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Research landmarks on the 60th anniversary of Epstein-Barr virus. Epstein-Barr 病毒 60 周年研究里程碑。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-04 DOI: 10.1007/s11427-024-2766-0
Lan-Yi Zhong, Chu Xie, Le-Le Zhang, Yan-Lin Yang, Yuan-Tao Liu, Ge-Xin Zhao, Guo-Long Bu, Xian-Shu Tian, Zi-Ying Jiang, Bo-Yu Yuan, Peng-Lin Li, Pei-Huang Wu, Wei-Hua Jia, Christian Münz, Benjamin E Gewurz, Qian Zhong, Cong Sun, Mu-Sheng Zeng

Epstein-Barr virus (EBV), the first human oncovirus discovered in 1964, has become a focal point in virology, immunology, and oncology because of its unique biological characteristics and significant role in human diseases. As we commemorate the 60th anniversary of EBV's discovery, it is an opportune moment to reflect on the major advancements in our understanding of this complex virus. In this review, we highlight key milestones in EBV research, including its virion structure and life cycle, interactions with the host immune system, association with EBV-associated diseases, and targeted intervention strategies.

Epstein-Barr 病毒(EBV)是 1964 年发现的第一种人类肿瘤病毒,由于其独特的生物学特性和在人类疾病中的重要作用,它已成为病毒学、免疫学和肿瘤学的焦点。在我们纪念 EBV 发现 60 周年之际,正是反思我们对这种复杂病毒的认识所取得的重大进展的好时机。在这篇综述中,我们将重点介绍 EBV 研究的重要里程碑,包括其病毒结构和生命周期、与宿主免疫系统的相互作用、与 EBV 相关疾病的关联以及有针对性的干预策略。
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引用次数: 0
COVID-19 vaccine updates for people under different conditions. 针对不同人群的 COVID-19 疫苗更新。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-29 DOI: 10.1007/s11427-024-2643-1
Yijiao Huang, Weiyang Wang, Yan Liu, Zai Wang, Bin Cao

SARS-CoV-2 has caused global waves of infection since December 2019 and continues to persist today. The emergence of SARS-CoV-2 variants with strong immune evasion capabilities has compromised the effectiveness of existing vaccines against breakthrough infections. Therefore, it is important to determine the best utilization strategies for different demographic groups given the variety of vaccine options available. In this review, we will discuss the protective efficacy of vaccines during different stages of the epidemic and emphasize the importance of timely updates to target prevalent variants, which can significantly improve immune protection. While it is recognized that vaccine effectiveness may be lower in certain populations such as the elderly, individuals with chronic comorbidities (e.g., diabetes with poor blood glucose control, those on maintenance dialysis), or those who are immunocompromised compared to the general population, administering multiple doses can result in a strong protective immune response that outweighs potential risks. However, caution should be exercised when considering vaccines that might trigger an intense immune response in populations prone to inflammatory flare or other complications. In conclusion, individuals with special conditions require enhanced and more effective immunization strategies to prevent infection or reinfection, as well as to avoid the potential development of long COVID.

自 2019 年 12 月以来,SARS-CoV-2 在全球范围内掀起了一波又一波的感染浪潮,并持续至今。具有强大免疫逃避能力的 SARS-CoV-2 变体的出现损害了现有疫苗对突破性感染的有效性。因此,考虑到现有疫苗的多样性,确定针对不同人群的最佳使用策略非常重要。在这篇综述中,我们将讨论疫苗在流行病不同阶段的保护效力,并强调针对流行变异株及时更新的重要性,这可以显著提高免疫保护效果。我们认识到,与普通人群相比,疫苗在某些人群中的效力可能较低,如老年人、患有慢性并发症的人(如血糖控制不佳的糖尿病患者、接受维持性透析的人)或免疫力低下的人,但接种多剂疫苗可产生强大的保护性免疫反应,从而超过潜在的风险。不过,在考虑接种可能会引起炎症复发或其他并发症的人群的强烈免疫反应的疫苗时应谨慎。总之,有特殊情况的人需要加强和更有效的免疫策略,以预防感染或再感染,并避免可能发展成长期的 COVID。
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引用次数: 0
Versatile and efficient mammalian genome editing with Type I-C CRISPR System of Desulfovibrio vulgaris. 利用普通脱硫弧菌的 I-C 型 CRISPR 系统进行多功能、高效的哺乳动物基因组编辑。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-07 DOI: 10.1007/s11427-023-2682-5
Pan Li, Dingcai Dong, Fei Gao, Yuyang Xie, Honglin Huang, Siwei Sun, Zhao Ma, Cheng He, Jinsheng Lai, Xuguang Du, Sen Wu

CRISPR-Cas tools for mammalian genome editing typically rely on single Cas9 or Cas12a proteins. While type I CRISPR systems in Class I may offer greater specificity and versatility, they are not well-developed for genome editing. Here, we present an alternative type I-C CRISPR system from Desulfovibrio vulgaris (Dvu) for efficient and precise genome editing in mammalian cells and animals. We optimized the Dvu type I-C editing complex to generate precise deletions at multiple loci in various cell lines and pig primary fibroblast cells using a paired PAM-in crRNA strategy. These edited pig cells can serve as donors for generating transgenic cloned piglets. The Dvu type I-C editor also enabled precise large fragment replacements with homology-directed repair. Additionally, we adapted the Dvu-Cascade effector for cytosine and adenine base editing, developing Dvu-CBE and Dvu-ABE systems. These systems efficiently induced C-to-T and A-to-G substitutions in human genes without double-strand breaks. Off-target analysis confirmed the high specificity of the Dvu type I-C editor. Our findings demonstrate the Dvu type I-C editor's potential for diverse mammalian genome editing applications, including deletions, fragment replacement, and base editing, with high efficiency and specificity for biomedicine and agriculture.

用于哺乳动物基因组编辑的 CRISPR-Cas 工具通常依赖单个 Cas9 或 Cas12a 蛋白。虽然I类CRISPR系统可能具有更高的特异性和多功能性,但它们在基因组编辑方面并不发达。在这里,我们介绍了一种来自Desulfovibrio vulgaris(Dvu)的I-C型CRISPR系统,用于在哺乳动物细胞和动物中进行高效、精确的基因组编辑。我们对 Dvu I-C 型编辑复合物进行了优化,利用成对的 PAM-in crRNA 策略在各种细胞系和猪原代成纤维细胞中生成多个位点的精确缺失。这些经过编辑的猪细胞可作为供体,用于产生转基因克隆仔猪。Dvu I-C 型编辑器还能通过同源定向修复实现大片段的精确替换。此外,我们还将 Dvu 级联效应器用于胞嘧啶和腺嘌呤碱基编辑,开发出了 Dvu-CBE 和 Dvu-ABE 系统。这些系统能有效地诱导人类基因中的 C 到 T 和 A 到 G 的置换,而不会发生双链断裂。脱靶分析证实了 Dvu I-C 型编辑器的高度特异性。我们的研究结果表明,Dvu I-C 型编辑器可用于多种哺乳动物基因组编辑应用,包括缺失、片段置换和碱基编辑,在生物医学和农业领域具有高效率和特异性。
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引用次数: 0
A CRISPR/RfxCas13d-mediated strategy for efficient RNA knockdown in mouse embryonic development. CRISPR/RfxCas13d 介导的小鼠胚胎发育中高效 RNA 敲除策略。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-02 DOI: 10.1007/s11427-023-2572-6
Lin Zhang, Shi-Meng Cao, Hao Wu, Meng Yan, Jinsong Li, Ling-Ling Chen

The growing variety of RNA classes, such as mRNAs, lncRNAs, and circRNAs, plays pivotal roles in both developmental processes and various pathophysiological conditions. Nonetheless, our comprehension of RNA functions in live organisms remains limited due to the absence of durable and effective strategies for directly influencing RNA levels. In this study, we combined the CRISPR-RfxCas13d system with sperm-like stem cell-mediated semi-cloning techniques, which enabled the suppressed expression of different RNA species. This approach was employed to interfere with the expression of three types of RNA molecules: Sfmbt2 mRNA, Fendrr lncRNA, and circMan1a2(2,3,4,5,6). The results confirmed the critical roles of these RNAs in embryonic development, as their loss led to observable phenotypes, including embryonic lethality, delayed embryonic development, and embryo resorption. In summary, our methodology offers a potent toolkit for silencing specific RNA targets in living organisms without introducing genetic alterations.

越来越多的 RNA 种类,如 mRNA、lncRNA 和 circRNA,在发育过程和各种病理生理状况中发挥着关键作用。然而,由于缺乏直接影响 RNA 水平的持久有效的策略,我们对 RNA 在活生物体中功能的理解仍然有限。在这项研究中,我们将 CRISPR-RfxCas13d 系统与类精干细胞介导的半克隆技术结合起来,从而抑制了不同 RNA 种类的表达。我们采用这种方法干扰了三种 RNA 分子的表达:Sfmbt2 mRNA、Fendrr lncRNA 和 circMan1a2(2,3,4,5,6)。结果证实了这些 RNA 在胚胎发育中的关键作用,因为它们的缺失会导致可观察到的表型,包括胚胎致死、胚胎发育延迟和胚胎吸收。总之,我们的方法为沉默生物体中的特定 RNA 靶标提供了一个有效的工具包,而无需引入基因改变。
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引用次数: 0
Activation of the PGC-1α-mediated mitochondrial glutamine metabolism pathway attenuates female offspring osteoarthritis induced by prenatal excessive prednisone. 激活 PGC-1α 介导的线粒体谷氨酰胺代谢途径可减轻产前过量泼尼松诱导的雌性后代骨关节炎。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-21 DOI: 10.1007/s11427-023-2593-4
Qingxian Li, Fan Zhang, Yongguo Dai, Liang Liu, Liaobin Chen, Hui Wang

Osteoarthritis is a chronic, age-related joint disease. Previous studies have shown that osteoarthritis develops during intrauterine development. Prednisone is frequently used to treat pregnancies complicated by autoimmune diseases. However, limited research has been conducted on the enduring effects of prednisone use during pregnancy on the offspring. In this study, we investigated the effect of excessive prednisone exposure on cartilage development and susceptibility to osteoarthritis in the offspring. We found that prenatal prednisone exposure (PPE) impaired cartilage extracellular matrix (ECM) synthesis, resulting in poor cartilage pathology in female offspring during the adult period, which was further exacerbated after long-distance running stimulation. Additionally, PPE suppressed cartilage development during the intrauterine period. Tracing back to the intrauterine period, we found that Pred, rather than prednisone, decreased glutamine metabolic flux, which resulted in increased oxidative stress, and decreased histone acetylation, and expression of cartilage phenotypic genes. Further, PGC-1α-mediated mitochondrial biogenesis, while PPE caused hypermethylation in the promoter region of PGC-1α and decreased its expression in fetal cartilage by activating the glucocorticoid receptor, resulting in a reduction of glutamine flux controlled by mitochondrial biogenesis. Additionally, overexpression of PGC-1α (either pharmacological or through lentiviral transfection) reversed PPE- and Pred-induced cartilage ECM synthesis impairment. In summary, this study demonstrated that PPE causes chondrodysplasia in female offspring and increases their susceptibility to postnatal osteoarthritis. Hence, targeting PGC-1α early on could be a potential intervention strategy for PPE-induced osteoarthritis susceptibility.

骨关节炎是一种与年龄有关的慢性关节疾病。以往的研究表明,骨关节炎是在宫内发育过程中形成的。泼尼松常用于治疗妊娠合并自身免疫性疾病。然而,关于孕期使用泼尼松对后代的持久影响的研究却很有限。在这项研究中,我们调查了过量泼尼松暴露对后代软骨发育和骨关节炎易感性的影响。我们发现,产前泼尼松暴露(PPE)会损害软骨细胞外基质(ECM)的合成,从而导致雌性后代成年后软骨病理状况不佳,而长跑刺激会进一步加剧这种状况。此外,PPE 还会抑制宫内软骨的发育。追溯到宫内期,我们发现Pred而不是泼尼松降低了谷氨酰胺代谢通量,从而导致氧化应激增加、组蛋白乙酰化减少以及软骨表型基因的表达。此外,PGC-1α 介导线粒体生物生成,而 PPE 通过激活糖皮质激素受体,导致 PGC-1α 启动子区域甲基化过度,并降低其在胎儿软骨中的表达,从而导致线粒体生物生成控制的谷氨酰胺通量减少。此外,过表达 PGC-1α(药理或通过慢病毒转染)可逆转 PPE 和 Pred 诱导的软骨 ECM 合成障碍。总之,本研究证明,PPE 会导致雌性后代软骨发育不良,并增加其对出生后骨关节炎的易感性。因此,早期靶向 PGC-1α 可能是干预 PPE 诱导的骨关节炎易感性的一种潜在策略。
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引用次数: 0
Innovative genome editing in plants: a transposase and CRISPR combination approach. 创新的植物基因组编辑:转座酶和 CRISPR 组合方法。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 DOI: 10.1007/s11427-024-2729-2
Hamza Sohail, Iqra Noor, Xuehao Chen, Xiaodong Yang
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引用次数: 0
Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome. 通过单细胞转录组分析雄激素在性别差异中发挥的多方面功能
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-26 DOI: 10.1007/s11427-024-2652-y
Xinxin Tang, Yinkun Fu, Zhihui Zou, Yue Li, Ming He
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引用次数: 0
Zika virus infection induces glycometabolic disorder in northern pig-tailed macaques. 寨卡病毒感染会诱发北方猪尾猕猴糖代谢紊乱。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-30 DOI: 10.1007/s11427-024-2663-6
Qing Li, Ren-Hua Yang, Yan Hu, Bei-Bei Tang, Ying-Jie Jiang, Chang-Bo Zheng, Tian-Zhang Song
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引用次数: 0
Temperature regulates negative supercoils to modulate meiotic crossovers and chromosome organization. 温度调节负超螺旋,从而调节减数分裂交叉和染色体组织。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-23 DOI: 10.1007/s11427-024-2671-1
Yingjin Tan, Taicong Tan, Shuxian Zhang, Bo Li, Beiyi Chen, Xu Zhou, Ying Wang, Xiao Yang, Binyuan Zhai, Qilai Huang, Liangran Zhang, Shunxin Wang

Crossover recombination is a hallmark of meiosis that holds the paternal and maternal chromosomes (homologs) together for their faithful segregation, while promoting genetic diversity of the progeny. The pattern of crossover is mainly controlled by the architecture of the meiotic chromosomes. Environmental factors, especially temperature, also play an important role in modulating crossovers. However, it is unclear how temperature affects crossovers. Here, we examined the distribution of budding yeast axis components (Red1, Hop1, and Rec8) and the crossover-associated Zip3 foci in detail at different temperatures, and found that both increased and decreased temperatures result in shorter meiotic chromosome axes and more crossovers. Further investigations showed that temperature changes coordinately enhanced the hyperabundant accumulation of Hop1 and Red1 on chromosomes and the number of Zip3 foci. Most importantly, temperature-induced changes in the distribution of axis proteins and Zip3 foci depend on changes in DNA negative supercoils. These results suggest that yeast meiosis senses temperature changes by increasing the level of negative supercoils to increase crossovers and modulate chromosome organization. These findings provide a new perspective on understanding the effect and mechanism of temperature on meiotic recombination and chromosome organization, with important implications for evolution and breeding.

交叉重组是减数分裂的一个标志,它将父源染色体和母源染色体(同源染色体)结合在一起,使其忠实分离,同时促进后代的遗传多样性。交叉模式主要受减数分裂染色体结构的控制。环境因素,尤其是温度,在调节交叉方面也起着重要作用。然而,目前还不清楚温度是如何影响交叉的。在这里,我们详细研究了不同温度下芽殖酵母轴成分(Red1、Hop1和Rec8)和与交叉相关的Zip3病灶的分布,发现温度升高和降低都会导致减数分裂染色体轴变短和交叉增多。进一步的研究表明,温度变化会协调增强染色体上Hop1和Red1的超量积累以及Zip3病灶的数量。最重要的是,温度诱导的轴蛋白和Zip3病灶分布变化取决于DNA负超螺旋的变化。这些结果表明,酵母减数分裂通过增加负超螺水平来感知温度变化,从而增加交叉和调节染色体组织。这些发现为理解温度对减数分裂重组和染色体组织的影响和机制提供了一个新的视角,对进化和育种具有重要意义。
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引用次数: 0
Unveiling potential sex-determining genes and sex-specific markers in autotetraploid Carassius auratus. 揭示自交系鲫鱼的潜在性别决定基因和性别特异性标记。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-09 DOI: 10.1007/s11427-023-2694-5
Kun Zhang, Xu Huang, Chongqing Wang, Xidan Xu, Xiaowei Xu, Xiaoping Dong, Qingwen Xiao, Jinhai Bai, Yue Zhou, Zhengkun Liu, Xinyi Deng, Yan Tang, Siyang Li, Enkui Hu, Wanjing Peng, Ling Xiong, Qinbo Qin, Shaojun Liu

Autotetraploid Carassius auratus is a stable hereditary autotetraploid fish resulting from the hybridization of Carassius auratus red var. (RCC, ♀) × Megalobrama amblycephala (BSB, ♂), containing four sets of RCC chromosomes. However, the molecular mechanism underlying the determination of sex in this species remains largely unknown. Currently, there lacks a full understanding of the molecular mechanisms governing sex determination and specific molecular markers to differentiate sex in this species. In this study, 25,801,677 SNPs (Single-nucleotide polymorphism) and 6,210,306 Indels (insertion-deletion) were obtained from whole-genome resequencing of 100 individuals (including 50 female and 50 male). Further identification confirmed the candidate chromosomes as Chr46B, with the sex-determining region located at Chr46B: 22,500,000-22,800,000 bp. Based on the male-specific insertion (26 bp) within the candidate sex-determining region, a pair of sex-specific molecular markers has been identified. In addition, based on the screening of candidate sex-determining region genes and RT-qPCR validation analysis, ADAM10, AQP9 and tc1a were identified as candidate sex-determining genes. These findings provide a robust foundation for investigating sex determination mechanisms in fish, the evolution of sex chromosomes, and the development of monosex populations.

自四倍体鲫鱼(Carassius auratus)是一种稳定的遗传性自四倍体鱼类,由鲫鱼红变种(Carassius auratus red var., RCC, ♀)×大鳞鲫(Megalobrama amblycephala, BSB, ♂)杂交而成,含有四组RCC染色体。然而,该物种性别决定的分子机制在很大程度上仍然未知。目前,人们对该物种性别决定的分子机制和区分性别的特异性分子标记缺乏全面了解。本研究通过对 100 个个体(包括 50 个雌性个体和 50 个雄性个体)进行全基因组重测序,获得了 25,801,677 个 SNPs(单核苷酸多态性)和 6,210,306 个 Indels(插入缺失)。进一步鉴定确认候选染色体为 Chr46B,性别决定区位于 Chr46B:22,500,000-22,800,000 bp。根据候选性别决定区内的雄性特异性插入(26 bp),确定了一对性别特异性分子标记。此外,根据对候选性别决定区基因的筛选和 RT-qPCR 验证分析,ADAM10、AQP9 和 tc1a 被确定为候选性别决定基因。这些发现为研究鱼类的性别决定机制、性染色体的进化以及单性种群的发展奠定了坚实的基础。
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引用次数: 0
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Science China Life Sciences
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