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
Deepsea mining has been proposed since the 1960s to alleviate the lack of resources on land.Vertical hydraulic transport of collected ores from the seabed to the sea surface is considered the most promising method for...Deepsea mining has been proposed since the 1960s to alleviate the lack of resources on land.Vertical hydraulic transport of collected ores from the seabed to the sea surface is considered the most promising method for industrial applications.In the present study,an indoor model test of the vertical hydraulic transport of particles was conducted.A noncontact optical method has been proposed to measure the local characteristics of the particles inside a vertical pipe,including the local concentration and particle velocity.The hydraulic gradient of ore transport was evaluated with various particle size distributions,particle densities,feeding concentrations and mixture flow velocities.During transport,the local concentration is larger than the feeding concentration,whereas the particle velocity is less than the mixture velocity.The qualitative effects of the local concentration and local fluid velocity on the particle velocity and slip velocity were investigated.The local fluid velocity contributes significantly to particle velocity and slip velocity,whereas the effect of the local concentration is marginal.A higher feeding concentration and mixture flow velocity result in an increased hydraulic gradient.The effect of the particle size gradation is slight,whereas the particle density plays a crucial role in the transport.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
Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq ...Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.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
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
The responses of ecosystem nitrogen (N) and phosphorus (P) to drought are an important component of globalchange studies. However, previous studies were more often based on site-specific experiments, introducing a sig...The responses of ecosystem nitrogen (N) and phosphorus (P) to drought are an important component of globalchange studies. However, previous studies were more often based on site-specific experiments, introducing a significantuncertainty to synthesis and site comparisons. We investigated the responses of vegetation and soil nutrientsto drought using a network experiment of temperate grasslands in Northern China. Drought treatment (66%reduction in growing season precipitation) was imposed by erecting rainout shelters, respectively, at the driest,intermediate, and wettest sites. We found that vegetation nutrient concentrations increased but soil nutrient concentrationsdecreased along the aridity gradient. Differential responses were observed under experimentaldrought among the three grassland sites. Specifically, the experimental drought did not change vegetation andsoil nutrient status at the driest site, while strongly reduced vegetation but increased soil nutrient concentrationsat the site with intermediate precipitation. On the contrary, experimental drought increased vegetation N concentrationsbut did not change vegetation P and soil nutrient concentrations at the wettest site. In general, the differentialeffects of drought on ecosystem nutrients were observed between manipulative and observationalexperiments as well as between sites. Our research findings suggest that conducting large-scale, consistent, andcontrolled network experiments is essential to accurately evaluate the effects of global climate change on terrestrialecosystem bio-geochemistry.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
Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks th...Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks through to the wellbore. Autonomous inflow control device(AICD) is an important instrument maintain normal production after bottom water coning, however, the resistance increasing ability of the swirl type AICD is insufficient at present, which seriously affects the water control effect. Aiming this problem, this paper designs a multi-stage resistance-increasing and composite type AICD. The separation mechanism of oil-water two phases in this structure, the resistance form of oil-water single phase and the resistance-increasing principle of water phase are analyzed. Establishing the dual-phase multi-stage separation and resistance-increasing model, and verified by measuring the throttling pressure drop and oil-water volume fraction of the AICD, it is found that the composite type AICD has the effect of ICD and AICD at the same time, which can balance the production rate of each well section at the initial stage of production, delay the occurrence of bottom water coning. In the middle and later stages of production, water-blocking can be effectively increased to achieve water control and stable production.After structural sensitivity analysis, the influence law of various structural parameters on the water control performance of composite AICD was obtained. The simulation calculation results show that,compared with the existing swirl type AICD, composite AICD has higher sensitivity to moisture content,the water phase throttling pressure drop is increased by 4.5 times on average. The composite AICD is suitable for the entire stage of horizontal well production.展开更多
Corrosion leakages often occur in the air cooler of a hydrocracking unit,with the failure sites mainly located in the entrance area of the tubes.An analysis of the macroscopic morphology and corrosion products confirm...Corrosion leakages often occur in the air cooler of a hydrocracking unit,with the failure sites mainly located in the entrance area of the tubes.An analysis of the macroscopic morphology and corrosion products confirmed that the damage was caused by erosion-corrosion(E-C).Numerical and experimental methods were applied to investigate the E-C mechanism in the air cooler.Computational fluid dynamics(CFD)was used to calculate the hydrodynamic parameters of the air cooler.The results showed that there was a biased flow in the air cooler,which led to a significant increase in velocity,turbulent kinetic energy and wall shear within 0.2 m of the tube entrance.A visualization experiment was then performed to determine the principles of migration and transformation of multiphase flow in the air cooler tubes.Various flow patterns(pure droplet flow,mist flow,and annular flow)and their evolutionary processes were clearly depicted experimentally.The initiation mechanism and processes leading to the development of E-C in the air cooler were also determined.This study provided a comprehensive explanation for the E-C failures that occur in air coolers during operation.展开更多
Karst fracture-cavity carbonate reservoirs,in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances,have become significant fields of oil and gas exploration and explo...Karst fracture-cavity carbonate reservoirs,in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances,have become significant fields of oil and gas exploration and exploitation.Proppant fracturing is considered as the best method for exploiting carbonate reservoirs;however,previous studies primarily focused on the effects of individual types of geological formations,such as natural fractures or cavities,on fracture propagation.In this study,true-triaxial physical simulation experiments were systematically performed under four types of stress difference conditions after the accurate prefabrication of four types of different fracture-cavity distributions in artificial samples.Subsequently,the interaction mechanism between the hydraulic fractures and fracture-cavity structures was systematically analyzed in combination with the stress distribution,cross-sectional morphology of the main propagation path,and three-dimensional visualization of the overall fracture network.It was found that the propagation of hydraulic fractures near the cavity was inhibited by the stress concentration surrounding the cavity.In contrast,a natural fracture with a smaller approach angle(0°and 30°)around the cavity can alleviate the stress concentration and significantly facilitate the connection with the cavity.In addition,the hydraulic fracture crossed the natural fracture at the 45°approach angle and bypassed the cavity under higher stress difference conditions.A new stimulation effectiveness evaluation index was established based on the stimulated reservoir area(SRA),tortuosity of the hydraulic fractures(T),and connectivity index(CI)of the cavities.These findings provide new insights into the fracturing design of carbonate reservoirs.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
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
The dynamic model of a bistable laminated composite shell simply supported by four corners is further developed to investigate the resonance responses and chaotic behaviors.The existence of the 1:1 resonance relations...The dynamic model of a bistable laminated composite shell simply supported by four corners is further developed to investigate the resonance responses and chaotic behaviors.The existence of the 1:1 resonance relationship between two order vibration modes of the system is verified.The resonance response of this class of bistable structures in the dynamic snap-through mode is investigated,and the four-dimensional(4D)nonlinear modulation equations are derived based on the 1:1 internal resonance relationship by means of the multiple scales method.The Hopf bifurcation and instability interval of the amplitude frequency and force amplitude curves are analyzed.The discussion focuses on investigating the effects of key parameters,e.g.,excitation amplitude,damping coefficient,and detuning parameters,on the resonance responses.The numerical simulations show that the foundation excitation and the degree of coupling between the vibration modes exert a substantial effect on the chaotic dynamics of the system.Furthermore,the significant motions under particular excitation conditions are visualized by bifurcation diagrams,time histories,phase portraits,three-dimensional(3D)phase portraits,and Poincare maps.Finally,the vibration experiment is carried out to study the amplitude frequency responses and bifurcation characteristics for the bistable laminated composite shell,yielding results that are qualitatively consistent with the theoretical results.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
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
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
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financially supported by the Hainan Provincial Joint Project of Sanya Yazhou Bay Science and Technology City(Grant No.520LH052)the National Natural Science Foundation of China(Grant No.51909164).
文摘Deepsea mining has been proposed since the 1960s to alleviate the lack of resources on land.Vertical hydraulic transport of collected ores from the seabed to the sea surface is considered the most promising method for industrial applications.In the present study,an indoor model test of the vertical hydraulic transport of particles was conducted.A noncontact optical method has been proposed to measure the local characteristics of the particles inside a vertical pipe,including the local concentration and particle velocity.The hydraulic gradient of ore transport was evaluated with various particle size distributions,particle densities,feeding concentrations and mixture flow velocities.During transport,the local concentration is larger than the feeding concentration,whereas the particle velocity is less than the mixture velocity.The qualitative effects of the local concentration and local fluid velocity on the particle velocity and slip velocity were investigated.The local fluid velocity contributes significantly to particle velocity and slip velocity,whereas the effect of the local concentration is marginal.A higher feeding concentration and mixture flow velocity result in an increased hydraulic gradient.The effect of the particle size gradation is slight,whereas the particle density plays a crucial role in the transport.
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supported by Natural Science Foundation of Fujian Province (CN) (2020I0009, 2022J01596)Cooperation Project on University Industry-Education-Research of Fujian Provincial Science and Technology Plan (CN) (2022N5011)+1 种基金Lancang-Mekong Cooperation Special Fund (2017-2020)International Sci-Tech Cooperation and Communication Program of Fujian Agriculture and Forestry University (KXGH17014)。
文摘Bulked-segregant analysis by deep sequencing(BSA-seq) is a widely used method for mapping QTL(quantitative trait loci) due to its simplicity, speed, cost-effectiveness, and efficiency. However, the ability of BSA-seq to detect QTL is often limited by inappropriate experimental designs, as evidenced by numerous practical studies. Most BSA-seq studies have utilized small to medium-sized populations, with F2populations being the most common choice. Nevertheless, theoretical studies have shown that using a large population with an appropriate pool size can significantly enhance the power and resolution of QTL detection in BSA-seq, with F_(3)populations offering notable advantages over F2populations. To provide an experimental demonstration, we tested the power of BSA-seq to identify QTL controlling days from sowing to heading(DTH) in a 7200-plant rice F_(3)population in two environments, with a pool size of approximately 500. Each experiment identified 34 QTL, an order of magnitude greater than reported in most BSA-seq experiments, of which 23 were detected in both experiments, with 17 of these located near41 previously reported QTL and eight cloned genes known to control DTH in rice. These results indicate that QTL mapping by BSA-seq in large F_(3)populations and multi-environment experiments can achieve high power, resolution, and reliability.
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 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the National Key Research and Development Program of China(2019YFE0117000)the National Natural Science Foundation of China(32171549 and 31971465)and the Youth Innovation Promotion Association CAS(2020199).
文摘The responses of ecosystem nitrogen (N) and phosphorus (P) to drought are an important component of globalchange studies. However, previous studies were more often based on site-specific experiments, introducing a significantuncertainty to synthesis and site comparisons. We investigated the responses of vegetation and soil nutrientsto drought using a network experiment of temperate grasslands in Northern China. Drought treatment (66%reduction in growing season precipitation) was imposed by erecting rainout shelters, respectively, at the driest,intermediate, and wettest sites. We found that vegetation nutrient concentrations increased but soil nutrient concentrationsdecreased along the aridity gradient. Differential responses were observed under experimentaldrought among the three grassland sites. Specifically, the experimental drought did not change vegetation andsoil nutrient status at the driest site, while strongly reduced vegetation but increased soil nutrient concentrationsat the site with intermediate precipitation. On the contrary, experimental drought increased vegetation N concentrationsbut did not change vegetation P and soil nutrient concentrations at the wettest site. In general, the differentialeffects of drought on ecosystem nutrients were observed between manipulative and observationalexperiments as well as between sites. Our research findings suggest that conducting large-scale, consistent, andcontrolled network experiments is essential to accurately evaluate the effects of global climate change on terrestrialecosystem bio-geochemistry.
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supported by National Natural Science Foundation(52204050)Sichuan Science and Technology Program(2021ZHCG0013,22ZDYF3009)。
文摘Bottom water coning is the main reason to reduce the recovery of horizontal bottom water reservoir. By water coning, we mean the oil-water interface changes from a horizontal state to a mound-shaped cone and breaks through to the wellbore. Autonomous inflow control device(AICD) is an important instrument maintain normal production after bottom water coning, however, the resistance increasing ability of the swirl type AICD is insufficient at present, which seriously affects the water control effect. Aiming this problem, this paper designs a multi-stage resistance-increasing and composite type AICD. The separation mechanism of oil-water two phases in this structure, the resistance form of oil-water single phase and the resistance-increasing principle of water phase are analyzed. Establishing the dual-phase multi-stage separation and resistance-increasing model, and verified by measuring the throttling pressure drop and oil-water volume fraction of the AICD, it is found that the composite type AICD has the effect of ICD and AICD at the same time, which can balance the production rate of each well section at the initial stage of production, delay the occurrence of bottom water coning. In the middle and later stages of production, water-blocking can be effectively increased to achieve water control and stable production.After structural sensitivity analysis, the influence law of various structural parameters on the water control performance of composite AICD was obtained. The simulation calculation results show that,compared with the existing swirl type AICD, composite AICD has higher sensitivity to moisture content,the water phase throttling pressure drop is increased by 4.5 times on average. The composite AICD is suitable for the entire stage of horizontal well production.
基金supported by the National Key R&D Program of China(2021YFB3301100)Beijing University of Chemical Technology Interdisciplinary Program(XK2023-07).
文摘Corrosion leakages often occur in the air cooler of a hydrocracking unit,with the failure sites mainly located in the entrance area of the tubes.An analysis of the macroscopic morphology and corrosion products confirmed that the damage was caused by erosion-corrosion(E-C).Numerical and experimental methods were applied to investigate the E-C mechanism in the air cooler.Computational fluid dynamics(CFD)was used to calculate the hydrodynamic parameters of the air cooler.The results showed that there was a biased flow in the air cooler,which led to a significant increase in velocity,turbulent kinetic energy and wall shear within 0.2 m of the tube entrance.A visualization experiment was then performed to determine the principles of migration and transformation of multiphase flow in the air cooler tubes.Various flow patterns(pure droplet flow,mist flow,and annular flow)and their evolutionary processes were clearly depicted experimentally.The initiation mechanism and processes leading to the development of E-C in the air cooler were also determined.This study provided a comprehensive explanation for the E-C failures that occur in air coolers during operation.
基金sponsored by the National Natural Science Foundation of China(Grants Nos.52104046 and 52104010).
文摘Karst fracture-cavity carbonate reservoirs,in which natural cavities are connected by natural fractures to form cavity clusters in many circumstances,have become significant fields of oil and gas exploration and exploitation.Proppant fracturing is considered as the best method for exploiting carbonate reservoirs;however,previous studies primarily focused on the effects of individual types of geological formations,such as natural fractures or cavities,on fracture propagation.In this study,true-triaxial physical simulation experiments were systematically performed under four types of stress difference conditions after the accurate prefabrication of four types of different fracture-cavity distributions in artificial samples.Subsequently,the interaction mechanism between the hydraulic fractures and fracture-cavity structures was systematically analyzed in combination with the stress distribution,cross-sectional morphology of the main propagation path,and three-dimensional visualization of the overall fracture network.It was found that the propagation of hydraulic fractures near the cavity was inhibited by the stress concentration surrounding the cavity.In contrast,a natural fracture with a smaller approach angle(0°and 30°)around the cavity can alleviate the stress concentration and significantly facilitate the connection with the cavity.In addition,the hydraulic fracture crossed the natural fracture at the 45°approach angle and bypassed the cavity under higher stress difference conditions.A new stimulation effectiveness evaluation index was established based on the stimulated reservoir area(SRA),tortuosity of the hydraulic fractures(T),and connectivity index(CI)of the cavities.These findings provide new insights into the fracturing design of carbonate reservoirs.
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 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Project supported by the National Natural Science Foundation of China(Nos.12293000,12293001,11988102,12172006,and 12202011)。
文摘The dynamic model of a bistable laminated composite shell simply supported by four corners is further developed to investigate the resonance responses and chaotic behaviors.The existence of the 1:1 resonance relationship between two order vibration modes of the system is verified.The resonance response of this class of bistable structures in the dynamic snap-through mode is investigated,and the four-dimensional(4D)nonlinear modulation equations are derived based on the 1:1 internal resonance relationship by means of the multiple scales method.The Hopf bifurcation and instability interval of the amplitude frequency and force amplitude curves are analyzed.The discussion focuses on investigating the effects of key parameters,e.g.,excitation amplitude,damping coefficient,and detuning parameters,on the resonance responses.The numerical simulations show that the foundation excitation and the degree of coupling between the vibration modes exert a substantial effect on the chaotic dynamics of the system.Furthermore,the significant motions under particular excitation conditions are visualized by bifurcation diagrams,time histories,phase portraits,three-dimensional(3D)phase portraits,and Poincare maps.Finally,the vibration experiment is carried out to study the amplitude frequency responses and bifurcation characteristics for the bistable laminated composite shell,yielding results that are qualitatively consistent with the theoretical results.
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.
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.