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Multi-omics analysis reveals the genetic and environmental factors in shaping the gut resistome of a keystone rodent species. 多组学分析揭示了形成一种关键啮齿动物肠道抗性组的遗传和环境因素。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-30 DOI: 10.1007/s11427-024-2679-3
Guoliang Li, Dong Zhu, Chaoyuan Cheng, Haiyan Chu, Fuwen Wei, Zhibin Zhang

Understanding the emergence and spread of antibiotic resistance genes (ARGs) in wildlife is critical for the health of humans and animals from a "One Health" perspective. The gut microbiota serve as a reservoir for ARGs; however, it remains poorly understood how environmental and host genetic factors influence ARGs by affecting the gut microbiota. To elucidate this, we analyzed whole-genome resequencing data from 79 individuals of Brandt's vole in two geographic locations with different antibiotics usage, together with metabolomic data and shotgun sequencing data. A high diversity of ARGs (851 subtypes) was observed in vole's gut, with a large variation in ARG composition between individuals from Xilingol and Hulunbuir in China. The diversity and composition of ARGs were strongly correlated with variations in gut microbiota community structure. Genome-wide association studies revealed that 803 loci were significantly associated (P<5.05×10-9) with 31 bacterial species, and bipartite networks identified 906 bacterial species-ARGs associations. Structural equation modeling analysis showed that host genetic factors, air temperature, and presence of pollutants (Bisphenol A) significantly affected gut microbiota community structure, which eventually regulated the diversity of ARGs. The present study advances our understanding of the complex host-environment interactions that underlie the spread of ARGs in the natural environments.

从 "一体健康 "的角度来看,了解野生动物抗生素耐药基因(ARGs)的出现和传播对人类和动物的健康至关重要。肠道微生物群是 ARGs 的储存库;然而,人们对环境和宿主遗传因素如何通过影响肠道微生物群来影响 ARGs 仍然知之甚少。为了弄清这个问题,我们分析了两个使用不同抗生素的地区的79只布氏田鼠的全基因组重测序数据,以及代谢组数据和枪式测序数据。在布氏田鼠肠道中观察到 ARGs 的高度多样性(851 个亚型),来自中国锡林郭勒和呼伦贝尔的布氏田鼠个体之间 ARGs 的组成差异很大。ARGs的多样性和组成与肠道微生物群落结构的变化密切相关。全基因组关联研究发现,803个基因位点与31种细菌有显著关联(P-9),双方位网络发现906种细菌与ARGs有关联。结构方程建模分析表明,宿主遗传因素、气温和污染物(双酚 A)的存在对肠道微生物群落结构有明显影响,最终调节了 ARGs 的多样性。本研究加深了我们对宿主与环境之间复杂的相互作用的理解,这种相互作用是 ARGs 在自然环境中传播的基础。
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引用次数: 0
Unveiling the evolutionary dynamics of microRNA-targeted plant laccase genes. 揭示微RNA靶向植物漆酶基因的进化动态。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1007/s11427-024-2678-1
Rui-Rui He, Meng-Qi Lei, Yan-Zhao Feng, Jiao Xue, Yu-Chan Zhang, Yue-Qin Chen, Yang Yu
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引用次数: 0
Nanowire-mediated miRNA delivery. 纳米线介导的 miRNA 递送。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1007/s11427-024-2641-y
Yuan Wang, Bing Chen
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引用次数: 0
NAP-seq: unveiling the hidden world of noncapped RNAs. NAP-seq:揭开非封顶 RNA 隐藏世界的神秘面纱。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-06-11 DOI: 10.1007/s11427-024-2623-5
Liang Liang, Yuanchao Xue
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引用次数: 0
Shifts in reproductive strategies in the evolutionary trajectory of plant lineages. 植物品系进化过程中生殖策略的转变。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1007/s11427-024-2597-9
Xin-Jian Zhang, Xian-Han Huang, Jacob B Landis, Quan-Sheng Fu, Jun-Tong Chen, Peng-Rui Luo, Li-Juan Li, Heng-Yi Lu, Hang Sun, Tao Deng

Understanding the maintenance and shift in reproductive strategies is a fundamental question in evolutionary research. Although many efforts have been made to compare different reproductive strategies, the association between reproductive strategies and lineage divergence is largely unknown. To explore the impact of different reproductive strategies on lineage divergence, we investigated the evolution of clonality in Saxifraga sect. Irregulares+Heterisia. By integrating several lines of evidence, we found that the loss of clonality in Irregulares+Heterisia was associated with a progressive increase in diversification rate and intraspecific morphological diversity but with a reduction in species distribution range. Our findings provide insights into the ecological and evolutionary effects of different reproductive strategies, suggesting the necessity of integrating clonality into ecological and evolutional research.

了解生殖策略的维持和转变是进化研究中的一个基本问题。尽管人们已经做了很多努力来比较不同的繁殖策略,但繁殖策略与世系分化之间的关系在很大程度上还是未知的。为了探索不同繁殖策略对世系分化的影响,我们研究了 Saxifraga sect.Irregulares+Heterisia的克隆进化。通过整合多种证据,我们发现Irregulares+Heterisia中克隆性的丧失与物种多样化率和种内形态多样性的逐渐增加有关,但与物种分布范围的缩小有关。我们的发现为不同繁殖策略对生态和进化的影响提供了见解,表明有必要将克隆性纳入生态和进化研究。
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引用次数: 0
Role of macrophages in aortic dissection pathogenesis: insights from preclinical studies to translational prospective. 巨噬细胞在主动脉夹层发病机制中的作用:从临床前研究到转化前瞻的见解。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-09-30 DOI: 10.1007/s11427-024-2693-5
Shiyi Li, Weiguo Fu, Lixin Wang

Aortic dissection is a critical vascular disease that is characterized by a high mortality rate and inflammation significantly influences its onset and progression. Recent studies highlight the integral role of macrophages, key players in the immune system, in the pathological landscape of aortic dissection. These cells are involved in crucial processes, such as the remodeling of the extracellular matrix, immunocyte infiltration, and phenotypic switching of smooth muscle cells, which are essential for the structural integrity and functional dynamics of the aortic wall. Despite these insights, the specific contributions of macrophages to the development and progression of aortic dissection remains unclear. This review explores the pathogenesis of aortic dissection with a focus on macrophages and describes their origins, phenotypic variations, and potential roles based on the most recent research findings. Furthermore, we discuss key molecules related to macrophages during aortic dissection, their interactions with other cellular components within the aorta, and the implications of these interactions for future therapeutic strategies. This comprehensive analysis aimed to improve our understanding of macrophages in aortic dissection and promote the development of targeted interventions.

主动脉夹层是一种严重的血管疾病,其特点是死亡率高,而炎症对其发病和发展有重大影响。最近的研究突出表明,巨噬细胞是免疫系统的关键角色,在主动脉夹层的病理过程中发挥着不可或缺的作用。这些细胞参与了细胞外基质的重塑、免疫细胞的浸润和平滑肌细胞的表型转换等关键过程,对主动脉壁的结构完整性和功能动态至关重要。尽管有了这些认识,但巨噬细胞对主动脉夹层发生和发展的具体作用仍不清楚。本综述以巨噬细胞为重点探讨了主动脉夹层的发病机制,并根据最新研究成果描述了巨噬细胞的起源、表型变化和潜在作用。此外,我们还讨论了主动脉夹层期间与巨噬细胞有关的关键分子、它们与主动脉内其他细胞成分的相互作用以及这些相互作用对未来治疗策略的影响。这项综合分析旨在增进我们对主动脉夹层中巨噬细胞的了解,促进有针对性的干预措施的开发。
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引用次数: 0
Single-cell immune landscape of measurable residual disease in acute myeloid leukemia. 急性髓性白血病可测量残留病的单细胞免疫图谱
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-19 DOI: 10.1007/s11427-024-2666-8
Xiaodong Mo, Weilong Zhang, Guomei Fu, Yingjun Chang, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Mengzhu Shen, Qiuxia Wei, Changjian Yan, Xiaojun Huang

Measurable residual disease (MRD) is a powerful prognostic factor of relapse in acute myeloid leukemia (AML). We applied the single-cell RNA sequencing to bone marrow (BM) samples from patients with (n=20) and without (n=12) MRD after allogeneic hematopoietic stem cell transplantation. A comprehensive immune landscape with 184,231 cells was created. Compared with CD8+ T cells enriched in the MRD-negative group (MRD-_CD8), those enriched in the MRD-positive group (MRD+_CD8) showed lower expression levels of cytotoxicity-related genes. Three monocyte clusters (i.e., MRD+_M) and three B-cell clusters (i.e., MRD+_B) were enriched in the MRD-positive group. Conversion from an MRD-positive state to an MRD-negative state was accompanied by an increase in MRD-_CD8 clusters and vice versa. MRD-enriched cell clusters employed the macrophage migration inhibitory factor pathway to regulate MRD-_CD8 clusters. These findings revealed the characteristics of the immune cell landscape in MRD positivity, which will allow for a better understanding of the immune mechanisms for MRD conversion.

可测量残留病(MRD)是急性髓性白血病(AML)复发的有力预后因素。我们对异体造血干细胞移植后有 MRD(20 例)和无 MRD(12 例)患者的骨髓(BM)样本进行了单细胞 RNA 测序。建立了一个包含 184 231 个细胞的综合免疫图谱。与富集在MRD阴性组(MRD-_CD8)的CD8+T细胞相比,富集在MRD阳性组(MRD+_CD8)的CD8+T细胞的细胞毒性相关基因表达水平较低。MRD阳性组中富集了三个单核细胞群(即MRD+_M)和三个B细胞群(即MRD+_B)。从MRD阳性转为MRD阴性时,MRD-_CD8细胞群也随之增加,反之亦然。MRD富集细胞集群利用巨噬细胞迁移抑制因子途径来调节MRD-_CD8集群。这些发现揭示了MRD阳性时免疫细胞景观的特征,有助于更好地理解MRD转换的免疫机制。
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引用次数: 0
Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation. 抗体体细胞超突变过程中 DNA 损伤和修复的分子机制。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-23 DOI: 10.1007/s11427-024-2615-1
Qian Hao, Jinfeng Li, Leng-Siew Yeap

Antibody diversification is essential for an effective immune response, with somatic hypermutation (SHM) serving as a key molecular process in this adaptation. Activation-induced cytidine deaminase (AID) initiates SHM by inducing DNA lesions, which are ultimately resolved into point mutations, as well as small insertions and deletions (indels). These mutational outcomes contribute to antibody affinity maturation. The mechanisms responsible for generating point mutations and indels involve the base excision repair (BER) and mismatch repair (MMR) pathways, which are well coordinated to maintain genomic integrity while allowing for beneficial mutations to occur. In this regard, translesion synthesis (TLS) polymerases contribute to the diversity of mutational outcomes in antibody genes by enabling the bypass of DNA lesions. This review summarizes our current understanding of the distinct molecular mechanisms that generate point mutations and indels during SHM. Understanding these mechanisms is critical for elucidating the development of broadly neutralizing antibodies (bnAbs) and autoantibodies, and has implications for vaccine design and therapeutics.

抗体多样化对有效的免疫反应至关重要,而体细胞超突变(SHM)是这一适应过程中的关键分子过程。活化诱导胞苷脱氨酶(AID)通过诱导 DNA 病变启动体细胞超突变,最终转化为点突变以及小的插入和缺失(indels)。这些突变结果有助于抗体亲和力的成熟。产生点突变和嵌合突变的机制涉及碱基切除修复(BER)和错配修复(MMR)途径,这两种途径协调良好,既能保持基因组的完整性,又能发生有益的突变。在这方面,转座子合成(TLS)聚合酶通过绕过 DNA 病变,促进了抗体基因突变结果的多样性。本综述总结了我们目前对在 SHM 过程中产生点突变和嵌合体的不同分子机制的理解。了解这些机制对于阐明广谱中和抗体(bnAbs)和自身抗体的发展至关重要,对疫苗设计和治疗也有影响。
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引用次数: 0
The single-cell transcriptomic landscape of the topological differences in mammalian auditory receptors. 哺乳动物听觉受体拓扑差异的单细胞转录组图谱
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-29 DOI: 10.1007/s11427-024-2672-1
Xiangyu Ma, Xin Chen, Yuwei Che, Siyao Zhu, Xinlin Wang, Shan Gao, Jiheng Wu, Fanliang Kong, Cheng Cheng, Yunhao Wu, Jiamin Guo, Jieyu Qi, Renjie Chai

Mammalian hair cells (HCs) are arranged spirally along the cochlear axis and correspond to different frequency ranges. Serving as primary sound detectors, HCs spatially segregate component frequencies into a topographical map. HCs display significant diversity in anatomical and physiological characteristics, yet little is known about the organization of the cochleotopic map of HCs or the molecules involved in this process. Using single-cell RNA sequencing, we determined the distinct molecular profiles of inner hair cells and outer hair cells, and we identified numerous position-dependent genes that were expressed as gradients. Newly identified genes such as Ptn, Rxra, and Nfe2l2 were found to be associated with tonotopy. We employed the SCENIC algorithm to predict the transcription factors that potentially shape these tonotopic gradients. Furthermore, we confirmed that Nfe2l2, a tonotopy-related transcription factor, is critical in mice for sensing low-to-medium sound frequencies in vivo. the analysis of cell-cell communication revealed potential receptor-ligand networks linking inner hair cells to spiral ganglion neurons, including pathways such as BDNF-Ntrk and PTN-Scd4, which likely play essential roles in tonotopic maintenance. Overall, these findings suggest that molecular gradients serve as the organizing principle for maintaining the selection of sound frequencies by HCs.

哺乳动物的毛细胞(HCs)沿耳蜗轴呈螺旋状排列,对应不同的频率范围。作为主要的声音检测器,HC 在空间上将频率分隔成一个地形图。HCs在解剖和生理特征方面表现出显著的多样性,但人们对HCs耳蜗地形图的组织或参与这一过程的分子却知之甚少。通过单细胞 RNA 测序,我们确定了内毛细胞和外毛细胞不同的分子特征,并发现了许多以梯度方式表达的位置依赖性基因。新发现的基因(如 Ptn、Rxra 和 Nfe2l2)与音调相关。我们利用 SCENIC 算法预测了可能形成这些声调梯度的转录因子。此外,我们还证实了与音调相关的转录因子 Nfe2l2 对小鼠在体内感知中低频声音至关重要。对细胞-细胞通讯的分析揭示了连接内毛细胞和螺旋神经节神经元的潜在受体-配体网络,包括 BDNF-Ntrk 和 PTN-Scd4 等通路,这些通路可能在维持音调梯度方面发挥重要作用。总之,这些研究结果表明,分子梯度是维持内毛细胞选择声音频率的组织原则。
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引用次数: 0
6-Phosphogluconate dehydrogenase 2 bridges the OPP and shikimate pathways to enhance aromatic amino acid production in plants. 6- 磷酸葡萄糖酸脱氢酶 2 是连接 OPP 和莽草酸途径的桥梁,可提高植物芳香族氨基酸的产量。
IF 8 2区 生物学 Q1 BIOLOGY Pub Date : 2024-11-01 Epub Date: 2024-07-24 DOI: 10.1007/s11427-024-2567-4
Qian Tang, Yuxin Huang, Zhuanglin Shen, Linhui Sun, Yang Gu, Huiqing He, Yanhong Chen, Jiahai Zhou, Limin Zhang, Cuihuan Zhao, Shisong Ma, Yunhai Li, Jie Wu, Qiao Zhao

The oxidative pentose phosphate (OPP) pathway provides metabolic intermediates for the shikimate pathway and directs carbon flow to the biosynthesis of aromatic amino acids (AAAs), which serve as basic protein building blocks and precursors of numerous metabolites essential for plant growth. However, genetic evidence linking the two pathways is largely unclear. In this study, we identified 6-phosphogluconate dehydrogenase 2 (PGD2), the rate-limiting enzyme of the cytosolic OPP pathway, through suppressor screening of arogenate dehydrogenase 2 (adh2) in Arabidopsis. Our data indicated that a single amino acid substitution at position 63 (glutamic acid to lysine) of PGD2 enhanced its enzyme activity by facilitating the dissociation of products from the active site of PGD2, thus increasing the accumulation of AAAs and partially restoring the defective phenotype of adh2. Phylogenetic analysis indicated that the point mutation occurred in a well-conserved amino acid residue. Plants with different amino acids at this conserved site of PGDs confer diverse catalytic activities, thus exhibiting distinct AAAs producing capability. These findings uncover the genetic link between the OPP pathway and AAAs biosynthesis through PGD2. The gain-of-function point mutation of PGD2 identified here could be considered as a potential engineering target to alter the metabolic flux for the production of AAAs and downstream compounds.

磷酸戊糖氧化途径(OPP)为莽草酸途径提供代谢中间产物,并将碳流引向芳香族氨基酸(AAA)的生物合成,芳香族氨基酸是基本的蛋白质组成成分,也是植物生长所必需的多种代谢物的前体。然而,将这两条途径联系起来的遗传证据在很大程度上还不清楚。在这项研究中,我们通过对拟南芥中的氮酸脱氢酶 2(adh2)进行抑制因子筛选,确定了细胞质 OPP 途径的限速酶--6-磷酸葡萄糖酸脱氢酶 2(PGD2)。我们的数据表明,PGD2 第 63 位的单个氨基酸替代(谷氨酸到赖氨酸)可促进产物从 PGD2 活性位点解离,从而增强其酶活性,增加 AAA 的积累,并部分恢复 adh2 的缺陷表型。系统进化分析表明,点突变发生在一个保存良好的氨基酸残基上。在 PGDs 的这一保守位点上存在不同氨基酸的植物具有不同的催化活性,从而表现出不同的 AAAs 生成能力。这些发现揭示了 OPP 途径与 AAAs 通过 PGD2 生物合成之间的遗传联系。在此发现的 PGD2 功能增益点突变可被视为一个潜在的工程目标,以改变 AAA 和下游化合物生产的代谢通量。
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