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Chapter 2: Consumption Tax in the World of Molecules. 第二章:分子世界中的消费税。
Pub Date : 2022-04-11 eCollection Date: 2021-01-01 DOI: 10.2142/biophysico.bppb-v18.s004
Readers, did you try the game out? What was the result? Here, I will show you the initial condition by the random distribution of the first 30 gaming chips and the subsequent results of the random exchange game that was performed by the 12 groups during the lecture (Table 2.1). The initial condition of Group 4 is remarkably unfair. Sometimes, this can happen. The distribution did not change significantly even after the exchange. Group 9 is nearly ideal. There is not much change in Group 11 before and after the exchange. Although the number of exchanges during the lecture were insufficient, the results resembled the theoretically expected distributions.
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引用次数: 0
Recent advances in single-molecule spectroscopy studies on light-harvesting processes in oxygenic photosynthesis 含氧光合作用捕光过程的单分子光谱研究进展
Pub Date : 2022-04-08 DOI: 10.2142/biophysico.bppb-v19.0013
T. Kondo, Yutaka Shibata
Photosynthetic light-harvesting complexes (LHCs) play a crucial role in concentrating the photon energy from the sun that otherwise excites a typical pigment molecule, such as chlorophyll-a, only several times a second. Densely packed pigments in the complexes ensure efficient energy transfer to the reaction center. At the same time, LHCs have the ability to switch to an energy-quenching state and thus play a photoprotective role under excessive light conditions. Photoprotection is especially important for oxygenic photosynthetic organisms because toxic reactive oxygen species can be generated through photochemistry under aerobic conditions. Because of the extreme complexity of the systems in which various types of pigment molecules strongly interact with each other and with the surrounding protein matrixes, there has been long-standing difficulty in understanding the molecular mechanisms underlying the flexible switching between the light-harvesting and quenching states. Single-molecule spectroscopy studies are suitable to reveal the conformational dynamics of LHCs reflected in the fluorescence properties that are obscured in ordinary ensemble measurements. Recent advanced single-molecule spectroscopy studies have revealed the dynamical fluctuations of LHCs in their fluorescence peak position, intensity, and lifetime. The observed dynamics seem relevant to the conformational plasticity required for the flexible activations of photoprotective energy quenching. In this review, we survey recent advances in the single-molecule spectroscopy study of the light-harvesting systems of oxygenic photosynthesis.
光合作用的光收集复合体(lhc)在集中来自太阳的光子能量方面起着至关重要的作用,否则,一种典型的色素分子,如叶绿素-a,每秒只能激发几次。配合物中密集堆积的色素确保了有效的能量转移到反应中心。同时,lhc具有切换到能量猝灭状态的能力,从而在过度光照条件下发挥光保护作用。光保护对氧光合生物尤其重要,因为在有氧条件下,有毒的活性氧可以通过光化学产生。由于各种类型的色素分子彼此之间以及与周围蛋白质基质之间强烈相互作用的系统的极端复杂性,长期以来,在理解光捕获和猝灭状态之间灵活切换的分子机制方面一直存在困难。单分子光谱研究适合揭示lhc的构象动力学,这些构象动力学反映在普通系综测量所掩盖的荧光特性中。最近先进的单分子光谱研究揭示了lhc荧光峰位置、强度和寿命的动态波动。观察到的动力学似乎与光保护能猝灭的柔性激活所需的构象可塑性有关。本文综述了含氧光合作用光收集系统的单分子光谱研究的最新进展。
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引用次数: 1
Dorsolateral prefrontal cortex sensing analgesia. 背外侧前额皮质感知镇痛。
Pub Date : 2022-04-08 eCollection Date: 2022-01-01 DOI: 10.2142/biophysico.bppb-v19.0014
Etsuro Ito, Kotaro Oka, Fusako Koshikawa

Chronic pain often has an unknown cause, and many patients with chronic pain learn to accept that their pain is incurable and pharmacologic treatments are only temporarily effective. Complementary and integrative health approaches for pain are thus in high demand. One such approach is soft touch, e.g., adhesion of pyramidal thorn patches in a pain region. The effects of patch adhesion on pain relief have been confirmed in patients with various types of pain. A recent study using near-infrared spectroscopy revealed that the dorsolateral prefrontal cortex (DLPFC), especially the left side, is likely to be inactivated in patients experiencing pain relief during patch treatment. Mindfulness meditation is another well-known complementary and integrative approach for achieving pain relief. The relation between pain relief due to mindfulness meditation and changes in brain regions, including the DLPFC, has long been examined. In the present review article, we survey the literature describing the effects of the above-mentioned complementary and integrative treatments on pain relief, and outline the important brain regions, including the DLPFC, that are involved in analgesia. We hope that the present article will provide clues to researchers who hope to advance neurosensory treatments for pain relief without medication.

慢性疼痛通常有一个未知的原因,许多慢性疼痛患者学会接受他们的疼痛是无法治愈的,药物治疗只是暂时有效。因此,对疼痛的补充和综合健康方法的需求很大。其中一种方法是软性接触,例如,在疼痛区域粘连锥体刺片。贴片粘连在不同类型疼痛患者中的镇痛作用已得到证实。最近一项使用近红外光谱的研究显示,在贴片治疗期间经历疼痛缓解的患者,背外侧前额叶皮层(DLPFC),特别是左侧,可能会失活。正念冥想是另一种众所周知的缓解疼痛的互补和综合方法。正念冥想带来的疼痛缓解与包括DLPFC在内的大脑区域变化之间的关系早已被研究过。在这篇综述文章中,我们回顾了描述上述补充和综合治疗对疼痛缓解作用的文献,并概述了包括DLPFC在内的重要脑区,这些脑区参与了镇痛。我们希望本文将提供线索,研究人员希望推进神经感觉治疗疼痛缓解药物。
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引用次数: 5
Phenotypic systems biology for organisms: Concepts, methods and case studies. 生物表型系统生物学:概念、方法和案例研究。
Pub Date : 2022-04-05 eCollection Date: 2022-01-01 DOI: 10.2142/biophysico.bppb-v19.0011
Takao K Suzuki

Design principles of phenotypes in organisms are fundamental issues in physical biology. So far, understanding "systems" of living organisms have been chiefly promoted by understanding the underlying biomolecules such as genes and proteins, and their intra- and inter-relationships and regulations. After a long period of sophistication, biophysics and molecular biology have established a general framework for understanding 'molecular systems' in organisms without regard to species, so that the findings of fly studies can be applied to mouse studies. However, little attention has been paid to exploring "phenotypic systems" in organisms, and thus its general framework remains poorly understood. Here I review concepts, methods, and case studies using butterfly and moth wing patterns to explore phenotypes as systems. First, I present a unifying framework for phenotypic traits as systems, termed multi-component systems. Second, I describe how to define components of phenotypic systems, and also show how to quantify interactions among phenotypic parts. Subsequently, I introduce the concept of the macro-evolutionary process, which illustrates how to generate complex traits. In this point, I also introduce mathematical methods, "phylogenetic comparative methods", which provide stochastic processes along molecular phylogeny as bifurcated paths to quantify trait evolution. Finally, I would like to propose two key concepts, macro-evolutionary pathways and genotype-phenotype loop (GP loop), which must be needed for the next directions. I hope these efforts on phenotypic biology will become one major target in biophysics and create the next generations of textbooks. This review article is an extended version of the Japanese article, Biological Physics in Phenotypic Systems of Living Organisms, published in SEIBUTSU-BUTSURI Vol. 61, p. 31-35 (2021).

生物体表型的设计原理是物理生物学的基本问题。迄今为止,对生物体 "系统 "的认识主要是通过了解基因和蛋白质等基本生物大分子及其内部和相互之间的关系和调控来实现的。经过长期的发展,生物物理学和分子生物学已经建立了不分物种理解生物体内 "分子系统 "的总体框架,因此,对蝇蛆的研究结果可以应用于对小鼠的研究。然而,人们很少关注生物体内 "表型系统 "的探索,因此对其总体框架的了解仍然很少。在此,我将回顾利用蝴蝶和飞蛾翅膀模式探索表型系统的概念、方法和案例研究。首先,我提出了表型特征作为系统的统一框架,即多组分系统。其次,我介绍了如何定义表型系统的组成部分,并展示了如何量化表型各部分之间的相互作用。随后,我介绍了宏观进化过程的概念,说明了如何产生复杂的性状。在这一点上,我还介绍了数学方法--"系统进化比较方法",它提供了分子系统进化的随机过程,作为量化性状进化的分叉路径。最后,我想提出两个关键概念,即宏观进化路径和基因型-表型循环(GP 循环),这两个概念是下一步发展方向所必须的。我希望这些关于表型生物学的努力能成为生物物理学的一个主要目标,并创造出下一代教科书。本评论文章是日文文章《生物体表型系统中的生物物理学》(Biological Physics in Phenotypic Systems of Living Organisms)的扩展版,发表于《SEIBUTSU-BUTSURI》第 61 卷第 31-35 页(2021 年)。
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引用次数: 0
Molecular dynamics simulations of amyloid-β peptides in heterogeneous environments 淀粉样蛋白-β肽在异质环境中的分子动力学模拟
Pub Date : 2022-04-02 DOI: 10.2142/biophysico.bppb-v19.0010
Yuhei Tachi, S. Itoh, H. Okumura
Alzheimer’s disease is thought to be caused by the aggregation of amyloid-β (Aβ) peptides. Their aggregation is accelerated at hydrophilic/hydrophobic interfaces such as the air–water interface and the surface of monosialotetrahexosylganglioside (GM1) clusters on neuronal cell membranes. In this review, we present recent studies of full-length Aβ (Aβ40) peptides and Aβ(16–22) fragments in such heterogeneous environments by molecular dynamics (MD) simulations. These peptides have both hydrophilic and hydrophobic amino-acid residues and tend to exist at the hydrophilic/hydrophobic interface. Therefore, the peptide concentration increases at the interface, which is one of the factors that promote aggregation. Furthermore, it was found that Aβ40 forms an α-helix structure and then a β-hairpin structure at the interface. The β-hairpin promotes the formation of oligomers with intermolecular β-sheets. It means that not only the high concentration of Aβ40 at the interface but also the structure of Aβ40 itself promotes aggregation. In addition, MD simulations of Aβ40 on recently-developed GM1-glycan clusters showed that the HHQ (13–15) segment of Aβ40 is important for the recognition of GM1-glycan clusters. It was also elucidated that Aβ40 forms a helix structure in the C-terminal region on the GM1-glycan cluster. This result suggests that the helix formation, which is the first step in the conformational changes toward pathological aggregation, is initiated at the GM1-glycan moieties rather than at the lipid-ceramide moieties. These studies will enhance the physicochemical understanding of the structural changes of Aβ at the heterogeneous interfaces and the mechanism of Alzheimer’s disease pathogenesis.
阿尔茨海默病被认为是由淀粉样蛋白-β (Aβ)肽聚集引起的。它们的聚集在亲水/疏水界面加速,如空气-水界面和神经元细胞膜上的单唾液四己糖神经节苷(GM1)簇的表面。在这篇综述中,我们通过分子动力学(MD)模拟介绍了在这种异质环境中全长Aβ(Aβ40)肽和Aβ(16-22)片段的最新研究。这些肽具有亲水性和疏水性氨基酸残基,并倾向于存在于亲水性/疏水性界面上。因此,界面处的肽浓度增加,这是促进聚集的因素之一。进一步发现,a - β40在界面处先形成α-螺旋结构,再形成β-发夹结构。β发夹促进分子间β片低聚物的形成。这说明除了界面处高浓度的Aβ40外,Aβ40本身的结构也促进了聚集。此外,Aβ40在gm1 -聚糖簇上的MD模拟表明,Aβ40的HHQ(13-15)段对gm1 -聚糖簇的识别很重要。结果表明,a - β40在gm1 -聚糖簇的c端形成螺旋结构。这一结果表明,螺旋形成是病理聚集构象变化的第一步,是在gm1 -聚糖部分而不是在脂质-神经酰胺部分开始的。这些研究将增强对异质界面上Aβ结构变化和阿尔茨海默病发病机制的物理化学认识。
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引用次数: 2
Current status of neutron crystallography in structural biology 中子晶体学在结构生物学中的研究现状
Pub Date : 2022-04-01 DOI: 10.2142/biophysico.bppb-v19.0009
Fumiaki Kono, K. Kurihara, T. Tamada
Hydrogen atoms and hydration water molecules in proteins are essential for many biochemical processes, especially enzyme catalysis. Neutron crystallography enables direct observation of hydrogen atoms, and reveals molecular recognition through hydrogen bonding and catalytic reactions involving proton-coupled electron transfer. The use of neutron crystallography is still limited for proteins, but its popularity is increasing owing to an increase in the number of diffractometers for structural biology at neutron facilities and advances in sample preparation. According to the characteristics of the neutrons, monochromatic or quasi-Laue methods and the time-of-flight method are used in nuclear reactors and pulsed spallation sources, respectively, to collect diffraction data. Growing large crystals is an inevitable problem in neutron crystallography for structural biology, but sample deuteration, especially protein perdeuteration, is effective in reducing background levels, which shortens data collection time and decreases the crystal size required. This review also introduces our recent neutron structure analyses of copper amine oxidase and copper-containing nitrite reductase. The neutron structure of copper amine oxidase gives detailed information on the protonation state of dissociable groups, such as the quinone cofactor, which are critical for catalytic reactions. Electron transfer via a hydrogen-bond jump and a hydroxide ion ligation in copper-containing nitrite reductase are clarified, and these observations are consistent with the results from the quantum chemical calculations. This review article is an extended version of the Japanese article, Elucidation of Enzymatic Reaction Mechanism by Neutron Crystallography, published in SEIBUTSU-BUTSURI Vol. 61, p.216–222 (2021).
蛋白质中的氢原子和水合水分子对许多生化过程,特别是酶催化都是必不可少的。中子晶体学可以直接观察氢原子,并通过氢键和质子耦合电子转移的催化反应揭示分子识别。中子晶体学对蛋白质的应用仍然有限,但由于中子设施中用于结构生物学的衍射仪数量的增加和样品制备的进步,中子晶体学的普及程度正在增加。根据中子的特性,在核反应堆和脉冲散裂源中分别采用单色法或准劳法和飞行时间法来收集衍射数据。生长大晶体是结构生物学中子晶体学中不可避免的问题,而样品的氘化,特别是蛋白质的氘化,可以有效地降低本底水平,从而缩短数据收集时间并减小所需的晶体尺寸。本文还介绍了近年来对铜胺氧化酶和含铜亚硝酸盐还原酶的中子结构分析。铜胺氧化酶的中子结构提供了可解离基团的质子化状态的详细信息,如醌辅因子,这是催化反应的关键。澄清了含铜亚硝酸盐还原酶中通过氢键跳跃和氢氧离子连接的电子转移,这些观察结果与量子化学计算结果一致。这篇综述文章是日本文章《阐明酶促反应机制的中子晶体学》的扩展版,发表在SEIBUTSU-BUTSURI Vol. 61, p.216-222(2021)。
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引用次数: 3
Slow and temperature-compensated autonomous disassembly of KaiB–KaiC complex 缓慢和温度补偿的KaiB-KaiC复合物的自主拆卸
Pub Date : 2022-03-30 DOI: 10.2142/biophysico.bppb-v19.0008
D. Simon, A. Mukaiyama, Y. Furuike, S. Akiyama
KaiC is the central pacemaker of the circadian clock system in cyanobacteria and forms the core in the hetero-multimeric complexes, such as KaiB–KaiC and KaiA–KaiB–KaiC. Although the formation process and structure of the binary and ternary complexes have been studied extensively, their disassembly dynamics have remained elusive. In this study, we constructed an experimental system to directly measure the autonomous disassembly of the KaiB–KaiC complex under the condition where the dissociated KaiB cannot reassociate with KaiC. At 30°C, the dephosphorylated KaiB–KaiC complex disassembled with an apparent rate of 2.1±0.3 d–1, which was approximately twice the circadian frequency. Our present analysis using a series of KaiC mutants revealed that the apparent disassembly rate correlates with the frequency of the KaiC phosphorylation cycle in the presence of KaiA and KaiB and is robustly temperature-compensated with a Q10 value of 1.05±0.20. The autonomous cancellation of the interactions stabilizing the KaiB–KaiC interface is one of the important phenomena that provide a link between the molecular-scale and system-scale properties.
KaiC是蓝藻生物钟系统的中心起搏器,是异多聚体复合物(如KaiB-KaiC和KaiA-KaiB-KaiC)的核心。虽然二元和三元配合物的形成过程和结构已经被广泛研究,但它们的分解动力学仍然是难以捉摸的。在本研究中,我们构建了一个实验系统,在游离的KaiB不能与KaiC重新结合的情况下,直接测量KaiB - KaiC配合物的自主分解。在30°C下,去磷酸化的KaiB-KaiC复合物以2.1±0.3 d-1的表观速率分解,这大约是昼夜节律频率的两倍。我们目前对一系列KaiC突变体的分析表明,在KaiA和KaiB存在的情况下,表观分解率与KaiC磷酸化周期的频率相关,并且Q10值为1.05±0.20,具有很强的温度补偿作用。相互作用的自动抵消稳定了KaiB-KaiC界面,是分子尺度和系统尺度之间的重要联系之一。
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引用次数: 1
Triple-color single-molecule imaging for analysis of the role of receptor oligomers in signal transduction 用于分析受体低聚物在信号转导中的作用的三色单分子成像
Pub Date : 2022-03-11 DOI: 10.2142/biophysico.bppb-v19.0007
Hideaki Yoshimura
Membrane receptors provide interfaces of various extracellular stimuli to transduce the signal into the cell. Receptors are required to possess such conflicting properties as high sensitivity and noise reduction for the cell to keep its homeostasis and appropriate responses. To understand the mechanisms by which these functions are achieved, single-molecule monitoring of the motilities of receptors and signaling molecules on the plasma membrane is one of the most direct approaches. This review article introduces several recent single-molecule imaging studies of receptors, including the author’s recent work on triple-color single-molecule imaging of G protein-coupled receptors. Based on these researches, advantages and perspectives of the single-molecule imaging approach to solving the mechanisms of receptor functions are illustrated.
膜受体提供各种细胞外刺激的接口,将信号转导到细胞内。受体需要具有高灵敏度和降噪等相互矛盾的特性,以保持细胞的稳态和适当的反应。为了了解这些功能实现的机制,对质膜上受体和信号分子的运动进行单分子监测是最直接的方法之一。本文综述了近年来受体单分子成像的研究进展,包括作者在G蛋白偶联受体三色单分子成像方面的研究进展。在此基础上,阐述了单分子成像技术在研究受体功能机制方面的优势和前景。
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引用次数: 0
Quantitative and kinetic single-molecule analysis of DNA unwinding by Escherichia coli UvrD helicase 大肠杆菌UvrD解旋酶解绕DNA的定量和动力学单分子分析
Pub Date : 2022-03-10 DOI: 10.2142/biophysico.bppb-v19.0006
H. Yokota
Helicases are nucleic acid-unwinding enzymes involved in the maintenance of genome integrity. Helicases share several “helicase motifs” that are highly conserved amino acid sequences and are classified into six superfamilies (SFs). The helicase SFs are further grouped into two classes based on their functional units. One class that includes SFs 3–6 functions as a hexamer that can form a ring around DNA. Another class that includes SFs 1 and 2 functions in a non-hexameric form. The high homology in the primary and tertiary structures among SF1 helicases suggests that SF1 helicases have a common underlying mechanism. However, two opposing models for the functional unit, monomer and dimer models, have been proposed to explain DNA unwinding by SF1 helicases. This paper briefly describes the classification of helicase SFs and discusses the structural homology and the two opposing non-hexameric helicase models of SF1 helicases by focusing on Escherichia coli SF1 helicase UvrD, which plays a significant role in both nucleotide-excision repair and methyl-directed mismatch repair. This paper reviews past and recent studies on UvrD, including the author's single-molecule direct visualization of wild-type UvrD and a UvrD mutant lacking the C-terminal 40 amino acids (UvrDΔ40C), the latter of which was used in genetic and biochemical assays that supported the monomer model. The visualization revealed that multiple UvrDΔ40C molecules jointly unwind DNA, presumably in an oligomeric form, similar to wild-type UvrD. Therefore, single-molecule direct visualization of nucleic acid-binding proteins can provide quantitative and kinetic information to reveal their fundamental mechanisms.
解旋酶是参与维持基因组完整性的核酸解绕酶。解旋酶共享几个“解旋酶基序”,这些基序是高度保守的氨基酸序列,被分为六个超家族(sf)。根据解旋酶的功能单元,将其进一步分为两类。其中一类包括sf3 - 6,其功能是六聚体,可以在DNA周围形成环。另一类以非六聚体形式包含sf1和sf2函数。SF1解旋酶一级和三级结构的高度同源性表明SF1解旋酶具有共同的潜在机制。然而,两种相反的功能单元模型,单体和二聚体模型,已经被提出来解释SF1解旋酶的DNA解绕。本文简要介绍了解旋酶SFs的分类,并以大肠杆菌SF1解旋酶UvrD为重点,讨论了SF1解旋酶的结构同源性和两种相反的非六聚体解旋酶模型,该解旋酶在核苷酸切除修复和甲基定向错配修复中都起着重要作用。本文综述了过去和最近关于UvrD的研究,包括作者的野生型UvrD的单分子直接可视化和缺乏c -末端40个氨基酸的UvrD突变体(UvrDΔ40C),后者用于支持单体模型的遗传和生化分析。可视化显示多个UvrDΔ40C分子共同解开DNA,可能以低聚形式,类似于野生型UvrD。因此,核酸结合蛋白的单分子直接可视化可以为揭示其基本机制提供定量和动力学信息。
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引用次数: 2
How evolution builds up complexity?: In vitro evolution approaches to witness complexification in artificial molecular replication systems 进化是如何构建复杂性的?:人工分子复制系统中复杂化的体外进化方法
Pub Date : 2022-02-15 DOI: 10.2142/biophysico.bppb-v19.0005
Taro Furubayashi, N. Ichihashi
How can evolution assemble lifeless molecules into a complex living organism? The emergent process of biological complexity in the origin of life is a big mystery in biology. In vitro evolution of artificial molecular replication systems offers unique experimental opportunities to probe possible pathways of a simple molecular system approaching a complex life-like system. This review focuses on experimental efforts to examine evolvability of molecules in vitro from the pioneering Spiegelman’s experiment to our latest research on an artificial RNA self-replication system. Genetic translation and compartmentalization are shown to enable sustainable replication and evolution. Latest studies are revealing that coevolution of self-replicating “host replicators” and freeloading “parasitic replicators” is crucial to extend evolvability of a molecular replication system for continuous evolution and emergence of diversity. Intense competition between hosts and parasites would have existed even before the origin of life and contributed to generating complex molecular ecosystems. This review article is an extended version of the Japanese article “An in vitro evolutionary journey of an artificial RNA replication system towards biological complexity” published in SEIBUTSU-BUTSURI Vol.61, p.240–244 (2021).”
进化是如何将无生命的分子组合成一个复杂的有生命的有机体的?生命起源中生物复杂性的涌现过程是生物学中的一大谜题。人工分子复制系统的体外进化为探索简单分子系统接近复杂类生命系统的可能途径提供了独特的实验机会。本文综述了从Spiegelman的开创性实验到我们对人工RNA自我复制系统的最新研究,在体外研究分子的可进化性的实验努力。遗传翻译和区隔化被证明能够实现可持续的复制和进化。最新研究表明,自我复制的“宿主复制子”和免费的“寄生复制子”的共同进化对于扩展分子复制系统的可进化性,实现持续进化和多样性的出现至关重要。宿主和寄生虫之间的激烈竞争甚至在生命起源之前就已经存在,并促成了复杂分子生态系统的产生。这篇评论文章是日本文章“人工RNA复制系统向生物复杂性的体外进化之旅”的扩展版本,发表在SEIBUTSU-BUTSURI Vol.61, p.240-244(2021)。
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引用次数: 0
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Biophysics and Physicobiology
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