Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs s...Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs suffer from having a higher volume,current leakage,complex connections,and difficulty in gas sealing.To solve these problems,Rolls-Royce has fabricated a simple design by stacking cells in series on an insulating porous support,resulting in the tubular segmented-in-series solid oxide fuel cells(SIS-SOFCs),which achieved higher output voltage.This work systematically reviews recent advances in the structures,preparation methods,perform-ances,and stability of tubular SIS-SOFCs in experimental and numerical studies.Finally,the challenges and future development of tubular SIS-SOFCs are also discussed.The findings of this work can help guide the direction and inspire innovation of future development in this field.展开更多
Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pat...Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.展开更多
Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal...Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal synergistically affected by solvents have not been fully understood.Ultrasonic testing,nuclear magnetic resonance analysis,liquid phase mass spectrometry was adopted to comprehensively analyze pore-fracture change characteristics of lean coal treated by combined solvent(NMP and CS_(2)).Meanwhile,quantitative characterization of above changing properties was conducted using geometric fractal theory.Relationship model between permeability,fractal dimension and porosity were established.Results indicate that the end face fractures of coal are well developed after CS2and combined solvent treatments,of which,end face box-counting fractal dimensions range from 1.1227 to 1.4767.Maximum decreases in ultrasonic longitudinal wave velocity of coal affected by NMP,CS_(2)and combined solvent are 2.700%,20.521%,22.454%,respectively.Solvent treatments could lead to increasing amount of both mesopores and macropores.Decrease ratio of fractal dimension Dsis 0.259%–2.159%,while permeability increases ratio of NMR ranges from 0.1904 to 6.4486.Meanwhile,combined solvent could dissolve coal polar and non-polar small molecules and expand flow space.Results could provide reference for solvent selection and parameter optimization of permeability-enhancement technology.展开更多
The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundar...The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundary effect is conducted,where the hydraulic head difference(DH)varies,and the boundary includes non-loss and soil-loss conditions.Soil samples are filled into seven soil storerooms connected in turn.After evaluation,the variation in content of fine sand(ΔR_(f))and the hydraulic conductivity of soils in each storeroom(C_(i))are analyzed.In the non-loss test,the soil sample filling area is divided into runoff,transited,and accumulated areas according to the negative or positive ΔR_(f) values.ΔR_(f) increases from negative to positive along the seepage path,and Ci decreases from runoff area to transited area and then rebounds in accumulated area.In the soil-loss test,all soil sample filling areas belong to the runoff area,where the gentle-loss,strengthened-loss,and alleviated-loss parts are further divided.ΔR_(f) decreases from the gentle-loss part to the strengthened-loss part and then rebounds in the alleviated-loss part,and C_(i) increases and then decreases along the seepage path.The relationship between ΔR_(f) and Ci is different with the boundary condition.Ci exponentially decreases with ΔR_(f) in the non-loss test and increases with ΔR_(f) generally in the soil-loss test.展开更多
Salt caverns are extensively utilized for storing various substances such as fossil energy,hydrogen,compressed air,nuclear waste,and industrial solid waste.In China,when the salt cavern is leached through single-well ...Salt caverns are extensively utilized for storing various substances such as fossil energy,hydrogen,compressed air,nuclear waste,and industrial solid waste.In China,when the salt cavern is leached through single-well water solution mining with oil as a cushion,engineering challenges arise with the leaching tubing,leading to issues like damage and instability.These problems significantly hinder the progress of cavern construction and the control of cavern shape.The primary cause of this is the flowinduced vibration instability of leaching tubing within a confined space,which results in severe bending or damage to the tubing.This study presents a model experimental investigation on the dynamic characteristics of leaching tubing using a self-developed liquid-solid coupling physical model experiment apparatus.The experiment utilizes a silicone-rubber pipe(SRP)and a polycarbonate pipe(PCP)to examine the effects of various factors on the dynamic stability of cantilevered pipes conveying fluid.These factors include external space constraint,flexural rigidity,medium outside the pipe,overhanging length,and end conditions.The experiments reveal four dynamic response phenomena:water hammer,static buckling,chaotic motion,and flutter instability.The study further demonstrates that the length of the external space constraint has a direct impact on the flutter critical flow velocity of the cantilevered pipe conveying fluid.Additionally,the flutter critical flow velocity is influenced by the end conditions and different external media.展开更多
This study proposes a novel open-type rectangular breakwater combined with horizontal perforated plates on both sides to enhance the sheltering effect of the rectangular box-type breakwaters against longer waves.The h...This study proposes a novel open-type rectangular breakwater combined with horizontal perforated plates on both sides to enhance the sheltering effect of the rectangular box-type breakwaters against longer waves.The hydrodynamic characteristics of this breakwater are analyzed through analytical potential solutions and experimental tests.The quadratic pressure drop conditions are exerted on the horizontal perforated plates to facilitate assessing the effect of wave height on the dissipated wave energy of breakwater through the analytical solution.The hydrodynamic quantities of the breakwater,including the reflection,transmission,and energyloss coefficients,together with vertical and horizontal wave forces,are calculated using the velocity potential decomposition method as well as an iterative algorithm.Furthermore,the reflection and transmission coefficients of the breakwater are measured by conducting experimental tests at various wave periods,wave heights,and both porosities and widths of the horizontal perforated plates.The analytical predicted results demonstrate good agreement with the iterative boundary element method solution and measured data.The influences of variable incident waves and structure parameters on the hydrodynamic characteristics of the breakwater are investigated through further calculations based on analytical solutions.Results indicate that horizontal perforated plates placed on the water surface for both sides of the rectangular breakwater can enhance the wave dissipation ability of the breakwater while effectively decreasing the transmission and reflection coefficients.展开更多
To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dime...To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dimensional numerical model of the augmented railgun with four parallel unconventional rails is introduced to simulate the internal ballistic process and realize the multi-physics field coupling calculation of the rail gun,and a test experiment of a medium-caliber electromagnetic launcher powered by pulse formation network(PFN)is carried out.Various test methods such as spectrometer,fiber grating and high-speed camera are used to test several parameters such as muzzle initial velocity,transient magnetic field strength and stress-strain of rail.Combining the simulation results and experimental data,the damage condition of the contact surface is analyzed.展开更多
Low damping characteristics have always been a key sticking points in the development of gas bearings.The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearing...Low damping characteristics have always been a key sticking points in the development of gas bearings.The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearings.This paper proposed a novel hermetic diaphragm squeeze film damper(HDSFD)for oil-free turbomachinery supported by gas lubricated bearings.Several types of HDSFDs with symmetrical structure were proposed for good damping performance.By considering the compressibility of the damper fluid,based on hydraulic fluid mechanics theory,a dynamic model of HDSFDs under medium is proposed,which successfully reflects the frequency dependence of force coefficients.Based on the dynamic model,the effects of damper fluid viscosity,bulk modulus of damper fluid,thickness of damper fluid film and plunger thickness on the dynamic stiffness and damping of HDSFDs were analyzed.An experimental test rig was assembled and series of experimental studies on HDSFDs were conducted.The damper fluid transverse flow is added to the existing HDSFD concept,which aims to make the dynamic force coefficients independent of frequency.Although the force coefficient is still frequency dependent,the damping coefficient at high frequency excitation with damper fluid supply twice as that without damper fluid supply.The results serve as a benchmark for the calibration of analytical tools under development.展开更多
The auto-parametric resonance of a continuous-beam bridge model subjected to a two-point periodic excitation is experimentally and numerically investigated in this study.An auto-parametric resonance experiment of the ...The auto-parametric resonance of a continuous-beam bridge model subjected to a two-point periodic excitation is experimentally and numerically investigated in this study.An auto-parametric resonance experiment of the test model is conducted to observe and measure the auto-parametric resonance of a continuous beam under a two-point excitation on columns.The parametric vibration equation is established for the test model using the finite-element method.The auto-parametric resonance stability of the structure is analyzed by using Newmark's method and the energy-growth exponent method.The effects of the phase difference of the two-point excitation on the stability boundaries of auto-parametric resonance are studied for the test model.Compared with the experiment,the numerical instability predictions of auto-parametric resonance are consistent with the test phenomena,and the numerical stability boundaries of auto-parametric resonance agree with the experimental ones.For a continuous beam bridge,when the ratio of multipoint excitation frequency(applied to the columns)to natural frequency of the continuous girder is approximately equal to 2,the continuous beam may undergo a strong auto-parametric resonance.Combined with the present experiment and analysis,a hypothesis of Volgograd Bridge's serpentine vibration is discussed.展开更多
Focusing on revealing the origin of high ammonia yield rate on Cu via nitrate reduction(NO3RR),we herein applied constant potential method via grand-canonical density functional theory(GC-DFT)with implicit continuum s...Focusing on revealing the origin of high ammonia yield rate on Cu via nitrate reduction(NO3RR),we herein applied constant potential method via grand-canonical density functional theory(GC-DFT)with implicit continuum solvation model to predict the reaction energetics of NO3RR on pure copper surface in alkaline media.The potential-dependent mechanism on the most prevailing Cu(111)and the minor(100)and(110)facets were established,in consideration of NO_(2)_(−),NO,NH_(3),NH_(2)OH,N_(2),and N_(2)O as the main products.The computational results show that the major Cu(111)is the ideal surface to produce ammonia with the highest onset potential at 0.06 V(until−0.37 V)and the highest optimal potential at−0.31 V for ammonia production without kinetic obstacles in activation energies at critical steps.For other minor facets,the secondary Cu(100)shows activity to ammonia from−0.03 to−0.54 V with the ideal potential at−0.50 V,which requires larger overpotential to overcome kinetic activation energy barriers.The least Cu(110)possesses the longest potential range for ammonia yield from−0.27 to−1.12 V due to the higher adsorption coverage of nitrate,but also with higher tendency to generate di-nitrogen species.Experimental evaluations on commercial Cu/C electrocatalyst validated the accuracy of our proposed mechanism.The most influential(111)surface with highest percentage in electrocatalyst determined the trend of ammonia production.In specific,the onset potential of ammonia production at 0.1 V and emergence of yield rate peak at−0.3 V in experiments precisely located in the predicted potentials on Cu(111).Four critical factors for the high ammonia yield and selectivity on Cu surface via NO3RR are summarized,including high NO3RR activity towards ammonia on the dominant Cu(111)facet,more possibilities to produce ammonia along different pathways on each facet,excellent ability for HER inhibition and suitable surface size to suppress di-nitrogen species formation at high nitrate coverage.Overall,our work provides comprehensive potential-dependent insights into the reaction details of NO3RR to ammonia,which can serve as references for the future development of NO3RR electrocatalysts,achieving higher activity and selectivity by maximizing these characteristics of copper-based materials.展开更多
A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevaryin...A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevarying but bounded uncertainty within the vertical electric stabilization system:model parameter uncertainty and uncertain nonlinearity.First,the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system.Second,the dynamical equation in the form of state space is established by designing the angular tracking error.Third,the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty.Finally,an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed.The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform.This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem,and validates the advanced servo control strategy through experiment for the first time.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
Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency ...Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency and frequency conversion modes,experiments were carried to determine the characteristic evolution of parameters such as speed,inlet and outlet pressure,head,flow rate and shaft power.A quasi-steady-state method was also used to further investigate these transient behaviors.The results show that,compared to the power frequency input,the performance parameter curves for the frequency conversion input are less volatile and smoother.The characteristic time is longer and the response to shutdown is slower.The quasi-steady-state theoretical head-flow curves match the experimental head-flow curves more closely at low flow rates when the frequency conversion input is considered.Moreover,in this case,the similarity law predicts the hydraulic performance more accurately.展开更多
When the amphibious vehicle navigates in water,the angle of the anti-wave plate and the position of the center of gravity greatly influence the navigation characteristics.In the relevant research on reducing the navig...When the amphibious vehicle navigates in water,the angle of the anti-wave plate and the position of the center of gravity greatly influence the navigation characteristics.In the relevant research on reducing the navigation resistance of amphibious vehicles by adjusting the angle of the anti-wave plate,there is a lack of scientific selection of parameters and reasonable research of simulation results by using mathematical methods,and the influence of the center of gravity position on navigation characteristics is not considered at the same time.To study the influence of the combinations of the angle of the anti-wave plate and the position of the center of gravity on the resistance reduction characteristics,a numerical calculation model of the amphibious unmanned vehicle was established by using the theory of computational fluid dynamics,and the experimental data verified the correctness of the numerical model.Based on this numerical model,the navigation characteristics of the amphibious unmanned vehicle were studied when the center of gravity was located at different positions,and the orthogonal experimental design method was used to optimize the parameters of the angle of the anti-wave plate and the position of the center of gravity.The results show that through the parameter optimization analysis based on the orthogonal experimental method,the combination of the optimal angle of the anti-wave plate and the position of the center of gravity is obtained.And the numerical simulation result of resistance is consistent with the predicted optimal solution.Compared with the maximum navigational resistance,the parameter optimization reduces the navigational resistance of the amphibious unmanned vehicle by 24%.展开更多
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 ...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.展开更多
Scouring experiments were conducted using a three-dimensional laser scanning technology for angles of the jet spanning the interval from 0°to 30°,and the characteristics of the scour hole in equilibrium cond...Scouring experiments were conducted using a three-dimensional laser scanning technology for angles of the jet spanning the interval from 0°to 30°,and the characteristics of the scour hole in equilibrium conditions were investigated accordingly.The results indicate that the optimal scouring effects occur when the jet angle is in the ranges between 15°and 20°.Moreover,the dimensionless profiles of the scour hole exhibit a high degree of similarity at different jet angles.Numerical simulations conducted using the Flow-3D software to investigate the bed shear stress along the jet impingement surface have shown that this stress is influenced by both the resultant force and the jet impingement surface area.It reaches its maximum value when the jet is vertical,decreases rapidly as the jet starts to tilt,then increases slightly,and decreases again significantly when the angle exceeds 20°.展开更多
Gastric cancer(GC)remains a formidable global health concern with significant morbidity and mortality rates,despite the fact that numerous advances have been made to improve conventional therapies.Xiaojianzhong decoct...Gastric cancer(GC)remains a formidable global health concern with significant morbidity and mortality rates,despite the fact that numerous advances have been made to improve conventional therapies.Xiaojianzhong decoction(XJZ),a traditional Chinese medicine,has garnered academic attention as a multicomponent,multitarget approach to managing GC.The present editorial explores the potential of XJZ in the treatment of GC through a comprehensive analysis of network pharmacology and experimental validation.Network pharmacology was used to identify key molecular targets of XJZ,including interleukin 6,prostaglandin-endoperoxide synthase 2,and matrix metalloproteinase 9,and in vitro experiments were used to confirm the efficacy of XJZ in inhibiting cell proliferation,inducing apoptosis,and modulating gene expression associated with GC progression.This editorial highlights XJZ as a promising therapeutic strategy for GC and indicates a need for further clinical exploration and validation of its efficacy.展开更多
With the rapid development of urban rail transit,there have been an urgent problem of excessive stray current.Because the stray current distribution is random and difficult to verify in the field,we designed an improv...With the rapid development of urban rail transit,there have been an urgent problem of excessive stray current.Because the stray current distribution is random and difficult to verify in the field,we designed an improved stray current experimental platform by replacing the simulated aqueous solution with a real soil environment and by calculating the transition resistance by measuring the soil resistivity,which makes up for the defects in the previous references.Firstly,the mathematical models of rail-drainage net and rail-drainage netground were established,and the analytical expressions of current and voltage of rail,drainage net and other structures were derived.In addition,the simulation model was built,and the mathematical analysis results were compared with the simulation results.Secondly,the accuracy of the improved stray current experimental platform was verified by comparing the measured and simulation results.Finally,based on the experimental results,the influence factors of stray current were analyzed.The relevant conclusions provide experimental data and theoretical reference for the study of stray current in urban rail transit.展开更多
Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal ex...Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.展开更多
BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
基金supported by the National Natural Science Foundation of China (Nos.21701083 and 22179054).
文摘Solid oxide fuel cells(SOFCs)have attracted a great deal of interest because they have the highest efficiency without using any noble metal as catalysts among all the fuel cell technologies.However,traditional SOFCs suffer from having a higher volume,current leakage,complex connections,and difficulty in gas sealing.To solve these problems,Rolls-Royce has fabricated a simple design by stacking cells in series on an insulating porous support,resulting in the tubular segmented-in-series solid oxide fuel cells(SIS-SOFCs),which achieved higher output voltage.This work systematically reviews recent advances in the structures,preparation methods,perform-ances,and stability of tubular SIS-SOFCs in experimental and numerical studies.Finally,the challenges and future development of tubular SIS-SOFCs are also discussed.The findings of this work can help guide the direction and inspire innovation of future development in this field.
基金supported by a grant from the Department of Science and Technology of Shanxi Province,China,No.20210302123477(to CL)Datong Bureau of Science and Technology of China,No.2020152(to CL)the Opening Foundation of Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine,No.2022-KF-03(to CL).
文摘Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous system.Macrophage polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple sclerosis.This study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune encephalomyelitis.We found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and interleukin-6.Crucially,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified macrophages.In addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced inflammation.These findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for multiple sclerosis.
基金financially supported by National Natural Science Foundation of China(No.52274171)Joint National-Local Engineering Research Centre for Safe and Precise Coal Mining Fund(No.EC2023015)+1 种基金Excellent Youth Project of Universities in Anhui Province(No.2023AH030042)Unveiled List of Bidding Projects of Shanxi Province(No.20201101001)。
文摘Chemical solvents instead of pure water being as hydraulic fracturing fluid could effectively increase permeability and improve clean methane extraction efficiency.However,pore-fracture variation features of lean coal synergistically affected by solvents have not been fully understood.Ultrasonic testing,nuclear magnetic resonance analysis,liquid phase mass spectrometry was adopted to comprehensively analyze pore-fracture change characteristics of lean coal treated by combined solvent(NMP and CS_(2)).Meanwhile,quantitative characterization of above changing properties was conducted using geometric fractal theory.Relationship model between permeability,fractal dimension and porosity were established.Results indicate that the end face fractures of coal are well developed after CS2and combined solvent treatments,of which,end face box-counting fractal dimensions range from 1.1227 to 1.4767.Maximum decreases in ultrasonic longitudinal wave velocity of coal affected by NMP,CS_(2)and combined solvent are 2.700%,20.521%,22.454%,respectively.Solvent treatments could lead to increasing amount of both mesopores and macropores.Decrease ratio of fractal dimension Dsis 0.259%–2.159%,while permeability increases ratio of NMR ranges from 0.1904 to 6.4486.Meanwhile,combined solvent could dissolve coal polar and non-polar small molecules and expand flow space.Results could provide reference for solvent selection and parameter optimization of permeability-enhancement technology.
基金The research work described herein was funded by the National Nature Science Foundation of China(Grant No.41877213).This financial support is gratefully acknowledged.
文摘The boundary condition is a crucial factor affecting the permeability variation due to suffusion.An experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering the boundary effect is conducted,where the hydraulic head difference(DH)varies,and the boundary includes non-loss and soil-loss conditions.Soil samples are filled into seven soil storerooms connected in turn.After evaluation,the variation in content of fine sand(ΔR_(f))and the hydraulic conductivity of soils in each storeroom(C_(i))are analyzed.In the non-loss test,the soil sample filling area is divided into runoff,transited,and accumulated areas according to the negative or positive ΔR_(f) values.ΔR_(f) increases from negative to positive along the seepage path,and Ci decreases from runoff area to transited area and then rebounds in accumulated area.In the soil-loss test,all soil sample filling areas belong to the runoff area,where the gentle-loss,strengthened-loss,and alleviated-loss parts are further divided.ΔR_(f) decreases from the gentle-loss part to the strengthened-loss part and then rebounds in the alleviated-loss part,and C_(i) increases and then decreases along the seepage path.The relationship between ΔR_(f) and Ci is different with the boundary condition.Ci exponentially decreases with ΔR_(f) in the non-loss test and increases with ΔR_(f) generally in the soil-loss test.
基金financial support received from the Open Research Fund of the State Key Laboratory of Geomechanics and Geotechnical Engineering,Institute of Rock and Soil Mechanics,Chinese Academy of Sciences (Grant No.Z019011)the Shandong Provincial Natural Science Foundation (Grant No.ZR2020QE112)+1 种基金the National Natural Science Foundation of China (No.51874273)the Excellent Young Scientists Fund Program of National Natural Science Foundation of China (No.52122403)。
文摘Salt caverns are extensively utilized for storing various substances such as fossil energy,hydrogen,compressed air,nuclear waste,and industrial solid waste.In China,when the salt cavern is leached through single-well water solution mining with oil as a cushion,engineering challenges arise with the leaching tubing,leading to issues like damage and instability.These problems significantly hinder the progress of cavern construction and the control of cavern shape.The primary cause of this is the flowinduced vibration instability of leaching tubing within a confined space,which results in severe bending or damage to the tubing.This study presents a model experimental investigation on the dynamic characteristics of leaching tubing using a self-developed liquid-solid coupling physical model experiment apparatus.The experiment utilizes a silicone-rubber pipe(SRP)and a polycarbonate pipe(PCP)to examine the effects of various factors on the dynamic stability of cantilevered pipes conveying fluid.These factors include external space constraint,flexural rigidity,medium outside the pipe,overhanging length,and end conditions.The experiments reveal four dynamic response phenomena:water hammer,static buckling,chaotic motion,and flutter instability.The study further demonstrates that the length of the external space constraint has a direct impact on the flutter critical flow velocity of the cantilevered pipe conveying fluid.Additionally,the flutter critical flow velocity is influenced by the end conditions and different external media.
基金supported by the National Natural Sci-ence Foundation of China(Nos.52201345,and 52001293)the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘This study proposes a novel open-type rectangular breakwater combined with horizontal perforated plates on both sides to enhance the sheltering effect of the rectangular box-type breakwaters against longer waves.The hydrodynamic characteristics of this breakwater are analyzed through analytical potential solutions and experimental tests.The quadratic pressure drop conditions are exerted on the horizontal perforated plates to facilitate assessing the effect of wave height on the dissipated wave energy of breakwater through the analytical solution.The hydrodynamic quantities of the breakwater,including the reflection,transmission,and energyloss coefficients,together with vertical and horizontal wave forces,are calculated using the velocity potential decomposition method as well as an iterative algorithm.Furthermore,the reflection and transmission coefficients of the breakwater are measured by conducting experimental tests at various wave periods,wave heights,and both porosities and widths of the horizontal perforated plates.The analytical predicted results demonstrate good agreement with the iterative boundary element method solution and measured data.The influences of variable incident waves and structure parameters on the hydrodynamic characteristics of the breakwater are investigated through further calculations based on analytical solutions.Results indicate that horizontal perforated plates placed on the water surface for both sides of the rectangular breakwater can enhance the wave dissipation ability of the breakwater while effectively decreasing the transmission and reflection coefficients.
文摘To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dimensional numerical model of the augmented railgun with four parallel unconventional rails is introduced to simulate the internal ballistic process and realize the multi-physics field coupling calculation of the rail gun,and a test experiment of a medium-caliber electromagnetic launcher powered by pulse formation network(PFN)is carried out.Various test methods such as spectrometer,fiber grating and high-speed camera are used to test several parameters such as muzzle initial velocity,transient magnetic field strength and stress-strain of rail.Combining the simulation results and experimental data,the damage condition of the contact surface is analyzed.
基金Supported by National Key Research and Development Program of China (Grant No.2021YFF0600208)National Natural Science Foundation of China (Grant No.52005170)Hunan Provincial Science and Technology Innovation Program of China (Grant No.2020RC4018)。
文摘Low damping characteristics have always been a key sticking points in the development of gas bearings.The application of squeeze film dampers can significantly improve the damping performance of gas lubricated bearings.This paper proposed a novel hermetic diaphragm squeeze film damper(HDSFD)for oil-free turbomachinery supported by gas lubricated bearings.Several types of HDSFDs with symmetrical structure were proposed for good damping performance.By considering the compressibility of the damper fluid,based on hydraulic fluid mechanics theory,a dynamic model of HDSFDs under medium is proposed,which successfully reflects the frequency dependence of force coefficients.Based on the dynamic model,the effects of damper fluid viscosity,bulk modulus of damper fluid,thickness of damper fluid film and plunger thickness on the dynamic stiffness and damping of HDSFDs were analyzed.An experimental test rig was assembled and series of experimental studies on HDSFDs were conducted.The damper fluid transverse flow is added to the existing HDSFD concept,which aims to make the dynamic force coefficients independent of frequency.Although the force coefficient is still frequency dependent,the damping coefficient at high frequency excitation with damper fluid supply twice as that without damper fluid supply.The results serve as a benchmark for the calibration of analytical tools under development.
基金National Natural Science Foundation of China under Grant No.51879191。
文摘The auto-parametric resonance of a continuous-beam bridge model subjected to a two-point periodic excitation is experimentally and numerically investigated in this study.An auto-parametric resonance experiment of the test model is conducted to observe and measure the auto-parametric resonance of a continuous beam under a two-point excitation on columns.The parametric vibration equation is established for the test model using the finite-element method.The auto-parametric resonance stability of the structure is analyzed by using Newmark's method and the energy-growth exponent method.The effects of the phase difference of the two-point excitation on the stability boundaries of auto-parametric resonance are studied for the test model.Compared with the experiment,the numerical instability predictions of auto-parametric resonance are consistent with the test phenomena,and the numerical stability boundaries of auto-parametric resonance agree with the experimental ones.For a continuous beam bridge,when the ratio of multipoint excitation frequency(applied to the columns)to natural frequency of the continuous girder is approximately equal to 2,the continuous beam may undergo a strong auto-parametric resonance.Combined with the present experiment and analysis,a hypothesis of Volgograd Bridge's serpentine vibration is discussed.
基金supported by is supported by the Shanghai Municipal Science and Technology Major Projectthe support from Shanghai Super Postdoctoral Incentive Program
文摘Focusing on revealing the origin of high ammonia yield rate on Cu via nitrate reduction(NO3RR),we herein applied constant potential method via grand-canonical density functional theory(GC-DFT)with implicit continuum solvation model to predict the reaction energetics of NO3RR on pure copper surface in alkaline media.The potential-dependent mechanism on the most prevailing Cu(111)and the minor(100)and(110)facets were established,in consideration of NO_(2)_(−),NO,NH_(3),NH_(2)OH,N_(2),and N_(2)O as the main products.The computational results show that the major Cu(111)is the ideal surface to produce ammonia with the highest onset potential at 0.06 V(until−0.37 V)and the highest optimal potential at−0.31 V for ammonia production without kinetic obstacles in activation energies at critical steps.For other minor facets,the secondary Cu(100)shows activity to ammonia from−0.03 to−0.54 V with the ideal potential at−0.50 V,which requires larger overpotential to overcome kinetic activation energy barriers.The least Cu(110)possesses the longest potential range for ammonia yield from−0.27 to−1.12 V due to the higher adsorption coverage of nitrate,but also with higher tendency to generate di-nitrogen species.Experimental evaluations on commercial Cu/C electrocatalyst validated the accuracy of our proposed mechanism.The most influential(111)surface with highest percentage in electrocatalyst determined the trend of ammonia production.In specific,the onset potential of ammonia production at 0.1 V and emergence of yield rate peak at−0.3 V in experiments precisely located in the predicted potentials on Cu(111).Four critical factors for the high ammonia yield and selectivity on Cu surface via NO3RR are summarized,including high NO3RR activity towards ammonia on the dominant Cu(111)facet,more possibilities to produce ammonia along different pathways on each facet,excellent ability for HER inhibition and suitable surface size to suppress di-nitrogen species formation at high nitrate coverage.Overall,our work provides comprehensive potential-dependent insights into the reaction details of NO3RR to ammonia,which can serve as references for the future development of NO3RR electrocatalysts,achieving higher activity and selectivity by maximizing these characteristics of copper-based materials.
基金supported in part by the Nation Natural Science Foundation of China under Grant No.52175099China Postdoctoral Science Foundation under Grant No.2020M671494Jiangsu Planned Projects for Postdoctoral Research Funds under Grant No.2020Z179。
文摘A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevarying but bounded uncertainty within the vertical electric stabilization system:model parameter uncertainty and uncertain nonlinearity.First,the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system.Second,the dynamical equation in the form of state space is established by designing the angular tracking error.Third,the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty.Finally,an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed.The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform.This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem,and validates the advanced servo control strategy through experiment for the first time.
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supported by the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(Grant No.2022C03170)Science and Technology Project of Quzhou(Grant No.2022K98)Hunan Province Key Field R&D Plan Project(Grant No.2022GK2068).
文摘Centrifugal pumps are widely used in the metallurgy,coal,and building sectors.In order to study the hydraulic characteristics of a closed impeller centrifugal pump during its shutdown in the so-called power frequency and frequency conversion modes,experiments were carried to determine the characteristic evolution of parameters such as speed,inlet and outlet pressure,head,flow rate and shaft power.A quasi-steady-state method was also used to further investigate these transient behaviors.The results show that,compared to the power frequency input,the performance parameter curves for the frequency conversion input are less volatile and smoother.The characteristic time is longer and the response to shutdown is slower.The quasi-steady-state theoretical head-flow curves match the experimental head-flow curves more closely at low flow rates when the frequency conversion input is considered.Moreover,in this case,the similarity law predicts the hydraulic performance more accurately.
基金supported by the National Natural Science Foundation of China(52174154).
文摘When the amphibious vehicle navigates in water,the angle of the anti-wave plate and the position of the center of gravity greatly influence the navigation characteristics.In the relevant research on reducing the navigation resistance of amphibious vehicles by adjusting the angle of the anti-wave plate,there is a lack of scientific selection of parameters and reasonable research of simulation results by using mathematical methods,and the influence of the center of gravity position on navigation characteristics is not considered at the same time.To study the influence of the combinations of the angle of the anti-wave plate and the position of the center of gravity on the resistance reduction characteristics,a numerical calculation model of the amphibious unmanned vehicle was established by using the theory of computational fluid dynamics,and the experimental data verified the correctness of the numerical model.Based on this numerical model,the navigation characteristics of the amphibious unmanned vehicle were studied when the center of gravity was located at different positions,and the orthogonal experimental design method was used to optimize the parameters of the angle of the anti-wave plate and the position of the center of gravity.The results show that through the parameter optimization analysis based on the orthogonal experimental method,the combination of the optimal angle of the anti-wave plate and the position of the center of gravity is obtained.And the numerical simulation result of resistance is consistent with the predicted optimal solution.Compared with the maximum navigational resistance,the parameter optimization reduces the navigational resistance of the amphibious unmanned vehicle by 24%.
基金Supported by National Natural Science Foundation of China,No.82260133 and No.82370661the Academic and Technical Leader of major disciplines in Jiangxi Province,No.20225BCJ23021+2 种基金the Jiangxi Medicine Academy of Nutrition and Health Management,No.2022-PYXM-01the Natural Science Foundation of Jiangxi Province,No.20224ACB216004the Technological Innovation Team Cultivation Project of the First Affiliated Hospital of Nanchang University,No.YFYKCTDPY202202.
文摘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.
基金supported by Research on the Influence of Nozzle Structure on the Scouring Effect of Submerged Water Jet(2023R411045)Design and Control Strategy Research of PEM Fuel Cell Hybrid Propulsion System for Ships(2024R411015)+1 种基金Zhejiang Ocean University Outstanding Master’s Thesis Cultivation Project(ZJOUYJS20230018)General Program of Education Department of Zhejiang Province(Y202250817)which was gained by Chen.
文摘Scouring experiments were conducted using a three-dimensional laser scanning technology for angles of the jet spanning the interval from 0°to 30°,and the characteristics of the scour hole in equilibrium conditions were investigated accordingly.The results indicate that the optimal scouring effects occur when the jet angle is in the ranges between 15°and 20°.Moreover,the dimensionless profiles of the scour hole exhibit a high degree of similarity at different jet angles.Numerical simulations conducted using the Flow-3D software to investigate the bed shear stress along the jet impingement surface have shown that this stress is influenced by both the resultant force and the jet impingement surface area.It reaches its maximum value when the jet is vertical,decreases rapidly as the jet starts to tilt,then increases slightly,and decreases again significantly when the angle exceeds 20°.
文摘Gastric cancer(GC)remains a formidable global health concern with significant morbidity and mortality rates,despite the fact that numerous advances have been made to improve conventional therapies.Xiaojianzhong decoction(XJZ),a traditional Chinese medicine,has garnered academic attention as a multicomponent,multitarget approach to managing GC.The present editorial explores the potential of XJZ in the treatment of GC through a comprehensive analysis of network pharmacology and experimental validation.Network pharmacology was used to identify key molecular targets of XJZ,including interleukin 6,prostaglandin-endoperoxide synthase 2,and matrix metalloproteinase 9,and in vitro experiments were used to confirm the efficacy of XJZ in inhibiting cell proliferation,inducing apoptosis,and modulating gene expression associated with GC progression.This editorial highlights XJZ as a promising therapeutic strategy for GC and indicates a need for further clinical exploration and validation of its efficacy.
基金supported by National Natural Science Foundation of China(Nos.51476073,51266004)Natural Science Foundation of Gansu Province(No.138RJZA199).
文摘With the rapid development of urban rail transit,there have been an urgent problem of excessive stray current.Because the stray current distribution is random and difficult to verify in the field,we designed an improved stray current experimental platform by replacing the simulated aqueous solution with a real soil environment and by calculating the transition resistance by measuring the soil resistivity,which makes up for the defects in the previous references.Firstly,the mathematical models of rail-drainage net and rail-drainage netground were established,and the analytical expressions of current and voltage of rail,drainage net and other structures were derived.In addition,the simulation model was built,and the mathematical analysis results were compared with the simulation results.Secondly,the accuracy of the improved stray current experimental platform was verified by comparing the measured and simulation results.Finally,based on the experimental results,the influence factors of stray current were analyzed.The relevant conclusions provide experimental data and theoretical reference for the study of stray current in urban rail transit.
基金funding from the Basic Research Project of the Education Department of Shaanxi Province(21JC010,21JP035)the Young and Middle-Aged Scientific Research and Innovation Team of the Shaanxi Provincial Administration of Traditional Chinese Medicine(2022SLRHLJ001)the 2023 Central Financial Transfer Payment Local Project“Innovation and Improvement of Five Types of Hospital Preparations,Such as Roumudan Granules”.
文摘Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
