Stem cell transplantation for treating stroke:status,trends and development

The developing approaches of thrombolytic therapy, endovascular treatment, neuroprotective therapy, and stem cell therapy have enabled breakthroughs in stroke treatment. In this study, we summarize and analyze trends and progress in stem cell transplantation for stroke treatment by retrieval of literature from Thomson Reuters Web of Science database, the NIH Clinical Trial Planning Grant Program, and Clinical Trials Registration Center in North America. In the last 10 years, there has been an increasing number of published articles on stem cell transplantation for stroke treatment. In particular, research from the USA and China has focused on stem cell transplantation. A total of 2,167 articles addressing stem cell transplantation for stroke treatment from 2004 to 2013 were retrieved from the Thomson Reuters Web of Science database. The ma- jority of these articles were from the USA （854, 39.4%）, with the journal Stroke publishing the most articles （145, 6.7%）. Of the published articles, 143 were funded by the National Institutes of Health （accounting for 6.6% of total publications）, and 91 by the National Natural Science Foundation of China. Between 2013 and 2014, the National Institutes of Health provided finan- cial support （$130 million subsidy） for 329 research projects on stroke therapy using stem cell transplantation. In 2014, 215 new projects were approved, receiving grants of up to $70,440,000. Ninety clinical trials focusing on stem cell transplantation for stroke were registered in the Clinical Trial Registration Center in North America, with 40 trials registered in the USA （ranked first place）. China had the maximum number of registered research or clinical trials （10 projects）.

Maternal and burial environment determine the physical dormancy release in tropical Senna auriculata(Fabaceae) seeds

In tropical ecosystems,species with an impermeable seed coat,i.e.physical dormancy(PY),are large in number and their seed coat is considered to be an adaptive trait for species persistence and colonization.However,only little is known about their mechanisms for breaking dormancy.The objective of this study was to understand the importance of seed maturation site and burial location in determining the PY release of Senna auriculata.Freshly collected seeds of S.auriculata from Vellore and Coimbatore,Tamil Nadu,India,germinated to 11±1.5%and19±2.5%respectively and remaining seeds did not imbibe water,thus had PY.Germination of seeds from both sites following hot-water treatment for 30 s and mechanical scarification increased significantly and seeds were able to germinate at a wide-range of temperatures(5–35℃)both in light and darkness.When incubated at 15/60℃for 3 months,dormancy release for seeds collected from Coimbatore(72%)was greater than seeds matured in Vellore(53%).Following 1 year of burial at three different locations,seeds from Coimbatore germinated to higher percentage than Vellore seeds at all locations.In particular,the higher temperature sites released dormancy to greater extent than the lower temperature site.Our results suggest that summer temperatures(>60℃)prevailing in the tropics provide appropriate cues for breaking PY,but this could be greatly affected by the initial state of seeds and the burial environment.

Seasonal change of circulating leptin associated with testicular activities of the wild ground squirrels(Citellus dauricus)

The purpose of this study was to explore the variations in the circulating leptin concentrations of the wild ground squirrels in relation to seasonal changes in testicular activities.Hematoxylin-eosin staining showed all types of elongated spermatids and spermatogenic cells existed in the testis in April,while the primary spermatocytes and spermatogonia were most advanced stages of germ cells in June.In addition,the primary spermatocytes,secondary spermatocytes,and spermatogonia were most advanced stages of germ cells in September.The highest circulating leptin concentration was consistent with the maximum body weight results from accumulation of adipose tissue in September.The mRNA expression level of leptin receptor(Ob-R)and STAT3 was lowest in June,raised in September,and remained increased in April.Ob-R and STAT3 were stronger staining in the Leydig cells in July.Moreover,the concentrations of testosterone(T)showed the maximum values in April,the minimum values in June,and significant increases in September.Furthermore,it is worth noting that the levels of T increased with the mRNA levels of Ob-R,STAT3,StAR,and testicular steroidogenic enzymes(3β-HSD,P450c17,and P450scc).Moreover,RNA-seq analyses of testis during the different periods showed that a total of 4209 genes were differ-entially expressed genes(DEGs);further analysis revealed that DEGs related with the Jak/STAT pathways and reproduction were altered.Taken together,the results suggested that the leptin regulated testicular function through the Jak/STAT pathways and testicular steroidogenic factor expressions.

A novel sprayable thermosensitive hydrogel coupled with zinc modified metformin promotes the healing of skin wound

A novel sprayable adhesive is established(ZnMet-PF127)by the combination of a thermosensitive hydrogel(Pluronic F127,PF127)and a coordination complex of zinc and metformin(ZnMet).Here we demonstrate that ZnMet-PF127 potently promotes the healing of traumatic skin defect and burn skin injury by promoting cell proliferation,angiogenesis,collagen formation.Furthermore,we find that ZnMet could inhibit reactive oxygen species(ROS)production through activation of autophagy,thereby protecting cell from oxidative stress induced damage and promoting healing of skin wound.ZnMet complex exerts better effects on promoting skin wound healing than ZnCl2 or metformin alone.ZnMet complex also displays excellent antibacterial activity against Staphylococcus aureus or Escherichia coli,which could reduce the incidence of skin wound infections.Collectively,we demonstrate that sprayable PF127 could be used as a new drug delivery system for treatment of skin injury.The advantages of this sprayable system are obvious:(1)It is convenient to use;(2)The hydrogel can cover irregular skin defect sites evenly in a liquid state.In combination with this system,we establish a novel sprayable adhesive(ZnMet-PF127)and demonstrate that it is a potential clinical treatment for traumatic skin defect and burn skin injury.

Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARγ/FABP4 signaling in mice

Osteoporosis(OP)is a systemic skeletal disease that primarily affects the elderly population,which greatly increases the risk of fractures.Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass.Kindlin-2 specific deletion(K2KO)controlled by Adipoq-Cre mice or adipose tissue-targeting AAV(AAV-Rec2-CasRx-sgK2)significantly increases bone mass.Mechanistically,Kindlin-2 promotes peroxisome proliferator-activated receptor gamma(PPARγ)activation and downstream fatty acid binding protein 4(FABP4)expression through stabilizing fatty acid synthase(FAS),and increased FABP4 inhibits insulin expression and decreases bone mass.Kindlin-2 inhibition results in accelerated FAS degradation,decreased PPARγactivation and FABP4 expression,and therefore increased insulin expression and bone mass.Interestingly,we find that FABP4 is increased while insulin is decreased in serum of OP patients.Increased FABP4 expression through PPARγactivation by rosiglitazone reverses the high bone mass phenotype of K2KO mice.Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice.Collectively,our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.

Ferrodifferentiation regulates neurodevelopment via ROS generation

Iron is important for life,and iron deficiency impairs development,but whether the iron level regulates neural differentiation remains elusive.In this study,with iron-regulatory proteins(IRPs)knockout embryonic stem cells(ESCs)that showed severe iron deficiency,we found that the Pax6-and Sox2-positive neuronal precursor cells and Tuj1 fibers in IRP1^(-/-)IRP2^(-/-)ESCs were significantly decreased after inducing neural differentiation.Consistently,in vivo study showed that the knockdown of IRP1 in IRP2^(-/-)fetal mice remarkably affected the differentiation of neuronal precursors and the migration of neurons.These findings suggest that low intracellular iron status significantly inhibits neurodifferentiation.When supplementing IRP1^(-/-)IRP2^(-/-)ESCs with iron,these ESCs could differentiate normally.Further investigations revealed that the underlying mechanism was associated with an increase in reactive oxygen species(ROS)production caused by the substantially low level of iron and the downregulation of iron-sulfur cluster protein ISCU,which,in turn,affected the proliferation and differentiation of stem cells.Thus,the appropriate amount of iron is crucial for maintaining normal neural differentiation that is termed ferrodifferentiation.

城市扶贫整体绩效评估:指标构建与实证研究

1949年后就开展了以'三无人员'为主体的城市扶贫工作。改革开放以来,随着农业人口向城市的快速转移和流动人口市民化的不断推进,城市贫困问题日益成为城市社会治理的重要议题。那么,城市扶贫整体绩效究竟如何呢?本文以广东省为考察对象,从贫困基础、社会救助、养老医疗和就业帮扶四个维度,构建了城市扶贫整体绩效评估的指标体系,进而以广东省城市扶贫为例开展实证研究。研究发现:广东省城市扶贫整体绩效(2005—2015)呈下降态势,但不同维度的绩效表现差异较大;在此基础上,基于十九大报告的最新精神和广东省的扶贫实践,本文提出了城市扶贫整体绩效改进的政策建议。

北京地区四个豹猫亚种群肠道菌群的组成

野生动物的肠道微生物组成受食物资源和遗传属性的影响较大,为了解北京地区小型猫科动物肠道菌群组成特点及其影响因素,本研究通过扩增细菌16S rRNA的V3‒V4高变区进行高通量测序,对云蒙山、云峰山、松山、百花山4个区域的豹猫(Prionailurus bengalensis)亚种群进行肠道菌群组成分析。结果表明,在门水平上,豹猫的肠道优势菌群主要由厚壁菌门(相对多度52.40%)、变形菌门(25.18%)、放线菌门(9.07%)、拟杆菌门(8.17%)和梭杆菌门(4.74%)组成。在属水平上,相对多度最高的前5个属为假单胞菌属(Pseudomonas,13.37%)、布劳特氏菌属(Blautia,11.20%)、梭菌属(Clostridium_sensu_stricto_1,9.10%)、消化梭菌属(Peptoclostridium,8.62%)、乳杆菌属(Lactobacillus,6.08%),共约占总多度的50%。各区域豹猫亚种群的肠道菌群β多样性不存在显著差异,松山区域的ACE指数和Chao 1指数与云蒙山和云峰山存在显著差异。鉴于松山亚种群的遗传结构与其他区域有所不同,而4个区域的气候类型和豹猫食物构成相似性高,推测该亚种群的肠道菌群主要受遗传结构分化的影响,对此还需进一步研究。

Single-cell transcriptome analysis reveals widespread monoallelic gene expression in individual rice mesophyll cells

Monoallelic gene expression refers to the phenomenon that all transcripts of a gene in a cell are expressed from only one of the two alleles in a diploid organism. Although monoallelic gene expression has been occasionally reported with bulk transcriptome analysis in plants, how prevalent it is in individual plant cells remains unknown. Here, we developed a single-cell RNA-seq protocol in rice and investigated allelic expression patterns in mesophyll cells of indica(93-11) and japonica(Nipponbare) inbred lines, as well as their F1 reciprocal hybrids. We observed pervasive monoallelic gene expression in individual mesophyll cells, which could be largely explained by stochastic and independent transcription of two alleles. By contrast, two mechanisms that were proposed previously based on bulk transcriptome analyses, parent-oforigin effects and allelic repression, were not well supported by our data. Furthermore, monoallelically expressed genes exhibited a number of characteristics, such as lower expression levels, narrower H3K4me3/H3K9ac/H3K27me3 peaks, and larger expression divergences between 93-11 and Nipponbare. Taken together, the development of a single-cell RNA-seq protocol in this study offers us an excellent opportunity to investigate the origins and prevalence of monoallelic gene expression in plant cells.

Direct imaging and determination of the crystal structure of six-layered graphdiyne

Since its discovery, the direct imaging and determination of the crystal structure of few-layer graphdiyne has proven difficult because it is too delicate under irradiation by an electron beam. In this work, the crystal structure of a six-layered graphdiyne nanosheet was directly observed by low-voltage transmission electron microscopy （TEM） using low current density. The combined use of high-resolution TEM （HRTEM） simulation, electron energy-loss spectroscopy, and electron diffraction revealed that the as-synthesized nanosheet was crystalline graphdiyne with a thickness of 2.19 nm （corresponding to a thickness of six layers） and showed ABC stacking. Thus, this work provides direct evidence for the existence and crystal structure of few-layer graphdiyne, which is a new type of two-dimensional carbon material complementary to graphene.