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.

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.

Evaluating the role of large language models in inflammatory bowel disease patient information

This letter evaluates the article by Gravina et al on ChatGPT’s potential in providing medical information for inflammatory bowel disease patients.While promising,it highlights the need for advanced techniques like reasoning+action and retrieval-augmented generation to improve accuracy and reliability.Emphasizing that simple question and answer testing is insufficient,it calls for more nuanced evaluation methods to truly gauge large language models’capabilities in clinical applications.

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.

A Biogas Production Model from the Combination of Pig Manure and Cow Dung in N’Zérékoré City, Republic of Guine

This present research work focuses on the valorization of pig droppings for production of biogas in mono digestion and co-digestion with proportions of cow dung from the urban commune of N’Zérékoré. It was carried out in December 2020 in the Physics laboratory of the University of N’Zérékoré. The anaerobic digestion process took 25 days in an almost constant ambient temperature of 25˚C. Five digesters were loaded on 12/06/2020, two of which with 1 kg of pig dung and 1 kg of cow dung both in mono-digestion. The 3 other digesters in co-digestion with different proportions of pig manure and cow dung. The substrate in each digester is diluted in 2 liters of water, with a proportion of (1/2). The main results obtained are: 1) the evolution of the temperature and pH during digestion process, 2) the average biogas productions 0.61 liters for (D1);1.20 liter for (D2);1.65 liter for (D3);1.51 liter for (D4) and 1.31 liter for (D5). The cumulative amounts of biogas are respectively: D1 (7.95 liters), D2 (15.60 liters), D3 (21.50 liters), D4 (19.65 liters) and D5 (17.05 liters). The total cumulative production is 81.75 liters at the end of the process. The originality of this research work is that the proposed model examines the relation between the daily biogas production and the variation of temperature, pH and pressure. The combustibility test showed the biogas produced during the first week was no combustible (contains less than 50% methane). Combustion started from the biogas produced from the 15th day and it is from the 20th day that a significant amount of stable yellow/blue flame was observed. The results of this study show the combination of pig manure and cow dung presents advantages for optimal biogas production.

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.

R-Factor Analysis of Data Based on Population Models Comprising R- and Q-Factors Leads to Biased Loading Estimates

Effects of performing an R-factor analysis of observed variables based on population models comprising R- and Q-factors were investigated. Although R-factor analysis of data based on a population model comprising R- and Q-factors is possible, this may lead to model error. Accordingly, loading estimates resulting from R-factor analysis of sample data drawn from a population based on a combination of R- and Q-factors will be biased. It was shown in a simulation study that a large amount of Q-factor variance induces an increase in the variation of R-factor loading estimates beyond the chance level. Tests of the multivariate kurtosis of observed variables are proposed as an indicator of possible Q-factor variance in observed variables as a prerequisite for R-factor analysis.

基于S-R和分解定理的二维几何非线性问题的虚单元法求解

应变-旋转(Strain-Rotation,S-R)和分解定理为分析几何非线性问题提供了合理可靠的理论基础,但用有限元求解时会遇到大变形发生后的网格畸变问题。近年提出的虚单元法(Virtual element method,VEM)适用于一般的多边形网格,因此,该文尝试使用一阶虚单元求解基于S-R和分解定理的二维几何非线性问题,以克服网格畸变的影响。基于重新定义的多项式位移空间基函数,推演获得一阶虚单元分析线弹性力学问题时允许位移空间向多项式位移空间的投影表达式;按照虚单元法双线性格式的计算规则,分析处理基于更新拖带坐标法和势能率原理的增量变分方程;进而建立离散系统方程及其矩阵表达形式,并编制MATLAB求解程序;采用常规多边形网格和畸变网格,应用该文算法分析均布荷载下的悬臂梁和均匀内压下的厚壁圆筒变形。结果与已有文献和ANSYS软件的对比表明:该文算法在两种网格中均可有效执行且具备足够数值精度。总体该文算法为基于S-R和分解定理的二维几何非线性问题求解提供了一种鲁棒方法。

Ⅰ导联R/(R+S)对胸前V3导联移行流出道室性心律失常起源部位的鉴别价值

目的:探索鉴别胸前V3导联移行流出道室性心律失常(OT-VA)起源部位的体表心电图指标。方法:连续选择2017年1月至2022年8月行导管射频消融术的胸前V3导联移行OT-VA患者65例。比较左室流出道起源组(LVOT组)和右室流出道起源组(RVOT组)室性心律失常发作时体表心电图QRS波振幅及相关指标的差异,选择差异有统计学意义的指标,绘制ROC曲线评价所选取指标鉴别OT-VA起源部位的效能。结果:LVOT组11例,RVOT组54例,两组间差异有统计学意义且ROC曲线下面积(AUC)最大的指标为Ⅰ导联R波/(R+S)波振幅比[R/(R+S)],其鉴别OT-VA起源部位的AUC(95%CI)为0.949(0.894~1.000),截断值为0.50。Ⅰ导联R/(R+S)<0.50诊断胸前V3导联移行LVOT起源OT-VA的敏感度、特异度和准确度分别为0.909、0.944和0.938。结论:Ⅰ导联R/(R+S)<0.50可准确鉴别LVOT起源的胸前V3导联移行OT-VA。

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。

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。

基于Mask R-CNN的电力关键设备运行状态检测

为判断电力关键设备两端负载电压与干路总电压之间的数值关系,提出基于Mask R-CNN的电力关键设备运行状态检测方法。在Mask R-CNN网络结构中,判断电量信号的时域范围与频域范围。然后根据负荷阻抗特征计算交流参数的取值结果,再联合已获取的电信号参量,求解连续相关函数,从而检测电力关键设备运行状态。实验过程中,设备两端负载电压、内阻消耗电压之和与干路总电压之间的差值未超过1.5 V,说明该方法能够证明电力关键设备两端负载电压、内阻消耗电压之和等于干路总电压数值的猜想成立,可以根据该验证检测电力关键设备运行状态是否正常。

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.

R.S.托马斯诗歌中的反田园书写

R.S.托马斯的诗歌展现了威尔士乡村一系列反田园特质,包括几乎绝望的风景、花园里的机器和自然界弱肉强食的暴力法则。这种现实主义的反田园书写反映了托马斯的民族主义情结、反现代主义和生态主义的立场。通过探讨田园与反田园的含义,分析托马斯诗歌中的反田园书写及其现实关怀,有助于挖掘他积极的入世态度和道德情怀。

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。

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

Artificial intelligence is increasingly entering everyday healthcare.Large language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM tools.The hype generated by such systems may lead to unweighted patient trust in these systems.Therefore,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for patients.This review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists.From the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases.Further studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

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.

(1R,2S)-2-氟环丙胺对甲苯磺酸盐合成工艺的改进

研究了(1R,2S)-2-氟环丙胺对甲苯磺酸盐的合成工艺。以丁二烯为原料,经过成环、氧化、还原、拆分等反应,设计合成(1S,2S)-2-氟环丙甲酸,通过考察与优化确定了最佳反应条件;进一步制得目标产物(1R,2S)-2-氟环丙胺对甲苯磺酸盐,产物收率达到75%。