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.

Unconfined compressive strength and failure behaviour of completely weathered granite from a fault zone

Understanding the strength characteristics and deformation behaviour of the tunnel surrounding rock in a fault zone is significant for tunnel stability evaluation.In this study,a series of unconfined compression tests were conducted to investigate the mechanical characteristics and failure behaviour of completely weathered granite(CWG)from a fault zone,considering with height-diameter(h/d)ratio,dry densities(ρd)and moisture contents(ω).Based on the experimental results,a regression mathematical model of unconfined compressive strength(UCS)for CWG was developed using the Multiple Nonlinear Regression method(MNLR).The research results indicated that the UCS of the specimen with a h/d ratio of 0.6 decreased with the increase ofω.When the h/d ratio increased to 1.0,the UCS increasedωwith up to 10.5%and then decreased.Increasingρd is conducive to the improvement of the UCS at anyω.The deformation and rupture process as well as final failure modes of the specimen are controlled by h/d ratio,ρd andω,and the h/d ratio is the dominant factor affecting the final failure mode,followed byωandρd.The specimens with different h/d ratio exhibited completely different fracture mode,i.e.,typical splitting failure(h/d=0.6)and shear failure(h/d=1.0).By comparing the experimental results,this regression model for predicting UCS is accurate and reliable,and the h/d ratio is the dominant factor affecting the UCS of CWG,followed byρd and thenω.These findings provide important references for maintenance of the tunnel crossing other fault fractured zones,especially at low confining pressure or unconfined condition.

Effect of compressive strength on the performance of the NEMO-LIM model in Arctic Sea ice simulation

Satellite records show that the extent and thickness of sea ice in the Arctic Ocean have significantly decreased since the early 1970s.The prediction of sea ice is highly important,but accurate simulation of sea ice variations remains highly challenging.For improving model performance,sensitivity experiments were conducted using the coupled ocean and sea ice model(NEMO-LIM),and the simulation results were compared against satellite observations.Moreover,the contribution ratios of dynamic and thermodynamic processes to sea ice variations were analyzed.The results show that the performance of the model in reconstructing the spatial distribution of Arctic sea ice is highly sensitive to ice strength decay constant(C^(rhg)).By reducing the C^(rhg) constant,the sea ice compressive strength increases,leading to improved simulated sea ice states.The contribution of thermodynamic processes to sea ice melting was reduced due to less deformation and fracture of sea ice with increased compressive strength.Meanwhile,dynamic processes constrained more sea ice to the central Arctic Ocean and contributed to the increases in ice concentration,reducing the simulation bias in the central Arctic Ocean in summer.The root mean square error(RMSE)between modeled and the CryoSat-2/SMOS satellite observed ice thickness was reduced in the compressive strength-enhanced model solution.The ice thickness,especially of multiyear thick ice,was also reduced and matched with the satellite observation better in the freezing season.These provide an essential foundation on exploring the response of the marine ecosystem and biogeochemical cycling to sea ice changes.

Novel Hybrid X GBoost Model to Forecast Soil Shear Strength Based on Some Soil Index Tests

When building geotechnical constructions like retaining walls and dams is of interest,one of the most important factors to consider is the soil’s shear strength parameters.This study makes an effort to propose a novel predictive model of shear strength.The study implements an extreme gradient boosting(XGBoost)technique coupled with a powerful optimization algorithm,the salp swarm algorithm(SSA),to predict the shear strength of various soils.To do this,a database consisting of 152 sets of data is prepared where the shear strength(τ)of the soil is considered as the model output and some soil index tests(e.g.,dry unit weight,water content,and plasticity index)are set as model inputs.Themodel is designed and tuned using both effective parameters of XGBoost and SSA,and themost accuratemodel is introduced in this study.Thepredictionperformanceof theSSA-XGBoostmodel is assessedbased on the coefficient of determination(R2)and variance account for(VAF).Overall,the obtained values of R^(2) and VAF(0.977 and 0.849)and(97.714%and 84.936%)for training and testing sets,respectively,confirm the workability of the developed model in forecasting the soil shear strength.To investigate the model generalization,the prediction performance of the model is tested for another 30 sets of data(validation data).The validation results(e.g.,R^(2) of 0.805)suggest the workability of the proposed model.Overall,findings suggest that when the shear strength of the soil cannot be determined directly,the proposed hybrid XGBoost-SSA model can be utilized to assess this parameter.

Solving the Olbers’s Paradox, Explaining the “Red-Shift”, and Challenging the Relativities by “Sun Matters Theory” and “Sun Model of Universe”, an Evolution of the Einstein’s Static Universe Model

Olbers’s paradox, known as the dark night paradox, is an argument in astrophysics that the darkness of the night sky conflicts with the assumption of an infinite and eternal static universe. Big-Bang theory was used to partially explain this paradox, while introducing new problems. Hereby, we propose a better theory, named Sun Matters Theory, to explain this paradox. Moreover, this unique theory supports and extended the Einstein’s static universe model proposed by Albert Einstein in 1917. Further, we proposed our new universe model, “Sun Model of Universe”. Based on the new model and novel theory, we generated innovative field equation by upgrading Einstein’s Field Equation through adding back the cosmological constant, introducing a new variable and modifying the gravitationally-related concepts. According to the Sun Model of Universe, the dark matter and dark energy comprise the so-called “Sun Matters”. The observed phenomenon like the red shift is explained as due to the interaction of ordinary light with Sun Matters leading to its energy and frequency decrease. In Sun Model, our big universe consists of many universes with ordinary matter at the core mixed and surrounded with the Sun Matters. In those universes, the laws of physics may be completely or partially different from that of our ordinary universe with parallel civilizations. The darkness of night can be easily explained as resulting from the interaction of light with the Sun Matters leading to the sharp decrease in the light intensity. Sun Matters also scatter the light from a star, which makes it shining as observed by Hubble. Further, there is a kind of Sun Matters named “Sun Waters”, surrounding every starts. When lights pass by the sun, the Sun Waters deflect the lights to bend the light path. According to the Sun Model, it is the light bent not the space bent that was proposed in the theory of relativities.

Hubble Tension Explanation from This Cosmological Model AΛΩ (Slow Bang Model, SB)

In this article we present a model of Hubble-Lemaître law using the notions of a transmitter (galaxy) and a receiver (MW) coupled to a model of the universe (Slow Bang Model, SB), based on a quantum approach of the evolution of space-time as well as an equation of state that retains all the infinitesimal terms. We find an explanation of the Hubble tension H0. Indeed, we have seen that this constant depends on the transceiver pair which can vary from the lowest observable value, from photons of the CMB (theoretical [km/s/Mpc]) to increasingly higher values depending on the earlier origin of the formation of the observed galaxy or cluster (ETG ~0.3 [Gy], ~74 [km/s/Mpc]). We have produced a theoretical table of the values of the constant according to the possible pairs of transmitter/receiver in the case where these galaxies follow the Hubble flow without large disturbance. The calculated theoretical values of the constant are in the order of magnitude of all values mentioned in past studies. Subsequently, we applied the models to 9 galaxies and COMA cluster and found that the models predict acceptable values of their distances and Hubble constant since these galaxies mainly follow the Hubble flow rather than the effects of a galaxy cluster or a group of clusters. In conclusion, we affirm that this Hubble tension does not really exist and it is rather the understanding of the meaning of this constant that is questioned.

Analysis of Porter’s Five Forces Competitive Model in China’s Property Rights Trading Market

In recent years,China’s property rights trading market has been extremely competitive,but there are also new contradictions and challenges.This paper aims to analyze the external and internal competitive market of the property rights market through Porter’s five forces competition model,then find out the problems and defects in the development,thereby promoting the better development and progress of China’s property rights trading market.

Strength Model of Soda Residue Soil Considering Consolidation Stress and Structural Influence

Soda residue(SR)is a type of industrial waste produced in the soda process with the ammonia-soda method.Applying SR to backfilling solves the land occupation and environmental pollution problems in coastal areas and saves material costs for foundation engineering.The strength characteristics of soda residue soil(SRS)under different consolidation conditions are the key points to be solved in the engineering application of SRS.Triaxial compression tests were performed on the undisturbed SRS of Tianjin Port.The shear properties of SRS under different consolidation conditions were then discussed.Meanwhile,a structural strength model(SSM)based on Mohr-Coulomb theory was proposed.SSM reflects the influence of soil structure on undrained strength(Cu)and divides the Cu into the following two parts:friction strength(C_(uf))and original structural strength(C_(u0)).C_(uf)characterizes the magnitude of friction between soil particles,which is related to the consolidation stress.Meanwhile,C_(u0)represents the structural effect on soil strength,which is related to the soil deposition and consolidation processes.SSM was validated by the test data of undisturbed soils.Results reveal that the undisturbed soil generally had a certain C_(u0).Therefore,the SRS strength model was established by combining the experimental law of SRS with SSM.Error analysis shows that the SRS strength model can effectively predict the Cu of undisturbed SRS in Tianjin Port under different consolidation conditions.

Strength prediction model for water-bearing sandstone based on nearinfrared spectroscopy

The strength of water-bearing rock cannot be obtained in real time and by nondestructive experiments,which is an issue at cultural relics protection sites such as grotto temples.To solve this problem,we conducted a near-infrared spectrum acquisition experiment in the field and laboratory uniaxial compression strength tests on sandstone that had different water saturation levels.The correlations between the peak height and peak area of the nearinfrared absorption bands of the water-bearing sandstone and uniaxial compressive strength were analyzed.On this basis,a strength prediction model for water-bearing sandstone was established using the long short-term memory full convolutional network(LSTM-FCN)method.Subsequently,a field engineering test was carried out.The results showed that:(1)The sandstone samples had four distinct characteristic absorption peaks at 1400,1900,2200,and 2325 nm.The peak height and peak area of the absorption bands near 1400 nm and 1900 nm had a negative correlation with uniaxial compressive strength.The peak height and peak area of the absorption bands near 2200 nm and 2325 nm had nonlinear positive correlations with uniaxial compressive strength.(2)The LSTM-FCN method was used to establish a strength prediction model for water-bearing sandstone based on near-infrared spectroscopy,and the model achieved an accuracy of up to 97.52%.(3)The prediction model was used to realize non-destructive,quantitative,and real-time determination of uniaxial compressive strength;this represents a new method for the non-destructive testing of grotto rock mass at sites of cultural relics protection.

Modeling the Undrained Shear Strength with Soil Index Properties for Niger Delta Soft Clays

The aim of this study was to model the Undrained Shear Strength (USS) of soil found in the coastal region of the Niger Delta in Nigeria with some soil properties. The undrained shear strength (USS) is a key parameter needed for most geotechnical/structural designs. Accurate determination of the USS of soft clays can be challenging to obtain in the laboratory due to the difficulty in remoulding the clay to its in-situ conditions before testing and more accurate test such as Cone Penetration test (CPT) can be quite expensive. This study was carried out at Escravos site which is located in Delta state, Nigeria. Three Boreholes were drilled and soil samples were collected at 0.75 m intervals up to a depth of 45 m. Laboratory tests were used to obtain the moisture content, bulk unit weight, liquid and plastic limit, while CPT was used in obtaining the undrained shear strength. Classification of the soil samples was done by adopting the Unified Soil Classification System and various models relating the USS with the soil properties were developed. The result showed that most of the soils at Escravos site were predominately inorganic clay of high plasticity which are problematic due to the expansion and shrinking nature of this type of soil. The model developed showed that the soil properties that gave the best fit with the USS were the moisture content and effective stress of the soil. The coefficient of determination (R2) and the root mean square error (RMSE) obtained for this model were 0.805 and 6.37 KN/m2, respectively.

高压管汇材料疲劳性能测试及P-S-N模型曲线的拟合

高压管汇作为压裂设备中的主要易损件之一,其失效危害较大。它的失效原因主要是疲劳、冲蚀、腐蚀或者材料缺陷引起的刺漏和爆裂,其中尤以疲劳失效最不可预估。目前,对于高压管汇材料的疲劳性能研究不够深入,为解决高压管汇材料疲劳寿命的准确描述问题,以某国产高压管汇材料为例,进行了一系列疲劳试验,并基于试验数据,采用多种分布模型和不同S-N模型进行拟合分析,得出综合评价拟合能力最强的P-S-N模型。结果表明,该材料在中长疲劳寿命区,Weibull三参数模型在7级应力水平下综合评价能力最好;在存活率分别为50%、90%、99%、99.9%时,指数S-N模型的拟合系数均大于0.98,拟合能力最好。得出的P-S-N模型曲线可以为高压管汇的疲劳寿命以及安全设计提供依据。

深水采油树Spring-Seal密封圈接触模型构建与实验测试

为提高深水采油树在高压、高温、低温等工况下长时间工作的稳定性,对采油树密封圈进行重新设计,提出Spring-Seal密封圈(以下简称S密封圈);基于赫兹接触理论、填料密封接触理论,重新构建S密封圈接触力学模型;建立有限元仿真分析模型,分析不同条件下S密封圈的密封性能,同时验证新建接触模型的合理性;利用实验测试S密封圈的实际密封效果。研究结果表明:S密封圈在高压、高温、低温等工况下能够长时间稳定工作且密封性能良好。研究结果可为S密封圈的接触研究及工程运用提供理论参考。

超高强Ti-15Mo-2.7Nb-3Al-0.2Si钛合金的强化行为及模型

基于XRD、OM、SEM和TEM分析,研究超高强Ti-15Mo-2.7Nb-3Al-0.2Si钛合金的组织演变及强化行为。结果表明,位错强化和析出强化效应对该合金的屈服强度影响较大。冷轧+再结晶+冷轧+双时效组合工艺可获得1518 MPa的最高屈服强度,这主要归因于显微组织中的高密度残存位错及密集而细小的次生α相。建立复合强化模型,其预测误差在16.6%以内。此外,研究发现次生α相体积分数的增加可以不断强化晶内区域,这使得沿晶断裂开始出现并逐渐占据整个断裂面。

D-S理论和Markov链组合的桥梁性能退化预测研究

为准确预测桥梁性能退化,考虑到数据随机性和微小扰动发生状态跳跃,提出了一种D-S(Dempster-Shafer)证据理论和Markov链组合的桥梁性能退化组合预测模型和性能退化率的概念.该模型基于指数平滑(exponential smoothing,ES)方法获得新的预测数据序列,并利用Markov链和D-S理论不断进行优化,从而实现桥梁性能退化的组合预测.实际工程的应用结果表明:性能退化率可以直观地表征在梁性能退化的速度.其次,该模型的平均相对误差为1.54%,较于回归、灰色和模糊加权Markov链模型,精度分别提高了1.11%,0.88%和2.8%,而后验差比值为0.242,小于0.35;模型的标准差为9.021,相比其他模型分别减小了3.978,3.405和7.500,而变异系数为0.109,均小于其他模型,验证了组合预测模型在精度和稳定性方面的优越性,可为在役桥梁结构性能退化预测与维护提供理论基础.

基于量子衍生涡流算法和T⁃S模糊推理模型的储层岩性识别

鉴于梯度下降法易陷入局部极值、普通群智能优化算法易早熟收敛,提出一种基于量子衍生涡流算法(Quantum Vortex Search Algorithm,QVSA)和T⁃S模糊推理模型的岩性识别方法,QVSA具有操作简单、收敛速度快、寻优能力强等优点,有助于T⁃S模糊推理模型获得最优参数配置,从而实现储层岩性的准确识别。首先利用具有全局搜索能力的QVSA优化T⁃S模糊推理模型的各种参数;然后利用主成分分析方法降低获取的地震属性维度;再利用优化的T⁃S模糊推理模型识别储层岩性。实验结果表明,利用反映储层特征的8个地震属性识别储层岩性时,所提方法的识别正确率达到92%,比普通BP网络方法高5.1%,同时查准率、查全率、F1分数等指标也较BP网络方法提升明显。

基于S变换模能量分析的直流电缆故障测距

针对现有高压直流电缆故障定位方法故障定位精度低、定位模型泛化能力差等问题,文中在考虑电缆故障后故障点产生的暂态信号中含有丰富的故障信息的特征,提出一种时频域能量分析的故障测距方法。该方法利用多分类支持向量机(SVM)的特性构建直流电缆故障定位模型,利用直流电缆相模解耦矩阵对电缆电气量解耦,并采用S变换进行时频域变换,将得到的模量构造模能量,将其作为样本对SVM模型训练。实验结果表明,所提方法对于不同故障类型在不同过渡电阻及不同位置故障下均可进行准确测距。

Effect of the mineral spatial distribution heterogeneity on the tensile strength of granite:Insights from PFC3D-GBM numerical analysis

The mechanical characteristics of crystalline rocks are affected by the heterogeneity of the spatial distribution of minerals.In this paper,a novel three-dimensional(3D)grain-based model(GBM)based on particle flow code(PFC),i.e.PFC3D-GBM,is proposed.This model can accomplish the grouping of mineral grains at the 3D scale and then filling them.Then,the effect of the position distribution,geometric size,and volume composite of mineral grains on the cracking behaviour and macroscopic properties of granite are examined by conducting Brazilian splitting tests.The numerical results show that when an external load is applied to a sample,force chains will form around each contact,and the orientation distribution of the force chains is uniform,which is independent of the external load level.Furthermore,the number of high-strength force chains is proportional to the external load level,and the main orientation distribution is consistent with the external loading direction.The main orientation of the cracks is vertical to that of the high-strength force chains.The geometric size of the mineral grains controls the mechanical behaviours.As the average grain size increases,the number of transgranular contacts with higher bonding strength in the region connecting both loading points increases.The number of high-strength force chains increases,leading to an increase in the stress concentration value required for the macroscopic failure of the sample.Due to the highest bonding strength,the generation of transgranular cracks in quartz requires a higher concentrated stress value.With increasing volume composition of quartz,the number of transgranular cracks in quartz distributed in the region connecting both loading points increases,which requires many high-strength force chains.The load level rises,leading to an increase in the tensile strength of the numerical sample.

Various admixtures to mitigate the long-term strength retrogression of Portland cement cured under high pressure and high temperature conditions

In order to investigate the problem of long-term strength retrogression in oil well cement systems exposed to high pressure and high temperature(HPHT)curing conditions,various influencing factors,including cement sources,particle sizes of silica flour,and additions of silica fume,alumina,colloidal iron oxide and nano-graphene,were investigated.To simulate the environment of cementing geothermal wells and deep wells,cement slurries were directly cured at 50 MPa and 200?C.Mineral compositions(as determined by X-ray diffraction Rietveld refinement),water permeability,compressive strength and Young’s modulus were used to evaluate the qualities of the set cement.Short-term curing(2e30 d)test results indicated that the adoption of 6 m m ultrafine crystalline silica played the most important role in stabilizing the mechanical properties of oil well cement systems,while the addition of silica fume had a detrimental effect on strength stability.Long-term curing(2e180 d)test results indicated that nano-graphene could stabilize the Young’s modulus of oil well cement systems.However,none of the ad-mixtures studied here can completely prevent the strength retrogression phenomenon due to their inability to stop the conversion of amorphous to crystalline phases.

A data assimilation-based forecast model of outer radiation belt electron fluxes

Because radiation belt electrons can pose a potential threat to the safety of satellites orbiting in space,it is of great importance to develop a reliable model that can predict the highly dynamic variations in outer radiation belt electron fluxes.In the present study,we develop a forecast model of radiation belt electron fluxes based on the data assimilation method,in terms of Van Allen Probe measurements combined with three-dimensional radiation belt numerical simulations.Our forecast model can cover the entire outer radiation belt with a high temporal resolution(1 hour)and a spatial resolution of 0.25 L over a wide range of both electron energy(0.1-5.0 MeV)and pitch angle(5°-90°).On the basis of this model,we forecast hourly electron fluxes for the next 1,2,and 3 days during an intense geomagnetic storm and evaluate the corresponding prediction performance.Our model can reasonably predict the stormtime evolution of radiation belt electrons with high prediction efficiency(up to~0.8-1).The best prediction performance is found for~0.3-3 MeV electrons at L=~3.25-4.5,which extends to higher L and lower energies with increasing pitch angle.Our results demonstrate that the forecast model developed can be a powerful tool to predict the spatiotemporal changes in outer radiation belt electron fluxes,and the model has both scientific significance and practical implications.

Outlook of PINK1/Parkin signaling in molecular etiology of Parkinson's disease,with insights into Pink1 knockout models

Parkinson’s disease(PD)relates to defective mitochondrial quality control in the dopaminergic motor network.Genetic studies have revealed that PINK1 and Parkin mutations are indicative of a heightened propensity to PD onset,pinpointing mitophagy and inflammation as the culprit pathways involved in neuronal loss in the substantia nigra(SNpc).In a reciprocal manner,LRRK2 functions in the regulation of basal flux and inflammatory responses responsible for PINK1/Parkin-dependent mitophagy activation.Pharmacological intervention in these diseasemodifying pathways may facilitate the development of novel PD therapeutics,despite the current lack of an established drug evaluation model.As such,we reviewed the feasibility of employing the versatile global Pink1knockout(KO)rat model as a self-sufficient,spontaneous PD model for investigating both disease etiology and drug pharmacology.These rats retain clinical features encompassing basal mitophagic flux changes with PD progression.We demonstrate the versatility of this PD rat model based on the incorporation of additional experimental insults to recapitulate the proinflammatory responses observed in PD patients.