Gene expression in rat mesenchymal stem cells following treatment with natural cerebrolysin-containing serum Validation of a whole genome microarray technique

BACKGROUND： Natural cerebrolysin （NC）, a Chinese herbal drug for the treatment of Alzheimer＇s disease （AD）, induces mesenchymal stem cell （MSC） differentiation into neuron-like cells, with low toxicity. But the mechanisms involved in NC effects on MSCs remain poorly understood. OBJECTIVE： We used a whole genome microarray technique to further investigate the molecular, genetic, and pharmacodynamic mechanisms of NC on MSC gene expression profiles. DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the First Affiliated Hospital of Shenzhen University, Shenzhen Institute of Integrated Chinese and Western Medicine, China, between September 2006 and October 2008. MATERIALS： NC was provided by Shenzhen Institute of Integrated Chinese and Western Medicine China. It was predominantly composed of Renshen （Radix Ginseng）, Tianma （Rhizoma Gastrodiae） and Yinxingye （Ginkgo Leaf） and prepared by conventional water extractJon technology. Twelve adult, male, New Zealand rabbits were included, six of which underwent intragastric administration of NC extract for 1 month to create NC-containing serum. METHODS： Bone marrow was collected from the tibia and femur of Sprague Dawley rats, aged 6 8 months old. Rat MSCs were isolated and purified by the whole bone marrow adherence method. After in vitro culture, MSCs from passage 4 were treated with NC-containing serum for 48 hours, and total RNA was extracted. Gene expression in MSCs was analyzed using Affymetrix whole genome microarray analysis. MAIN OUTCOME MEASURES： Differentially expressed genes in NC serum-treated MSCs. RESULTS： NC treated MSCs displayed 46 differentially expressed genes, 22 with upregulated expression （fold change 〉 2） and 24 with downregulated expression （fold change 〈 -2）. Differentially expressed genes participated in neuronal growth, differentiation, and function, cell growth, differentiation, proliferation, apoptosis, signal transduction, substance/energy metabolism, ion transport, and immune responses. NC treatment changed levels of transforming growth factor β/ bone morphogenetic proteins, Hedgehog, Bmp, and Wntsignaling pathways, which regulate nerve cell differentiation, development and function, as well as learning and memory; Ras, G protein- coupled receptor signal pathways that are related to cell growth, proliferation, and apoptosis; and mitogen-activated protein kinase kinase kinase signaling cascades. CONCLUSION： NC can regulate gene expression for many signal transduction pathways related to nerve cell differentiation, development and function, learning and memory function, as well as regulation of cell growth, differentiation, proliferation, or apoptosis to mediate the genetic effects of NC treatment on AD.

Changes in gene expression in liver tissue from patients with fulminant hepatitis E

AIM: To study host gene expression and numberof immune cells in liver tissues from patients with fulminant hepatitis E(FH-E).METHODS: Microarray-based expression profiling was done using Illumina Human WG-6_v3_Bead Chip arrays on post-mortem liver tissue from 5 patients with FH-E,and compared with similar tissue from 6 patients with fulminant hepatitis B(FH-B; disease controls) and normal liver tissue from 6 persons.Differential expression was defined as ≥ 2.0-fold change with Benjamini-Hochberg false discovery rate below 0.05 using t-test in liver tissue from FH-B and FH-E,than healthy liver tissue.For some genes that showed differential expression in FH-E,microarray data were validated using quantitative reverse transcription PCR.Differentially expressed gene lists were then subjected to "Gene Ontology" analysis for biological processes,and pathway analysis using Bio Carta database on the DAVID server.In addition,tissue sections were stained for CD4+,CD8+ and CD56+ cells using indirect immunohistochemistry; cells staining positive for each of these markers were counted and compared between groups.RESULTS: Compared to normal livers,those from patients with FH-E and FH-B showed differential expression of 3377 entities(up-regulated 1703,downregulated 1674) and 2572 entities(up 1164,down 1408),respectively.This included 2142(up 896,down 1246) entities that were common between the two sets; most of these belonged to metabolic,hemostatic and complement pathways,which are active in normal livers.Gene expression data from livers of patients with FH-E but not those of FH-B showed activation of several immune response pathways,particularly those involving cytotoxic T cells.The fold-change values of m RNA for selected genes in livers from FH-E than in normal liver tissue determined using quantitative reverse transcription PCR showed excellent concordance with microarray analysis.At immunohistochemistry,CD8+ T cells showed an increase in liver biopsies from both FH-E [median 53.4 per arbitrary unit area(range 31.2-99.9)] and FH-B [median 49.3(19.3-51.0); P = 0.005] compared to control liver tissue [median 6.9(3.1-14.9)].CONCLUSION: FH-E patients show CD8+ T cell infiltration and increased gene expression of cytotoxic T cell pathways in liver,suggesting a possible pathogenetic role for these cells.

Construction of plasmid containing human blood- clotting factor Ⅷ and observation its expression in Cos-7 cells

Factor Ⅷ deficiency or hemophilia A is X-linkedgenetic disorder in human. General treatment of severehemophilia A consists of adiministration of plasma-derived or recombinant clotting factor concentrates. Ithas caused a series of problems, i. e. viral infection andcost too much to use rF Ⅷ. Nowadays, people havedeveloped the retroviral vector and the adcnoviral

Heterogeneity of mature oligodendrocytes in the central nervous system

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.

Heterologous expression facilitates the discovery and characterization of marine microbial natural products

Microbial natural products and their derivatives have been developed as a considerable part of clinical drugs and agricultural chemicals.Marine microbial natural products exhibit diverse chemical structures and bioactivities with substantial potential for the development of novel pharmaceuticals.However,discovering compounds with new skeletons from marine microbes remains challenging.In recent decades,multiple approaches have been de-veloped to discover novel marine microbial natural products,among which heterologous expression has proven to be an effective method.Facilitated by large DNA cloning and comparative metabolomic technologies,a few novel bioactive natural products from marine microorganisms have been identified by the expression of their biosynthetic gene clusters(BGCs)in heterologous hosts.Heterologous expression is advantageous for character-izing gene functions and elucidating the biosynthetic mechanisms of natural products.This review provides an overview of recent progress in heterologous expression-guided discovery,biosynthetic mechanism elucidation,and yield optimization of natural products from marine microorganisms and discusses the future directions of the heterologous expression strategy in facilitating novel natural product exploitation.

Molecular Targets of Combined Natural Antioxidants Against Diabetes in Streptozotocin-induced Diabetic Mice

Natural antioxidants, due to the different chemical structures and their unique biological protection effects on islet cell, have been received much attention in applied chemistry field for developing a new diabetic drug. However, the molecular targets of the islet cell protection have been remained obscure. For investigating molecular targets of combined natural antioxidant’s（CNA） roles in against diabetes, type 1 diabetic mouse model was made by multiple injection of low doses of streptozotocin into C57BL mice. Two combinations of natural antioxidants were orally supplemented to the mice. Blood glucose level, glutathione peroxidase（GSH-Px） and superoxide dismutase （SOD） activities, and malondialdehyde（MDA） contents were measured via biochemical assays. Tumor necrosis factor α（TNF-α）, interferon γ（IFN-γ） and Interleukin-12（IL-12） in CD4＋ Peripheral blood mononuclear cells（PBMC） were evaluated with flow cytometry（FCM）. In situ hybridization（ISH） and immunohistochemistry（IHC） were used to detect insulin gene expression. The results demonstrate both the combinations significantly： increased GSH-px and SOD, but decreased MDA levels in pancreas（p〈0.05―0.01）; up-regulated insulin expression at both mRNA and protein levels in islet cells（p〈0.05―0.01）; down-regulated TNF-α and IL-12 expression in PBMC（p〈0.05―0.01）. Our data suggest that the CAN may regulate multiple key molecular targets related to β cell function, including reduction of oxidative stress and pre-inflammatory cytokines, and upregulate insulin gene expression to reduce the development of diabetes.

基于AGEP-DNN的水下聚能装药比冲量预测模型

聚能装药比冲量是表征水下爆炸中冲击波对目标破坏作用的重要参数。为实现水下聚能装药比冲量智能预测,提出一种自适应基因表达式编程(adaptive gene expression programming, AGEP)优化深度神经网络(deep neural network, DNN)的聚能装药比冲量预测模型(AGEP-DNN)。考虑装药结构与比冲量数值之间的复杂非线性关系,通过AUTODYN软件建立有限元模型,对水下爆炸过程进行仿真,采用经验公式验证仿真数据的有效性;基于仿真实验数据,设计AGEP算法优化DNN超参数,构建AGEP-DNN模型,对比冲量进行智能预测。实验结果显示,AGEP-DNN聚能装药比冲量预测模型在9种对比智能预测模型中具有最优的预测精度。

朱熹诗歌自然意象的理学表达探析

朱熹诗歌用丰富的自然意象来表达理学。这些自然意象主要有山水描绘、季节变迁、花草植株、动物鸟兽、云气夜色等。朱熹诗歌通过自然意象不仅表达了理气论、心性论和认识修养论等哲学思想,而且表达了忧国忧民的思想、坚守理学的信念决心和治学体验。促成朱熹这种艺术自觉和诗歌成就的文化渊源是自然意象言志抒情的诗骚传统、自然山水象物比德的文化传统、理学前辈以诗言理的深厚积淀。朱熹诗歌自然意象理学表达的美学特征体现为俗与理一体、情与理交融、美与理统一。

形式的哲学精神探本

文章认为形式与理性之间具有本源关联,这一关联肇始于柏拉图的理性的形式化。西方心灵崇尚的理想之美有两种形态:一种是源于理性的自我聚集本性的和谐美,另一种是构建超验的、纯粹形式的、真善美统一的世界。形式的撼天动地的伟大能量体现在两个方面:其一是为目的论的解释和美的概念产生联系提供深刻的存在论、认识论和价值论的根据,另一是作为理性的基本同一性的外化的赋型、抽象和表现这三种活动。理性-形式不会随着现代社会和文化的反传统浪潮而终结,它与非理性的矛盾本质上是化解自然与文化之冲突的表征。

基于转录组测序的金银花提取物抗鸽源新城疫病毒感染的作用机制研究

[目的]探究金银花提取物抗鸽源新城疫病毒(Newcastle disease virus,NDV)感染的作用机制。[方法]选取未接种NDV疫苗的健康28日龄美国王鸽40只,适应性饲养7 d,于35日龄随机分为金银花预防(KO)组和攻毒对照(OE)组,每组20只。KO组试验鸽于35日龄开始在饮水中添加1.2%的金银花提取物,持续饮用7 d,42日龄时肌肉注射HA效价为5log2的鸽源NDV Pi/NJ/CH/4416/2016株0.5 mL/只;OE组试验鸽于35日龄进入正式试验,正常饮水,42日龄时肌肉注射HA效价为5log2的鸽源NDV Pi/NJ/CH/4416/2016株0.5 mL/只。攻毒7 d后,每组选取3只试验鸽采集脾脏组织样本制备组织切片,同时提取总RNA构建转录组文库,利用转录组测序(RNA-sequencing,RNA-Seq)技术进行差异表达基因(differentially expressed genes,DEGs)鉴定、GO功能富集分析和KEGG通路富集分析。随机选取4个显著差异表达基因,利用qRT-PCR验证测序结果。[结果]OE组鸽子脾细胞核异常增大且出现白色空泡,并伴有大量粒细胞浸润,而KO组脾脏组织仅见较多白色空泡和少量粒细胞浸润,未见脾细胞核异常增大。利用RNA-Seq技术从KO组鸽脾脏中共鉴定出374个DEGs,其中,112个基因表达显著上调,262个基因表达显著下调。GO功能富集分析显示,共有875个DEGs富集到312个GO条目,其中,生物学过程富集到149个条目,细胞组成过程富集到33个条目,分子功能过程富集到130个条目。KEGG通路富集分析显示,共有226个DEGs主要被富集在信息传递通路、代谢通路、天然免疫相关通路、细胞凋亡通路等93条KEGG信号通路。qRT-PCR验证结果显示,从DEGs中随机选取的4个显著差异表达基因(LOC110360702、LOC110360688、SFRP5、CHAD)的相对mRNA丰度变化趋势与RNA-Seq结果显示的4个基因变化趋势一致。[结论]金银花提取物通过激活宿主的信息传递、代谢调节及免疫应答等重要生理过程发挥抗鸽源NDV感染作用。研究结果为进一步探究鸽源NDV感染中免疫应答的分子机制提供了科学依据。

多元历史空间信息挖掘与可视化表达技术研究——以上海红色地名文化为例

上海作为中国共产党的诞生地,留下了丰富的红色资源。在制作红色文化产品时总是需要花费大量的人力物力去搜集和分析资料,进而提取有用的信息,且这些产品的表现形式较为单一,没有形成系统的技术体系去完善资源挖掘分析、数据整合存储以及多样可视化表达。为解决这一问题,本文以上海红色地名文化为例,通过研究多元历史文化综合数据库结构、基于语义分析的红色地名文化挖掘技术、基于多元时空叠加的可视化表达三个关键技术点,形成以空间地理信息为基础的多元历史文化成果转化体系,并在系统开发和红色图集制作方面得到了较好的应用。

CRISPR/Cas9编辑系统在微生物天然产物研究中的应用

微生物作为天然产物的巨大宝库,一直以来都是研究人员挖掘和开发新的活性化合物的重要来源。目前,利用基因编辑工具发现、生物合成和代谢调控天然产物的研究方法受到该领域研究者的广泛关注。CRISPR/Cas9遗传编辑系统以其独特的灵活靶向优势克服了其他遗传编辑方法常见的对序列同源或位点限制,简化了实验步骤,提高了实验效率,促进了天然产物研究领域的发展。本文主要介绍CRISPR/Cas9系统在微生物天然产物发现、生物合成和工程改造方面的应用,分别从CRISPR/Cas9系统的发展、天然产物生物合成基因簇的克隆和遗传编辑、天然产物结构衍生化和代谢调节、沉默天然产物基因簇的激活这几个方面阐述CRISPR/Cas9系统在微生物天然产物研究领域的优势。最后,针对CRISPR/Cas9系统无法克服的重组效率和宿主适应性问题提供了可行的解决思路。相信随着合成生物学和信息技术的发展,越来越多的与CRISPR/Cas9系统相关的遗传操作工具和方法会被开发,将不断推动天然产物领域的发展进步。

Advances in the role of natural products in human gene expression

Natural products(NPs),especially those from traditional herbal medicines,can evidently modulate human gene expression at multiple levels,leading to a wide diversity of bioactivities.Although numerous bio-functions of NPs for human body have been found,there is little understanding about how NPs achieve it,as less attention was drawn to the definite mechnism by which NPs regulate gene expression.Furthermore,based on the rapidly advancing knowledge of mechanisms for gene regulation in recent years,newly-understood mechanisms,such as post-transcriptional regulation,are found to be involved in NP-elicited bio-effects,providing a new perspective on understanding the role of NPs in gene expression.Therefore,in the current review,we summarize the function of NPs in gene expression from the perspectives of transcriptional,post-transcriptional,and post-translational regulation,which will reinforce the understanding of NP-induced effects in gene expression and facilitate the exploration of more NPs with potential therapeutic effects.

性恶与性朴:荀子人性论的二重向度与性恶论新解

基于前人对荀子人性论的分析,性可以分为物性和人性两面,性朴是就物性而言,性恶是就人性而言,二者并不矛盾,可以相互综合。物性为人与一切生物所共有,人性为人所特有,人性不同于物性,性恶才是人性。荀子从思想实验出发,论述了其性恶论的真正内涵:顺性则必然为恶。圣人逆性,所以能够克服自己的性恶来“化性起伪”。“伪”是人性由恶转善的必经之途,只有通过后天的礼义教化等人为之“伪”,才能真正实现从善、达善。因此,人之性可分为“朴—恶—善”三个层次。通过试图赋予荀子人性论一种二重向度的阐释,可形成对其更为整体性的认识。

实景三维在自然资源调查成果可视化中的应用

自然资源调查成果的三维立体可视化表达对实现各类自然资源的分析与应用具有重要意义。本文以自然资源综合调查监测国家试点一查多用子任务成果数据为基础,基于地形级实景三维提供的统一空间基底,以二三维一体化的系统开发技术为支撑,结合自然资源管理中的分析与可视化需求,开发了自然资源综合调查监测成果分析与展示系统,实现了多源数据的融合浏览、自然资源图斑的动态查询与实时渲染、自然资源体模型的模拟与查询、空间重叠资源的立体表达以及自然资源分类面积统计可视化,可以为加强自然资源的统一管理和开发利用提供有益助力。

Natural Variation in the Sequence of SNAC1 and Its Expression Level Polymorphism in Rice Germplasms under Drought Stress

Water is a major limiting factor for food production and many countries fail to produce sufficient food for their population due to severe water scarcity （Jury and Vaux, 2005）. Rice is the main staple food worldwide. More than 50% of rice in the world is rain-fed and drought causes severe reduction in rice grain yield in rain-fed environments （Venuprasad et al., 2007; Zhang, 2007; Sandhu et al., 2014）. Therefore, enhancing drought resistance （DR） of rice is important for food security. However, DR is a complex trait, which is controlled by a large number of loci with small effect and is also affected by different genetic background, genotype-by-environment interaction and other stresses such as heat （Hu and Xiong, 2014）.

维特根斯坦私人语言研究的“语法”性质

维特根斯坦的私人语言研究是语法研究。私人语言的定义表明私人说话者对他的感觉没有自然表现。这就意味着他对他的感觉词汇没有正确性标准。如果一个词的使用没有正确性标准,那么它就是无意义的;这是一条语法规则。根据这条语法规则,私人的感觉词汇是无意义的,私人语言也就是无意义的了。维特根斯坦通过语法研究成功消解了私人语言问题,他对私人语言的处理与他的哲学理念是一致的。此外,维特根斯坦还对认为私人语言有可能的哲学家们所犯的错误进行了诊断并为其提供了治疗。

The expression tractability of biological traits shaped by natural selection

Understanding how gene expression is translated to phenotype is central to modern molecular biology,and the success is contingent on the intrinsic tractability of the specific traits under examination.However, an a priori estimate of trait tractability from the perspective of gene expression is unavailable.Motivated by the concept of entropy in a thermodynamic system, we here propose such an estimate(S_T)by gauging the number(N) of expression states that underlie the same trait abnormality, with large S_T corresponding to large N. By analyzing over 200 yeast morphological traits, we show that S_T predicts the tractability of an expression-trait relationship. We further show that S_T is ultimately determined by natural selection, which builds co-regulated gene modules to minimize possible expression states.

账与礼:礼的义务性与表达性的转换与过渡——基于滇南HW村葬礼礼簿的研究

礼物交换被认为是人类普遍的互惠形式,错综复杂的社会关系网络通过礼物流动来缔结和维系。在对滇南HW村葬礼的多次田野调查中发现,一场葬礼中明确命名并登记在册的礼簿包括“柴账”“自带口粮账”“老账”“新账”“祭账”五种。这五种礼簿对应着与邻里、村落、宗亲、姻亲及祖先的互惠关系。对礼簿的细分是当地集体互助治丧习俗的产物,集体互助治丧习俗建构的权利与义务体系,使特定互惠圈中礼的流动超越了表达性而呈现出明确的义务性特征。随着集体互助治丧逐渐被家庭治丧所取代,礼的义务性逐渐向表达性过渡。

浅谈巴西陶瓷艺术及其在双年展中的表现

“瓷的旅程”——2023景德镇国际陶瓷艺术双年展——巴西特别展于2023年10月17日在景德镇陶瓷大学开幕。在这里,不同文化相互碰撞与交流,每一件作品都是作者的一次旅程,将观众带入一个丰富的视觉世界。本文简要介绍了巴西陶瓷艺术的历史背景、影响因素、发展现状及成因等,并从色彩运用、造型设计、装饰手法方面探讨了巴西陶瓷艺术的独特之处,旨在分析双年展中的巴西陶瓷艺术作品。