Improved STNModels and Heuristic Rules for Cooperative Scheduling in Automated Container Terminals

Improving the cooperative scheduling efficiency of equipment is the key for automated container terminals to copewith the development trend of large-scale ships. In order to improve the solution efficiency of the existing spacetimenetwork (STN) model for the cooperative scheduling problem of yard cranes (YCs) and automated guidedvehicles (AGVs) and extend its application scenarios, two improved STN models are proposed. The flow balanceconstraints in the original model are decomposed, and the trajectory constraints of YCs and AGVs are added toacquire the model STN_A. The coupling constraint in STN_A is updated, and buffer constraints are added toSTN_A so that themodel STN_B is built.As the size of the problem increases, the solution speed of CPLEX becomesthe bottleneck. So a heuristic method containing three groups of heuristic rules is designed to obtain a near-optimalsolution quickly. Experimental results showthat the computation time of STN_A is shortened by 49.47% on averageand the gap is reduced by 1.69% on average compared with the original model. The gap between the solution ofthe heuristic rules and the solution of CPLEX is less than 3.50%, and the solution time of the heuristic rules is onaverage 99.85% less than the solution time of CPLEX. Compared with STN_A, the computation time for solvingSTN_B increases by 58.93% on average.

A Pre-Selection-Based Ant Colony System for Integrated Resources Scheduling Problem at Marine Container Terminal

Marine container terminal(MCT)plays a key role in the marine intelligent transportation system and international logistics system.However,the efficiency of resource scheduling significantly influences the operation performance of MCT.To solve the practical resource scheduling problem(RSP)in MCT efficiently,this paper has contributions to both the problem model and the algorithm design.Firstly,in the problem model,different from most of the existing studies that only consider scheduling part of the resources in MCT,we propose a unified mathematical model for formulating an integrated RSP.The new integrated RSP model allocates and schedules multiple MCT resources simultaneously by taking the total cost minimization as the objective.Secondly,in the algorithm design,a pre-selection-based ant colony system(PACS)approach is proposed based on graphic structure solution representation and a pre-selection strategy.On the one hand,as the RSP can be formulated as the shortest path problem on the directed complete graph,the graphic structure is proposed to represent the solution encoding to consider multiple constraints and multiple factors of the RSP,which effectively avoids the generation of infeasible solutions.On the other hand,the pre-selection strategy aims to reduce the computational burden of PACS and to fast obtain a higher-quality solution.To evaluate the performance of the proposed novel PACS in solving the new integrated RSP model,a set of test cases with different sizes is conducted.Experimental results and comparisons show the effectiveness and efficiency of the PACS algorithm,which can significantly outperform other state-of-the-art algorithms.

Container-Based Internet of Vehicles Edge Application Migration Mechanism

Internet of Vehicles(IoV)applications integrating with edge com-puting will significantly drive the growth of IoV.However,the contradiction between the high-speed mobility of vehicles,the delay sensitivity of corre-sponding IoV applications and the limited coverage and resource capacity of distributed edge servers will pose challenges to the service continuity and stability of IoV applications.IoV application migration is a promising solution that can be supported by application containerization,a technology for seamless cross-edge-server application migration without user perception.Therefore,this paper proposes the container-based IoV edge application migration mechanism,consisting of three parts.The first is the migration trigger determination algorithm for cross-border migration and service degra-dation migration,respectively,based on trajectory prediction and traffic awareness to improve the determination accuracy.The second is the migration target decision calculation model for minimizing the average migration time and maximizing the average service time to reduce migration times and improve the stability and adaptability of migration decisions.The third is the migration decision algorithm based on the improved artificial bee colony algorithm to avoid local optimal migration decisions.Simulation results show that the proposed migration mechanism can reduce migration times,reduce average migration time,improve average service time and enhance the stability and adaptability of IoV application services.

“Smart”micro/nano container-based self-healing coatings on magnesium alloys:A review

Coating technologies are a commonly used way to protect metals against corrosion.However,with more and more severe service environments of materials,many protective coating systems often are not environmentally friendly or toxic as in the case of chromates.Based on the world’s abundant ideal magnesium(Mg)and its alloy,the smart self-healing anticorrosive coating can autonomously restore the damaged part of the coating according to the environmental changes,strengthen the corrosion protection ability,and prolong its service life.This paper reviews the research progress of smart self-healing coatings on Mg alloys.These coatings mostly contain suitable corrosion inhibitors encapsulated into micro/nano containers.Moreover,the different self-healing mechanisms and functionalities of micro/nano containers are discussed.The micro/nano containers range from inorganic nanocontainers such as mesoporous nanoparticles(silica(SiO_(2)),titanium dioxide(TiO_(2)),etc.),over inorganic clays(halloysite,hydrotalcite-like,zeolite),to organic nanocontainers such as polymer microcapsules,nanofibers,chitosan(CS)and cyclodextrin(CD),as well as,carbon materials such as graphene and carbon nanotubes and hybrids such as metal organic frameworks.The functioning of micro/nano containers can be divided in two principal groups:autonomous(based on defect filling and corrosion inhibition)and non-autonomous(based on dynamic bonds and shape memory polymers).Moreover,multi functionalities and composite applications of various micro/nano containers are summarized.At present,significant progress has been made in the preparation methods and technologies of micro/nano containers.Achieving long-term self-healing properties of coatings sensing of coating failure and early warning after self-healing function failure can be expected as the main development direction of self-healing corrosion protection coatings in the future.

Nonlinear semi-analytical modeling of liquid sloshing in rectangular container with horizontal baffles

A nonlinear semi-analytical scheme is proposed for investigating the finiteamplitude nonlinear sloshing in a horizontally baffled rectangular liquid container under the seismic excitation.The sub-domain method is developed to analytically derive the modal behaviors of the baffled linear sloshing.The viscosity dissipation effects from the interior liquid and boundary layers are considered.With the introduction of the generalized time-dependent coordinates,the surface wave elevation and velocity potential are represented by a series of linear modal eigenfunctions.The infinite-dimensional modal system of the nonlinear sloshing is formulated based on the Bateman-Luke variational principle,which is further reduced to the finite-dimensional modal system by using the NarimanovMoiseev asymptotic ordering.The base force and overturning moment induced by the nonlinear sloshing are derived as the functions of the generalized time-dependent coordinates.The present results match well with the available analytical,numerical,and experimental results.The paper examines the surface wave elevation,base force,and overturning moment versus the baffle parameters and excitation amplitude in detail.

Vertical Pod Autoscaling in Kubernetes for Elastic Container Collaborative Framework

Kubernetes is an open-source container management tool which automates container deployment,container load balancing and container(de)scaling,including Horizontal Pod Autoscaler(HPA),Vertical Pod Autoscaler(VPA).HPA enables flawless operation,interactively scaling the number of resource units,or pods,without downtime.Default Resource Metrics,such as CPU and memory use of host machines and pods,are monitored by Kubernetes.Cloud Computing has emerged as a platform for individuals beside the corporate sector.It provides cost-effective infrastructure,platform and software services in a shared environment.On the other hand,the emergence of industry 4.0 brought new challenges for the adaptability and infusion of cloud computing.As the global work environment is adapting constituents of industry 4.0 in terms of robotics,artificial intelligence and IoT devices,it is becoming eminent that one emerging challenge is collaborative schematics.Provision of such autonomous mechanism that can develop,manage and operationalize digital resources like CoBots to perform tasks in a distributed and collaborative cloud environment for optimized utilization of resources,ensuring schedule completion.Collaborative schematics are also linked with Bigdata management produced by large scale industry 4.0 setups.Different use cases and simulation results showed a significant improvement in Pod CPU utilization,latency,and throughput over Kubernetes environment.

Container Instrumentation and Enforcement System for Runtime Security of Kubernetes Platform with eBPF

Containerization is a fundamental component of modern cloud-native infrastructure,and Kubernetes is a prominent platform of container orchestration systems.However,containerization raises significant security concerns due to the nature of sharing a kernel among multiple containers,which can lead to container breakout or privilege escalation.Kubernetes cannot avoid it as well.While various tools,such as container image scanning and configuration checking,can mitigate container workload vulnerabilities,these are not foolproof and cannot guarantee perfect isolation or prevent every active threat in runtime.As such,a policy enforcement solution is required to tackle the problem,and existing solutions based on LSM(Linux Security Module)frameworks may not be adequate for some situations.To address this,we propose an enforcement system based on BPF-LSM,which leverages eBPF(extended Berkeley Packet Filter)technology to provide fine-grained control and dynamic adoption of security policies.In this paper,we compare different LSM implementations to highlight the challenges of current enforcement solutions before detailing the design of our eBPF-based Kubernetes Runtime Instrumentation and Enforcement System(KRSIE).Finally,we evaluate the effectiveness of our system using a real-world scenario,as measuring the performance of a policy enforcement system is a complex task.Our results show that KRSIE can successfully control containers’behaviors using LSM hooks at container runtime,offering improved container security for cloud-native infrastructure.

Adaptive resource allocation for workflow containerization on Kubernetes

In a cloud-native era,the Kubernetes-based workflow engine enables workflow containerized execution through the inherent abilities of Kubernetes.However,when encountering continuous workflow requests and unexpected resource request spikes,the engine is limited to the current workflow load information for resource allocation,which lacks the agility and predictability of resource allocation,resulting in over and underprovisioning resources.This mechanism seriously hinders workflow execution efficiency and leads to high resource waste.To overcome these drawbacks,we propose an adaptive resource allocation scheme named adaptive resource allocation scheme(ARAS)for the Kubernetes-based workflow engines.Considering potential future workflow task requests within the current task pod’s lifecycle,the ARAS uses a resource scaling strategy to allocate resources in response to high-concurrency workflow scenarios.The ARAS offers resource discovery,resource evaluation,and allocation functionalities and serves as a key component for our tailored workflow engine(KubeAdaptor).By integrating the ARAS into KubeAdaptor for workflow containerized execution,we demonstrate the practical abilities of KubeAdaptor and the advantages of our ARAS.Compared with the baseline algorithm,experimental evaluation under three distinct workflow arrival patterns shows that ARAS gains time-saving of 9.8% to 40.92% in the average total duration of all workflows,time-saving of 26.4% to 79.86% in the average duration of individual workflow,and an increase of 1% to 16% in centrol processing unit(CPU)and memory resource usage rate.

Container Based Nomadic Vehicular Cloud Using Cell Transmission Model

Nomadic Vehicular Cloud(NVC)is envisaged in this work.The predo-minant aspects of NVC is,it moves along with the vehicle that initiates it and functions only with the resources of moving vehicles on the heavy traffic road without relying on any of the static infrastructure and NVC decides the initiation time of container migration using cell transmission model(CTM).Containers are used in the place of Virtual Machines(VM),as containers’features are very apt to NVC’s dynamic environment.The specifications of 5G NR V2X PC5 interface are applied to NVC,for the feature of not relying on the network coverage.Nowa-days,the peak traffic on the road and the bottlenecks due to it are inevitable,which are seen here as the benefits for VC in terms of resource availability and residual in-network time.The speed range of high-end vehicles poses the issue of dis-connectivity among VC participants,that results the container migration failure.As the entire VC participants are on the move,to maintain proximity of the containers hosted by them,estimating their movements plays a vital role.To infer the vehicle movements on the road stretch and initiate the container migration prior enough to avoid the migration failure due to vehicles dynamicity,this paper proposes to apply the CTM to the container based and 5G NR V2X enabled NVC.The simulation results show that there is a significant increase in the success rate of vehicular cloud in terms of successful container migrations.

Scale Breeding and Reproduction Technique of Ficus tikoua Bur.Container Seedlings

Based on the principle of asexual reproduction,a kind of scale breeding and reproduction technique of Ficus tikoua Bur.container seedlings was explored by using the characteristics of strong adaptability to the environment and fast growth and reproduction.Using non-woven bag as a breeding container for seedlings,the scale breeding and reproduction technique of F.tikoua container seedlings was summarized through the important links of seedling bed construction,seedling collection,soil configuration,container selection,cutting cultivation,field management,and disease and pest control.This technique can achieve differential,massive and sustainable efficient breeding and reproduction of F.tikoua seedlings in a short time.

不同装载条件下小型渔船参数横摇的非定常RANS CFD仿真

Fishing boats have unique features that make them prone to changing loading conditions.When the boat leaves the port,the empty fish tank gradually fills up during fishing operations which may result in parametric roll(PR).This dangerous phenomenon that can lead to capsizing.The present study aims to understand better the behaviour of parametric roll in fishing boats and its relation to changing loading conditions.The study considers the effects of displacement and the GM/KM ratio on parametric roll,as well as the longitudinal flare distribution at the waterline.Two assessments to detect the parametric roll occurrence in early stage were carried out by using the level 1 assessment of parametric roll based on the Second Generation of Intact Stability criteria(SGIS)from International maritime Organisation(IMO)and the Susceptibility criteria of Parametric roll from the American Bureau of Shipping(ABS).Then,the CFD method is used to predict the amplitude of the parametric roll phenomenon.The results provide important insights to fishing vessel operators on how to manage loading conditions to maintain stability and avoid hazardous situations.By following the guidelines outlined in this study,fishing boats can operate more safely and efficiently,reducing the risk of accidents and improving the overall sustainability of the fishing industry.

Effect of forging on the microstructure and texture of a high Nb containing γ-TiAl alloy

The effect of forging on the microstructure and texture evolution of a high Nb containing Ti-45Al-7Nb-0.3W(at.%)alloy was investigated by X-ray diffractometer(XRD),scanning electron microscopy(SEM),and transmission electron microscopy(TEM).The results show that the as-cast alloy is mainly composed of α_(2)/γ lamellar colonies with a mean size of 70μm,but the hot-forged pancake displays a near duplex microstructure(DP).Kinking and bending of lamellar colonies,deformation twinning and dynamic recrystallization(DRX)occur during hot forging.Meanwhile,dense dislocations in theβphase after forging suggest that the high-temperature β phase with a disordered structure is favorable for improving the hot-workability of the alloy.Unlike the common TiAl casting texture,the solidification process of the investigated as-cast alloy with high Nb content is completely via the β phase region,resulting in the formation of a<110>γ fiber texture where the<110>γ aligns parallel to the heat-flow direction.In comparison,the relatively strong<001>and weak<302>texture components in the as-forged alloy are attributed to the deformation twinning.After annealing,static recrystallization occurs at the twin boundary and intersections,which weakens the deformation texture.

Liquefaction and post-liquefaction behaviors of sands affected by immersion-induced degradation of crushed mudstone

A series of undrained triaxial tests was conducted to investigate the effect of crushed mudstone with the immersion-induced degradation on the liquefaction and post-liquefaction properties,and the undrained shearing behavior without precedent cyclic-loading histories of sands containing crushed mudstone.The tested materials with a main particle diameter of 2-0.85 mm were prepared by mixing sands and crushed mudstone to reach the prescribed mudstone content defined by dry mass ranging from 0% to 50%.The mixtures were subjected to immersion under a certain stress level and were subsequently tested.In addition,one-dimensional compression tests were also supplementally performed to visually observe the immersion-induced degradation of crushed mudstone.The test results mainly showed that: (1) the liquefaction resistance,the post-liquefaction undrained strength,and the undrained strength without a precedent cyclic-loading history decreased significantly with increasing mudstone content,M c ,up to 20%;(2) even a small amount of crushed mudstone affected these strengths;(3) the above-mentioned large reductions in the strengths were attributed to the immersion-induced degradation of crushed mudstone;(4) at M_(c) >20%,the liquefaction resistance increased while the significant increase in the undrained static strengths with and without precedent cyclic-loading histories was not observed;and (5) the increase in the liquefaction resistance at M_(c) >20% may have been attributed to both the gradual increase in the plasticity and the formation of the soil aggregates among deteriorated crushed mudstone,while the increase in the specimen density did not play an important role in such behavior.

Adaptive Event-Triggered Time-Varying Output Group Formation Containment Control of Heterogeneous Multiagent Systems

In this paper,a class of time-varying output group formation containment control problem of general linear hetero-geneous multiagent systems(MASs)is investigated under directed topology.The MAS is composed of a number of tracking leaders,formation leaders and followers,where two different types of leaders are used to provide reference trajectories for movement and to achieve certain formations,respectively.Firstly,compen-sators are designed whose states are estimations of tracking lead-ers,based on which,a controller is developed for each formation leader to accomplish the expected formation.Secondly,two event-triggered compensators are proposed for each follower to evalu-ate the state and formation information of the formation leaders in the same group,respectively.Subsequently,a control protocol is designed for each follower,utilizing the output information,to guide the output towards the convex hull generated by the forma-tion leaders within the group.Next,the triggering sequence in this paper is decomposed into two sequences,and the inter-event intervals of these two triggering conditions are provided to rule out the Zeno behavior.Finally,a numerical simulation is intro-duced to confirm the validity of the proposed results.

High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer

BACKGROUND Patatin like phospholipase domain containing 8(PNPLA8)has been shown to play a significant role in various cancer entities.Previous studies have focused on its roles as an antioxidant and in lipid peroxidation.However,the role of PNPLA8 in colorectal cancer(CRC)progression is unclear.AIM To explore the prognostic effects of PNPLA8 expression in CRC.METHODS A retrospective cohort containing 751 consecutive CRC patients was enrolled.PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores.CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off va-lues,which were calculated by X-tile software.The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis.The over-all survival(OS)rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test.RESULTS PNPLA8 expression was significantly associated with distant metastases in our cohort(P=0.048).CRC patients with high PNPLA8 expression indicated poor OS(median OS=35.3,P=0.005).CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS.For patients with left-sided colon and rectal cancer,the survival curves of two PN-PLA8-expression groups showed statistically significant differences.Multivariate analysis also confirmed that high PNPLA8 expression was an independent prog-nostic factor for overall survival(hazard ratio HR=1.328,95%CI:1.016-1.734,P=0.038).

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ANKRD26.However,the positive regulators of ANKRD26 are still unknown.AIM To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 transcription.METHODS Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family POTE.According to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activity of the mitogen activated protein kinase and extracellular signal regulated kinase 1/2 signaling pathways,which are potentially involved in the regulation of thrombopoietin-dependent signaling and further impair proplatelet formation by megakaryocytes(MKs)[11].However,the positive regulators of ANKRD26,which might be associated with THC2 pathology,are still unknown.

CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in in vitro and in vivo models of Parkinson's disease

Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.

Application of Thermodynamic Database to Corrosion of ZrO_(2) Containing Submerged Entry Nozzle in Steel Continuous Casting Process

The CALPHAD thermodynamic databases are very useful to analyze the complex chemical reactions happening in high temperature material process.The FactSage thermodynamic database can be used to calculate complex phase diagrams and equilibrium phases involving refractories in industrial process.In this study,the FactSage thermodynamic database relevant to ZrO_(2)-based refractories was reviewed and the application of the database to understanding the corrosion of continuous casting nozzle refractories in steelmaking was presented.

Optimal Scheduling of Multiple Rail Cranes in Rail Stations with Interference Crane Areas

In this paper,we consider a multi-crane scheduling problem in rail stations because their operations directly influence the throughput of the rail stations.In particular,the job is not only assigned to cranes but also the job sequencing is implemented for each crane to minimize the makespan of cranes.A dual cycle of cranes is used to minimize the number of working cycles of cranes.The rail crane scheduling problems in this study are based on the movement of containers.We consider not only the gantry moves,but also the trolley moves as well as the rehandle cases are also included.A mathematical model of multi-crane scheduling is developed.The traditional and parallel simulated annealing(SA)are adapted to determine the optimal scheduling solutions.Numerical examples are conducted to evaluate the applicability of the proposed algorithms.Verification of the proposed parallel SA is done by comparing it to existing previous works.Results of numerical computation highlighted that the parallel SA algorithm outperformed the SA and gave better solutions than other considered algorithms.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.