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Mini-organs and early embryos in vitro: what is at stake? 体外微型器官和早期胚胎:有什么危险?
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-07-23 DOI: 10.5802/crbiol.185
Melina Thetiot, Pascale Cossart, Laure Bally-Cuif

Organoids and embryoids are self-organizing 3D cellular models derived from human pluripotent stem cells or dissociated stem cells from primary tissue, able of partially mimicking the development and function of tissues, organs, or embryos in vitro. Research using these models is advancing rapidly, starting to overcome challenges in studying human development, evolution, and disease. The conference from the French Académie des Sciences "Mini-organs and early embryos in vitro: what is at stake?" illustrated the promise of organoids and embryoids in basic and translational research. The lectures emphasized recent biomedical applications, particularly in disease modeling, drug discovery, and regenerative medicine. Current challenges and future directions have also been discussed alongside with the ethical implications of generating functional structures from human cells in vitro.

类器官和类胚胎是源自人类多能干细胞或原代组织分离的干细胞的自组织三维细胞模型,能够在体外部分模仿组织、器官或胚胎的发育和功能。使用这些模型的研究进展迅速,开始克服研究人类发展、进化和疾病方面的挑战。法国科学院召开的题为“体外微型器官和早期胚胎:有什么危险?”的会议说明了类器官和类胚胎在基础研究和转化研究中的前景。讲座强调了最近的生物医学应用,特别是在疾病建模、药物发现和再生医学方面。目前的挑战和未来的方向也讨论了伦理影响,从人类细胞在体外产生功能结构。
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引用次数: 0
Atomic insights reveal fidelity mechanisms of eukaryotic protein synthesis. 原子洞察揭示真核蛋白合成的保真机制。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-07-22 DOI: 10.5802/crbiol.180
Nemanja Milicevic, Lasse Jenner, Alexander Myasnikov, Marat Yusupov, Gulnara Yusupova

Protein synthesis involves a critical step where messenger RNA (mRNA) and transfer RNAs (tRNAs) must move in tandem to advance the mRNA reading frame by one codon. This process, known as translocation, is catalyzed by elongation factor G (EF-G) in prokaryotes and elongation factor 2 (eEF2) in archaea and eukaryotes. While eEF2 not only accelerates translocation but also maintains reading frame fidelity, high-resolution structural insights into eukaryotic translocation have remained limited compared to the extensively studied prokaryotic system. In our recently published study, we employed cryogenic-electron microscopy (cryo-EM) to determine ten high-resolution reconstructions of the elongating eukaryotic ribosome in complex with the full translocation module, including mRNA, peptidyl-tRNA, and deacylated tRNA (Milicevic et al.,2024). Seven of these structures included ribosome-bound, naturally modified eEF2. These snapshots captured the stepwise progression of the mRNA-tRNA2-peptide module through the eukaryotic 80S ribosome, from the initial accommodation of eEF2 until the final stages of translocation (Milicevic et al.,2024). We further showed a complex network of interactions that safeguards against reading frame slippage during translation. Additionally, we illustrated how the accuracy of translocation in eukaryotes is reinforced by specific features of the 80S ribosome and eEF2. Finally, we suggested that diphthamide, a conserved post-translational modification in eEF2, not only stabilizes correct Watson-Crick codon-anticodon pairing, but also restricts Wobble geometry of the second base pair.

蛋白质合成涉及到一个关键步骤,信使RNA (mRNA)和转移RNA (tRNAs)必须串联移动以推进mRNA阅读框一个密码子。这一过程被称为易位,由原核生物中的延伸因子G (EF-G)和古细菌和真核生物中的延伸因子2 (eEF2)催化。虽然eEF2不仅加速易位,而且保持阅读帧保真度,但与广泛研究的原核系统相比,真核易位的高分辨率结构见解仍然有限。在我们最近发表的研究中,我们使用低温电子显微镜(cro - em)确定了具有完整易位模块的延长的真核核糖体复合体的十个高分辨率重建,包括mRNA,肽基tRNA和脱酰基tRNA (Milicevic et al.,2024)。其中7个结构包括核糖体结合的,自然修饰的eEF2。这些快照捕捉了mrna - trna2肽模块通过真核80S核糖体的逐步进展,从eEF2的初始调节到易位的最后阶段(Milicevic et al.,2024)。我们进一步展示了一个复杂的相互作用网络,以防止翻译过程中的阅读框滑动。此外,我们说明了真核生物中易位的准确性如何通过80S核糖体和eEF2的特定特征得到加强。最后,我们认为二苯二胺是eEF2中一个保守的翻译后修饰,它不仅稳定了正确的沃森-克里克密码子-反密码子配对,而且还限制了第二碱基对的摆动几何形状。
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引用次数: 0
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-06-18 DOI: 10.5802/crbiol.178
Vincent Debat, Manuela López-Villavicencio, Violaine Llaurens

How do closely related species interact in sympatry? And how do these interactions influence the evolution of their traits and the dynamics of species diversification? In this review, we show how recent research on the evolution of Morpho butterflies contributes to address these questions. We first show how sympatric species have colonized different vertical strata in the neotropical forest and how this divergence has produced cascading adaptive effects on behavioural (flight) but also morphological traits, including wing size, shape and coloration. We then focus on the evolution of peculiar dorsal blue coloration within the genus Morpho. During flight, the blue iridescence produces bright flashes that confuse predators and likely enhance the escape abilities of these butterflies. In turn, predators learn the association between such conspicuous coloration and escaping capacities. Such learning favours the locally abundant colour pattern and promotes the local convergence in sympatric species. However, this tight resemblance also induces sexual interference between mimetic species. Capture-Mark-Recapture data uncovered that mimetic species do not fly at the same hours: competition seems to have driven the divergence in the timing of flight activity between species. Overall, sympatry therefore promotes the intricated evolution of convergent and divergent traits among tightly related species, that jointly facilitate their coexistence. Whether ecological speciation was involved in this evolution is an intriguing open question. At the genomic level, analyses revealed a faster evolution of the sexual chromosome Z as compared to the autosomes, with extensive rearrangements and molecular signals of positive selection: these data thus suggest an important role for the Z chromosome in adaptive evolution in Morpho and possibly in speciation. Paving the way for future research, these various, multilevel studies show that Morpho are not just those showy butterflies in the box: they can also teach us much about evolutionary processes.

密切相关的物种是如何在同属关系中相互作用的?这些相互作用是如何影响它们特征的进化和物种多样化的动态的?在这篇综述中,我们展示了最近关于大闪蝶进化的研究如何有助于解决这些问题。我们首先展示了同域物种如何在新热带森林的不同垂直地层中定居,以及这种差异如何在行为(飞行)和形态特征(包括翅膀大小、形状和颜色)上产生级联适应效应。然后,我们将重点放在Morpho属中特殊背部蓝色颜色的进化上。在飞行过程中,蓝色彩虹色会产生明亮的闪光,迷惑捕食者,并可能提高这些蝴蝶的逃跑能力。反过来,捕食者学会了这种显眼的颜色和逃跑能力之间的联系。这种学习有利于局部丰富的色彩模式,促进同域物种的局部收敛。然而,这种紧密的相似性也导致了模仿物种之间的性干扰。“捕捉-标记-再捕捉”数据揭示,模仿物种不会在相同的时间飞行:竞争似乎导致了物种之间飞行活动时间的差异。总的来说,因此,在密切相关的物种中,共情促进了趋同和分化特征的复杂进化,这些特征共同促进了它们的共存。生态物种形成是否参与了这种进化是一个有趣的开放性问题。在基因组水平上,分析显示,与常染色体相比,性染色体Z的进化速度更快,具有广泛的重排和正选择的分子信号:这些数据表明,Z染色体在Morpho的适应性进化中发挥了重要作用,可能在物种形成中也发挥了重要作用。这些不同的、多层次的研究为未来的研究铺平了道路,它们表明大闪蝶不仅仅是盒子里那些华丽的蝴蝶:它们还能告诉我们很多关于进化过程的知识。
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引用次数: 0
Evolutionary convergences and divergences in sympatric species: Morpho butterflies as a case study. 同域物种的进化趋同与分化:以大闪蝶为例。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-06-18 DOI: 10.5802/crbiol.178
Vincent Debat, Manuela López-Villavicencio, Violaine Llaurens

How do closely related species interact in sympatry? And how do these interactions influence the evolution of their traits and the dynamics of species diversification? In this review, we show how recent research on the evolution of Morpho butterflies contributes to address these questions. We first show how sympatric species have colonized different vertical strata in the neotropical forest and how this divergence has produced cascading adaptive effects on behavioural (flight) but also morphological traits, including wing size, shape and coloration. We then focus on the evolution of peculiar dorsal blue coloration within the genus Morpho. During flight, the blue iridescence produces bright flashes that confuse predators and likely enhance the escape abilities of these butterflies. In turn, predators learn the association between such conspicuous coloration and escaping capacities. Such learning favours the locally abundant colour pattern and promotes the local convergence in sympatric species. However, this tight resemblance also induces sexual interference between mimetic species. Capture-Mark-Recapture data uncovered that mimetic species do not fly at the same hours: competition seems to have driven the divergence in the timing of flight activity between species. Overall, sympatry therefore promotes the intricated evolution of convergent and divergent traits among tightly related species, that jointly facilitate their coexistence. Whether ecological speciation was involved in this evolution is an intriguing open question. At the genomic level, analyses revealed a faster evolution of the sexual chromosome Z as compared to the autosomes, with extensive rearrangements and molecular signals of positive selection: these data thus suggest an important role for the Z chromosome in adaptive evolution in Morpho and possibly in speciation. Paving the way for future research, these various, multilevel studies show that Morpho are not just those showy butterflies in the box: they can also teach us much about evolutionary processes.

密切相关的物种是如何在同属关系中相互作用的?这些相互作用是如何影响它们特征的进化和物种多样化的动态的?在这篇综述中,我们展示了最近关于大闪蝶进化的研究如何有助于解决这些问题。我们首先展示了同域物种如何在新热带森林的不同垂直地层中定居,以及这种差异如何在行为(飞行)和形态特征(包括翅膀大小、形状和颜色)上产生级联适应效应。然后,我们将重点放在Morpho属中特殊背部蓝色颜色的进化上。在飞行过程中,蓝色彩虹色会产生明亮的闪光,迷惑捕食者,并可能提高这些蝴蝶的逃跑能力。反过来,捕食者学会了这种显眼的颜色和逃跑能力之间的联系。这种学习有利于局部丰富的色彩模式,促进同域物种的局部收敛。然而,这种紧密的相似性也导致了模仿物种之间的性干扰。“捕捉-标记-再捕捉”数据揭示,模仿物种不会在相同的时间飞行:竞争似乎导致了物种之间飞行活动时间的差异。总的来说,因此,在密切相关的物种中,共情促进了趋同和分化特征的复杂进化,这些特征共同促进了它们的共存。生态物种形成是否参与了这种进化是一个有趣的开放性问题。在基因组水平上,分析显示,与常染色体相比,性染色体Z的进化速度更快,具有广泛的重排和正选择的分子信号:这些数据表明,Z染色体在Morpho的适应性进化中发挥了重要作用,可能在物种形成中也发挥了重要作用。这些不同的、多层次的研究为未来的研究铺平了道路,它们表明大闪蝶不仅仅是盒子里那些华丽的蝴蝶:它们还能告诉我们很多关于进化过程的知识。
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引用次数: 0
Obligate intracellular bacterial pathogens as major players in the metabolic integration of organelles 专性细胞内细菌病原体作为细胞器代谢整合的主要参与者
IF 0.6 4区 生物学 Q4 BIOLOGY Pub Date : 2025-06-11 DOI: 10.5802/crbiol.176
Steven Ball, Denis Baurain, Marie Leleu, Ingrid Lafontaine, Ugo Cenci, Christophe Colleoni, Olivier Vallon, Gilbert Greub, Andreas Weber, Debashish Bhattacharya

Endosymbionts are very common in nature, offering multiple occasions to recapitulate events that have led to the generation of mitochondria and plastids. However, both these organelles are unique because they are thought to derive from two individual events that gave rise to all eukaryotes and the plastids in algae and plants (excluding Paulinella chromatophora), respectively. This review focuses on the differences and similarities existing between extant endosymbionts and the two major endosymbiont derived organelles: the mitochondria and plastids. Emphasis is put on recent developments that point to the major role of intracellular pathogens in the establishment of these organelles. We argue that metabolic integration of bacterial endosymbionts into mitochondria and plastids required an unusually high degree of preadaptation not shared by most extant endosymbionts. We propose that this was achieved by either recruiting intracellular bacterial pathogens as "helper genomes" providing needed gene products, or by selecting endosymbionts destined to become organelles directly from such obligate intracellular bacteria.

内共生体在自然界中非常普遍,提供了多种机会来概括导致线粒体和质体产生的事件。然而,这两种细胞器都是独一无二的,因为它们被认为分别来源于两个单独的事件,这两个事件分别产生了所有真核生物和藻类和植物中的质体(不包括Paulinella chroophora)。本文综述了现存内生共生体与内生共生体来源的两种主要细胞器:线粒体和质体之间存在的异同。重点放在最近的发展,指出主要作用的细胞内病原体在建立这些细胞器。我们认为细菌内共生体进入线粒体和质体的代谢整合需要异常高度的预适应,这是大多数现存的内共生体所没有的。我们提出,这是通过募集细胞内细菌病原体作为提供所需基因产物的“辅助基因组”,或通过选择注定要直接从这种专性细胞内细菌中成为细胞器的内共生体来实现的。
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引用次数: 0
Uncovering the mechanisms of sexual differentiation: insights from Drosophila research. 揭示性别分化的机制:来自果蝇研究的见解。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-06-04 DOI: 10.5802/crbiol.177
Bruno Hudry

The differences between males and females represent the largest phenotypic dimorphism observed in most species. In humans, this variation contributes to disparities in the risk, incidence, and treatment responses for numerous diseases, with many of these significant differences remaining unexplained. While hormones derived from sex organs play critical roles in shaping and maintaining certain sex differences, recent research using the Drosophila model underscores the significance of cell-intrinsic mechanisms linked to the sex chromosomes.

雄性和雌性之间的差异代表了在大多数物种中观察到的最大的表型二态性。在人类中,这种变异导致了许多疾病在风险、发病率和治疗反应方面的差异,其中许多显著差异仍未得到解释。虽然来自性器官的激素在形成和维持某些性别差异方面发挥着关键作用,但最近使用果蝇模型的研究强调了与性染色体相关的细胞内在机制的重要性。
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引用次数: 0
Use and dual use of synthetic biology. 合成生物学的使用和双重使用。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-03-07 DOI: 10.5802/crbiol.173
Antoine Danchin

A brief history of the field shows that the impression of novelty we have today when we talk about synthetic biology is merely the sign of a rapid loss of memory of the events surrounding its creation. The dangers of misuse were identified even before the first experiments, but this has not led to a shared awareness. Building a cell ab initio involves combining a machine (called a chassis by specialists in the field) and a program in the form of synthetic DNA. Only the latter—the program—is the subject of the vast majority of work in the field, and it is there that the risks of misuse appear. Combined with knowledge of the genomic sequence of pathogens, DNA synthesis makes it possible to reconstitute dangerous organisms or even to develop new ways of propagating malicious software. Finally, the lack of thought given to the risk of accidents when laboratories develop gain-of-function experiments that increase the virulence of a pathogen makes a world where this type of experiments is developed particularly dangerous.

该领域的简史表明,当我们今天谈论合成生物学时,我们对新奇的印象仅仅是对围绕其创造的事件的记忆迅速丧失的标志。甚至在第一次实验之前就已经发现了滥用的危险,但这并没有导致一种共同的意识。从头开始构建细胞需要将机器(该领域的专家称之为底盘)和合成DNA形式的程序结合起来。只有后者——程序——是该领域绝大多数工作的主题,而滥用的风险也正是在那里出现的。结合病原体基因组序列的知识,DNA合成使重建危险生物体甚至开发传播恶意软件的新方法成为可能。最后,当实验室开展增加病原体毒性的功能获得性实验时,缺乏对事故风险的考虑,使得开展这类实验的世界特别危险。
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引用次数: 0
[Socio-ecological restoration, a concrete transposition of the normative concept of nature-based solutions?] [社会生态恢复,基于自然的解决方案的规范概念的具体转换?]
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-03-05 DOI: 10.5802/crbiol.175
Nathalie Frascaria-Lacoste, Pierre-Antoine Versini, Chloé Duffaut, Juan Fernández-Manjarrés

“Nature-based solutions” (NBS) are now widely referred to as a way of making anthropized ecosystems more sustainable. NBS stems from the principles of ecological engineering as conceptualized by H. T. Odum. Odum (1962), based on an approach centered on energy flows and ecosystem self-regulation. Despite their growing popularity, the implementation of these NBS remains complex and often focused solely on societal benefits, with little benefit to biodiversity.The current climate and ecological crisis calls for a reconsideration of our relationship with nature, integrating both social and ecological objectives in a new mobilization of societies and ecosystems in crisis. This is what is advocated by socio-ecological restoration, a recent concept developed during the reconstruction of coastal cities after the 2011 tsunami in Japan. This concept proposes the joint repair of ecosystems and human social cohesion, using elements of the ecosystem taken as historical landmarks before disturbance, enabling a local anchoring to regain a viable social and ecological trajectory. Socio-ecological restoration is not a classic program activity, but a social process in which several actors get involved by relying on each other, without using the expression itself.We propose to generalize this socio-ecological restoration, beyond post-disaster or post-conflict situations, to modify development practices and create real synergies between living humans and non-humans. In this respect, we use the reopening of the Bièvre River in the Paris region as an example of relevant socio-ecological restoration, because it involves the local community and responds to ecological issues. In conclusion, we make five recommendations for adapting the principles of socio-ecological restoration to the implementation of NBS, with a view to making not only our environments more resilient in the face of global change, but also those environments that concern the entire non-human living world and are often overlooked in field practices. By opting for a more eco-centric approach, NBSs could be in line with the IUCN’s initial definition, ultimately becoming Solutions Based For and By Nature, in line with the challenges of an effective ecological transition in the field.

“基于自然的解决方案”(NBS)现在被广泛认为是一种使人类生态系统更具可持续性的方法。NBS源于H. T. Odum提出的生态工程原理。Odum(1962),基于一种以能量流动和生态系统自我调节为中心的方法。尽管它们越来越受欢迎,但这些国家统计局的实施仍然很复杂,往往只关注社会效益,对生物多样性几乎没有好处。当前的气候和生态危机要求我们重新考虑我们与自然的关系,在危机中的社会和生态系统的新动员中整合社会和生态目标。这就是社会生态恢复所倡导的,这是2011年日本海啸后沿海城市重建期间发展起来的一个新概念。这一概念提出了生态系统和人类社会凝聚力的联合修复,利用生态系统元素作为干扰前的历史地标,使当地锚定能够重新获得可行的社会和生态轨迹。社会生态修复不是一个经典的程序活动,而是一个社会过程,在这个过程中,几个参与者相互依赖,而不使用表达本身。我们建议将这种社会生态恢复推广到灾后或冲突后的情况,以修改发展实践,并在活着的人类和非人类之间创造真正的协同效应。在这方面,我们以巴黎地区bi vre河的重新开放作为相关社会生态恢复的一个例子,因为它涉及当地社区并对生态问题作出反应。最后,我们提出了适应NBS实施的社会生态恢复原则的五点建议,以期不仅使我们的环境在面对全球变化时更具弹性,而且使那些涉及整个非人类生活世界的环境在野外实践中经常被忽视。通过选择更以生态为中心的方法,nbs可以符合世界自然保护联盟的最初定义,最终成为基于自然和自然的解决方案,以应对该领域有效生态转型的挑战。
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引用次数: 0
A possible role for epigenetics in cancer initiation. 表观遗传学在癌症发生中的可能作用。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-02-25 DOI: 10.5802/crbiol.171
Anne-Marie Martinez, Giacomo Cavalli

Cancer is one of the leading causes of mortality worldwide. Known since antiquity, its understanding has evolved over time and has significantly advanced with new technologies over the past four decades. Cancer initiation is currently admitted to be explainable by the somatic mutation theory, which postulates that DNA mutations altering the function of oncogenes and tumor suppressor genes initiate cancer. In addition to these mutations, epigenetic alterations, which heritably change gene expression without altering the DNA sequence, also play a key role. Recent data suggests that epigenetic components regulate all aspects of tumor progression, including cancer initiation. These discoveries prompt a reevaluation of the somatic mutation theory, of cancer prevention and treatment strategies.

癌症是全球死亡的主要原因之一。自古以来就为人所知,它的理解随着时间的推移而发展,在过去的四十年里,随着新技术的发展,它取得了显著的进步。癌症的发生目前被认为可以用体细胞突变理论来解释,该理论假设DNA突变改变了癌基因和肿瘤抑制基因的功能,从而引发了癌症。除了这些突变之外,表观遗传改变,即在不改变DNA序列的情况下遗传性地改变基因表达,也起着关键作用。最近的数据表明,表观遗传成分调节肿瘤进展的各个方面,包括癌症的发生。这些发现促使对体细胞突变理论、癌症预防和治疗策略的重新评估。
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引用次数: 0
[The diversification of the protein kinase R contributes to the specificity of bat-virus interactions]. [蛋白激酶R的多样化有助于蝙蝠与病毒相互作用的特异性]。
IF 0.7 4区 生物学 Q4 BIOLOGY Pub Date : 2025-02-25 DOI: 10.5802/crbiol.170
Stéphanie Jacquet, Dominique Pontier, Lucie Etienne

Several bat species asymptomatically harbor certain viruses that are highly pathogenic in other mammals. The underlying mechanisms involve an evolutionary balance between tolerance and immune resistance to viral infections. However, how bats innate immunity has evolved in response to viruses remains to be elucidated. Here, we review the evolution of the protein kinase R (PKR) in bats, a major antiviral protein of vertebrate innate antiviral defense. Our recent results indicate that PKR has evolved under selective pressure and has undergone genomic duplications in bats, in contrast to all mammals studied, which possess only a single copy of the gene. The genetic changes in bat PKR are probably partly the result of genetic conflicts with ancient pathogenic poxviruses, shaping a bat-specific host–virus interface. Furthermore, the duplicated PKRs in Myotis species enable them to collectively escape viruses and enhance their viral control. These results suggest that viral adaptations of PKR contribute to the specificity of modern interactions between viruses and bats, and may explain unique antiviral mechanisms in bats.

几种蝙蝠无症状地携带在其他哺乳动物中具有高致病性的某些病毒。潜在的机制涉及对病毒感染的耐受性和免疫抗性之间的进化平衡。然而,蝙蝠对病毒的先天免疫是如何进化的仍有待阐明。在这里,我们回顾了蝙蝠蛋白激酶R (PKR)的进化,PKR是脊椎动物先天抗病毒防御的主要抗病毒蛋白。我们最近的研究结果表明,PKR是在选择压力下进化的,并且在蝙蝠中经历了基因组复制,而所有研究的哺乳动物只有一个基因拷贝。蝙蝠PKR的遗传变化可能部分是与古老的致病性痘病毒发生遗传冲突的结果,形成了蝙蝠特异性宿主-病毒界面。此外,Myotis物种中重复的PKRs使它们能够集体逃离病毒并增强其病毒控制能力。这些结果表明,PKR的病毒适应性有助于病毒与蝙蝠之间现代相互作用的特异性,并可能解释蝙蝠独特的抗病毒机制。
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引用次数: 0
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