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The mechanism and related research progress of GLP-1 receptor agonists in treating Alzheimer's disease. GLP-1受体激动剂治疗阿尔茨海默病的机制及相关研究进展。
Q3 Medicine Pub Date : 2024-12-01 DOI: 10.16288/j.yczz.24-178
Xiao-Cheng Zhu, Yi-Wen Wang, Hong-Wen Zhou

GLP-1 receptor agonists are primarily used clinically for the treatment of type 2 diabetes and have the potential for weight loss, while they are currently expanding their horizons in the treatment of hypertension, non-alcoholic liver disease, depression, and neurodegenerative diseases. In particular, in the treatment of Alzheimer's disease, a large number of animal models and a handful of clinical studies have demonstrated the potential efficacy of GLP-1 receptor agonists, making it highly probable that they will become a new entrant in the drug list for Alzheimer's disease. At present, the research on the mechanism of GLP-1 receptor agonist in the treatment of Alzheimer's disease is mainly based on in-depth analysis of the pathogenesis of Alzheimer's disease and exploration of the mechanism of its comorbidity with diabetes. This article mainly reviews the latest advances in the mechanism of GLP-1 receptor agonists in the treatment of Alzheimer's disease, introduces the latest achievements in animal studies and clinical studies, and aims to provide reference for the subsequent relevant basic research and clinical application.

GLP-1受体激动剂在临床上主要用于治疗2型糖尿病,具有减肥的潜力,目前正在扩大其在高血压、非酒精性肝病、抑郁症和神经退行性疾病的治疗领域。特别是在阿尔茨海默病的治疗方面,大量的动物模型和少量的临床研究已经证明了GLP-1受体激动剂的潜在疗效,使其极有可能成为阿尔茨海默病药物清单中的新进入者。目前对GLP-1受体激动剂治疗阿尔茨海默病机制的研究主要基于对阿尔茨海默病发病机制的深入分析和对其与糖尿病合并症机制的探索。本文主要综述GLP-1受体激动剂治疗阿尔茨海默病机制的最新进展,介绍动物研究和临床研究的最新成果,旨在为后续相关基础研究和临床应用提供参考。
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引用次数: 0
The carboxy-terminal domain of RNA polymerase II large subunit: simple repeats are not simple. RNA聚合酶ⅱ大亚基羧基末端结构域:简单重复序列并不简单。
Q3 Medicine Pub Date : 2024-12-01 DOI: 10.16288/j.yczz.24-200
Qi Li, Zhi-Cheng Dong, Min Liu

Transcription, as a crucial step in the transmission of genetic information, is completed by DNA-dependent RNA polymerase. In eukaryotes, the transcription of protein-coding genes is completed by RNA polymerase II (Pol II). A distinctive feature of Pol II is the carboxy-terminal domain (CTD) of its largest subunit, RPB1, which is composed of a series of heptapeptide repeats that play a vital role in transcription. Here, we provide a comprehensive review and summary of the sequence characteristics and evolutionary trajectory of the eukaryotic RPB1 CTD, as well as its regulatory function within the transcription cycle. We particularly focus on the mechanisms by which the CTD participates in the regulation of transcription and co-transcriptional processing through post-translational modifications. This deepens our understanding of the intricate regulatory mechanisms governing gene transcription in eukaryotes and lays the groundwork for further investigation into the role of the RPB1 CTD.

转录是遗传信息传递的关键步骤,是由依赖dna的RNA聚合酶完成的。在真核生物中,蛋白质编码基因的转录是由RNA聚合酶II (Pol II)完成的。Pol II的一个显著特征是其最大亚基RPB1的羧基末端结构域(CTD),它由一系列七肽重复组成,在转录中起着至关重要的作用。本文对真核生物RPB1 CTD的序列特征、进化轨迹及其在转录周期中的调控功能进行了综述。我们特别关注CTD通过翻译后修饰参与转录和共转录过程调控的机制。这加深了我们对真核生物基因转录复杂调控机制的理解,并为进一步研究RPB1 CTD的作用奠定了基础。
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引用次数: 0
Progress on molecular mechanisms of bacterial transcription termination. 细菌转录终止的分子机制研究进展。
Q3 Medicine Pub Date : 2024-12-01 DOI: 10.16288/j.yczz.24-244
Lin-Lin You, Yu Zhang

Transcription is the process by which genetic information is copied from DNA to RNA, and it can be divided into three stages: transcription initiation, elongation, and termination. Transcription termination is the last step of gene transcription and is crucial for accurate gene expression. Two prevailing modes of transcription termination exist in bacteria: Rho-dependent termination and intrinsic termination (Rho-independent termination). Transcription termination is positively and negatively regulated by bacterial or bacteriophage proteins. In this review, we summarize the research progress of bacterial transcription and its regulation, with the aim of providing a theoretical foundation for further studies and understanding of transcription termination process.

转录是遗传信息从DNA复制到RNA的过程,它可以分为三个阶段:转录起始、转录延伸和转录终止。转录终止是基因转录的最后一步,是基因准确表达的关键。细菌中存在两种主要的转录终止模式:rho依赖性终止和内在终止(rho非依赖性终止)。转录终止受细菌或噬菌体蛋白的正向和负向调节。本文就细菌转录及其调控的研究进展进行综述,以期为进一步研究和理解转录终止过程提供理论基础。
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引用次数: 0
Research progresses on non-coding DNA regulatory elements in the evolution of animal adaptive traits. 非编码DNA调控元件在动物适应性状进化中的研究进展。
Q3 Medicine Pub Date : 2024-12-01 DOI: 10.16288/j.yczz.24-272
Xiu-Hong Wu, Ya-Jun Wang, Li-Feng Che, Xiao-Ping Wang

Driven by adaptive evolution, animals have developed a variety of adaptive traits that are critical to their survival and reproduction. Unraveling the molecular mechanisms of adaptive evolution is of key significance for understanding important biological phenomena such as species diversification and phenotypic convergence, etc. With the development and maturation of multi-omics technologies, genomic non-coding DNA regulatory elements have been proven to play important regulatory roles in the evolution of adaptive traits in animals. In this review, we summarize the characteristics and mechanisms of non-coding DNA regulatory elements and reviews their molecular mechanisms in the evolution of adaptive traits in animals from three aspects: adaptive traits of animal appendages, traits for adaptation to extreme environments, and other special phenotypic adaptive traits. It offers significant insights for understanding the molecular mechanisms of adaptive trait evolution in animals.

在适应性进化的推动下,动物已经发展出各种适应特征,这些特征对它们的生存和繁殖至关重要。揭示适应进化的分子机制对理解物种多样化、表型趋同等重要生物现象具有重要意义。随着多组学技术的发展和成熟,基因组非编码DNA调控元件已被证明在动物适应性状的进化中发挥着重要的调控作用。本文从动物附属物的适应性状、极端环境的适应性状和其他特殊的表型适应性状三个方面,综述了非编码DNA调控元件的特点和作用机制,并对其在动物适应性状进化中的分子机制进行了综述。它为理解动物适应性状进化的分子机制提供了重要的见解。
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引用次数: 0
Design and practice of educational experiments on genetic epistasis. 遗传表观性教育实验的设计与实践。
Q3 Medicine Pub Date : 2024-11-01 DOI: 10.16288/j.yczz.24-248
Yi Shi, Yao Yu, Yi-Lin Lü, Hong Lü

Genetic epistasis is a fundamental concept in genetics that describes how interactions between genes determine phenotypic traits. To enhance students' understanding and practical application of genetic epistasis, this experiment is designed and conducted using gene mutations in the adenine biosynthesis pathway of Saccharomyces cerevisiae (baker's yeast). S. cerevisiae is a classic model organism for genetic teaching experiments. In its adenine biosynthesis pathway, a mutation in the ADE2 gene leads to the accumulation of the intermediate 5'-phosphoribosylaminoimidazole (AIR), causing the cells to appear red. However, if a gene upstream of ADE2 in the adenine biosynthesis pathway (such as ADE8) is defective, the red phenotype of yeast will disappear. Conversely, a defect in a gene downstream of ADE2 (such as ADE1) does not alter the red phenotype. Therefore, ADE8 is epistatic to ADE2. In this experiment, the CRISPR-Cas9 genome editing technology is employed, allowing students to perform single knockout of ade2Δ, as well as double knockouts of ade2Δade8Δ and ade2Δade1Δ in S. cerevisiae. By observing the phenotypic changes in yeast mutants from white to red and back to white, students gain a profound understanding of the basic genetic theory of how genes determine phenotypes and the concept of epistasis in gene interactions. This experiment also enables students to master fundamental yeast genetic techniques, significantly enhancing their ability to design and conduct experiments in real research environments. This is of great significance for their future research work and academic development.

遗传表观性是遗传学中的一个基本概念,它描述了基因之间的相互作用如何决定表型性状。为了加强学生对遗传表观性的理解和实际应用,本实验设计并使用了酿酒酵母(面包酵母)腺嘌呤生物合成途径中的基因突变。酿酒酵母是遗传教学实验的经典模式生物。在其腺嘌呤生物合成途径中,ADE2 基因突变会导致中间体 5'- 磷酸核糖基氨基咪唑(AIR)的积累,从而使细胞呈现红色。但是,如果腺嘌呤生物合成途径中 ADE2 上游的一个基因(如 ADE8)出现缺陷,酵母的红色表型就会消失。相反,ADE2 下游基因(如 ADE1)的缺陷不会改变红色表型。因此,ADE8 是 ADE2 的外显子。在本实验中,学生利用 CRISPR-Cas9 基因组编辑技术,对 S. cerevisiae 进行了 ade2Δ 的单基因敲除,以及 ade2Δade8Δ 和 ade2Δade1Δ 的双基因敲除。通过观察酵母突变体从白色到红色再到白色的表型变化,学生深刻理解了基因决定表型的基本遗传理论和基因相互作用中的表观遗传概念。本实验还使学生掌握了基本的酵母遗传技术,大大提高了他们在实际研究环境中设计和进行实验的能力。这对他们今后的研究工作和学术发展具有重要意义。
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引用次数: 0
Identification and functional characterization of CD209 homologous genes in zebrafish. 斑马鱼 CD209 同源基因的鉴定和功能表征
Q3 Medicine Pub Date : 2024-11-01 DOI: 10.16288/j.yczz.24-181
Xiao-Jun Yang, Zhen-Han Huang, Wei Liu, Wen-Qing Zhang, Zhi-Bin Huang

Innate immune responses play a crucial role in maintaining homeostasis, their initiation closely related to pattern recognition receptors or damage-associated molecules on the surface of innate immune cells. CD209, a pattern recognition receptor on the surface of macrophages or dendritic cells, plays an important role in immune functions. However, the impact of CD209 on innate immune cells such as macrophages or neutrophils in vivo remains unclear. In this study, through multiple sequence alignment and phylogenetic tree construction, three genes homologous to human CD209 were found in zebrafish. These are cd209(Ensembl ID:ENSDARG00000029461), zgc:174904(Ensembl ID:ENSDARG00000059049) and si:dkey-187I7.2(Ensembl ID: ENSDARG00000096624).Compared to the cd209 and si:dkey-187i8.2 genes in the Ensembl database, zgc:174904 is more similar to human CD209 in sequence. Using whole-mount in situ hybridization and fluorescence co-localization experiments, it was found that zgc:174904 is mainly expressed in macrophages. Further morpholino knockdown experiments showed that knocking down zgc:174904 leads to an upregulation of M1-type macrophage-related genes and a decrease in the number of mature neutrophils, indicating that zgc:174904 is functionally more similar to CD209. These findings not only reveal the potential role of CD209 in regulating macrophage function and neutrophil development but also provide significant insights for research into the mechanisms of innate immunity.

先天性免疫反应在维持体内平衡方面发挥着至关重要的作用,其启动与先天性免疫细胞表面的模式识别受体或损伤相关分子密切相关。CD209 是巨噬细胞或树突状细胞表面的一种模式识别受体,在免疫功能中发挥着重要作用。然而,CD209 在体内对巨噬细胞或中性粒细胞等先天性免疫细胞的影响仍不清楚。本研究通过多序列比对和系统发生树的构建,在斑马鱼中发现了三个与人类 CD209 同源的基因。与Ensembl数据库中的cd209和si:dkey-187i8.2基因相比,zgc:174904与人类CD209的序列更为相似。通过整装原位杂交和荧光共定位实验发现,zgc:174904 主要在巨噬细胞中表达。进一步的吗啉敲除实验表明,敲除zgc:174904会导致M1型巨噬细胞相关基因的上调和成熟中性粒细胞数量的减少,这表明zgc:174904在功能上与CD209更为相似。这些发现不仅揭示了CD209在调控巨噬细胞功能和中性粒细胞发育中的潜在作用,而且为先天性免疫机制的研究提供了重要启示。
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引用次数: 0
Progress on the mining of functional genes of Lonicera japonica. 忍冬功能基因的挖掘进展。
Q3 Medicine Pub Date : 2024-11-01 DOI: 10.16288/j.yczz.24-190
Nan Sun, Lu-Yao Huang, Sheng Yang, Jia Li, Cong-Zhe Hou, Zhen-Hua Liu

Lonicera japonica Thunb. is a semi-evergreen climbing shrub belonging to the Caprifoliaceae family, whose dried flower buds or flowers on the verge of blooming are known as Jin Yin Hua in traditional Chinese medicine. This plant is not only a high-value and widely used medicinal material but also possesses characteristics that make it suitable for both medicinal and culinary purposes. Currently, there is a robust market demand for Jin Yin Hua, yet the breeding technology for new varieties of Lonicera japonica lags behind, necessitating the integration of modern breeding techniques. With the advancement of genomics in Lonicera japonica, an increasing number of functional genes have been identified, amassing a rich reservoir of genetic resources for molecular breeding of this species. In this review, we summarize the progress in Lonicera japonica genomics, functional gene mining, and the establishment of genetic transformation systems. In light of the existing challenges and deficiencies in the research of functional genes and quality breeding of Lonicera japonica, it is imperative to establish a germplasm resource bank, a mutant library, and an efficient genetic transformation system for this plant. Intensive research into the mining and identification of functional genes should be conducted, and molecular markers closely linked to the functional genes of Lonicera japonica should be developed. This will lay a foundational basis for the identification and cultivation of breakthrough varieties with superior qualities in Lonicera japonica.

忍冬是一种半常绿攀援灌木,属于木犀科,其干燥花蕾或即将绽放的花朵在传统中药中被称为金银花。这种植物不仅是一种价值高、用途广的药材,还具有药食两用的特点。目前,市场对金银花的需求旺盛,但忍冬新品种的育种技术却相对滞后,因此有必要整合现代育种技术。随着忍冬基因组学的发展,越来越多的功能基因被鉴定出来,为该品种的分子育种积累了丰富的遗传资源。在本综述中,我们总结了忍冬基因组学、功能基因挖掘和遗传转化系统建立方面的进展。鉴于目前在忍冬功能基因研究和优质育种方面存在的挑战和不足,建立忍冬种质资源库、突变体库和高效的遗传转化系统势在必行。应深入开展功能基因的挖掘和鉴定研究,开发与忍冬功能基因密切相关的分子标记。这将为鉴定和培育具有优异品质的忍冬突破性品种奠定基础。
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引用次数: 0
Dual-localization signals enhance mitochondrial targeted presentation of engineered proteins. 双定位信号增强了线粒体对工程蛋白质的定向呈现。
Q3 Medicine Pub Date : 2024-11-01 DOI: 10.16288/j.yczz.24-171
Bing-Qian Zhou, Shang-Pu Li, Xu Wang, Xiang-Yu Meng, Jing-Rong Deng, Jin-Liang Xing, Jian-Gang Wang, Kun Xu

Effective delivery of engineered proteins into mitochondria is of great significance for developing efficient mitochondrial DNA editing tools and realizing accurate treatment of mitochondrial diseases. Here, the candidate genes, eGFP and Cas9, were engineered with different mitochondrial localization signal (MLS) sequences introduced at their up- or/and down-streams. The corresponding expression vectors for the engineered proteins were constructed respectively, and HEK293T cells were transfected with these vectors. The fluorescence colocalization and Western blotting assays were used to analyze the mitochondrial targeting presentation effect of different engineered proteins. The results demonstrated that the daul-MLS modification of the eGFP and Cas9 proteins significantly improved the efficiency of mitochondrial targeted presentation, compared with the engineered proteins with single MLS added. Hence, it is speculated that dual MLS strategy can enhance the mitochondrial targeting of engineered proteins, which lays a theoretical foundation for the future development of efficient mitochondrial DNA editing tools.

将工程蛋白有效地输送到线粒体对开发高效的线粒体 DNA 编辑工具和实现线粒体疾病的精确治疗具有重要意义。在这里,候选基因eGFP和Cas9在其上/下游引入了不同的线粒体定位信号(MLS)序列。分别构建了工程蛋白的相应表达载体,并用这些载体转染 HEK293T 细胞。利用荧光共定位和 Western 印迹法分析了不同工程蛋白的线粒体靶向表达效果。结果表明,与添加了单MLS的工程蛋白相比,eGFP和Cas9蛋白经daul-MLS修饰后,线粒体靶向呈现的效率明显提高。因此,可以推测双MLS策略可以提高工程蛋白的线粒体靶向性,这为未来开发高效的线粒体DNA编辑工具奠定了理论基础。
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引用次数: 0
Drug resistance mechanism of anti-angiogenesis therapy in tumor. 肿瘤抗血管生成治疗的耐药机制。
Q3 Medicine Pub Date : 2024-11-01 DOI: 10.16288/j.yczz.24-110
Xu Yan, Ying Guo, Dong-Lin Sun, Nan Wu, Yan Jin

Angiogenesis refers to the process of forming a new network of blood vessels from existing ones through the migration, proliferation, and differentiation of endothelial cells. This process is crucial for the growth and spread of solid tumors, particularly once the tumor volume exceeds 2 mm3, as the newly formed vascular network provides essential oxygen, nutrients, and growth factors to the tumor. Anti-angiogenesis therapy has become one of the commonly used targeted treatments for cancer in clinical practice. Bevacizumab, the first anti-angiogenesis drug, has been widely applied in the treatment of various solid tumors. However, due to acquired resistance, its efficacy is typically sustained for only 1 to 2 years. Despite the relative genomic stability of endothelial cells, which makes resistance less likely, various types of resistance phenomena have been observed in clinical practice, indicating that resistance to anti-angiogenic therapy remains a challenging research area. This review focuses on the latest advances in the mechanisms of resistance to anti-angiogenic therapy in tumors and explores new prospects for anti-tumor angiogenesis treatment, in order to provide strong theoretical support and guidance for clinical practice.

血管生成是指通过内皮细胞的迁移、增殖和分化,在原有血管的基础上形成新的血管网络的过程。这一过程对实体瘤的生长和扩散至关重要,尤其是当肿瘤体积超过 2 立方毫米时,因为新形成的血管网络可为肿瘤提供必需的氧气、营养物质和生长因子。抗血管生成疗法已成为临床上常用的癌症靶向治疗方法之一。贝伐单抗作为首个抗血管生成药物,已广泛应用于各种实体瘤的治疗。然而,由于存在获得性耐药性,其疗效通常只能维持 1 到 2 年。尽管内皮细胞的基因组相对稳定,不易产生耐药性,但在临床实践中还是观察到了各种类型的耐药现象,这表明抗血管生成治疗的耐药性仍然是一个具有挑战性的研究领域。本综述重点探讨肿瘤抗血管生成治疗耐药机制的最新进展,探索抗肿瘤血管生成治疗的新前景,以期为临床实践提供有力的理论支持和指导。
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引用次数: 0
Processing pipelines and analytical methods for single-cell DNA methylation sequencing data. 单细胞 DNA 甲基化测序数据的处理管道和分析方法。
Q3 Medicine Pub Date : 2024-10-01 DOI: 10.16288/j.yczz.24-154
Yan-Ni Wang, Jia Li

Single-cell DNA methylation sequencing technology has seen rapid advancements in recent years, playing a crucial role in uncovering cellular heterogeneity and the mechanisms of epigenetic regulation. As sequencing technologies have progressed, the quality and quantity of single-cell methylation data have also increased, making standardized preprocessing workflows and appropriate analysis methods essential for ensuring data comparability and result reliability. However, a comprehensive data analysis pipeline to guide researchers in mining existing data has yet to be established. This review systematically summarizes the preprocessing steps and analysis methods for single-cell methylation data, introduces relevant algorithms and tools, and explores the application prospects of single-cell methylation technology in neuroscience, hematopoietic differentiation, and cancer research. The aim is to provide guidance for researchers in data analysis and to promote the development and application of single-cell methylation sequencing technology.

近年来,单细胞 DNA 甲基化测序技术突飞猛进,在揭示细胞异质性和表观遗传调控机制方面发挥了至关重要的作用。随着测序技术的进步,单细胞甲基化数据的质量和数量也在不断增加,因此标准化的预处理工作流程和适当的分析方法对于确保数据的可比性和结果的可靠性至关重要。然而,指导研究人员挖掘现有数据的综合数据分析管道尚未建立。本综述系统总结了单细胞甲基化数据的预处理步骤和分析方法,介绍了相关算法和工具,并探讨了单细胞甲基化技术在神经科学、造血分化和癌症研究中的应用前景。旨在为研究人员提供数据分析指导,促进单细胞甲基化测序技术的发展和应用。
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引用次数: 0
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