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bta-miR-224 regulates milk fat metabolism by targeting FABP4 in bovine mammary epithelial cells bta-miR-224 通过靶向牛乳腺上皮细胞中的 FABP4 来调节乳脂代谢。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110955
Chuanchuan Wang , Jinyan Zhao , Xiaofang Feng , Wei Zhao , Ruoshuang Ma , Baojun Yu , Lin Xue , Hua Wang , Yafei Chen , Juan Zhang professor , Yaling Gu
Milk fat is produced and secreted by the mammary gland, which is mainly regulated by diet and gene-molecule network. Therefore, understanding the molecular mechanism of milk fat synthesis is of practical significance for improving milk quality. Fatty acid-binding protein 4 (FABP4) is a candidate messenger RNA (mRNA) closely linked to milk fat metabolism obtained from transcriptomic analysis of mammary epithelial cells of cows in the pre-existing high- and low-milk-fat groups, and its expression pattern and function are still unclear. The qRT-PCR results depicted that FABP4 was highly expressed in bovine mammary epithelial cells (BMECs) in breast tissues and the high milk fat group. Subsequently, the regulatory effects of FABP4 on BMECs were analyzed by CCK8, EdU, and flow cytometry, and the results demonstrated that FABP4 inhibited the proliferation and viability of BMECs and promoted their apoptosis. Next, the effect of FABP4 on milk lipid metabolism was explored. pEGFP-N1-FABP4 was transfected into BMECs, and FABP4 upregulated the expression levels of the milk lipid marker genes XDH, PPARG, and ACSS2, and promoted the formation of triglycerides (TGs), cholesterol, lipid droplets, and β-casein. Strong interactions between FABP4 and PPARG were identified using STRING prediction. Western blotting revealed that FABP4 interacted with PPARG to promote PPARG expression, while the opposite result was observed after interfering with FABP4. The gene regulation of microRNA (miRNA) is essential for fatty acid metabolism and synthesis. Predicted by website and combined with pre-miRNA transcriptome sequencing results, we hypothesized that FABP4 might be the target gene of bta-miR-224. The results of the dual-luciferase reporter gene and qRT-PCR revealed that bta-miR-224 negatively regulated FABP4 expression by targeting the 3′-UTR of FABP4. By exploring the function of bta-miR-224, we observed that bta-miR-224 mimics downregulated the expression of the milk fat marker genes AGPAT6, ACSS2, and XDH and inhibited TG synthesis and lipid droplet secretion. However, the bta-miR-224 inhibitor depicted the opposite results. In conclusion, FABP4 plays a crucial role in regulating BMEC proliferation and differentiation. Bta-miR-224 targeting FABP4 may promote biological processes such as TG synthesis and lipid droplet formation through PPARG, which lays a solid foundation for further analysis of the functional mechanism of milk lipid metabolism in dairy cows from a miRNA-mRNA perspective.
乳脂由乳腺产生和分泌,主要受饮食和基因-分子网络调控。因此,了解乳脂合成的分子机制对提高牛奶质量具有重要的现实意义。脂肪酸结合蛋白 4(FABP4)是对高奶脂组和低奶脂组奶牛乳腺上皮细胞进行转录组学分析获得的与乳脂代谢密切相关的候选信使 RNA(mRNA),其表达模式和功能尚不清楚。qRT-PCR 结果显示,FABP4 在乳腺组织和高乳脂组的牛乳腺上皮细胞(BMECs)中高表达。随后,通过CCK8、EdU和流式细胞术分析了FABP4对BMECs的调控作用,结果表明FABP4抑制了BMECs的增殖和活力,促进了其凋亡。将 pEGFP-N1-FABP4 转染到 BMECs 中,FABP4 上调了乳脂标志基因 XDH、PPARG 和 ACSS2 的表达水平,并促进了甘油三酯(TGs)、胆固醇、脂滴和 β-酪蛋白的形成。利用 STRING 预测发现了 FABP4 和 PPARG 之间的强相互作用。Western印迹显示,FABP4与PPARG相互作用促进PPARG的表达,而干扰FABP4后则观察到相反的结果。microRNA(miRNA)的基因调控对脂肪酸的代谢和合成至关重要。根据网站预测并结合前期 miRNA 转录组测序结果,我们推测 FABP4 可能是 bta-miR-224 的靶基因。双荧光素酶报告基因和 qRT-PCR 的结果显示,bta-miR-224 通过靶向 FABP4 的 3'-UTR 负向调控 FABP4 的表达。通过探索 bta-miR-224 的功能,我们观察到 bta-miR-224 模拟物下调了乳脂标记基因 AGPAT6、ACSS2 和 XDH 的表达,并抑制了 TG 的合成和脂滴的分泌。然而,bta-miR-224 抑制剂则表现出相反的结果。总之,FABP4 在调节 BMEC 的增殖和分化过程中起着至关重要的作用。靶向 FABP4 的 Bta-miR-224 可通过 PPARG 促进 TG 合成和脂滴形成等生物学过程,这为从 miRNA-mRNA 角度进一步分析奶牛乳脂代谢的功能机制奠定了坚实的基础。
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引用次数: 0
A systematic benchmark of copy number variation detection tools for high density SNP genotyping arrays 高密度 SNP 基因分型阵列拷贝数变异检测工具的系统基准。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110962
M.N. van Baardwijk , L.S.E.M. Heijnen , H. Zhao , M. Baudis , A.P. Stubbs
Copy Number Variations (CNVs) are crucial in various diseases, especially cancer, but detecting them accurately from SNP genotyping arrays remains challenging. Therefore, this study benchmarked five CNV detection tools—PennCNV, QuantiSNP, iPattern, EnsembleCNV, and R-GADA—using SNP array and WGS data from 2002 individuals of the DRAGEN re-analysis of the 1000 Genomes project. Results showed significant variability in tool performance. R-GADA had the highest recall but low precision, while PennCNV was the most reliable in terms of precision and F1 score. EnsembleCNV improved recall by combining multiple callers but increased false positives. Overall, current tools, including new methods, do not outperform PennCNV in precise CNV detection. Improved reference data and consensus on true positive CNV calls are necessary. This study provides valuable insights and scalable workflows for researchers selecting CNV detection methods in future studies.
拷贝数变异(CNV)在各种疾病尤其是癌症中至关重要,但从 SNP 基因分型阵列中准确检测 CNV 仍是一项挑战。因此,本研究利用千人基因组计划 DRAGEN 再分析 2002 个个体的 SNP 阵列和 WGS 数据,对五种 CNV 检测工具--PennCNV、QuantiSNP、iPattern、EnsembleCNV 和 R-GADA 进行了基准测试。结果显示,工具性能存在很大差异。R-GADA 的召回率最高,但精确度较低,而 PennCNV 在精确度和 F1 分数方面最为可靠。EnsembleCNV 通过结合多个调用者提高了召回率,但增加了假阳性。总体而言,包括新方法在内的现有工具在精确 CNV 检测方面并没有超过 PennCNV。有必要改进参考数据并就真阳性 CNV 调用达成共识。这项研究为研究人员在未来的研究中选择 CNV 检测方法提供了宝贵的见解和可扩展的工作流程。
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引用次数: 0
Whole-Genome sequencing of Calonectria dianii: An important pathogen causing Eucalyptus leaf blight Calonectria dianii 的全基因组测序:引起桉树叶枯病的一种重要病原体。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110967
QianLi Liu , FeiFei Liu , GuoQing Li , KaiDong Liu , ZhenChi Huang , ShanNi Cao , JunDi Zhong
Eucalyptus leaf blight, caused by Calonectria spp., significantly impacts the global Eucalyptus industry. Calonectria dianii, as one of the predominant causal agents, poses a serious threat to Eucalyptus plantations in China. To enhance our understanding of its pathogenic mechanisms, we sequenced the genome of C. dianii RIFT 6520 using both Nanopore PromethION and Illumina NovaSeq PE150 platforms. Our analysis revealed a 61.76 Mb genome comprising 30 contigs with an N50 of 4,726,631 bp, a GC content of 49.74 %, and 10,184 predicted coding genes. Additionally, comparative genomic analysis between C. dianii and seven other significant plant-pathogenic Calonectria species was conducted. This analysis provided insights into the evolutionary relationships and adaptive mechanisms of these pathogens. Our study elucidates the genetic basis of C. dianii's pathogenicity and evolution, providing valuable information for future research on its molecular interactions with Eucalyptus and aiding in the development of precise control measures for Eucalyptus leaf blight.
Calonectria spp.引起的桉树叶枯病严重影响着全球桉树产业。Calonectria dianii 是主要病原菌之一,对中国的桉树种植园构成严重威胁。为了加深对其致病机制的了解,我们使用 Nanopore PromethION 和 Illumina NovaSeq PE150 平台对 C. dianii RIFT 6520 的基因组进行了测序。我们的分析结果显示,基因组大小为 61.76 Mb,由 30 个等位基因组成,N50 为 4,726,631 bp,GC 含量为 49.74 %,预测编码基因为 10,184 个。此外,还对 C. dianii 和其他 7 个重要的植物致病性 Calonectria 物种进行了基因组比较分析。这项分析有助于深入了解这些病原体的进化关系和适应机制。我们的研究阐明了 C. dianii 的致病性和进化的遗传基础,为今后研究其与桉树的分子相互作用提供了宝贵的信息,并有助于制定精确的桉树叶枯病控制措施。
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引用次数: 0
Determining the effect of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) on the transcriptome profile in cervical cancer cell lines 确定长非编码 RNA 母系表达基因 3(lncRNA MEG3)对宫颈癌细胞系转录组特征的影响
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110957
Solomon Arega , Suchanda Dey , Sunil Pani , Somya Ranjan Dash , Roli Budhwar , Chanakya Nath Kundu , Niladri Ganguly
This study investigates the role of the long non-coding RNA Maternally Expressed Gene3 (lncRNA MEG3) gene in cervical cancer, as evidenced by its downregulation in cancerous cell lines. The study demonstrates the effects of the overexpression of lncRNA MEG3 in cervical cancer cell lines, particularly in C33A and CaSki. Through comprehensive analyses, including Next-Generation Sequencing (NGS), alterations in global mRNA expression were analyzed. In C33A cells, 67 genes were upregulated, while 303 genes were downregulated. Similarly, in CaSki cells, 221 genes showed upregulation and 248 genes displayed downregulation. Gene ontology and KEGG pathway analyses were conducted to gain insight into potential mechanisms. Furthermore, the study delves into gene regulatory networks, uncovering intricate interactions among genes. The RNA sequencing data were confirmed for eight genes: PAX3, EGR2, ROR1, NRP1, OAS2, STRA6, CA9, and EDN2 by Real-time PCR. The findings illuminate the complex landscape of gene expression alterations and pathways impacted by the overexpression of lncRNA MEG3. The impact of MEG3 on the overall cervical cancer cells' mRNA profile is reported for the first time. New biomarkers for the prognosis of cervical cancer are also reported in this study. Moreover, identifying specific genes within the regulatory networks provides valuable insights into potential therapeutic targets for managing cervical cancer.
本研究调查了长非编码 RNA 母系表达基因 3(lncRNA MEG3)基因在宫颈癌中的作用,该基因在癌细胞系中的下调证明了这一点。该研究证明了 lncRNA MEG3 在宫颈癌细胞系中过表达的影响,尤其是在 C33A 和 CaSki 中。通过综合分析,包括下一代测序(NGS),分析了全球 mRNA 表达的变化。在 C33A 细胞中,67 个基因上调,303 个基因下调。同样,在 CaSki 细胞中,221 个基因上调,248 个基因下调。通过基因本体和 KEGG 通路分析,研究人员深入了解了潜在的机制。此外,该研究还深入研究了基因调控网络,揭示了基因之间错综复杂的相互作用。RNA测序数据确认了八个基因:Real-time PCR对PAX3、EGR2、ROR1、NRP1、OAS2、STRA6、CA9和EDN2八个基因的RNA测序数据进行了确认。研究结果阐明了受 lncRNA MEG3 过表达影响的基因表达改变和通路的复杂情况。该研究首次报道了MEG3对宫颈癌细胞整体mRNA谱的影响。该研究还报告了宫颈癌预后的新生物标志物。此外,识别调控网络中的特定基因为宫颈癌的潜在治疗目标提供了宝贵的见解。
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引用次数: 0
Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen 通过颌下淋巴结、外周血和脾脏中的长非编码 RNA 调节奶牛的细胞介导免疫反应。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110958
Xiuxin Zhao , Xiao Wang , Guanghui Xue , Yundong Gao , Yuanpei Zhang , Yanqin Li , Yachun Wang , Jianbin Li
Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with heat-killed preparation of Candida albicans (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.
细胞介导的免疫应答(CMIRs)对于建立强大的免疫系统和降低牛的疾病易感性至关重要。长非编码 RNA(lncRNA)可调控各种生物过程。然而,据我们所知,lncRNA 的特征和功能及其对牛 CMIR 的调控尚未得到全面研究。本研究用白念珠菌热处理制剂(HKCA)对实验公牛进行免疫,以诱导迟发型超敏反应(DTH)。根据其典型的 DTH 皮肤反应,三头公牛被归类为高 CMIR 反应者,三头为低 CMIR 反应者。利用链特异性 RNA 测序鉴定了高 CMIR 和低 CMIR 动物颌下淋巴结、外周血和脾脏中的 LncRNA。在各组织中共鉴定出 21,003 个推测的 lncRNA,在两组动物的颌下淋巴结、外周血和脾脏组织中,分别有 420、468 和 599 个 lncRNA 存在差异表达。对差异表达的lncRNA(DElncRNA)靶基因进行的功能分析显示,富集了许多与免疫相关的基因本体(GO)术语和京都基因组百科全书(KEGG)通路,包括免疫反应、细胞粘附、核小体、DNA包装、抗原加工和递呈以及补体和凝血级联。组织特异性分析表明,与 mRNA 相比,lncRNA 转录本具有更强的组织特异性。此外,基于DElncRNA和DEGs构建了一个相互作用网络,并分别鉴定出11、14和11个有希望的lncRNA作为影响颌下淋巴结、外周血和脾脏组织免疫应答调控的潜在候选基因。这些结果为进一步研究与牛CMIR相关的lncRNA的生物学功能以及鉴定细胞介导免疫反应的候选lncRNA标记物奠定了基础。
{"title":"Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen","authors":"Xiuxin Zhao ,&nbsp;Xiao Wang ,&nbsp;Guanghui Xue ,&nbsp;Yundong Gao ,&nbsp;Yuanpei Zhang ,&nbsp;Yanqin Li ,&nbsp;Yachun Wang ,&nbsp;Jianbin Li","doi":"10.1016/j.ygeno.2024.110958","DOIUrl":"10.1016/j.ygeno.2024.110958","url":null,"abstract":"<div><div>Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with heat-killed preparation of <em>Candida albicans</em> (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"116 6","pages":"Article 110958"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142618326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genomic evolution and patterns of horizontal gene transfer in Papilio Papilio 的基因组进化和水平基因转移模式。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110956
Jiajia Wang, Yunfei Wu, Linxin Zhu, Kaixin Guo, Shichen Gao, Yan Dong
The Papilio genus, known for its ecological and phenotypic diversity, is a valuable model for evolutionary studies. This study conducted a comparative genomic analysis of 11 Papilio species, revealing species-specific gene family expansions, including the UDP-glucosyltransferase 2 gene associated with insect detoxification, particularly expanding in Papilio polyxenes. Our analysis also revealed 199 horizontal gene transfer (HGT) acquired genes from 76 microbial species, with Pseudomonadota and Bacillota as common HGT donors across these genomes. Furthermore, we examined the evolutionary patterns of nine ABC transporter subfamilies, uncovering potential links between gene family evolution and environmental adaptation. This study provides new insights into evolutionary relationships and genomic adaptations within the Papilio genus, contributing to broader butterfly evolutionary research.
以生态和表型多样性著称的雉鸡属是一个宝贵的进化研究模型。本研究对 11 个蝶形目物种进行了基因组比较分析,发现了物种特异性基因家族的扩展,包括与昆虫解毒有关的 UDP- 葡糖基转移酶 2 基因,该基因在多蝶形目中的扩展尤为明显。我们的分析还揭示了从 76 个微生物物种中获得的 199 个水平基因转移(HGT)基因,假单胞菌和芽孢杆菌是这些基因组中常见的 HGT 供体。此外,我们还研究了九个 ABC 转运体亚家族的进化模式,发现了基因家族进化与环境适应之间的潜在联系。这项研究为我们了解蝶属的进化关系和基因组适应性提供了新的视角,有助于更广泛的蝴蝶进化研究。
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引用次数: 0
Identification of heat stress-related genomic regions by genome-wide association study in Solanum tuberosum 通过对 Solanum tuberosum 进行全基因组关联研究,确定与热胁迫相关的基因组区域。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-11-01 DOI: 10.1016/j.ygeno.2024.110954
Alexander Kaier , Selina Beck , Markus Ingold , José María Corral , Stephan Reinert, Uwe Sonnewald, Sophia Sonnewald
The climate crisis impairs yield and quality of crucial crops like potatoes. We investigated the effects of heat stress on five morpho-physiological parameters in a diverse panel of 178 potato cultivars under glasshouse conditions. Overall, heat stress increased shoot elongation and green fresh weight, but reduced tuber yield, starch content and harvest index. Genomic information was obtained from 258 tetraploid and three diploid cultivars by a genotyping-by-sequencing approach using methylation-sensitive restriction enzymes. This resulted in an enrichment of sequences in gene-rich regions. Population structure analyses using genetic distances and hierarchical clustering revealed strong kinship but weak overall population structure cultivars. A genome-wide association study (GWAS) was conducted with a subset of 20 K stringently filtered SNPs to identify quantitative trait loci (QTL) linked to heat tolerance. We identified 67 QTL and established haploblock boundaries to narrow down the number of candidate genes. Additionally, GO-enrichment analyses provided insights into gene functions. Heritability and genomic prediction were conducted to assess the usability of the collected data for selecting breeding material. The detected QTL might be exploited in marker-assisted selection to develop heat-resilient potato cultivars.
气候危机损害了马铃薯等重要作物的产量和质量。我们研究了热胁迫对玻璃温室条件下 178 个马铃薯栽培品种的五个形态生理参数的影响。总体而言,热胁迫增加了芽的伸长率和绿色鲜重,但降低了块茎产量、淀粉含量和收获指数。利用甲基化敏感的限制性酶,通过基因分型测序方法从 258 个四倍体和 3 个二倍体栽培品种中获得了基因组信息。这使得基因富集区的序列更加丰富。利用遗传距离和分层聚类进行的种群结构分析表明,栽培品种的亲缘关系很强,但总体种群结构较弱。我们利用经过严格筛选的 20 K 个 SNPs 子集进行了全基因组关联研究(GWAS),以确定与耐热性相关的数量性状位点(QTL)。我们确定了 67 个 QTL,并建立了单倍块边界以缩小候选基因的数量。此外,GO 富集分析还提供了对基因功能的深入了解。为了评估所收集数据在选育材料中的可用性,研究人员进行了遗传性和基因组预测。检测到的 QTL 可用于标记辅助选择,以培育抗热性马铃薯栽培品种。
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引用次数: 0
Association between salivary microbiota and tacrolimus pharmacokinetic variability in kidney transplant 肾移植患者唾液微生物群与他克莫司药代动力学变异之间的关系
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-18 DOI: 10.1016/j.ygeno.2024.110952
Xuyu Xiang , Yi Zhu , Tianyin Wang , Peng Ding , Ke Cheng , Yingzi Ming
Kidney transplantation (KT) serves as a highly effective treatment for end-stage renal disease (ESRD). Nonetheless, the administration of tacrolimus, a commonly used immunosuppressant in KT, faces challenges due to the lack of dependable biomarkers for its efficacy and the considerable variability in tacrolimus pharmacokinetics (TacIPV). In this study, 183 saliva samples from 48 KT recipients under tacrolimus therapy, alongside 9 healthy control samples, were subjected to 16S rRNA sequencing. The analysis revealed significant differences in the composition of salivary microbiota among KT recipients, patients with ESRD, and healthy controls. Moreover, trough blood concentrations (C0) of tacrolimus were associated with alterations in microbiota composition. Notably, Capnocytophage consistently exhibited a negative correlation in both group-level and individual trends. Furthermore, distinct taxa were identified that effectively distinguished recipients with varying TacIPV, as demonstrated by a cross-validation random forest model (mean AUC = 0.7560), with Anaerolinea emerging as a prominent contributor to the classifier. These findings suggest that salivary microbiota is closely linked to tacrolimus C0 levels and could aid clinicians in differentiating KT recipients based on TacIPV.
肾移植(KT)是治疗终末期肾病(ESRD)的高效疗法。然而,由于缺乏可靠的生物标志物来衡量他克莫司的疗效,而且他克莫司的药代动力学(TacIPV)存在很大的变异性,因此肾移植中常用的免疫抑制剂他克莫司的用药面临着挑战。在这项研究中,对来自 48 名接受他克莫司治疗的 KT 患者的 183 份唾液样本和 9 份健康对照样本进行了 16S rRNA 测序。分析结果显示,KT 受者、ESRD 患者和健康对照组的唾液微生物群组成存在明显差异。此外,他克莫司的血液谷浓度(C0)与微生物群组成的改变有关。值得注意的是,Capnocytophage 在群体水平和个体趋势中始终表现出负相关。此外,交叉验证随机森林模型(平均 AUC = 0.7560)表明,不同的分类群能有效区分不同 TacIPV 的受试者,其中 Anaerolinea 是分类群的主要贡献者。这些研究结果表明,唾液微生物群与他克莫司 C0 水平密切相关,可以帮助临床医生根据 TacIPV 区分 KT 受体。
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引用次数: 0
Characterization of small RNAs in the spleen of MASH in a non-human primate model 非人灵长类动物模型 MASH 脾脏中小 RNA 的特征。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.ygeno.2024.110953
Juan Zhao , Yuelei Zhao , Hongyu Qin , Yun Ye , Liwei Zhang , Ruike Ding , Wenbin Cao , Yanru Zhang , Chenjing Duan , Haoze Leng , Yandong Li , Bo Wang , Liangshuo Hu , Enqi Liu , Pengxiang Qu
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its advanced stage, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as a global health issue. This study examines the role of small RNAs in the spleen of MASH using a non-human primate model. We performed high-throughput small RNA sequencing on spleen tissues from MASH-primates, revealing significant alterations in the expression of small non-coding RNAs, especially miRNAs. Notably, miR-96, miR-182, miR-183, and miR-122 showed differential expression in MASH spleens. Predictive and validation studies have identified potential target genes, such as PTX3 and NFIX, that were significantly dysregulated in spleens of MASH. These findings characterized small RNAs in spleen of MASH and offer a novel insight for further research for MASH.
代谢功能障碍相关性脂肪性肝病(MASLD)及其晚期阶段--代谢功能障碍相关性脂肪性肝炎(MASH)--越来越被认为是一个全球性的健康问题。本研究利用非人灵长类动物模型研究了小 RNA 在 MASH 脾脏中的作用。我们对 MASH-原猴的脾脏组织进行了高通量小 RNA 测序,发现小非编码 RNA,尤其是 miRNA 的表达发生了显著变化。值得注意的是,miR-96、miR-182、miR-183 和 miR-122 在 MASH 脾脏中的表达存在差异。预测和验证研究发现了潜在的靶基因,如 PTX3 和 NFIX,这些基因在 MASH 脾脏中明显失调。这些发现揭示了MASH脾脏中小RNA的特征,为进一步研究MASH提供了新的视角。
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引用次数: 0
PLOD1 promote proliferation and migration with glycolysis via the Wnt/β-catenin pathway in THCA PLOD1通过Wnt/β-catenin途径促进THCA中糖酵解的增殖和迁移。
IF 3.4 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-10-16 DOI: 10.1016/j.ygeno.2024.110943
Wei Cong, Jingfu Sun, Zhanyu Hao, Maosong Gong, Jianing Liu
THCA (Thyroid carcinoma) is the most common endocrine malignancy in the world. The PLOD1 is highly expressed in THCA, but the mechanism is still unclear. It is found that the cell proliferation and migration were inhibited in si-PLOD1 group, and promoted with PLOD1 overexpression. MAZ is the transcription factor of PLOD1. The cell activities induced MAZ were reversed by si-PLOD1. The Glucose uptake, lactate production and ATP/ADP ratio were decreased with si-PLOD1. The glycolysis related proteins GLUT1, HK2, PFKP, PKM2, LDHA and Wnt/β-catenin pathway proteins WNT5A, cyclin D1, β-catenin were inhibited, GSK-3β is increased in si-PLOD1 group. BML-284 could reversed the si-PLOD1 effects on cell activities and Wnt/β-catenin pathway. The tumor xenografts were inhibited in si-PLOD1 group. As a potential therapeutic target, PLOD1 is regulated by MAZ in THCA. PLOD1 depletion could inhibit THCA cell proliferation and metastasis by glycolysis, which is inhibited by Wnt/β-catenin pathway in THCA.
甲状腺癌(THCA)是世界上最常见的内分泌恶性肿瘤。PLOD1 在 THCA 中高表达,但其机制尚不清楚。研究发现,si-PLOD1 组细胞增殖和迁移受抑制,而 PLOD1 过表达组细胞增殖和迁移受促进。MAZ 是 PLOD1 的转录因子。si-PLOD1 逆转了 MAZ 诱导的细胞活性。si-PLOD1 可降低葡萄糖摄取、乳酸生成和 ATP/ADP 比率。糖酵解相关蛋白 GLUT1、HK2、PFKP、PKM2、LDHA 和 Wnt/β-catenin 通路蛋白 WNT5A、细胞周期蛋白 D1、β-catenin 在 si-PLOD1 组受到抑制,GSK-3β 在 si-PLOD1 组增加。BML-284 可逆转 si-PLOD1 对细胞活性和 Wnt/β-catenin 通路的影响。si-PLOD1组的肿瘤异种移植受到抑制。作为一个潜在的治疗靶点,PLOD1在THCA中受MAZ调控。抑制PLOD1可以通过糖酵解抑制THCA细胞的增殖和转移,而糖酵解在THCA中受到Wnt/β-catenin通路的抑制。
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