综合scRNA-Seq和Bulk RNA-Seq技术建立与肝癌CD8^(+)T细胞相关的预后模型

目的 通过单细胞测序(scRNA-Seq)和Bulk转录组测序(Bulk RNA-Seq)技术鉴定出与肝癌CD8^(+)T细胞相关的生物标志物并建立预后模型。方法 从GEO数据库中下载肝癌的单细胞数据集,通过scRNA-Seq技术提取患者与对照组间CD8^(+)T细胞的差异表达基因。从TCGA数据库中下载肝癌的基因表达谱数据及临床数据,使用CIBERSORT算法、WGCNA技术筛选出与CD8^(+)T细胞具有相关性的模块基因。将差异基因与模块基因取交集基因并进行GO、KEGG分析,应用单因素COX回归分析和LASSO算法建立预后模型。通过K-M曲线和ROC曲线对模型在内、外部数据集中的预测效果进行验证。根据风险评分的中位值划分高低风险组,对高低风险组间的浸润性免疫细胞分布情况和肿瘤突变情况进行分析。结果 构建出具有9个基因的预后模型,K-M曲线及ROC曲线表明模型在内、外部数据集中均具有良好的预测能力,在高低风险组中,浸润性免疫细胞的分布情况和基因突变情况均存在显著差异。结论 本研究结合scRNA-Seq和Bulk RNA-Seq技术利用生物信息学方法开发出了一种基于CD8^(+)T细胞的新型预后模型,为肝癌患者的预后改善和生存预测提供了可靠的理论依据。

Single-cell RNA-sequencing combined with bulk RNA-sequencing analysis of peripheral blood reveals the characteristics and key immune cell genes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is a complicated disease caused by the interaction between genetic and environmental factors that affects mucosal homeostasis and triggers an inappropriate immune response.Single-cell RNA sequencing(scRNA-seq)can be used to rapidly obtain the precise gene expression patterns of thousands of cells in the intestine,analyze the characteristics of cells with the same phenotype,and provide new insights into the growth and development of intestinal organs,the clonal evolution of cells,and immune cell changes.These findings can provide new ideas for the diagnosis and treatment of intestinal diseases.To identify clinical phenotypes and biomarkers that can predict the response of UC patients to specific therapeutic drugs and thus aid the diagnosis and treatment of UC.METHODS Using the Gene Expression Omnibus(GEO)database,we analyzed peripheral blood cell subtypes of patients with UC by scRNA-seq combined with bulk RNA sequencing(RNA-seq)to reveal the core genes of UC.We then combined weighted gene correlation network analysis(WGCNA)and least absolute shrinkage and selection operator(LASSO)analysis to reveal diagnostic markers of UC.RESULTS After processing the scRNA-seq data,we obtained data from approximately 24340 cells and identified 17 cell types.Through intercellular communication analysis,we selected monocyte marker genes as the candidate gene set for the prediction model.Construction of a WGCNA coexpression network identified RhoB,cathepsin D(CTSD)and zyxin(ZYX)as core genes.Immune infiltration analysis showed that these three core genes were strongly correlated with immune cells.Functional enrichment analysis showed that the differentially expressed genes were closely related to immune and inflammatory responses,which are associated with many challenges in the diagnosis and treatment of UC.CONCLUSION Through scRNA-seq analysis,LASSO diagnostic model building and WGCNA,we identified RhoB,CTSD and ZYX as core genes of UC that are closely related to monocyte infiltration that may serve as diagnostic markers and molecular targets for UC therapeutic intervention.

基于RNA-Seq技术探讨生(麸炒)白术对大鼠基因表达的差异性分析

目的:考察麸炒白术及生白术对实验大鼠肝脏转录组学的影响,从机体转录组角度筛选差异基因,探求白术炮制后对大鼠生物学效应的表达差异。方法:SD大鼠随机分为空白组、生白术组和麸炒组,每组3只。生白术组按照7.0 g/kg灌胃生品白术提取液,麸炒组按照6.0 g/kg灌胃麸炒白术提取液,空白组给予同体积生理盐水,连续给药21 d。给药结束后取大鼠肝脏,采用RNA-Seq全基因转录组法分析差异基因的表达。结果:生白术可上调Cyp7b1、Btg2 Pc3、Enpp2、Hao2等功能基因的表达,下调Ppplr3c、Car12功能基因的表达;麸炒白术可上调Cyp7b1、Enpp2、Hao2、Cy3a18、Cyp2c11等9个功能基因的表达,下调Aacs Hmgcs 1、Hmgcs1 Aacs、Alpl、Per3等7个功能基因的表达,生白术与麸炒白术均能上调Cyp7b1、Enpp2、Hao2等3个功能基因的表达,体现在促进类固醇激素合成、醚脂代谢、维持脂质平衡、增加机体代谢水平等生物功能。麸炒白术组与生白术组差异基因筛选结果表明,白术经过麸炒后对大鼠肝脏组织的基因表达同样存在特征性差异表达,麸炒白术组与生白术组相比,上调Car12、Arntl、Cldn1等3个功能基因,下调Rpl8、LOC等2个功能基因,麸炒白术可促进氮代谢、促进昼夜节律、增加机体免疫监视、提高免疫应答、对抗炎症等生物学功能。结论:研究表明生白术及麸炒白术均对大鼠肝脏组织的基因表达产生较为明显的影响,主要体现在对调控脂肪代谢、蛋白质代谢、类固醇合成、不饱和脂肪酸合成、糖原合成等多个功能基因的调控作用。

Bulked Segregant RNA-Seq Analysis of Pollinated Pistils Reveals Genes Influencing Spikelet Fertility in Rice

Prezygotic isolation is important for successful fertilization in rice, significantly affecting yield. This study focused on F_(5:6) generation plants derived from inter-subspecific crosses(Nipponbare × KDML105) with low(LS) and high seed-setting rates(HS), in which normal pollen fertility was observed. However, LS plants showed a reduced number of pollen grains adhering to the stigma and fewer pollen tubes reaching the ovules at 4-5 h post-pollination, compared with HS plants. Bulked segregant RNA-Seq analysis of pollinated pistils from the HS and LS groups revealed 249 and 473 differentially expressed genes(DEGs), respectively. Kyoto Encyclopedia of Genes and Genomes analysis of the HS and LS-specific DEGs indicated enrichment in metabolic pathways, pentose and glucuronate interconversions, and flavonoid biosynthesis. Several of these DEGs exhibited co-expression with pollen development genes and formed extensive clusters of co-expression networks. Compared with LS pistils, enzyme genes controlling pectin degradation, such as OsPME35 and OsPLL9, showed similar expression patterns, with higher levels in HS pistils pre-pollination. Os02g0467600, similar to cinnamate 4-hydroxylase gene(CYP73), involved in flavonoid biosynthesis, displayed higher expression in HS pistils post-pollination. Our findings suggest that OsPME35, OsPLL9, and Os02g0467600 contribute to prezygotic isolation by potentially modifying the stigma cell wall(OsPME35 and OsPLL9) and controlling later processes such as pollen-stigma adhesion(Os02g0467600) genes. Furthermore, several DEGs specific to HS and LS were co-localized with QTLs and functional genes associated with spikelet fertility. These findings provide valuable insights for further research on rice spikelet fertility, ultimately contributing to the development of high-yielding rice varieties.

基于RNA-Seq技术对不同品种猪排卵前卵泡差异表达基因的筛选与注释

[目的]筛选淮猪和大约克猪排卵前卵泡组织差异表达基因。[方法]采集淮猪和大约克猪各3头的排卵前卵泡,提取RNA,个体独立建库。采用RNA测序技术以及GO和pathway方法对所获序列进行显著性富集分析。[结果]测序后,获得的淮猪clean reads数分别为85958912、91701082、84448828,其中有效Reads数分别达到98.39%、98.59%、96.04%;获得的大约克猪clean reads数分别为87914166、80480542、85994612,其中有效reads数分别达到98.61%、96.95%、98.80%,测序饱和度良好(证明测序数据真实可靠)。结果表明,筛选到上调基因67个,下调基因54个。GO和Pathway分析发现,差异表达基因富集在繁殖过程、生长过程和代谢过程及WNT信号通路、卵巢类固醇生成通路和类固醇生物合成通路等。[结论]获得了猪排卵前卵泡基因表达谱,并筛选到与繁殖性状相关的关键候选基因。

基于RNA-seq对复合益生菌作用于肉鸡回肠中新转录本预测及可变剪接、SNP分析

为分析复合益生菌饲喂肉鸡回肠转录组中的新转录本预测、可变剪接事件和SNP,选择200只1日龄黄麻肉鸡随机分为2组,每组5个重复,每个重复20只。对照组正常饮水,益生菌组饮用水中补充1%复合菌制剂,试验分为生长前期(1~21 d)、后期(22~42 d)两个阶段。42日龄时进行肉鸡屠宰试验,取对照组和益生菌组回肠各3个样本进行转录组测序。对测序数据进行分析,共发现1047个新基因,20176个新转录本,276个新基因在GO数据库中得到归类注释。对转录组数据进行可变剪接分析,外显子跳跃(SE)占可变剪接类型的比例最高,共筛选到1131个显著的差异剪接基因,在外显子跳跃(SE)、第一个外显子可变剪接(A5SS)、最后一个外显子可变剪接(A3SS)、外显子选择性跳跃(MXE)、内含子滞留(RI)事件中鉴定到的差异剪接基因数分别为588、139、176、136、92。对获得的差异剪接基因进行GO富集分析,主要富集在代谢和免疫GO term。KEGG富集到了胞吞作用、MAPK信号通路等。在各样品中大多数碱基取代均为转换大于颠换,其中转换单核苷酸多态性(SNP)所占百分比为73.53%~73.94%;颠换型SNP所占百分比为26.05%~26.47%。试验对对照组、益生菌组肉鸡的回肠进行了RNA-seq测序分析,为发掘复合益生菌作用于肉鸡回肠中的可变剪接事件提供基础,为进一步了解复合益生菌作用于肉鸡回肠中新转录本的发现和SNP位点提供了数据支撑。

BSA-Seq结合RNA-Seq技术挖掘大豆叶片提前黄化衰老基因

大豆产量与其生殖生长的持续时间呈正相关,延缓其开花后叶片的衰老,提高其生理功能,有利于增加植物的粒重。叶片黄化是植物衰老的显著特征之一。关于在大豆鼓粒后期叶片黄化的研究鲜见报道。本研究对鼓粒后期叶片提前黄化突变体ly和野生型ofc杂交组合进行遗传分析,结果表明,大豆鼓粒后期叶片提前黄化性状受单隐性核基因控制。通过BSA-Seq在19号染色体得到一个2.23Mb的初定位区间,经开发标记图位克隆后将区间缩短至1.75 Mb,区间内有219个基因,再结合RNA-Seq分析,得到了区间内12个候选基因,其中有4个SNP变异基因和8个差异表达基因。本研究结果为大豆鼓粒后期叶片黄化衰老基因的克隆奠定了基础。

15 nm Bulk nFinFET器件性能研究及参数优化

为研究Bulk FinFET工作时基本结构参数、器件温度和栅极材料对其性能的影响,建立了一个15 nm n型Bulk FinFET器件模型,仿真分析了不同栅长、鳍宽、鳍高、沟道掺杂浓度、器件工作温度、栅极材料对器件性能的影响,发现增长栅长、降低鳍宽和增加鳍高有助于抑制短沟道效应;1×10^(17)cm^(-3)以下的低沟道掺杂浓度对器件特性影响不大,但高掺杂会使器件失效;器件工作温度的升高会导致器件性能的下降;采用高K介质材料作为栅极器件性能优于传统材料SiO_(2)。

A Survey on Methods for Predicting Polyadenylation Sites from DNA Sequences,Bulk RNA-seq,and Single-cell RNA-seq

Alternative polyadenylation(APA)plays important roles in modulating mRNA stability,translation,and subcellular localization,and contributes extensively to shaping eukaryotic transcriptome complexity and proteome diversity.Identification of poly(A)sites(pAs)on a genomewide scale is a critical step toward understanding the underlying mechanism of APA-mediated gene regulation.A number of established computational tools have been proposed to predict pAs from diverse genomic data.Here we provided an exhaustive overview of computational approaches for predicting pAs from DNA sequences,bulk RNA sequencing(RNA-seq)data,and single-cell RNA sequencing(scRNA-seq)data.Particularly,we examined several representative tools using bulk RNA-seq and scRNA-seq data from peripheral blood mononuclear cells and put forward operable suggestions on how to assess the reliability of pAs predicted by different tools.We also proposed practical guidelines on choosing appropriate methods applicable to diverse scenarios.Moreover,we discussed in depth the challenges in improving the performance of pA prediction and benchmarking different methods.Additionally,we highlighted outstanding challenges and opportunities using new machine learning and integrative multi-omics techniques,and provided our perspective on how computational methodologies might evolve in the future for non-30 untranslated region,tissuespecific,cross-species,and single-cell pA prediction.

袋型阻尼密封动力学特性双控制体Bulk Flow模型

为快速准确预测袋型阻尼密封泄漏特性和动力学特性,针对传统单控制体Bulk Flow模型预测精度低、无法预测交叉动力系数的问题,提出了袋型阻尼密封双控制体Bulk Flow模型和动力学特性数值预测方法,并开发了计算程序。首先,依据边界层理论,将袋型密封腔室划分为两个控制体,推导了控制体的连续性、周向动量和能量方程,引入Swamee-Jain和Takahashi方程,计算流体-壁面间和流体-流体间的周向黏性摩擦力;其次,采用牛顿-拉夫森算法和摄动分析法分别求解0阶和1阶控制方程,获得各刚度、阻尼动力特性系数;然后,通过与袋型阻尼密封泄漏量和动力特性系数的实验值、单控制体Bulk Flow模型和非定常计算流体动力学(CFD)数值结果进行比较,验证了模型和方法的准确性和可靠性;最后,研究了转子转速(10 000、15 000、20 000 r/min)和预旋比(0.067、0.724、0.997)对袋型阻尼密封动力学特性的影响。结果表明:所发展的模型和方法具有计算速度快、预测精度高(泄漏量预测误差小于6%,动力特性系数预测误差小于38%)的优点;转子转速和进口预旋的增大均会导致袋型阻尼密封有效阻尼显著减小,穿越频率显著增大,易诱发轴系失稳。

RNA-Seq and Bulked Segregant Analysis of Genes Related to High Growth in <i>Ginkgo biloba</i>Half-Sibling Families

The lifetime of G. biloba is very long, and its growth is relatively slow. However, little is known about growth-related genes in this species. We combined mRNA sequencing (RNA-Seq) with bulked segregant analysis (BSA) to fine map significant agronomic trait genes by developing polymorphism molecular markers at the transcriptome level. In this study, transcriptome sequencing of high growth (GD) and low growth (BD) samples of G. biloba half-sib families was performed. After assembling the clean reads, 601 differential expression genes were detected and 513 of them were assigned functional annotations. Single nucleotide polymorphism (SNP) analysis identified SNPs associated with 119 genes in the GD and BD groups;58 of these genes were annotated. Two Homeobox-leucine zipper protein genes were up-regulated in the GD group compared with the BD group;therefore, these are very likely related to high growth of G. biloba. This study provides molecular level data that could be used for seed selection of high growth G. biloba half-sib families for future breeding programs.

基于RNA-Seq分析大白猪和巴马香猪背最长肌组织基因表达差异

以180日龄的大白猪(n=6)与巴马香猪(n=6)为研究对象,屠宰后测定肌内脂肪、肉色、嫩度、pH、滴水损失等肉质性状,采集背最长肌组织提取总RNA,利用RNA-Seq技术鉴定大白猪和巴马香猪背最长肌组织中的表达差异基因及其功能富集通路。结果发现,以大白猪为对照组,在巴马香猪和大白猪背最长肌组织中共鉴定到5 037个差异表达基因,其中有3 326个上调表达基因,1 711个下调表达基因。经过KEGG富集通路分析,发现巴马香猪和大白猪一共有168条显著富集通路,其中上调DEGs有92条富集路径,下调DEGs有76条富集路径;GO功能分析中上调表达基因富集到BP有3 058条、CC有413条、MF有559条,下调表达基因富集到BP有3 050条、CC有415条、MF有557条。大白猪与巴马香猪肉色的亮度L在45min时呈极显著差异;大白猪与巴马香猪之间的肌内脂肪、水分均呈现显著差异。本文对大白猪与巴马香猪肌内脂肪含量进行转录组测序分析,初步认为CAPN3、MTM1、TMOD4等基因在巴马香猪肉质中发挥重要作用。

基于RNA-Seq探究蔗糖影响黑果枸杞枝刺发生的机理

【目的】黑果枸杞Lycium ruthenicum是集生态、经济和药用价值等为一体的灌木。然而,其密集的枝刺严重阻碍其作为经济林推广,本研究旨在探究蔗糖(Suc)促进黑果枸杞(黑杞)枝刺的发生机理,为培育其无刺优良品种提供依据。【方法】在证明Suc通过能量和信号路径促进黑杞枝刺发生的基础上,利用RNA-Seq对无刺茎顶芽(TleCK)、有刺茎顶芽(ThoCK)、黑暗处理的有刺茎顶芽(ThoDCK)、减少内源Suc处理后有刺变无刺茎顶芽(TleDPL)和喷施外源Suc后无刺变有刺茎顶芽(ThoSuc)5种样品的差异表达基因(DEG)和叶绿体差异基因(cpDEG)进行筛选和分析,并采用RT-qPCR验证了9个DEG的表达情况。【结果】5组有刺和无刺材料顶芽之间(ThoCK vs.TleCK、ThoCK vs.TleDPL、ThoDCK vs.TleDPL、TleCK vs.ThoSuc和TleDPL vs.ThoSuc)的DEG分别为5281、4363、3125、5226和3278个,这5组DEG共同显著富集在9个GO条目和4个KEGG通路(“类黄酮生物合成”“二萜生物合成”“苯丙烷生物合成”、“芪类、二芳基庚烷和姜辣素生物合成”)。韦恩图显示5组比较组共有的DEG是196个,其中33个被预测为转录因子基因,较多转录因子基因被预测为NAC和WRKY家族。5组比较组有3个共有DEG注释在植物激素信号转导KEGG通路,分别参与生长素、茉莉酸和水杨酸信号传导。3个关键有刺和无刺比较组(ThoCK vs.TleCK、ThoCK vs.TleDPL和TleCK vs.ThoSuc)中共有2个DEG被预测为TCP转录因子基因,这3个比较组均有cpDEG被注释到光合作用KEGG通路。9个DEG的RT-qPCR验证了RNA-Seq结果的可靠性。【结论】Suc可能通过影响生长素、茉莉酸和水杨酸信号传导以及赤霉素合成基因表达来促进黑杞枝刺发生,枝刺发生也可能与类黄酮积累和木质素减少有关,而且增施外源和减少内源Suc并非通过简单地逆转cpDEG的表达来影响枝刺发生。注释到WRKY、TCP和NAC转录因子家族的共有DEG可能是调控枝刺发生的关键基因。本研究建立了Suc影响黑杞枝刺发生的机理模型图。

Anisotropic Band Evolution of Bulk Black Phosphorus Induced by Uniaxial Tensile Strain

We investigate the anisotropic band structure and its evolution under tensile strains along different crystallographic directions in bulk black phosphorus(BP)using angle-resolved photoemission spectroscopy and density functional theory.The results show that there are band crossings in the Z-L(armchair)direction.

Influences of polymorphism of packed particles on bulk characterizations in fluidization realm

The characterization of a particle ensemble(rather than a single particle) is of paramount significance to various particle technologies and has long been a fundamental subject in the fluidization realm. However, many of such bulk characterizations as loosely-packed density(ρbl), minimum fluidization velocity(Umf), sphericity(φ), discharge rate through orifice(q), angle of repose(β), and segregation index(S),were found to be poorly reproducible, making the reported results seldom comparable. Since these bulk characterizations started from the packed state of particles, such poor reproducibility was ascribed to the polymorphism of packed particles in this work. We observed that in the fluidized bed, the settled/packed state of particles varied monotonously with the settling rate(a) from complete fluidization to zero. This phenomenon confirmed the polymorphic characteristic of packed particles and further enabled us to systematically disclose/clarify its influences on the aforementioned bulk characterizations. Such influences could be comprehensively and intuitively reflected by the impacts induced by a. With the decrease of a, ρbl, φ and q first increased, then decreased, and finally leveled off while Umfand β showed an opposite trend. On the other hand, S first increased and then remained invariant. As per these findings and definitions of these bulk characterizations, benchmarks were indicated to unify the selection of settled state among future scholars and further make their outcomes become fairly comparable. Additionally, most packed states of the particle ensemble were proved to be metastable with their formation and behavior being identical to those of the amorphous state.

“Glass-quake”in elastically loaded bulk metallic glasses

Amorphous solids exhibit scale-free avalanches,even under small external loading,and thus can work as suitable systems to study critical behavior and universality classes.The abundance of scale-free avalanches in the entire elastic tension regime of bulk metallic glass(BMG)samples has been experimentally observed using acoustic emission(AE)measurements.In this work,we compare the statistics of avalanches with those of earthquakes,and find that they both follow the Gutenberg–Richter law in the statistics of energies and Omori’s law of aftershock rates,and share the same characteristics in the distribution of recurrence times.These resemblances encourage us to propose the term“glass-quake”to describe avalanches in elastically loaded BMGs.Furthermore,our work echoes the potential universality of critical behavior in disordered physical systems from atomic to planetary scales,and motivates the use of elastic loaded BMGs as valuable laboratory simulators of seismic dynamics.

A bulk extraction method to determine the stable isotope ratios of iron,nickel,copper,zinc,and cadmium in seawater using multi-collector inductively coupled plasma mass spectrometry

The oceanic trace metals iron(Fe),nickel(Ni),copper(Cu),zinc(Zn),and cadmium(Cd)are crucial to marine phytoplankton growth and global carbon cycle,and the analysis of their stable isotopes can provide valuable insights into their biogeochemical cycles within the ocean.However,the simultaneous isotopic analysis of multiple elements present in seawater is challenging because of their low concentrations,limited volumes of the test samples,and high salt matrix.In this study,we present the novel method developed for the simultaneous analysis of five isotope systems by 1 L seawater sample.In the developed method,the NOBIAS Chelate-PA1 resin was used to extract metals from seawater,the AG MP-1M anion-exchange resin to purify Cu,Fe,Zn,Cd,and the NOBIAS Chelate-PA1 resin to further extract Ni from the matrix elements.Finally,a multi-collector inductively coupled plasma mass spectroscope(MC-ICPMS)was employed for the isotopic measurements using a doublespike technique or sample-standard bracketing combined with internal normalization.This method exhibited low total procedural blanks(0.04 pg,0.04 pg,0.21 pg,0.15 pg,and 3 pg for Ni,Cu,Fe,Zn,and Cd,respectively)and high extraction efficiencies(100.5%±0.3%,100.2%±0.5%,97.8%±1.4%,99.9%±0.8%,and 100.1%±0.2%for Ni,Cu,Fe,Zn,and Cd,respectively).The external errors and external precisions of this method could be considered negligible.The proposed method was further tested on the seawater samples obtained from the whole vertical profile of a water column during the Chinese GEOTRACES GP09 cruise in the Northwest Pacific,and the results showed good agreement with previous related data.This innovative method will contribute to the advancement of isotope research and enhance our understanding of the marine biogeochemical cycling of Fe,Ni,Cu,Zn,and Cd.

Bulk geochemistry,Rb-Sr,Sm-Nd,and stable O-H isotope systematics of the Metzimevin high-grade iron ore deposit,Mbalam iron ore district,southern Cameroon

Bulk geochemistry,Sr,Nd,and O-H isotope systematics are reported for the first time on banded iron formation(BIF)-hosted high-grade iron ore at the northwestern segment of Congo Craton(CC).Located in Mbalam iron ore district,Southern Cameroon,Metzimevin iron ore deposit is a hematite-magnetite BIF system,dominated by SiO_(2)+Fe_(2)O_(3)(97.1 to 99.84 wt%),with low concentrations of clastic elements e.g.,Al_(2)O_(3),TiO_(2),and HFSE,depicting a nearly pure chemical precipitate.The REE+Y signature of the iron deposit displays strong positive Eu anomaly,strong negative Ce anomaly,and chondritic to superchondritic Y/Ho ratios,suggestive of formation by mixed seawater-high temperature hydrothermal fluids in oxidising environment.The^(87)Sr/^(86)Sr ratios of the BIF are higher than the maximum^(87)Sr/^(86)Sr evolution curves for all Archean reservoirs(bulk silicate earth,Archean crust and Archean seawater),indicating involvement of continentally-derived components during BIF formation and alteration.TheƐ_(Nd)(t)(+2.26 to+3.77)and Nd model age indicate that chemical constituents for the BIF were derived from undifferentiated crustal source,between 3.002 and 2.88 Ga.The variable and diverse O and H isotope data(−1.9‰to 17.3‰and−57‰to 136‰respectively)indicate that the Metzimevin iron ore formed initially from magmatic plumes and later enriched by magmatic-metamorphic-modified meteoric fluids.Mass balance calculations indicate mineralisation by combined leaching and precipitation,with an average iron enrichment factor of>2.67 and SiO_(2)depletion factor of>0.99.This is associated with an overall volume reduction of 28.27%,reflecting net leaching and volume collapse of the BIF protholith.

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.

Meiotic transcriptional reprogramming mediated by cell-cell communications in humans and mice revealed by scATACseq and scRNA-seq

Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.