20 related signaling pathways along with 4 hub genes.Subsequently,our molecular docking results revealed that QSYQ might interact with PTGS2,PTGS1,SCN5A,and HSP90AB1.We observed dose-dependent beneficial effects of QSYQ in significantly improving neurological function and alleviating histopathological damage in middle cerebral artery occlusion model,while decreasing infarct volume.Notablely,QSYQ markedly downregulates tumor necrosis factor-α,interleukin-6,and interleukin-1 beta.Overall,this study demonstrates the synergetic effects of QSYQ on regulating multi-targets in IS through inhibiting inflammatory processes and neuronal apoptosis,these findings may expand the understanding of QSYQ and provide guidance for its clinical application in treating IS.Conclusion:Current study reveals the protective roles of QSYQ against IS through modulating PTGS2/PTGS1/SCN5A/HSP90AB1 and TNF signaling pathways.
