基于一维序列的三维染色质相分离:驱动力、过程与功能

染色质高级结构在基因调控中起到不可忽视的作用,染色质结构的形成与调控机制受到广泛关注。"相分离"理论近年来受到较多关注,异染色质与转录因子在其中的作用引人瞩目。但是,目前的相分离模型更关注结合因子与表观遗传性质,对DNA序列自身的作用理解尚较不充分。许多物种基因组的序列分布均具有多尺度的不均一性,仅基于Cp G岛(Cp G island,CGI)密度差异这一序列性质,就可以划分出基因、表观遗传、结构和转录性质都截然不同的高CGI密度"森林"和低CGI密度"草原"两种序列区域,体现了基因组自身的马赛克性。本文聚焦染色质结构的序列依赖性,讨论了染色质结构模型的研究进展,关注在序列几乎相同的不同细胞类型中的序列–结构关系及其功能调控,对发育、分化、衰老、疾病等多种过程的染色质结构变化进行了系统分析。针对基于序列的染色质相分离模型,对其物理驱动力进行了讨论,并在该模型的框架下基于相分离的物理特性,对温度、序列不均一性等物理因素对染色质结构可能造成的影响进行了探讨。

Photoacoustic detection of follicular thyroid carcinoma using targeted Nano-Au-Tripods

Follicular thyroid carcinoma(FTC)is the second most common form of thyroid malignancy,and it is associated with more aggressive growth and worse long-term survival outcomes relative to papillary thyroid carcinoma(PTC).Reliable approaches to preoperative FTC detection,however,remain to be established.Herein,a targeted Affibody-Au-Tripod nanoprobe was developed and successfully utilized to facilitate the targeted photoacoustic imaging(PAI)of epidermal growth factor receptor(EGFR)-positive cells and tumors.These Affibody-Au-Tripods were found to be highly sensitive and specific for cells expressing EGFR when used as a PA contrast agent in vitro,and studies conducted in an FTC-133 subcutaneous tumor model system in mice further revealed that these Affibody-Au-Tripods were able to specifically target these EGFR-expressing tumors while providing a strong photoacoustic signal in vivo.Importantly,these nanoprobes exhibited negligible cytotoxicity and robust chemical and physical stability,making Affibody-Au-Tripods promising candidates for targeted PAI-based FTC diagnosis.In addition,these nanoprobes have the potential to facilitate the individualized treatment of patients harboring EGFRpositive tumors.

Efficacy and safety of Guipi Decoction combined with conventional Western medicine in the treatment of insomnia with deficiency of heart and spleen:a meta-analysis

Objective:To systematically evaluate the efficacy and safety of Guipi Decoction combined with Western medicine in the treatment of insomnia with deficiency of heart and spleen.Methods:English databases(PubMed,Web of Science,The Cochrane Library,EMBASE)and Chinese databases(CNKI,Wanfang database,China Biomedical Literature Service System,VIP database)were searched by computer.Randomized controlled trials of Guipi Decoction on insomnia with deficiency of heart and spleen were searched from the database construction to November 2021.After the first and second authors independently screened the literature,extracted the data and evaluated the risk of bias in the included studies,meta-analysis was performed using RevMan5.3 software.Results:A total of 9 RCTS were included after screening,including 914 patients.Meta-analysis results showed that:Total effective rate[RR=1.22,95%CI(1.16,1.30),P<0.00001],total PSQI score[MD=-3.05,95%CI(-3.96,-2.14),P=0.008],number of night awakening times[[MD=-1.18,95%CI(-1.42,-0.94),P<0.00001],adverse reaction rate[RR=0.32,95%CI(0.21,0.51),P<0.00001]were better than the control group,and the differences were statistically significant.Conclusion:The current evidence shows that,compared with pure using conventional western medicine,belongs to the spleen decoction combined western medicine therapy,cases both deficiency type of insomnia in the total effective rate,reducing the total PSQI score(improve sleep quality,sleep efficiency,sleep disorder,daytime function,etc.),reducing frequency of nighttime awakening,security,have more advantages.However,due to the limitation of the quality and quantity of articles included in the study,more randomized,double-blind,large-sample clinical studies are needed to confirm the above conclusions.

Treated dentin matrix induces odontogenic differentiation of dental pulp stem cells via regulation of Wnt/β-catenin signaling

Treated dentin matrix(TDM)is an ideal scaffold material containing multiple extracellular matrix factors.The canonical Wnt signaling pathway is necessary for tooth regeneration.Thus,this study investigated whether the TDM can promote the odontogenic differentiation of human dental pulp stem cells(hDPSCs)and determined the potential role of Wnt/β-catenin signaling in this process.Different concentrations of TDM promoted the dental differentiation of the hDPSCs and meanwhile,the expression of GSK3βwas decreased.Of note,the expression of the Wnt/β-catenin pathway-related genes changed significantly in the context of TDM induction,as per RNA sequencing(RNA seq)data.In addition,the experiment showed that new dentin was visible in rat mandible cultured with TDM,and the thickness was significantly thicker than that of the control group.In addition,immunohistochemical staining showed lower GSK3βexpression in new dentin.Consistently,the GSK3βknockdown hDPSCs performed enhanced odotogenesis compared with the control groups.However,GSK3βoverexpressing could decrease odotogenesis of TDM-induced hDPSCs.These results were confirmed in immunodeficient mice and Wistar rats.These suggest that TDM promotes odontogenic differentiation of hDPSCs by directly targeting GSK3βand activating the canonical Wnt/β-catenin signaling pathway and provide a theoretical basis for tooth regeneration engineering.

Toward an understanding of the relation between gene regulation and 3D genome organization

Background:High-order chromatin structure has been shown to play a vital role in gene regulation.Previously we identified two types of sequence domains,CGI(CpG island)forest and CGI prairie,which tend to spatially segregate,but to different extent in different tissues.Here we aim to further quantify the association of domain segregation with gene regulation and therefore differentiation.Methods:By means of the published RNA-seq and Hi-C data,we identified tissue-specific genes and quantitatively investigated how their regulation is relevant to chromatin structure.Besides,two types of gene networks were constructed and the association between gene pair co-regulation and genome organization is discussed.Results:We show that compared to forests,tissue-specific genes tend to be enriched in prairies.Highly specific genes also tend to cluster according to their functions in a relatively small number of prairies.Furthermore,tissue-specific forest-prairie contact formation was associated with the regulation of tissue-specific genes,in particular those in the prairie domains,pointing to the important role of gene positioning,in the linear DNA sequence as well as in 3D chromatin structure,in gene regulatory network formation.Conclusion:We investigated how gene regulation is related to genome organization from the perspective of forest-prairie spatial interactions.Since unlike compartments A and B,forest and prairie are identified solely based on sequence properties.Therefore,the simple and uniform framework(forest-prairie domain segregation)provided here can be utilized to further understand the chromatin structure changes as well as the underlying biological significances in different stages,such as tumorgenesis.