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.

Role of cancer stem cell ecosystem on breast cancer metastasis and related mouse models

Breast cancer metastasis is responsible for most breast cancer-related deaths and is influenced by many factors within the tumor ecosystem,including tumor cells and microenvironment.Breast cancer stem cells(BCSCs)constitute a small population of cancer cells with unique characteristics,including their capacity for self-renewal and differentiation.Studies have shown that BCSCs not only drive tumorigenesis but also play a crucial role in promoting metastasis in breast cancer.The tumor microenvironment(TME),composed of stromal cells,immune cells,blood vessel cells,fibroblasts,and microbes in proximity to cancer cells,is increasingly recognized for its crosstalk with BCSCs and role in BCSC survival,growth,and dissemination,thereby influencing metastatic ability.Hence,a thorough understanding of BCSCs and the TME is critical for unraveling the mechanisms underlying breast cancer metastasis.In this review,we summarize current knowledge on the roles of BCSCs and the TME in breast cancer metastasis,as well as the underlying regulatory mechanisms.Furthermore,we provide an overview of relevant mouse models used to study breast cancer metastasis,as well as treatment strategies and clinical trials addressing BCSC-TME interactions during metastasis.Overall,this study provides valuable insights for the development of effective therapeutic strategies to reduce breast cancer metastasis.

Acute liver failure:A systematic review and network meta-analysis of optimal type of stem cells in animal models

BACKGROUND The therapeutic effects of various stem cells in acute liver failure(ALF)have been demonstrated in preclinical studies.However,the specific type of stem cells with the highest therapeutic potential has not been determined.AIM To validate the efficacy of stem cells in ALF model and to identify the most promising stem cells.METHODS A search was conducted on the PubMed,Web of Science,Embase,Scopus,and Cochrane databases from inception to May 3,2022,and updated on November 16,2022 to identify relevant studies.Two independent reviewers performed the literature search,identification,screening,quality assessment,and data extraction.RESULTS A total of 89 animal studies were included in the analysis.The results of traditional meta-analysis showed that stem cell therapy could significantly reduce the serum levels of alanine aminotransferase[weighted mean difference(WMD)=-181.05(-191.71,-170.39)],aspartate aminotransferase[WMD=-309.04(-328.45,-289.63)],tumor necrosis factor-alpha[WMD=-8.75(-9.93,-7.56)],and interleukin-6[WMD=-10.43(-12.11,-8.76)]in animal models of ALF.Further subgroup analysis and network meta-analysis showed that although mesenchymal stem cells are the current research hotspot,the effect of liver stem cells(LSCs)on improving liver function is significantly better than that of the other five types of stem cells.In addition,the ranking results showed that the possibility of LSCs improving liver function ranked first.This fully proves the great therapeutic potential of LSCs,which needs to be paid more attention in the future.CONCLUSION LSCs may have a higher therapeutic potential.Further high-quality animal experiments are needed to explore the most effective stem cells for ALF.

素养本位的STEM教育:理念、目标与实践模式——美国、法国、新加坡比较研究

STEM教育自20世纪90年代诞生之初,就以跨学科整合性作为共同的核心理念。植根于不同文化、哲学、认知论的传统,美国、法国、新加坡三国发展出多元化优势探究系统,并在21世纪核心素养多层次目标的定向下,派生出三维教学、大概念探究性学习、设计思维赋能项目工作三种典型的实践模式。在培养跨学科能力方面,项目化学习和问题化学习作为支撑不同STEM教育实践模式的两大主流教学法,各有优势,也面临不同挑战。三个国家分别用以问题化学习为支架的项目化学习、论证式科学教学、以项目化学习为支架的问题化学习予以回应。基于此,文章初步提出STEM教育的目的—教学法—探究系统三维实践模型。

Phosphorus limitation on CO_(2)fertilization effect in tropical forests informed by a coupled biogeochemical model

Tropical forests store more than half of the world's terrestrial carbon(C)pool and account for one-third of global net primary productivity(NPP).Many terrestrial biosphere models(TBMs)estimate increased productivity in tropical forests throughout the 21st century due to CO_(2)fertilization.However,phosphorus(P)liaitations on vegetation photosynthesis and productivity could significantly reduce the CO_(2)fertilization effect.Here,we used a carbon-nitrogen-phosphorus coupled model(Dynamic Land Ecosystem Model;DLEM-CNP)with heterogeneous maximum carboxylation rates to examine how P limitation has affected C fluxes in tropical forests during1860-2018.Our model results showed that the inclusion of the P processes enhanced model performance in simulating ecosystem productivity.We further compared the simulations from DLEM-CNP,DLEM-CN,and DLEMC and the results showed that the inclusion of P processes reduced the CO_(2)fertilization effect on gross primary production(GPP)by 25%and 45%,and net ecosystem production(NEP)by 28%and 41%,respectively,relative to CN-only and C-on ly models.From the 1860s to the 2010s,the DLEM-CNP estimated that in tropical forests GPP increased by 17%,plant respiration(Ra)increased by 18%,ecosystem respiration(Rh)increased by 13%,NEP increased by 121%per unit area,respectively.Additionally,factorial experiments with DLEM-CNP showed that the enhanced NPP benefiting from the CO_(2) fertilization effect had been offset by 135%due to deforestation from the 1860s to the 2010s.Our study highlights the importance of P limitation on the C cycle and the weakened CO_(2)fertilization effect resulting from P limitation in tropical forests.

“GNSS测量原理与应用”的STEM教学模式探索

在STEM教学模式下剖析了“GNSS测量原理与应用”课程的瓶颈,提出以STEM教育理念为向导的跨学科、跨专业融合测绘知识的课程体系教学新模式。面向“学、赛、研”三位一体教学框架,在协同创新中创建了立体化课程框架,搭建了互联网虚拟仿真实验STEM教学信息化平台,并对该模式进行教学应用,取得较好的教改成效,为测绘类课程的教学模式探索提供实践参考资料。

Modification of streamer-to-leader transition model based on radial thermal expansion in the sphere-plane gap discharge at high altitude

Historically,streamer-to-leader transition studies mainly focused on the rod-plane gap and low altitude analysis,with limited attention paid to the sphere-plane gap at high altitude analysis.In this work,sphere-plane gap discharge tests were carried out under the gap distance of 5 m at the Qinghai Ultra High Voltage(UHV)test base at an altitude of 2200 m.The experiments measured the physical parameters such as the discharge current,electric field intensity and instantaneous optical power.The duration of the dark period and the critical charge of streamer-toleader transition were obtained at high altitude.Based on radial thermal expansion of the streamer stem,we established a modified streamer-to-leader transition model of the sphere-plane gap discharge at high altitude,and calculated the stem temperature,stem radii and the duration of streamer-to-leader transition.Compared with the measured duration of sphere-plane electrode discharge at an altitude of 2200 m,the error rate of the modified model was 0.94%,while the classical model was 6.97%,demonstrating the effectiveness of the modified model.From the comparisons and analysis,several suggestions are proposed to improve the numerical model for further quantitative investigations of the leader inception.

Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal kidney.However,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary filtrate.Therefore,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug screening.In this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease modeling.Additionally,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

中小学STEM教师专业素养模型的理论建构

21世纪的挑战在中小学催生了全新的学习范式,STEM教育是应对的主要路径之一,STEM教师是其中重要的力量,因此有必要构建素养模型为教师的专业发展、专业实践赋能。文章在文献研究和案例研究的基础上,提出中小学STEM教育的总体认知框架,包括跨学科整合性、真实问题驱动、各学科平等性等基本假设,莱斯转换模型、STEM转换模型等参照系,经验学习、具体操作物、多元表征等理论框架和七个特征的概念框架;梳理了专业素养研究的发展脉络和重要概念,提出在情景专业主义视角下构建中小学教师专业素养模型;最后以美国州首席教育官员理事会提出的素养导向的教师核心教学标准模型为蓝本,综合总体STEM教育认知框架和专业素养理论,构建了包含学习者和学习、内容知识、教学实践、专业责任四大素养,12个亚素养的中小学STEM教师专业素养模型,并细化了指标体系。

CIPP视域下我国中小学校STEM教育实施评价体系构建研究

STEM教育作为新兴的人才培养模式,注重学生批判性思维、逻辑思维以及问题解决能力的培养,我国一些中小学采用了STEM教育的培养方式,但在评价阶段出现了评价理念功利化、评价导向游离化、评价指标单一化、评价对象消极化等问题。当前,我国缺乏成熟且适用的中小学STEM教育评价体系,阻碍了STEM教育的实施。因此,以中小学校STEM教育质量为评价对象,依据中小学STEM教育评价面临的困境,基于CIPP评估模型,结合综合指标体系的构建原则,将中小学STEM教育评价体系分为5个部分:学校STEM教育需求评估、学校STEM教育投入评估、学校STEM教育实施评估、学校STEM教育成果评估、学校STEM教育增值评估,具体为13个二级指标、36个观察要点,并对中小学STEM教育评价体系的构建和实施提出建议。

基于工程设计的STEM教学培养学生计算思维的研究与实践

STEM课程是培养学生计算思维的重要载体,计算思维则可促成学生在真实情景下多元能力的发展。在新工程教育背景下,本研究提出以工程设计循环组织教学过程、以史密斯框架五要素创建支持学生运用计算思维的STEM教学活动设计框架。并以小学“船模”课程为例,进行具体的活动设计与实施。本研究采用单组前后测实验,通过为期九周的跟踪,同时辅以任务单,探究课程实施对小学生计算思维能力与计算思维实践的影响。结果表明,课程教学对小学生计算思维能力有促进作用;认知网络分析结果表明,课程实施推动了学生计算思维实践,船模制作完成后,学生的算法思维有明显发展且各要素连接更紧密。

中职电工实训STEM教育模式应用研究

该文以中职电工实训课程为例,探讨STEM教育模式在中等职业学校电工专业实训中的应用优势与构建模式,通过将科学、技术、工程和数学融入电工实训课程,旨在提升学生问题解决能力,同时有助于培养学生的创新思维和团队协作能力。研究结果旨在提供STEM教育模式在中等职业学校电工实训中的应用方法,未来研究可以进一步深入探讨如何更好地整合STEM元素到电工实训中,并评估其长期影响,以不断提升中职学生的综合能力和就业竞争力。

试论物理教学渗透STEM教育模式的途径

STEM教育模式创造性地将科学、技术、工程、数学领域的内容与学科教学相结合,扭转了课堂教学中学生被动学习知识的局面,鼓励学生在极具综合性的问题中主动探索未知。教师应在初中物理教学中挖掘教材内容、创设问题情境、引入游戏教学、创新实验教学、推动课后服务、融合多科知识、联系实际生活,从而在知识讲解、自主探索、寓教于乐、动手操作、专题活动、学科整合、知识应用中合理渗透STEM教育模式,以有效提升学生的学习主动性与实践操作能力。

Study on Desiccation and Collection Models for Banana Stems

In this study, 8 kinds of desiccation models and 3 kinds of collection models were studied for banana stems. The results showed that the crushing-com- pression-air drying processing model showed the best desiccation effect for banana stems. Under this desiccation model, the moisture content was reduced from 90.5% to 19.93% with weight reduced by 75.2%; after 3 to 6 months of storage, the mois- ture content was still remained within 17%-20%, and the volume was decreased to 30%-40% of the original volume of fresh banana stems. This desiccation model made banana stems basically meet the requirements by drying storage. The plant- cutting down-crushing-compression-transportation-desiccation-storage production model was initially developed for desiccation and collection of banana stems, which would lay a certain foundation for the utilization of banana stem resource by enterprises.

“新医科”视角下STEM教育对实验针灸学教学模式与人才培养的启发与思考

在贯彻党的二十大精神和教育部“新医科”建设的大背景下,结合当前中医药现代化与中医院校高质量发展的要求,通过借鉴STEM教育模式与人才培养,以实验针灸学创新教学实验课程为例,分析目前实验针灸学实验教学的现状,提出“新医科”视角下实验针灸学实验课程的教学设计、学习方式及人才培养,思考以学生培养为中心,以学科交叉为目标,以创新实践为导向,以探索性实验设计为全过程的实验课程教学方案,并将创新思维应用到实验教学中,着力培养针灸复合型人才,为全面推行中医药现代化建设作出贡献。

Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.

Stem cell therapy for Parkinson’s disease: safety and modeling

For decades,clinicians have developed medications and therapies to alleviate the symptoms of Parkinson’s disease,but no treatment currently can slow or even stop the progression of this localized neurodegeneration.Fortunately,sparked by the genetic revolution,stem cell reprogramming research and the advancing capabilities of personalization in medicine enable forward-thinking to unprecedented patient-specific modeling and cell therapies for Parkinson’s disease using induced pluripotent stem cells(iPSCs).In addition to modeling Parkinson’s disease more accurately than chemically-induced animal models,patient-specific stem cell lines can be created,elucidating the effects of genetic susceptibility and sub-populations’differing responses to in vitro treatments.Sourcing cell therapy with iPSC lines provides ethical advantages because these stem cell lines do not require the sacrifice of human zygotes and genetically-specific drug trails can be tested in vitro without lasting damage to patients.In hopes of finally slowing the progression of Parkinson’s disease or re-establishing function,iPSC lines can ultimately be corrected with gene therapy and used as cell sources for neural transplantation for Parkinson’s disease.With relatively localized neural degeneration,similar to spinal column injury,Parkinson’s disease presents a better candidacy for cell therapy when compared to other diffuse degeneration found in Alzheimer’s or Huntington’s Disease.Neurosurgical implantation of pluripotent cells poses the risk of an innate immune response and tumorigenesis.Precautions,therefore,must be taken to ensure cell line quality before transplantation.While cell quality can be quantified using a number of assays,a yielding a high percentage of therapeutically relevant dopaminergic neurons,minimal de novo genetic mutations,and standard chromosomal structure is of the utmost importance.Current techniques focus on iPSCs because they can be matched with donors using human leukocyte antigens,thereby reducing the severity and risk of immune rejection.In August of 2018,researchers in Kyoto,Japan embarked on the first human clinical trial using iPSC cell therapy transplantation for patients with moderate Parkinson’s disease.Transplantation of many cell sources has already proven to reduce Parkinson’s disease symptoms in mouse and primate models.Here we discuss the history and implications for cell therapy for Parkinson’s disease,as well as the necessary safety standards needed for using iPSC transplantation to slow or halt the progression of Parkinson’s disease.

Using induced pluripotent stem cells as a tool for modelling carcinogenesis

Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells(i PSCs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly i PSCs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, i PSCs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate i PSC models for a number of cancers.

Three-dimensional cell culture systems as an in vitro platform for cancer and stem cell modeling

Three-dimensional(3D)culture systems are becoming increasingly popular due to their ability to mimic tissue-like structures more effectively than the monolayer cultures.In cancer and stem cell research,the natural cell characteristics and architectures are closely mimicked by the 3D cell models.Thus,the 3D cell cultures are promising and suitable systems for various proposes,ranging from disease modeling to drug target identification as well as potential therapeutic substances that may transform our lives.This review provides a comprehensive compendium of recent advancements in culturing cells,in particular cancer and stem cells,using 3D culture techniques.The major approaches highlighted here include cell spheroids,hydrogel embedding,bioreactors,scaffolds,and bioprinting.In addition,the progress of employing 3D cell culture systems as a platform for cancer and stem cell research was addressed,and the prominent studies of 3D cell culture systems were discussed.

Platelet-rich plasma enhances adipose-derived stem cell-mediated angiogenesis in a mouse ischemic hindlimb model

AIM To evaluate the angiogenic effect of platelet-rich plasma(PRP)-preconditioned adipose-derived stem cells(ADSCs) both in vitro and in a mouse ischemic hindlimb model.METHODS ADSCs were divided based on culture medium: 2.5% PRP, 5% PRP, 7.5% PRP, and 10% PRP. Cell proliferation rate was analyzed using the MTS assay. The gene expression of CD31, vascular endothelial growth factor, hypoxia-inducible factors, and endothelial cell nitric oxide synthase was analyzed using reverse transcription polymerase chain reaction. Cell markers and structural changes were assessed through immunofluorescence staining and the tube formation assay. Subsequently, we studied the in vivo angiogenic capabilities of ADSCs by a mouse ischemic hindlimb model.RESULTS The proliferation rate of ADSCs was higher in the 2.5%, 5%, and 7.5% PRP groups. The expression of hypoxia-inducible factor, CD31, vascular endothelial growth factor, and endothelial cell nitric oxide synthase in the 5% and 7.5% PRP groups increased. The 5%, 7.5%, and 10% PRP groups showed higher abilities to promote both CD31 and vascular endothelial growth factor production and tubular structure formation in ADSCs. According to laser Doppler perfusion scan, the perfusion ratios of ischemic limb to normal limb were significantly higher in 5% PRP, 7.5% PRP, and human umbilical vein endothelial cells groups compared with the negative control and fetal bovine serum(FBS) groups(0.88 ± 0.08, 0.85 ± 0.07 and 0.81 ± 0.06 for 5%, 7.5% PRP and human umbilical vein endothelial cells compared with 0.42 ± 0.17 and 0.54 ± 0.14 for the negative control and FBS, P < 0.01).CONCLUSION PRP-preconditioned ADSCs presented endothelial cell characteristics in vitro and significantly improved neovascularization in ischemic hindlimbs. The optimal angiogenic effect occurred in 5% PRP-and 7.5% PRPpreconditioned ADSCs.