cell geometry

单元几何体
  • 文章类型: Journal Article
    尽管在植物细胞分裂过程中新壁的形成倾向于遵循最大拉伸应力方向,随着时间的推移,对单个细胞的分析揭示了一种更加多变的行为。迄今为止,这种变异性的起源以及细胞分裂前相间微管行为的确切作用仍然是神秘的。为了解决这个问题,我们利用了拟南芥的茎,其中拉伸应力模式是高度各向异性和稳定的。尽管皮质微管(CMT)通常与最大拉伸应力对齐,我们检测到一个特定的时间窗口,CA.细胞分裂前3小时,其中细胞形成CMT的放射状模式。这种微管阵列组织先于前期带(PPB)形成,预测未来分割平面位置的瞬态CMT阵列。在不同的生长条件下观察到,与细胞几何形状或极性生长素转运无关。有趣的是,这种皮质放射状模式与有据可查的细胞分裂前细胞质微管积累的增加相关.这种放射状组织在trm678突变体的细胞中延长,其中CMT无法形成PPB。而trm678中的划分平面方向更嘈杂,我们发现细胞分裂对称性在子细胞之间的差异较小。我们建议此“径向步长”反映了两个基本细胞分裂属性的鲁棒性权衡:对称性和方向性。这涉及G2中的“重置”阶段,其中细胞质微管积累的增加会暂时破坏CMT与组织应激的对齐。
    Although the formation of new walls during plant cell division tends to follow maximal tensile stress direction, analyses of individual cells over time reveal a much more variable behavior. The origin of such variability as well as the exact role of interphasic microtubule behavior before cell division have remained mysterious so far. To approach this question, we took advantage of the Arabidopsis stem, where the tensile stress pattern is both highly anisotropic and stable. Although cortical microtubules (CMTs) generally align with maximal tensile stress, we detected a specific time window, ca. 3 h before cell division, where cells form a radial pattern of CMTs. This microtubule array organization preceded preprophase band (PPB) formation, a transient CMT array predicting the position of the future division plane. It was observed under different growth conditions and was not related to cell geometry or polar auxin transport. Interestingly, this cortical radial pattern correlated with the well-documented increase of cytoplasmic microtubule accumulation before cell division. This radial organization was prolonged in cells of the trm678 mutant, where CMTs are unable to form a PPB. Whereas division plane orientation in trm678 is noisier, we found that cell division symmetry was in contrast less variable between daughter cells. We propose that this \"radial step\" reflects a trade-off in robustness for two essential cell division attributes: symmetry and orientation. This involves a \"reset\" stage in G2, where an increased cytoplasmic microtubule accumulation transiently disrupts CMT alignment with tissue stress.
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  • 文章类型: Journal Article
    为了生存的植物运动是不平凡的。苔藓中的AntheridiaPhyscomitriumpatens(P.patens)在水的存在下使用运动来排出精子。然而,驱动该过程的生物和机械机制是未知的。这里,P.patens花药的爆发,由水引发,由弹性不稳定性引起,并由细胞几何形状的不对称变化决定。Antheridium的护套单元壁中产生的张力来自膨胀压力,当顶点的内壁在水合作用中破裂时,导致顶端的水分和细胞内容物迅速流入精子室。NAC转录因子VNS4增强了护套细胞的外壁,并作为关键的形态力学创新,可在P.patens的密闭空间中存储静水能量。然而,紫草中的花药(M.polymorpha)采用不同的精子释放策略;就像P.patens的外套细胞外壁一样,多形性分枝杆菌花药周围的细胞似乎在能量储存中起着类似的作用。总的来说,这项工作表明,植物已经进化出不同的精巧的精子排出装置,形态创新可能有所不同。
    Plant movements for survival are nontrivial. Antheridia in the moss Physcomitrium patens (P. patens) use motion to eject sperm in the presence of water. However, the biological and mechanical mechanisms that actuate the process are unknown. Here, the burst of the antheridium of P. patens, triggered by water, results from elastic instability and is determined by an asymmetric change in cell geometry. The tension generated in jacket cell walls of antheridium arises from turgor pressure, and is further promoted when the inner walls of apex burst in hydration, causing water and cellular contents of apex quickly influx into sperm chamber. The outer walls of the jacket cells are strengthened by NAC transcription factor VNS4 and serve as key morphomechanical innovations to store hydrostatic energy in a confined space in P. patens. However, the antheridium in liverwort Marchantia polymorpha (M. polymorpha) adopts a different strategy for sperm release; like jacket cell outer walls of P. patens, the cells surrounding the antheridium of M. polymorpha appear to play a similar role in the storage of energy. Collectively, the work shows that plants have evolved different ingenious devices for sperm discharge and that morphological innovations can differ.
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  • 文章类型: Journal Article
    细胞感知来自周围环境的机械信号,并通过机械传导将其传递到细胞核,以调节细胞行为。微接触印刷,利用弹性体邮票,是模拟细胞微环境和操纵细胞形态的有效方法。然而,硅母版和弹性体邮票的常规制造工艺需要复杂的程序和专用设备,这限制了微模式在细胞生物学中的广泛应用,并阻碍了研究细胞几何形状在调节细胞行为中的作用。在这项研究中,我们提出了一种基于数字微镜器件平面光刻的方便树脂印章微加工的创新方法。使用此方法,我们生成了一系列从毫米到微米级的模式,并验证了它们在集体和单个细胞水平上控制粘附的有效性.此外,我们研究了在细长的微图案化基底上的机械转导和细胞行为。然后我们检查了细胞伸长对细胞骨架组织的影响,核变形,焦点粘附形成,牵引力的产生,核力学,和HeLa细胞的生长。我们的发现揭示了细胞长度和机械转导之间的正相关。有趣的是,中等长度的HeLa细胞表现出最高的细胞分裂和增殖率。这些结果强调了细胞伸长在机械转导中的调节作用及其对癌细胞生长的显著影响。此外,我们控制细胞粘附的方法具有解决细胞生物学和生物医学工程中基本问题的潜力。
    Cells sense mechanical signals from the surrounding environment and transmit them to the nucleus through mechanotransduction to regulate cellular behavior. Microcontact printing, which utilizes elastomer stamps, is an effective method for simulating the cellular microenvironment and manipulating cell morphology. However, the conventional fabrication process of silicon masters and elastomer stamps requires complex procedures and specialized equipment, which restricts the widespread application of micropatterning in cell biology and hinders the investigation of the role of cell geometry in regulating cell behavior. In this study, we present an innovative method for convenient resin stamp microfabrication based on digital micromirror device planar lithography. Using this method, we generated a series of patterns ranging from millimeter to micrometer scales and validated their effectiveness in controlling adhesion at both collective and individual cell levels. Additionally, we investigated mechanotransduction and cell behavior on elongated micropatterned substrates. We then examined the effects of cell elongation on cytoskeleton organization, nuclear deformation, focal adhesion formation, traction force generation, nuclear mechanics, and the growth of HeLa cells. Our findings reveal a positive correlation between cell length and mechanotransduction. Interestingly, HeLa cells with moderate length exhibit the highest cell division and proliferation rates. These results highlight the regulatory role of cell elongation in mechanotransduction and its significant impact on cancer cell growth. Furthermore, our methodology for controlling cell adhesion holds the potential for addressing fundamental questions in both cell biology and biomedical engineering.
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  • 文章类型: Journal Article
    细胞的几何形状受到细胞骨架的强烈影响,which,反过来,受整合素介导的细胞-细胞外基质(ECM)相互作用调节。为了研究整合素在细胞和ECM之间的几何相互作用中的机械作用,我们提出了一种结合分子张力荧光显微镜(MTFM)的单细胞微图案化技术,这使我们能够用规定的几何形状表征细胞的机械性能。我们的结果表明,曲率是细胞以膜张力和肌动球蛋白依赖性方式分化形状的关键几何线索。具体来说,曲率影响粘着斑(FA)的大小,并诱导强整合素的曲率依赖性密度和空间分布。此外,我们发现整合素亚基β1在几何信息的检测中起着至关重要的作用。总的来说,MTFM和单细胞微图案化的整合为研究机械线索和细胞反应之间的联系提供了一种强大的方法,具有促进我们对机械生物学的理解的潜力。
    The geometric shape of a cell is strongly influenced by the cytoskeleton, which, in turn, is regulated by integrin-mediated cell-extracellular matrix (ECM) interactions. To investigate the mechanical role of integrin in the geometrical interplay between cells and the ECM, we proposed a single-cell micropatterning technique combined with molecular tension fluorescence microscopy (MTFM), which allows us to characterize the mechanical properties of cells with prescribed geometries. Our results show that the curvature is a key geometric cue for cells to differentiate shapes in a membrane-tension- and actomyosin-dependent manner. Specifically, curvatures affect the size of focal adhesions (FAs) and induce a curvature-dependent density and spatial distribution of strong integrins. In addition, we found that the integrin subunit β1 plays a critical role in the detection of geometric information. Overall, the integration of MTFM and single-cell micropatterning offers a robust approach for investigating the nexus between mechanical cues and cellular responses, holding potential for advancing our understanding of mechanobiology.
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  • 文章类型: Journal Article
    胚胎干细胞(ESC)自组织成具有三个不同胚层的组织化组织对于形态发生和早期发育至关重要。虽然可溶性信号对这种自组织的调节已经建立,由于缺乏合适的研究平台,机械力梯度在这一过程中的参与尚不清楚.在这项研究中,我们开发了一个3D微环境,通过控制ESC菌落的几何信号(形状和大小)来检查机械张力梯度对形态发生过程中ESC模式分化的影响。我们发现菌落几何形状的变化会影响胚层模式,Cdx2阳性细胞在边缘和高曲率区域更丰富。通过几何介导的细胞张力梯度确定分化模式,在高张力区域形成胚外中胚层样层,在中心的低张力区域形成外胚层样谱系。细胞骨架张力的抑制阻碍了ESC自组织。这些结果表明,几何限制介导的机械张力在将多细胞组织与细胞分化联系起来并影响组织模式中起着至关重要的作用。
    The self-organization of embryonic stem cells (ESCs) into organized tissues with three distinct germ layers is critical to morphogenesis and early development. While the regulation of this self-organization by soluble signals is well established, the involvement of mechanical force gradients in this process remains unclear due to the lack of a suitable platform to study this process. In this study, we developed a 3D microenvironment to examine the influence of mechanical tension gradients on ESC-patterned differentiation during morphogenesis by controlling the geometrical signals (shape and size) of ESC colonies. We found that changes in colony geometry impacted the germ layer pattern, with Cdx2-positive cells being more abundant at edges and in areas with high curvatures. The differentiation patterns were determined by geometry-mediated cell tension gradients, with an extraembryonic mesoderm-like layer forming in high-tension regions and ectodermal-like lineages at low-tension regions in the center. Suppression of cytoskeletal tension hindered ESC self-organization. These results indicate that geometric confinement-mediated mechanical tension plays a crucial role in linking multicellular organization to cell differentiation and impacting tissue patterning.
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  • 文章类型: Journal Article
    癌细胞在不同身体部位之间的迁移是癌症转移的驱动力,是导致患者死亡的主要原因。癌细胞的迁移通常通过穿透局部僵硬的狭窄腔来进行,然而灵活的组织。在我们之前的工作中,我们开发了入侵过程中细胞几何进化的模型,我们在这里扩展到研究仅机械相互作用的前导和跟随(癌症)细胞是否可以从通过狭窄的微通道和腔的顺序迁移中受益。我们考虑了两种通过灵活通道顺序迁移的细胞的情况:前导细胞和跟随细胞紧密相邻或远离。对从蒙特卡洛模拟中收集的数据使用Wilcoxon的符号秩检验,我们得出的结论是,当细胞远离时,跟随细胞的模拟迁移速度明显大于前导细胞,即跟随细胞在前导完成杂交后迁移。此外,似乎存在关于通道的宽度的最优值,使得细胞移动最快。另一方面,在紧密相邻的细胞的情况下,有效地执行集体迁移,领导者单元移动速度快12%,因为追随者单元推动它。这项工作表明,细胞之间的机械相互作用可以增加癌细胞的净迁移速度,导致侵袭性增加。换句话说,癌细胞之间的相互作用可以加速转移侵袭。
    Cancer cell migration between different body parts is the driving force behind cancer metastasis, which is the main cause of mortality of patients. Migration of cancer cells often proceeds by penetration through narrow cavities in locally stiff, yet flexible tissues. In our previous work, we developed a model for cell geometry evolution during invasion, which we extend here to investigate whether leader and follower (cancer) cells that only interact mechanically can benefit from sequential transmigration through narrow micro-channels and cavities. We consider two cases of cells sequentially migrating through a flexible channel: leader and follower cells being closely adjacent or distant. Using Wilcoxon\'s signed-rank test on the data collected from Monte Carlo simulations, we conclude that the modelled transmigration speed for the follower cell is significantly larger than for the leader cell when cells are distant, i.e. follower cells transmigrate after the leader has completed the crossing. Furthermore, it appears that there exists an optimum with respect to the width of the channel such that cell moves fastest. On the other hand, in the case of closely adjacent cells, effectively performing collective migration, the leader cell moves 12% faster since the follower cell pushes it. This work shows that mechanical interactions between cells can increase the net transmigration speed of cancer cells, resulting in increased invasiveness. In other words, interaction between cancer cells can accelerate metastatic invasion.
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  • 文章类型: Journal Article
    评估了来自远洋系统的浮游植物群落,以探索使用常用性状(例如细胞几何形状和分类群)作为生态功能指标的潜力,这些数据是在阿拉伯海东部(AS)的冬季季风期间产生的。总之,来自两个海洋的数据,即,对流混合影响的非贫营养东北AS(NEAS-O)和罗斯比波影响的贫营养东南AS(SEAS-O)和一次沿海(NEAS-C)航行被用来破译生态推论。总体浮游植物的形状显示出高水平的冗余,只选择了几个优势形状(22个形状中的5个),虽然分类多样性丰富(164种)。采用的分类学和形态学方法显示,NEAS-O的物种和形状多样性高于高丰度NEAS-C和低丰度SEAS-O。此外,形状多样性和主导形状(圆柱体,椭圆棱镜,和平行四边形棱镜)在海洋中与NEAS-C保持相同,NEAS-C组合(2个半球)和简单(椭圆棱镜)形状占主导地位。此外,Rossby波前及其在SEAS-O中的回忆和NEAS-C中的海面温度前沿偏爱简单和组合形状的浮游植物,分别。形态特性评估表明,无论NEAS-O和SEAS-O中最大轴向线性尺寸(GALD)的变化如何,占主导地位的形状都采用了保留最佳表面体积比(S:V)的策略,而不是在NEAS-C中。然而,NEAS-O和SEAS-O中的主要形状选择了具有低GALD的高S:V和具有高GALD的低S:V,分别,虽然NEAS-C中与GALD无关的高S:V表明了应对各自水文条件的不同适应性策略的普遍性,特别是营养供应。
    Phytoplankton communities from pelagic systems were assessed to explore the potential of using commonly used traits (such as cell geometry and taxa) as ecological function indicators from the data generated during the winter monsoon in the eastern Arabian Sea (AS). Altogether, data from two oceanic, i.e., convective mixing influenced non-oligotrophic northeastern-AS (NEAS-O) and Rossby wave-influenced oligotrophic southeastern-AS (SEAS-O) and one coastal (NEAS-C) cruises were utilized to decipher the ecological inferences. Overall phytoplankton shapes showed a high level of redundancy by selecting only a few dominant shapes (5 of 22 shapes), though taxonomic diversity was rich (164 species). The taxonomic and morphological approach adopted revealed high species and shape diversity in NEAS-O than in high-abundance NEAS-C and low-abundance SEAS-O. Also, the shape diversity and dominant shapes (cylinder, elliptic-prism, and prism-on-parallelogram) remained the same in oceans than NEAS-C where combined (cylinder + 2 half-sphere) and simple (elliptic-prism) shapes dominated. Additionally, the Rossby-wave front and its reminiscence in SEAS-O and sea-surface-temperature fronts in NEAS-C favored simple and combine shaped phytoplankton, respectively. The morphological properties assessment revealed that the dominant shapes adapted the strategy to conserve the optimal surface-to-volume ratio (S:V) irrespective of changes in greatest-axial-linear-dimension (GALD) in NEAS-O and SEAS-O but not in NEAS-C. However, the dominant shapes in the NEAS-O and SEAS-O opted for high S:V with low GALD and low S:V with high GALD, respectively, while high S:V with no relation with GALD in NEAS-C suggests the prevalence of different adaptive strategies to cope with the respective hydrographic conditions, particularly nutrient availability.
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  • 文章类型: Journal Article
    背景:最近的实验数据支持以下观点:膜上的信号活动取决于其几何参数,例如表面积和曲率。然而,一个数学,缺少将形状与受体信号联系起来的生物物理概念。由于收缩和松弛的循环,心肌细胞的膜不断重塑。根据心肌细胞收缩的恒定体积行为,长度的缩短由两个相邻Z盘之间的Z盘肌丝晶格扩张和膜的动态变形来补偿。两种形态变化都强烈依赖于收缩频率。这里,我们提出了一个假设,即心肌细胞的动态几何形状对其可塑性和信号传导可能很重要。这种影响可能取决于跳动的心脏的频率,并且可能代表一个新的概念来解释频率变化如何影响心脏信号传导。方法:这个假设几乎不可能用实验来回答,因为体外心肌细胞几乎是二维的,并且是扁平的,而不是真正的体内形状。因此,我们设计了一个COMSOL多物理场程序来对人心肌细胞的动态几何进行数学建模,并探索搏动频率是否可以调节膜信号转导。Src激酶是心脏机械传导的重要组成部分。我们首先提出了Src主要位于科斯塔姆。然后,通过对Src介导的PDGFR信号通路的数值模拟,对频率依赖性信号效应进行了数学研究.建立了反应-对流-扩散偏微分方程,以模拟1至4Hz频率范围内收缩肌节圆盘中的PDGFR路径。结果:当心肌细胞以更高的速率搏动时,模拟显示更高浓度的磷酸-Src。在4、2和1Hz拍频下计算的磷酸Src浓度,与0Hz相比,为21.5%,9.4%,高出4.7%,分别。结论:在这里,我们为生物学中的一个新概念提供了数学证据。细胞形状直接转化为信号,特别是对心肌的重要影响,细胞不断重塑细胞膜。表面体积比的局部概念被证明会导致膜介导的信号传导发生变化,并且可能有助于解释心肌对生物力学应力的显着可塑性。
    Background: Recent experimental data support the view that signaling activity at the membrane depends on its geometric parameters such as surface area and curvature. However, a mathematical, biophysical concept linking shape to receptor signaling is missing. The membranes of cardiomyocytes are constantly reshaped due to cycles of contraction and relaxation. According to constant-volume behavior of cardiomyocyte contraction, the length shortening is compensated by Z-disc myofilament lattice expansion and dynamic deformation of membrane between two adjacent Z-discs. Both morphological changes are strongly dependent on the frequency of contraction. Here, we developed the hypothesis that dynamic geometry of cardiomyocytes could be important for their plasticity and signaling. This effect may depend on the frequency of the beating heart and may represent a novel concept to explain how changes in frequency affect cardiac signaling. Methods: This hypothesis is almost impossible to answer with experiments, as the in-vitro cardiomyocytes are almost two-dimensional and flattened rather than being in their real in-vivo shape. Therefore, we designed a COMSOL multiphysics program to mathematically model the dynamic geometry of a human cardiomyocyte and explore whether the beating frequency can modulate membrane signal transduction. Src kinase is an important component of cardiac mechanotransduction. We first presented that Src mainly localizes at costameres. Then, the frequency-dependent signaling effect was studied mathematically by numerical simulation of Src-mediated PDGFR signaling pathway. The reaction-convection-diffusion partial differential equation was formulated to simulate PDGFR pathway in a contracting sarcomeric disc for a range of frequencies from 1 to 4 Hz. Results: Simulations exhibits higher concentration of phospho-Src when a cardiomyocyte beats with higher rates. The calculated phospho-Src concentration at 4, 2, and 1 Hz beat rates, comparing to 0 Hz, was 21.5%, 9.4%, and 4.7% higher, respectively. Conclusion: Here we provide mathematical evidence for a novel concept in biology. Cell shape directly translates into signaling, an effect of importance particularly for the myocardium, where cells continuously reshape their membranes. The concept of locality of surface-to-volume ratios is demonstrated to lead to changes in membrane-mediated signaling and may help to explain the remarkable plasticity of the myocardium in response to biomechanical stress.
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  • 文章类型: Journal Article
    植物中的细胞生长是由于细胞壁响应于由膨大压力产生的机械力的松弛而发生的。生长可以是各向异性的,生长的主要方向通常与细胞壁的较低刚度的方向相关。然而,在洋葱表皮果皮上的引伸计实验表明,组织在主要生长方向上更坚硬。这里,我们使用了表皮洋葱皮的微引伸计实验和有限元方法(FEM)建模的组合,以研究细胞几何形状和细胞模式如何影响在组织水平上进行的机械测量。各向同性细胞壁材料参数的模拟表明,细长细胞的方向影响组织的表观刚度,组织在横向与纵向上显得柔软得多。我们的模拟表明,虽然引伸计实验表明,洋葱组织在纵向拉伸时更硬,细胞几何形状的影响意味着墙壁实际上在这个方向上更柔软,与细胞的初级生长方向相匹配。
    Cell growth in plants occurs due to relaxation of the cell wall in response to mechanical forces generated by turgor pressure. Growth can be anisotropic, with the principal direction of growth often correlating with the direction of lower stiffness of the cell wall. However, extensometer experiments on onion epidermal peels have shown that the tissue is stiffer in the principal direction of growth. Here, we used a combination of microextensometer experiments on epidermal onion peels and finite element method (FEM) modeling to investigate how cell geometry and cellular patterning affects mechanical measurements made at the tissue level. Simulations with isotropic cell-wall material parameters showed that the orientation of elongated cells influences tissue apparent stiffness, with the tissue appearing much softer in the transverse versus the longitudinal directions. Our simulations suggest that although extensometer experiments show that the onion tissue is stiffer when stretched in the longitudinal direction, the effect of cellular geometry means that the wall is in fact softer in this direction, matching the primary growth direction of the cells.
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  • 文章类型: Journal Article
    细胞或结构在组织平面内的协调被称为平面极化。它通常受细胞内平面极性蛋白的不对称分布支配。已经开发了许多定量方法来提供平面极化蛋白质分布的读数。然而,以前的平面极性量化方法可能会受到细胞几何形状变化的影响。因此,我们开发了一种基于形状不敏感的主成分分析(PCA)的新型平面极性量化方法。这里,我们在模拟模型和生物数据集上比较了这种方法与其他最先进的方法。我们发现,PCA方法在量化平面极性方面表现强劲,与细胞几何形状和其他图像条件的变化无关。我们设计了一个用户友好的图形用户界面,称为QuantifyPolarity,配备三种极性自动量化的极性方法。QuantifyPolarity还提供了量化细胞形态和堆积几何形状的工具,允许研究这些特性与平面极化的关系。该工具使没有先前计算专业知识的实验人员能够自动高效地执行高通量细胞极性和形状分析。
    The coordination of cells or structures within the plane of a tissue is known as planar polarization. It is often governed by the asymmetric distribution of planar polarity proteins within cells. A number of quantitative methods have been developed to provide a readout of planar polarized protein distributions. However, previous planar polarity quantification methods can be affected by variation in cell geometry. Hence, we developed a novel planar polarity quantification method based on Principal Component Analysis (PCA) that is shape insensitive. Here, we compare this method with other state-of-the-art methods on simulated models and biological datasets. We found that the PCA method performs robustly in quantifying planar polarity independently of variation in cell geometry and other image conditions. We designed a user-friendly graphical user interface called QuantifyPolarity, equipped with three polarity methods for automated quantification of polarity. QuantifyPolarity also provides tools to quantify cell morphology and packing geometry, allowing the relationship of these characteristics to planar polarization to be investigated. This tool enables experimentalists with no prior computational expertise to perform high-throughput cell polarity and shape analysis automatically and efficiently.
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