MicroRNAs在皮肤生物学中的研究进展

microRNAs(miRNAs)是内源性转录后非编码小RNA分子,定向作用于靶基因,在细胞分化、组织发育等多个过程中发挥作用.皮肤是人类和动物身体最大的器官系统,miRNAs在动物皮肤形态发生和维持正常的生理生态功能等方面发挥重要作用.主要从miRNAs在皮肤形态发生、皮肤癌、皮肤伤口创伤愈合、色素形成等方面入手,对近期研究进展进行简要阐述和总结,为miRNAs在皮肤生物学研究上提供帮助.     

microRNAs家族间负关联模式挖掘

microRNAs(miRNAs)广泛地存在于动植物的细胞中,它的前体具有发夹结构,并且具有很好的保守性.miRNAs在生物体内对细胞的生长、发育、死亡和病变起着重要作用.研究miRNAs家族间在生物体内的调控关系,对miRNAs在生物组织中的表达进行关联分析和对miRNAs成熟序列、种子区域以及二级结构数据进行相似性比较,从而了解miRNAs家族对生物体的调节机制.为了识别具有高相关性的miRNAs家族负关联模式,引入相关系数来改进传统的挖掘频繁项集算法和用互信息来衡量miRNAs家族间的交互性.     

影响口腔癌发生潜在MicroRNAs的生物信息学分析

为获得口腔癌组织和正常组织之间差异表达的miRNAs,从分子水平研究相关的miRNAs在肿瘤发生发展中的作用,从GEO数据库筛选并下载口腔癌及正常组织的基因芯片,运用GEO2R工具分析筛选口腔癌与正常组织间的差异表达miRNAs. 采用FunRich软件对将所得差异miRNAs进行GO功能注释、KEGG信号通路分析. 通过对GSE124566和GSE113956两个芯片数据进行分析,分别筛选得到109、1 079个差异表达miRNAs,分别包括41、673个上调基因和68、406个下调基因,筛选得到共同差异表达miRNAs有30个,其中上调16个,参与的生物过程主要有细胞间通讯等,细胞成分主要有细胞核等,分子功能主要有转录因子活性等;下调14个,参与的生物过程主要有信号转导等,细胞成分主要有细胞质等,分子功能主要有转录因子活性等. 通过对口腔癌芯片数据的生物信息学分析,发现30个差异表达miRNAs是口腔癌发生、发展的重要miRNAs,囊泡介导的转运,核苷酸的代谢等过程. 最后预测出了13 796个靶基因,并通过PPI互作分析筛选出了联系最紧密的10个靶基因.     

疾病相关miRNAs识别方法研究进展

miRNAs是一类内源性短序列非编码RNAs小分子,广泛参与细胞的增殖、分化、凋亡等生物学过程.miRNAs的异常表达与包括肿瘤在内的多种复杂疾病的发生、发展有着密切的关系,筛选与疾病相关的miRNAs,对于药物靶点的发现及新型药物的开发,具有十分重要的作用.笔者拟通过逐步递进的方式,从miRNA靶基因预测、miRNA生物功能作用机制、疾病相关miRNAs计算筛选方法、miRNA小分子药物多个方面,综述疾病相关miRNAs研究进展,为推进miRNA在临床医学中的应用提供参考.     

探究CUL4B在结直肠癌患者来源的肿瘤类器官中调控miRNAs

目的 探究CUL4B在肿瘤患者来源的结直肠癌肿瘤类器官中调控miRNAs。方法 利用干扰CUL4B的和其对照的PDOs样本,进行miRNA-seq,对差异miRNAs的靶基因进行KEGG和GO等分析。利用TargetScan和miRDB 2个数据库分别预测可能受CUL4B调控的并且评分≥85分的miRNAs,结合miRNA-seq差异miRNAs进行韦恩分析。结果 miRNA-seq结果显示共有41个差异miRNAs。TargetScan和miRDB两个数据库和测序数据韦恩分析发现miR495-3p、miR381-3p和miR148b-5p 3个共同交集的miRNAs。KEGG结果显示代谢通路富集的基因个数最多,溶酶体富集基因Q值最小。GO分析结果显示单有机体过程、蛋白质结合和细胞质富集基因最多。流式细胞仪检测发现干扰CUL4B的表达并不影响PDOs的细胞周期。结论 CUL4B可能是通过代谢通路和溶酶体2个信号通路调控miR495-3p、miR381-3p和miR148b-5p。     

前列腺癌的生物标记物——外分泌miRNAs

miRNAs是一类非编码RNAs,可以调节基因表达。现发现miRNAs的表达与癌症发生相关,可以作为一种癌症的生物标记物。在胞外液中miRNAs以不同形式存在:miRNAs与Ago2蛋白结合后进入细胞外囊泡中,或者进入高密度脂蛋白分子中。这些miRNAs被认为是潜在的,非入侵性的疾病诊断和检查工具。在本文中,我们主要讨论胞外miRNAs的生物学功能,以及这些胞外囊泡中miRNAs作为前列腺癌生物标记物的潜在作用。     

miRNAs基因的结构保守模式挖掘

miRNA前体（pre-miRNAs）是产生成熟miRNAs的基因表达产物,能够形成较为稳定的茎—环（stem-loop）结构.为了深入研究miRNAs,对miRNAs前体的二级结构建模,并采用关联规则识别miRNAs基因在进化过程中的结构模式.通过分析产生的结构—类别关系（structure-category relationships）来探索miRNAs的功能特征和调节机制.为了获得较好的实验结果,改进传统的关联规则挖掘算法,应用支持度约束和频繁项集的聚类来优化数据挖掘结果.     

基于序列结构的miRNAs的聚类分析

microRNAs(miRNAs)是一类高度保守的序列片段,能调控生物体的生长发育。至今对它的聚类研究,还处在基于传统遗传模型的分析阶段。本文根据miRNAs本身的结构特点,提出了一种基于序列结构的聚类分析算法。该算法通过借鉴组合数学中随机排列及稀疏矩阵的思想,利用序列的各个组成成分的相似性来表征miRNAs序列间的距离。本算法不仅大大减少了人为因素的影响,还有效的反映成熟miRNAs间在结构上的关联性,为进一步研究miRNAs的功能提供了便利。     

不同运动强度对急性心肌梗死大鼠心功能的影响及循环miRNAs差异表达

研究不同运动强度对急性心肌梗死大鼠心功能的影响, 分析循环微小RNA(microRNAs, miRNAs)的差异表达与靶基因及基因功能. 制作急性心肌梗死大鼠模型40只,分为4组, 每组10只, 分别为假手术组、单纯心肌梗死组、中等强度持续运动(continuous moderate training, CMT)组和间歇高强度运动(high intensity interval training, HIT)组, CMT组和HIT组大鼠接受运动治疗8周, 用超声心动图评估心功能, 用基因芯片技术测定4组大鼠模型循环miRNAs差异表达, 用生物信息学技术分析不同运动强度下循环miRNAs相关靶基因及基因功能. CMT组和HIT组的治疗显著改善了心肌梗死大鼠心功能和运动耐量, HIT组显著优于CMT组. 单纯心肌梗死组与假手术组相比, 明显上调的循环miRNAs有14个, 明显下调的循环miRNAs有4个. 与单纯心肌梗死组相比, CMT组明显上调的循环miRNAs有11个, 明显下调的循环miRNAs有2个; HIT组明显上调的循环miRNAs有53个, 明显下调的关键miRNAs有41个. 与假手术组相比, 单纯心肌梗死组心肌相关循环miRNAs的差异表达有miR-26a-5p, miR-92a-3p和miR-378a-3p; 与单纯心肌梗死组相比, CMT组有miR-92a-3p, HIT组有miR-34c-3p, miR-23a-3p, miR-98-3p, miR-208a-5p和miR-92-3p. 高强度间歇运动对心肌梗死大鼠心功能和运动耐量的改善作用优于中等强度持续运动, 其循环miRNAs及心肌相关循环miRNAs的差异表达数量明显高于中等强度持续运动, 循环miRNAs差异表达有望作为运动强度和运动效果判断的分子生物学标志物.     

miRNAs在不同物种进化中序列保守性的研究

miRNAs在不同物种的进化中存在保守性,不仅单独在动物或是植物中存在保守性,而且在动植物之间也同样存在．本研究在人和动物的不同组织中克隆到了同源性很高的序列,将所得结果与已发表的成熟的miRNAs比对,发现克隆到的序列与植物中miRNA319家族的相似性较高,并且保守区靠近其5’端,推测新miRNAs可能与miRNA319扮演相似的角色,而这些序列的保守性跨越不同进化阶段的物种,也为miRNAs广泛的保守性增加新的证据,显示miRNAs在物种进化过程中发挥着重要的功能．     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Features of Women's language

Language is a means of verbal communication. People use language to communicate with each other. In the society, no two speakers are exactly alike in the way of speaking. Some differences are due to age, gender, statue and personality. Above all, gender is one of the obvious reasons. The writer of this paper tries to describe the features of women＇s language from these perspectives： pronunciation, intonation, diction, subjects, grammar and discourse. From the discussion of the features of women＇s language, more attention should be paid to language use in social context. What＇s more, the linguistic phenomena in a speaking community can be understood more thoroughly.     

An Analysis of Catherine＇s Character——Wuthering Heights

Wuthering Heights, Emily Bronte＇s only novel, was published in December of 1847 under the pseudonym Ellis Bell. The book did not gain immediate success, but it is now thought one of the finest novels in the English language. Catherine is the key character of this masterpiece, because everybody and everything center on her though she had a short life. We can understand this masterpiece better if we know Catherine well.     

Lower Paleozoic oil relationships within Williston Basin, Canada

The Williston Basin is a significant petroleum province, containing oil production zones that include the Middle Cambrian to Lower Ordovician, Upper Ordovician, Middle Devonian, Upper Devonian and Mississippian and within the Jurassic and Cretaceous. The oils of the Williston Basin exhibit a wide range of geochemical characteristics defined as "oil families", although the geochemical signature of the Cambrian Deadwood Formation and Lower Ordovician Winnipeg reservoired oils does not match any "oil family". Despite their close stratigraphic proximity, it is evident that the oils of the Lower Palaeozoic within the Williston Basin are distinct. This suggests the presence of a new "oil family" within the Williston Basin. Diagnostic geochemical signatures occur in the gasoline range chromatograms, within saturate fraction gas chromatograms and biomarker fingerprints. However, some of the established criteria and cross-plots that are currently used to segregate oils into distinct genetic families within the basin do not always meet with success, particularly when applied to the Lower Palaeozoic oils of the Deadwood and Winnipeg Formation.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

Design and analysis of generic LBS application developing platform

Location based services is promising due to its novel working style and contents.A software platform is proposed to provide application programs of typical location based services and support new applications developing efficiently. The analysis shows that this scheme is easy implemented, low cost and adapt to all kinds of mobile nework system.     

Achieving Unusual States of Matter Under High Pressure

正The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry,rooted in the atomic shell structure.Within compounds,Group I elements,for example,invariably assume the+1 oxidation state,and their chemical properties differ completely from those of the p-block elements.These general rules govern our understanding of chemical structures and reactions.Using first principles calcula-     

Exchange-Correlation and Electronic Excitation Energies from Pairing Matrix Fluctuations

We have developed an adiabatic connection to formulate the ground-state exchange-correlation energy in terms of pairing matrix linear fluctuations.This formulation of the exchange-correlation energy opens a new channel for density functional approximations based on the many-body perturbation theory.We illustrate the potential of such approaches with an approximation based on the particle-particle Random Phase Approximation(pp-RPA).This re-     

Density Functional Theory for the Response of Periodic Systems to Electric Fields Based on the Vector Potential Approach

正The electronic and nuclear(structural/vibrational)response of 1D-3D nanoscale systems to electric fields gives rise to a host of optical,mechanical,spectral,etc.properties that are of high theoretical and applied interest.Due to the computational difficulty of treating such large systems it is convenient to model them as infinite and periodic(at least,in first approximation).The fundamental theoretical/computational problem in doing so is that