Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Ground-based and additional science support for SMILE

The joint European Space Agency and Chinese Academy of Sciences Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)mission will explore global dynamics of the magnetosphere under varying solar wind and interplanetary magnetic field conditions,and simultaneously monitor the auroral response of the Northern Hemisphere ionosphere.Combining these large-scale responses with medium and fine-scale measurements at a variety of cadences by additional ground-based and space-based instruments will enable a much greater scientific impact beyond the original goals of the SMILE mission.Here,we describe current community efforts to prepare for SMILE,and the benefits and context various experiments that have explicitly expressed support for SMILE can offer.A dedicated group of international scientists representing many different experiment types and geographical locations,the Ground-based and Additional Science Working Group,is facilitating these efforts.Preparations include constructing an online SMILE Data Fusion Facility,the discussion of particular or special modes for experiments such as coherent and incoherent scatter radar,and the consideration of particular observing strategies and spacecraft conjunctions.We anticipate growing interest and community engagement with the SMILE mission,and we welcome novel ideas and insights from the solar-terrestrial community.

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

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.

Effect of stress-dependent microannulus aperture on well leakage

Debonding at the cement-casing interface is recognized as a principal failure mechanism leading to CO_(2) leakage in wells.This detachment gives rise to a microannulus,which notably possesses greater permeability than undamaged cement,undermining its sealing efficacy.Conventionally,the permeability of the microannulus is regarded as a uniform value throughout the well.However,fundamentally,a microannulus is one type of fracture,and its gap or aperture size is affected by the effective stress.In this work,we developed a unique experimental apparatus.This equipment facilitates the curing of cement inside a steel casing,the formation of a microannulus between the casing and the cement,and the investigation of the fluid flow dynamics along the microannulus under laboratory-replicated in situ conditions.The microannulus was formed by injecting fluid from one end of the setup,and receiving similar amount of fluid on the other end signified the development of the leakage channel.Additionally,strain gauges affixed to the casing’s external surface yielded key information on the microannulus’s opening and closure.We observed a noticeable decline in microannulus hydraulic aperture(or permeability)in relation to effective stress and an exponential equation fits their relationship.Our findings also indicate a distinct behavior when comparing liquid CO_(2) with water.Specifically,it is easier for liquid CO_(2) to create the microannulus.However,the hydraulic aperture range for this microannulus(0.7-6 mm)is considerably smaller than that created by water flow(2-17 mm).Finally,we integrated the stressdependent microannulus aperture size into the combined analysis of well mechanical integrity and well leakage.The outcomes consistently demonstrated that when factoring in the stress-dependent aperture sizes,the leakage rates are 3e5 times compared to a fixed aperture model.The traditional assumption of a constant aperture significantly underestimates fluid leakage risks.

Recent progresses in the development of tubular segmented-in-series solid oxide fuel cells:Experimental and numerical study

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.

Field test of high-power microwave-assisted mechanical excavation for deep hard iron ore

Microwave-assisted mechanical excavation has great application prospects in mines and tunnels,but there are few field experiments on microwave-assisted rock breaking.This paper takes the Sishanling iron mine as the research object and adopts the self-developed high-power microwave-induced fracturing test system for hard rock to conduct field experiments of microwave-induced fracturing of iron ore.The heating and reflection evolution characteristics of ore under different microwave parameters(antenna type,power,and working distance)were studied,and the optimal microwave parameters were obtained.Subsequently,the ore was irradiated with the optimal microwave parameters,and the cracking effect of the ore under the action of the high-power open microwave was analyzed.The results show that the reflection coefficient(standing wave ratio)can be rapidly(<5 s)and automatically adjusted below the preset threshold value(1.6)as microwave irradiation is performed.When using a right-angle horn antenna with a working distance of 5 cm,the effect of automatic reflection adjustment reaches the best among other antenna types and working distances.When the working distance is the same,the average temperature of the irradiation surface and the area of the high-temperature area under the action of the two antennas(right-angled and equal-angled horn antenna)are basically the same and decrease with the increase of working distance.The optimal microwave parameters are:a right-angle horn antenna with a working distance of 5 cm.Subsequently,in further experiments,the optimal parameters were used to irradiate for 20 s and 40 s at a microwave power of 60 kW,respectively.The surface damage extended 38 cm×30 cm and 53 cm×30 cm,respectively,and the damage extended to a depth of about 50 cm.The drilling speed was increased by 56.2%and 66.5%,respectively,compared to the case when microwaves were not used.

Understanding the spectrum of non-motor symptoms in multiple sclerosis:insights from animal models

Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.

Characteristics and control factors of feldspar dissolution in gravity flow sandstone of Chang 7 Member,Triassic Yanchang Formation,Ordos Basin,NW China

To clarify the formation and distribution of feldspar dissolution pores and predict the distribution of high-quality reservoir in gravity flow sandstone of the 7^(th) member of Triassic Yanchang Formation(Chang 7 Member)in the Ordos Basin,thin sections,scanning electron microscopy,energy spectrum analysis,X-ray diffraction whole rock analysis,and dissolution experiments are employed in this study to investigate the characteristics and control factors of feldspar dissolution pores.The results show that:(1)Three types of diagenetic processes are observed in the feldspar of Chang 7 sandstone in the study area:secondary overgrowth of feldspar,replacement by clay and calcite,and dissolution of detrital feldspar.(2)The feldspar dissolution of Chang 7 tight sandstone is caused by organic acid,and is further affected by the type of feldspar,the degree of early feldspar alteration,and the buffering effect of mica debris on organic acid.(3)Feldspars have varying degrees of dissolution.Potassium feldspar is more susceptible to dissolution than plagioclase.Among potassium feldspar,orthoclase is more soluble than microcline,and unaltered feldspar is more soluble than early kaolinized or sericitized feldspar.(4)The dissolution experiment demonstrated that the presence of mica can hinder the dissolution of feldspar.Mica of the same mass has a significantly stronger capacity to consume organic acids than feldspar.(5)Dissolution pores in feldspar of Chang 7 Member are more abundant in areas with low mica content,and they improve the reservoir physical properties,while in areas with high mica content,the number of feldspar dissolution pores decreases significantly.

Mechanical heterogeneity characterization of coal materials based on nano-indentation experiments

To investigate the complex macro-mechanical properties of coal from a micro-mechanical perspective,we have conducted a series of micro-mechanical experiments on coal using a nano-indentation instrument.These experiments were conducted under both dynamic and static loading conditions,allowing us to gather the micro-mechanical parameters of coal for further analysis of its micro-mechanical heterogeneity using the box counting statistical method and the Weibull model.The research findings indicate that the load–displacement curves of the coal mass under the two different loading modes exhibit noticeable discreteness.This can be attributed to the stress concentration phenomenon caused by variations in the mechanical properties of the micro-units during the loading process of the coal mass.Consequently,there are significant fluctuations in the micro-mechanical parameters of the coal mass.Moreover,the mechanical heterogeneity of the coal at the nanoscale was confirmed based on the calculation results of the standard deviation coefficient and Weibull modulus of the coal body’s micromechanical parameters.These results reveal the influence of microstructural defects and minerals on the uniformity of the stress field distribution within the loaded coal body,as well as on the ductility characteristics of the micro-defect structure.Furthermore,there is a pronounced heterogeneity in the micromechanical parameters.Furthermore,we have established a relationship between the macro and micro elastic modulus of coal by applying the Mori-Tanaka homogenization method.This relationship holds great significance for revealing the micro-mechanical failure mechanism of coal.

Experimental investigation on the permeability of gap-graded soil due to horizontal suffusion considering boundary effect

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.

A systematic scoping review of study methodology for randomized controlled trials investigating probiotics in athletic and physically active populations

Background:The purported ergogenic and health effects of probiotics have been a topic of great intrigue among researchers,practitioners,and the lay public alike.There has also been an increased research focus within the realm of sports science and exercise medicine on the athletic gut microbiota.However,compared to other ergogenic aids and dietary supplements,probiotics present unique study challenges.The objectives of this systematic scoping review were to identify and characterize study methodologies of randomized controlled trials investigating supplementation with probiotics in athletes and physically active individuals.Methods:Four databases(MEDLINE,CINAHL,Cochrane CENTRAL,and Cochrane Database of Systematic Reviews)were searched for randomized controlled studies involving healthy athletes or physically active individuals.An intervention with probiotics and inclusion of a control and/or placebo group were essential.Only peer-reviewed articles in English were considered,and there were no date restrictions.Results were extracted and presented in tabular form to detail study protocols,characteristics,and outcomes.Bias in randomized controlled trials was determined with the RoB 2.0 tool.Results:A total of 45 studies were included in the review,with 35 using a parallel group design and 10 using a cross-over design.Approximately half the studies used a single probiotic and the other half a multi-strain preparation.The probiotic dose ranged from 2×10^(8)to 1×10^(11)colony forming units daily,and the length of intervention was between 7 and 150 days.Fewer than half the studies directly assessed gastrointestinal symptoms,gut permeability,or the gut microbiota.The sex ratio of participants was heavily weighted toward males,and only 3 studies exclusively investigated females.Low-level adverse events were reported in only 2 studies,although the methodology of reporting varied widely.The risk of bias was generally low,although details on randomization were lacking in some studies.Conclusion:There is a substantial body of research on the effects of prob iotic supplementation in healthy athletes and physically active individuals.Considerable heterogeneity in probiotic selection and dosage as well as outcome measures has made clinical and mechanistic interpretation challenging for both health care practitioners and researchers.Attention to issues of randomization of participants,treatments and interventions,selection of outcomes,demographics,and reporting of adverse events will facilitate more trustworthy interpretation of probiotic study results and inform evidence-based guidelines.

Multi-omics Approach Reveals Influenza-A Virus Target Genes Associated Genomic,Clinical and Immunological Characteristics in Cancers

Objective To examine the precise function of influenza A virus target genes(IATGs)in malignancy.Methods Using multi-omics data from the TCGA and TCPA datasets,33 tumor types were evaluated for IATGs.IATG expression in cancer cells was analyzed using transcriptome analysis.Copy number variation(CNV)was assessed using GISTICS 2.0.Spearman’s analysis was used to correlate mRNA expression with methylation levels.GSEA was used for the enrichment analysis.Pearson’s correlation analysis was used to examine the association between IATG mRNA expression and IC50.The ImmuCellAI algorithm was used to calculate the infiltration scores of 24 immune cell types.Results In 13 solid tumors,IATG mRNA levels were atypically expressed.Except for UCS,UVM,KICH,PCPG,THCA,CHOL,LAMI,and MESO,most cancers contained somatic IATG mutations.The main types of CNVs in IATGs are heterozygous amplifications and deletions.In most tumors,IATG mRNA expression is adversely associated with methylation.RT-PCR demonstrated that EGFR,ANXA5,CACNA1C,CD209,UVRAG were upregulated and CLEC4M was downregulated in KIRC cell lines,consistent with the TCGA and GTEx data.Conclusion Genomic changes and clinical characteristics of IATGs were identified,which may offer fresh perspectives linking the influenza A virus to cancer.

Experimental and numerical study of buckling-restrained braces configured with out-of-plane eccentricity under cyclic loading

This study focuses on variations in the hysteretic behavior of buckling-restrained braces(BRBs)configured with or without out-of-plane eccentricity under cyclic loading.Quasi-static experiments and numerical simulations were carried out on concentrically and eccentrically loaded BRB specimens to investigate the mechanical properties,energy dissipation performance,stress distribution,and high-order deformation pattern.The experimental and numerical results showed that compared to the concentrically loaded BRBs,the stiffness,yield force,cumulated plastic ductility(CPD)coefficient,equivalent viscous damping coefficient and energy dissipation decreased,and the yield displacement and compression strength adjustment factor increased for the eccentrically loaded BRBs.With the existence of the out-of-plane eccentricity,the initial yield position changes from the yield segment to the junction between the yield segment and transition segment under a tensile load,while the initial high-order buckling pattern changes from a first-order C-shape to a secondorder S-shape under a compressive load.

Experimental Investigation on Vertical Hydraulic Transport of Ores in Deepsea Mining

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.

In-situ electrochemical study on the eff ects of Fe(Ⅲ)on kinetics of pyrite acidic pressure oxidation

Fe(Ⅲ)has been proved to be a more eff ective oxidant than dissolved oxygen at ambient temperature,however,the role of Fe(Ⅲ)in pyrite acidic pressure oxidation was rarely discussed so far.In this paper,in-situ electrochemical investigation was performed using a flow-through autoclave system in acidic pressure oxidation environment.The results illustrated that increasing Fe(Ⅲ)concentrations led to raising in redox potential of the solution,and decreased passivation of pyrite caused by deposition of elemental sulfur.Reduction of Fe(Ⅲ)at pyrite surface was a fast reaction with low activation energy,it was only slightly promoted by rising temperatures.While,the oxidation rate of pyrite at all investigated Fe(Ⅲ)concentrations increased obviously with rising temperatures,the anodic reaction was the rate-limiting step in the overall reaction.Activation energy of pyrite oxidation decreased from 47.74 to 28.79 kJ/mol when Fe(Ⅲ)concentration was increased from 0.05 to 0.50 g/L,showing that the reaction kinetics were limited by the rate of electrochemical reaction at low Fe(Ⅲ)concentrations,while,it gradually turned to be diffusion control with increasing Fe(Ⅲ)concentrations.

Probing the peripheral self-generated magnetic field distribution in laser-plasma magnetic reconnection with Martin-Puplett interferometer polarimeter

Magnetic reconnection of the self-generated magnetic fields in laser-plasma interaction is an important laboratory method for modeling high-energy density astronomical and astrophysical phenomena.We use the Martin-Puplett interferometer(MPI)polarimeter to probe the peripheral magnetic fields generated in the common magnetic reconnection configuration,two separated coplanar plane targets,in laser-target interaction.We introduce a new method that can obtain polarization information from the interference pattern instead of the sinusoidal function fitting of the intensity.A bidirectional magnetic field is observed from the side view,which is consistent with the magneto-hydro-dynamical(MHD)simulation results of self-generated magnetic field reconnection.We find that the cancellation of reverse magnetic fields after averaging and integration along the observing direction could reduce the magnetic field strength by one to two orders of magnitude.It indicates that imaging resolution can significantly affect the accuracy of measured magnetic field strength.

Impacts of information about COVID-19 on pig farmers'production willingness and behavior:Evidence from China

This paper examines the impacts of information about COVID-19 on pig farmers'production willingness by using endorsement experiments and follow-up surveys conducted in 2020 and 2021 in China.Our results show that,first,farmers were less willing to scale up production when they received information about COVID-19.The information in 2020 that the second wave of COVID-19 might occur without a vaccine reduced farmers'willingness to scale up by 13.4%,while the information in 2021 that COVID-19 might continue to spread despite the introduction of vaccine reduced farmers'willingness by 4.4%.Second,farmers whose production was affected by COVID-19 were considerably less willing to scale up,given the access to COVID-19 information.Third,farmers'production willingness can predict their actual production behavior.

Numerical Simulation on Radon Retardation Behavior of Covering Floats in Radon-Containing Water

Objective This study aimed to efficiently reduce the release of radon from water bodies to protect the environment.Methods Based on the sizes of the experimental setup and modular float,computational fluid dynamics(CFD)was used to assess the impact of the area coverage rate,immersion depth,diffusion coefficient,and radon transfer velocity at the gas–liquid interface on radon migration and exhalation of radon-containing water.Based on the numerical simulation results,an estimation model for the radon retardation rate was constructed.The effectiveness of the CFD simulation was evaluated by comparing the experimental and simulated variation values of the radon retardation rate with the coverage area rates.Results The effect of radon transfer velocity on radon retardation in water bodies was minor and insignificant according to the appropriate value;therefore,an estimation model of the radon retardation rate of the coverage of a radon-containing water body was constructed using the synergistic impacts of three factors:area coverage rate,immersion depth,and diffusion coefficient.The deviation between the experimental and simulated results was<4.3%.Conclusion Based on the numerical simulation conditions,an estimation model of the radon retardation rate of covering floats in water bodies under the synergistic effect of multiple factors was obtained,which provides a reference for designing covering floats for radon retardation in radoncontaining water.

Analysis and experimental study on resistance-increasing behavior of composite high efficiency autonomous inflow control device

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.

Sliding and damming properties of granular debris with different geometric configurations and grain size distributions

Granular debris plays a significant role in determining damming deposit characteristics. An indepth understanding of how variations in grain size distribution(GSD) and geometric configurations impact the behavior of granular debris during the occurrence of granular debris is essential for precise assessment and effective mitigation of landslide hazards in mountainous terrains. This research aims to investigate the impact of GSD and geometric configurations on sliding and damming properties through laboratory experiments. The geometric configurations were categorized into three categories based on the spatial distribution of maximum volume: located at the front(Type Ⅰ), middle(Type Ⅱ), and rear(Type Ⅲ) of the granular debris. Our experimental findings highlight that the sliding and damming processes primarily depend on the interaction among the geometric configuration, grain size, and GSD in granular debris. Different sliding and damming mechanisms across various geometric configurations induce variability in motion parameters and deposition patterns. For Type Ⅰ configurations, the front debris functions as the critical and primary driving component, with energy dissipation primarily occurring through inter-grain interactions. In contrast, Type Ⅱ configurations feature the middle debris as the dominant driving component, experiencing hindrance from the front debris and propulsion from the rear, leading to complex alterations in sliding motion. Here, energy dissipation arises from a combination of inter-grain and grain-substrate interactions. Lastly, in Type Ⅲ configurations, both the middle and rear debris serve as the main driving components, with the rear sliding debris impeded by the front. In this case, energy dissipation predominantly results from grainsubstrate interaction. Moreover, we have quantitatively demonstrated that the inverse grading in damming deposits, where coarse grain moves upward and fine grain moves downward, is primarily caused by grain sorting due to collisions among the grains and between the grain and the base. The impact of grain on the horizontal channel further aids grain sorting and contributes to inverse grading. The proposed classification of three geometric configurations in our study enhances the understanding of damming properties from the view of mechanism, which provides valuable insights for related study about damming granular debris.