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.

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.

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。

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.

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.

基于S-O-R模型的视觉营销对消费者购买意愿的影响研究——以红色文创网店为例

为提高红色文创网店的点击转化率,文章从消费者视角出发,研究影响消费者购买意愿的视觉因素。基于S-O-R模型理论,构建红色文创网店视觉营销对消费者购买意愿因素的理论模型。利用S-O-R模型分析了红色文创网店视觉营销中的商品形象、界面形象以及品牌视觉形象对顾客感知价值及顾客购买意向的影响。通过设计量表和调查问卷进行实证研究,并结合结构方程模型加以论证,得出品牌视觉形象和界面形象是影响消费者购买意愿的关键因素,为设计师和红色文创品牌进行网店设计提供了一定的理论参考和建议。

Philosophy and Philology:Two Approaches of Commentating the Shen Nong Ben Cao Jing(Shen Nong's Classic of the Materia Medica)in the Ming and Qing Dynasties

This paper tests the hypothesis that the commentary trend of the Shen Nong Ben Cao Jing(Shen Nong’s Classic of the Materia Medica)arises alongside the fashionable philology of the time,or the aversion against the Jin-Yuan medical philosophy.After surveying 12 major commentaries,it is concluded that the situation is more complicated than a simple assertion.The seemingly opposite philosophy and philology approaches have been used eclectically to innovate the understanding of ancient traditional Chinese medicine texts.

Modeling the energetic electron fluxes in the inner radiation belt based on a drift-source model

The Macao Science Satellite-1(MSS-1),designed by the Macao University of Science and Technology and the National Space Science Center(NSSC)of China,is equipped to detect the fine structure of the magnetic field over the South Atlantic Anomaly(SAA)region,monitoring geomagnetic field variations,and obtaining the energetic electron spectrum distributions in the Earth’s inner radiation belt.In this study,we simulate the distributions of trapped,quasi-trapped,and untrapped electrons along the orbit of MSS-1 based on a drift-source model.The simulation results show that the particle detector with 90°looking direction can observe trapped electrons in the SAA region,untrapped electrons in the regions conjugated with the SAA region at the north hemisphere,and quasitrapped electrons in all other regions.In contrast,the detectors with<60°looking directions can measure only untrapped electrons.Generally,quasi-trapped electron fluxes accumulate along the drift trajectory and are due primarily to CRAND,until reaching the SAA region where quasi-trapped electrons are all lost into the atmosphere.

Quantification of Ride Comfort Using Musculoskeletal Mathematical Model Considering Vehicle Behavior

This research aims to quantify driver ride comfort due to changes in damper characteristics between comfort mode and sport mode,considering the vehicle’s inertial behavior.The comfort of riding in an automobile has been evaluated in recent years on the basis of a subjective sensory evaluation given by the driver.However,reflecting driving sensations in design work to improve ride comfort is abstract in nature and difficult to express theoretically.Therefore,we evaluated the human body’s effects while driving scientifically by quantifying the driver’s behavior while operating the steering wheel and the behavior of the automobile while in motion using physical quantities.To this end,we collected driver and vehicle data using amotion capture system and vehicle CAN and IMU sensors.We also constructed a three-dimensional musculoskeletal mathematical model to simulate driver movements and calculate the power and amount of energy per unit of time used for driving the joints and muscles of the human body.Here,we used comfort mode and sport mode to compare damper characteristics in terms of hardness.In comfort mode,damper characteristics are soft and steering stability is mild,but vibration from the road is not easily transmitted to the driver making for a lighter load on the driver.In sport mode,on the other hand,damper characteristics are hard and steering stability is comparatively better.Still,vibration from the road is easily transmitted to the driver,whichmakes it easy for a load to be placed on the driver.As a result of this comparison,it was found that a load was most likely to be applied to the driver’s neck.This result in relation to the neck joint can therefore be treated as an objective measure for quantifying ride comfort.

Model test of negative Poisson’s ratio cable for supporting super-largespan tunnel using excavation compensation method

In recent years,there is a scenario in urban tunnel constructions to build super-large-span tunnels for traffic diversion and route optimization purposes.However,the increased size makes tunnel support more difficult.Unfortunately,there are few studies on the failure and support mechanism of the surrounding rocks in the excavation of supported tunnel,while most model tests of super-large-span tunnels focus on the failure characteristics of surrounding rocks in tunnel excavation without supports.Based on excavation compensation method(ECM),model tests of a super-large-span tunnel excavation by different anchor cable support methods in the initial support stage were carried out.The results indicate that during excavation of super-large-span tunnel,the stress and displacement of the shallow surrounding rocks decrease,following a step-shape pattern,and the tunnel failure is mainly concentrated on the vault and spandrel areas.Compared with conventional anchor cable supports,the NPR(negative Poisson’s ratio)anchor cable support is more suitable for the initial support stage of the super-large-span tunnels.The tunnel support theory,model test materials,methods,and the results obtained in this study could provide references for study of similar super-large-span tunnels。

Compound Danshen tablets downregulate amyloid protein precursor mRNA expression in a transgenic cell model of Alzheimer's disease Effects and a comparison with donepezil

After gene mutation, the pcDNA3.1/APP595/596 plasmid was transfected into HEK293 cells to establish a cell model of Alzheimer＇s disease. The cell model was treated with donepezil or compound Danshen tablets after culture for 72 hours. Reverse transcription-PCR showed that the mRNA expression of amyloid protein precursor decreased in all groups following culture for 24 hours, and that there was no significant difference in the amount of decrease between donepezil and compound Danshen tablets. Our results suggest that compound Danshen tablets can reduce expression of the mRNA for amyloid protein precursor in a transgenic cell model of Alzheimer＇s disease, with similar effects to donepezil.

东北地区土地覆被格局变化模拟:基于CLUE-S和Markov-CA模型的对比分析

研究以遥感解译的东北地区2000年、2010年、2015年的土地覆被变化为基础,充分考虑自然和社会因素对土地覆被变化的影响,分别通过CLUE-S模型和Markov-CA模型对东北地区2015年和2030年土地覆被格局进行模拟,研究结果表明:通过与遥感解译的2015年实际土地覆被类型数据对比验证,CLUE-S模型和Markov-CA模型模拟结果的总体Kappa指数分别为0.9700和0.9649,结果表明2种模型的模拟结果较为理想,CLUE-S模型的模拟精度较Markov-CA模型更高。2015—2030年东北地区草地、耕地、湿地、其他用地和水体面积呈现下降趋势,林地、人工表面面积呈现增加趋势,人地关系越发紧张。东北地区作为生态环境相对脆弱的区域需警惕不可持续的土地覆被变化,需权衡生态保护、粮食增加与基础设施建设的用地需求和协调发展。

Utilizing the Vector Autoregression Model (VAR) for Short-Term Solar Irradiance Forecasting

Forecasting solar irradiance is a critical task in the renewable energy sector, as it provides essential information regarding the potential energy production from solar panels. This study aims to utilize the Vector Autoregression (VAR) model to forecast solar irradiance levels and weather characteristics in the San Francisco Bay Area. The results demonstrate a correlation between predicted and actual solar irradiance, indicating the effectiveness of the VAR model for this task. However, the model may not be sufficient for this region due to the requirement of additional weather features to reduce disparities between predictions and actual observations. Additionally, the current lag order in the model is relatively low, limiting its ability to capture all relevant information from past observations. As a result, the model’s forecasting capability is limited to short-term horizons, with a maximum horizon of four hours.

通州—三河地区沉积层高分辨率三维S波速度结构和径向各向异性

北京大都市区位于冀中凹陷与太行山隆起和燕山褶皱带的交汇区,区内被第四系松软沉积层覆盖,历史和现今的地震活动性表明,其面临潜在的巨震风险.地震风险评估和强地面运动模拟依赖准确的沉积层三维S波速度模型.本文基于布设在通州—三河地区前所未有的密集台阵数据,构建了该区域高分辨率三维S波速度结构和径向各向异性模型.首先将919个台站组成的密集台阵划分为若干子台阵,利用修正的背景噪声聚束分析方法,提取各个子台阵的Love波频散曲线,通过深度反演构建了通州—三河地区三维SH波速度模型.结合由基阶和一阶Rayleigh波模式反演构建的三维SV波速度模型,获得了台阵下方的径向各向异性模型.模型显示,大兴断裂在穿过牛堡屯之后,继续向北东向延伸约20 km.大兴凸起以大兴断裂为界,表现出明显不同的构造特征和沉积过程.断裂的北西侧第四系沉积层较浅,推测约为100~400 m;断裂的南东侧第四系沉积层厚度横向变化较大,发育夏垫凹陷和甘棠凹陷.沉积盆地径向各向异性的幅度可达±20%,地表约0~60 m范围有一较强的负径向各向异性(VSH<VSV)覆盖层,推测与该地区垂直地裂缝发育有关.正的径向各向异性(VSH>VSV)是沉积作用造成的水平层序排列的沉积分层的反映.

GP断层破裂模型在青海门源M_(S)6.9地震强地面运动模拟的适用性研究

2022年1月8日青海省门源县发生M_(S)6.9地震,震中附近遭受了强烈地震破坏.为验证Graves和Pitarka开发的GP断层破裂模型在震前对中国地区地震动场的预测与评估能力,本文基于GP法,考虑不同上升时间系数(rc)的影响,对门源地震进行了确定性地震动模拟.将模拟结果在地震动衰减规律、波形与幅值和烈度分布三个方面分别与青藏地区的地震动峰值预测方程、强震观测记录和根据强震记录自动产出的烈度图进行了对比.结果表明,当rc为9.0时,模拟记录与实测记录和地震动峰值预测方程基本一致.本文较好的重现了门源地震的强震动场,在合理选取rc的情况下,GP法可以应用于中国地区震前强地震动场的预测和估计.

Elevation transition of aquatic insects closely matches a thermal feature in the Yungas of Northwestern Argentina

Temperature is a key factor that shapes the distribution of organisms.Having knowledge about how species respond to temperature is relevant to devise strategies for addressing the impacts of climate change.Aquatic insects are particularly vulnerable to climate change,yet there is still much to learn about their ecology and distribution.In the Yungas ecoregion of Northwestern Argentina,cold-and warm-adapted species of the orders Ephemeroptera,Plecoptera,and Trichoptera(EPT)are segregated by elevation.We modeled the ecological niche of South American EPT species in this region using available data and projected their potential distribution in geographic space.Species were grouped based on their ecogeographic similarity,and we analyzed their replacement pattern along elevation gradients,focusing on the ecotone where opposing thermal preferences converge.Along this interface,we identified critical points where the combined incidence of cold and warm assemblages maximizes,indicating a significant transition zone.We found that the Montane Cloud Forest holds the interface,with a particularly greater suitability at its lower boundary.The main axis of the interface runs in a N-S direction and falls between 14°C-16°C mean annual isotherms.The probability of a particular location within a basin being classified as part of the interface increases as Kira’s warmth index approaches a score around 150.Understanding the interface is critical for defining the thermal limits of species distribution and designing biomonitoring programs.Changes in the location of thermal constants related to mountainous ecotones may cause vertical displacement of aquatic insects and vegetation communities.We have recognized significant temperature thresholds that serve as indicators of suitability for the interface.As global warming is anticipated to shift these indicators,we suggest using them to monitor the imprints of climate change on mountain ecosystems.

集体经营性建设用地入市农户满意度影响因素研究——基于Logistic-ISM模型的分析

农户满意程度可以反映政策改革成效,探究农户集体经营性建设用地入市满意度影响因素,有助于评价政策实施效果,同时对提升农村发展和农民幸福感也有一定的现实意义.采用问卷调查和访谈的方式,选取重庆市大足区作为研究区域,基于Logistic模型确定农户满意度的影响因素,结合ISM模型分析各影响因素之间的层次关系,对农民的政策实施满意度影响因素进行实证分析.研究结果显示:(1)针对入市实施效果,绝大部分农户持满意态度,不满意的地方集中在收益分配不及时和环境污染方面;(2)家中是否有村干部、生态环境变化情况、是否参与表决、分配公平性、入市实际收益、程序透明性、入市风险存在情况、对入市土地所有者的认知对入市农户满意度有显著影响.其中对入市土地所有者的认知、入市风险存在情况、入市实际收益为表层直接因素,中层间接因素有生态环境变化情况、是否参与表决、分配公平性以及程序透明性,家中是否有村干部为深层根源因素.应进一步完善土地产权制度,明晰入市到期后土地权属问题;健全监督管理机制,建立集体经营性建设用地入市单位的产业目录和准入标准制度;完善收益分配机制,制定集体土地入市指导性分配意见;将村集体负责人纳入政府基层领导队伍体系,提高程序透明性.

Crohn’s disease as the intestinal manifestation of pan-lymphatic dysfunction:An exploratory proposal based on basic and clinical data

Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.