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.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

A Model of Grand Unified Theory: Suggested Solution for CP-Violation Using Ideas of Phase Paths

This study demonstrates that beyond standard model (BSM) cosmic fundamental interactions—weak, strong, and electromagnetic forces—can be unified through a common basis of representation. This unification allows for the derivation of the fine structure constant with running points of α(t) ≈ 1/(136.9038) at high energy scales, based on electroweak interactions. Through the application of the Ising model, the running point of the elementary charge e at high energy scales is determined, and Coulomb’s law is actually derived from the Yukawa potential. Theoretically, based on S. Weinberg’s electroweak interaction theory, this study unifies the strong and electromagnetic forces by representing them with rYuka, and further advances the reconstruction of the SU(3)C×SU(1)L×U(1)EMframework on the basis of electroweak interaction concepts. In fact, the cosmic fundamental forces can interchange at the mass gap, defined as the Yukawa turning phase at rYuka ≃1.9404 fm, with the SU(3)Diag structural constant fijk on glueballs calculated, estimating a spectrum mass gap of ∆0 > 0.

Multi-scale Modeling and Finite Element Analyses of Thermal Conductivity of 3D C/SiC Composites Fabricating by Flexible-Oriented Woven Process

Thermal conductivity is one of the most significant criterion of three-dimensional carbon fiber-reinforced SiC matrix composites(3D C/SiC).Represent volume element(RVE)models of microscale,void/matrix and mesoscale proposed in this work are used to simulate the thermal conductivity behaviors of the 3D C/SiC composites.An entirely new process is introduced to weave the preform with three-dimensional orthogonal architecture.The 3D steady-state analysis step is created for assessing the thermal conductivity behaviors of the composites by applying periodic temperature boundary conditions.Three RVE models of cuboid,hexagonal and fiber random distribution are respectively developed to comparatively study the influence of fiber package pattern on the thermal conductivities at the microscale.Besides,the effect of void morphology on the thermal conductivity of the matrix is analyzed by the void/matrix models.The prediction results at the mesoscale correspond closely to the experimental values.The effect of the porosities and fiber volume fractions on the thermal conductivities is also taken into consideration.The multi-scale models mentioned in this paper can be used to predict the thermal conductivity behaviors of other composites with complex structures.

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.

The construction and practice of humanistic care teaching model based on 5C care theory

Objective:To construct a scientific and feasible teaching mode based on 5C caring theory and evaluate it,so as to provide a reference basis for future study about nursing humanistic quality education.Methods:Based on the 5C caring theory,the teaching design and teaching content were revising and implementing in the intervention group.Before and after the implementation of the course,a questionnaire survey was conducted using the Caring Ability Inventory(CAI).The results of the surveys were collected,and the data were statistically analysis using SPSS.Results:After the implementation of the course,the cognitive dimension,patience dimension,and humanistic caring ability scores of the nursing students in the intervention group improved compared with those before the implementation of the course(P<0.05).There were no significant difference in the control group(P>0.05).Conclusion:The humanistic caring teaching model based on 5C caring theory has a positive effect on improving nursing students'humanistic caring ability.In the future nursing teaching,the modules with the characteristics of humanistic caring ability can be increased,and carry out the educational reform throughout the humanistic caring ability.Actively guiding nursing students to establish the awareness of humanistic caring,so as to lay a solid foundation for high-quality clinical nursing work.

妊娠糖尿病患者蛋白C、蛋白S和抗凝血酶Ⅲ水平及其与孕周的关系

目的探讨妊娠糖尿病(GDM)患者蛋白C(PC)、蛋白S(PS)和抗凝血酶Ⅲ(ATⅢ)水平及其与孕周的关系。方法选择2019年1月至2023年3月在医院就诊的232例GDM孕妇作为观察组,同时随机选取同期在医院进行孕检的268例正常孕妇作为对照组,比较两组一般资料和PC、PS和ATⅢ水平;按孕周将观察组和对照组分为孕中期和孕晚期,分别比较孕中期和孕晚期观察组和对照组PC、PS和ATⅢ水平。通过相关性分析,分析PC、PS和ATⅢ水平与孕周的相关性。结果与对照组相比,观察组PS和PC水平降低(P<0.05),但ATⅢ水平差异无统计学意义(P>0.05)。GDM患者PC和ATⅢ水平与孕周呈负相关(r=-0.156、-0.134,P<0.05)。结论GDM患者PS和PC水平降低,且随孕周增大,PC、PS和ATⅢ水平降低,应尽早进行干预,以减少血栓形成的风险。

基于C/S架构和物联网技术的可移动医疗设备共享调配系统的设计与应用

目的 设计一个可移动医疗设备高效管理与临床科室共享调配相结合的医疗设备共享管理平台,实现可移动医疗设备使用的全过程管理。方法 基于C/S架构,利用物联网技术优化整合现有医疗设备大数据资源,结合医院需求,构建可移动医疗设备共享调配系统,实现医疗设备共享管理、预约借用、统计分析等核心功能。通过比较系统上线前后呼吸机调配次数、平均调配时间、呼吸机使用率、单台呼吸机日均收入4个指标,分析系统应用效果。结果 系统上线后,呼吸机调配次数明显增加、平均调配时间明显降低,呼吸机使用率、单台呼吸机日均收入明显升高,且差异均有统计学意义(P﹤0.05),表明系统对提高呼吸机调配效率与使用效率有促进作用。结论 可移动医疗设备共享调配系统优化了医院设备管理流程,实现了医疗资源的统一调配,有效满足临床紧急抢救时医疗设备调配使用的相关需求,提高了医疗设备周转率以及设备管理人员的工作效率,有助于医院节约人员成本、降低采购费用,为医院管理者制定相关决策提供数据支撑。

NOTCH3基因C260S位点突变导致CADASIL的临床和影像学特征分析

目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。

基于STC12C5A60S2单片机显示模块的实验研究

以常用的STC12C5A60S2单片机为主控芯片,以实验室单片机平台为载体,分别对数码管、LCD1602、LCD12864、OLED以及TFT五种显示屏进行DS18B20温度传感器采集与显示实验。实验测试结果表明五种显示模块均能有效采集并显示当前温度值,对比分析各种显示模块的性能,为不同应用场景下的显示需求提供了参考和借鉴,具有重要的实际应用价值。

纳米C-S-H/PCE对蒸养UHPC力学性能增强机理研究

目前超高性能混凝土(UHPC)制品的力学性能有待进一步提升,采用纳米C-S-H/PCE对UHPC进行增强在理论上是一种可行的技术途径。本文研究了蒸养条件下掺入以聚羧酸(PCE)为分散剂的纳米水化硅酸钙(C-S-H/PCE)对UHPC力学性能的影响,通过测试水化热、水化产物、微观形貌和孔结构等对其机理进行了分析。结果表明,掺入3.0%(质量分数)纳米C-S-H/PCE可以显著提高蒸养UHPC的抗压强度和抗折强度。掺入纳米C-S-H/PCE可以促进UHPC的早期水化,生成更多的水化硅酸钙(C-S-H)凝胶,使水化放热温峰增高,并缩短达到水化温峰的时间。掺入纳米C-S-H/PCE可有效改善蒸养UHPC的孔结构,在掺量为3.0%(质量分数)时总孔隙率最小,有害孔比例最低。该研究可为纳米C-S-H/PCE在蒸养UHPC中的应用提供参考。

基于STC12C5A60S2的温湿度控制系统设计

文章针对环境温湿度对纺织生产影响很大的情况,设计温湿度控制系统。系统采用STC12C5A60S2为控制核心,由DHT11进行数据采集,并且采用直观的1602LCD数字显示模块,以实现温度和湿度实时显示,高温时启动外部负载降温,低温时外部负载停止工作的控制,以将温湿度控制在一定的范围内,可以帮助纺织厂生产区域控制环境温湿度,确保纺织厂的温湿度符合要求。

基于剩余电流和不平衡电流突变向量比的TN-C-S系统漏电故障检测方法

TN-C-S系统在我国应用广泛,但由于固有剩余电流大,无法区分负荷投切和故障引起的剩余电流变化,漏电总保和中保无法投运,存在安全隐患。针对该问题,提出一种基于剩余电流和不平衡电流突变量之比的漏电故障保护方法。首先,分析剩余电流回路,剩余电流和不平衡电流突变量之比在单相接地故障发生时刻突变,在负荷投切时不变。其次,基于中性线阻抗和接地阻抗不会发生突变的特征,计算故障电流突变量幅值,以故障电流突变量幅值越限作为故障判别依据,实现漏电故障检测。仿真及试验证明,所提方法可有效区分负荷投切和漏电故障,实现大幅值固有剩余电流下的漏电故障检测,在单支路和多支路系统中的检测灵敏度分别为70、150 mA,满足TN-C-S系统多级漏电保护的灵敏度要求。

10℃条件下纳米C-S-H掺量对水泥早期水化的影响

目的探究10℃条件下不同掺量纳米C-S-H对水泥早期水化进程及强度发展的影响,并分析其早强剂作用机理。方法通过溶液共沉淀法制备纳米C-S-H悬浮液,将其掺入到普通硅酸盐水泥中,在10℃条件下进行养护,分析其对水泥凝结时间、抗折强度、抗压强度的影响;通过XRD、TG等检测手段分析水泥的水化进程及对水化产物的影响。结果掺入0.05%纳米C-S-H,可使水泥初凝时间缩短9.9%,终凝时间缩短10.4%;24 h时抗折强度和抗压强度分别提高了34%和33.5%。纳米C-S-H的掺入造成水泥3 d抗折强度略有降低。水化产物中Ca(OH)2质量分数在12 h、16 h和24 h时较参比样分别提高了17.6%、21.3%和29.6%。结论在10℃条件下,纳米C-S-H的加入能够有效促进C 3S和C 2S的水化过程,形成更多的水化产物,从而缩短水泥凝结时间,提高24 h内水泥砂浆强度,28 d强度没有显著降低。

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。

补体C1s对食管鳞状细胞癌生物学行为的影响

目的:探究补体分子C1s对食管鳞状细胞癌(ESCC)细胞增殖、迁移、黏附以及裸鼠移植瘤生长的影响。方法:利用NCBI-GEO数据库分析ESCC组织和癌旁正常组织(ANTs)中C1S mRNA的表达;采用RT-qPCR和Western blot检测ESCC细胞系中C1s的表达;利用C1s小干扰RNA(siRNA)、C1s短发夹RNA(shRNA)或C1s过表达慢病毒对ESCC细胞进行C1s的敲低或过表达,CCK-8法检测细胞增殖,细胞划痕实验检测细胞迁移,细胞-基质黏附实验检测细胞黏附能力;Western blot检测基质金属蛋白酶MMP1和MMP13表达;裸鼠皮下成瘤实验检测C1s对裸鼠移植瘤生长的影响,免疫组织化学法检测移植瘤中CD34表达,分析肿瘤微血管的形成。结果:ESCC组织中C1S mRNA表达明显高于ANTs,敲低C1s可明显抑制ESCC细胞的增殖、迁移、细胞-基质黏附以及裸鼠移植瘤的生长,而过表达C1S则具有相反的效果;C1s敲低的ESCC细胞TE-1中MMP1和MMP13的表达降低;与对照组相比,C1s过表达组移植瘤中的微血管更加丰富。结论:C1s在ESCC组织中显著上调,并促进ESCC细胞的增殖、迁移、细胞-基质黏附以及裸鼠移植瘤的生长。C1s可能在ESCC发生发展中发挥重要作用。

感应加热温度对滚珠丝杠用S55C钢微观组织及力学性能的影响

为了优化感应淬火工艺参数,改善滚珠丝杠表面硬度和力学性能,研究了滚珠丝杠用S55C钢的感应淬火工艺.利用自行设计的感应加热工装对滚珠丝杠用S55C钢试样进行感应淬火处理,使用光学显微镜和扫描电子显微镜进行微观结构表征,并采用拉伸试验、金相实验和显微硬度测试,分析了感应加热温度对试样的微观组织、显微硬度和断口形貌等方面的影响.结果表明:油冷时,当试样加热至960℃左右,微观组织为均匀细小马氏体,维氏硬度约为750,抗拉强度约为1200 MPa;水冷时,当试样加热至860℃左右,微观组织也为均匀细小马氏体,维氏硬度约为800,抗拉强度约为780 MPa;油冷试样和水冷试样在室温拉伸时所展现的断裂方式均为脆性断裂,油冷试样多表现出解理断裂特征,而水冷试样沿晶断裂特征更明显,并出现明显的冰糖状断裂形貌.该研究结果可为滚珠丝杠用S55C钢感应淬火工艺的设计提供理论依据和技术指导.

血清CysC、α-Syn联合MRI对帕金森病病情评估及诊断的意义

目的 探讨血清胱抑素C(CysC)、α-突触核蛋白(α-Syn)联合磁共振成像(MRI)对帕金森病(PD)病情评估及诊断的意义。方法 将2019年4月至2021年4月于河北省沧州中西医结合医院(下称该院)治疗的PD患者87例纳入研究作为PD组。根据Hoehn-Yahr(H-Y)分期,将PD患者分为Ⅰ~Ⅱ期13例,Ⅲ~Ⅳ期45例,Ⅴ期29例。另外,选取同期于该院进行体检的健康志愿者87例作为对照组。比较各组血清CysC、α-Syn水平,分析血清CysC、α-Syn联合MRI对PD的诊断效能。结果 PD组血清CysC、α-Syn水平均高于对照组,差异有统计学意义(P<0.05);血清CysC、α-Syn水平随着H-Y分期递增升高(P<0.05)。PD组MRI各相位值与对照组比较,黑质致密带、苍白球、壳核、尾状核相位值均降低(P<0.05);不同H-Y分期的PD患者黑质致密带、苍白球、壳核相位值比较,差异均有统计学意义(P<0.05)。CysC、α-Syn单独诊断PD的AUC分别为0.786、0.767,灵敏度分别为58.62%、64.37%,特异度分别为88.51%、87.36%;与MRI、血清CysC、α-Syn单独诊断相比,三项联合诊断PD的灵敏度和准确度较高同,差异有统计学意义(P<0.05)。结论 血清CysC、α-Syn联合MRI对PD诊断效能较高,能为评估PD病情严重程度和早期诊断提供依据。