Models, Biological

模型, 生物
  • 文章类型: Journal Article
    肿瘤模型的出现极大地促进了治疗药物和方法的发展。然而,由于其固有的复杂性,建立一个可以完全复制肿瘤组织情况的模型仍然极具挑战性。随着组织工程学的发展,生物打印技术的进步促进了肿瘤模型的升级。本文重点介绍生物打印的最新进展,特别强调3D肿瘤模型的构建,并强调了这两种技术的集成。此外,它讨论了相关技术的挑战和未来方向,同时还强调通过类似于体外器官的3D肿瘤模型的出现来有效地重建肿瘤微环境,从而加速新的抗癌疗法的发展。
    The development of therapeutic drugs and methods has been greatly facilitated by the emergence of tumor models. However, due to their inherent complexity, establishing a model that can fully replicate the tumor tissue situation remains extremely challenging. With the development of tissue engineering, the advancement of bioprinting technology has facilitated the upgrading of tumor models. This article focuses on the latest advancements in bioprinting, specifically highlighting the construction of 3D tumor models, and underscores the integration of these two technologies. Furthermore, it discusses the challenges and future directions of related techniques, while also emphasizing the effective recreation of the tumor microenvironment through the emergence of 3D tumor models that resemble in vitro organs, thereby accelerating the development of new anticancer therapies.
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  • 文章类型: Journal Article
    近年来,基于植物的肉类类似物越来越引起食品工业的关注。然而,人们对这种创新的固体食物在人体胃中的消化行为知之甚少。在这项研究中,在使用/不使用高水分挤压技术和在不同温度下制备具有不同内部结构的基于植物的肉类似物。应用了半动态胃消化系统,该系统涉及胃液分泌和胃排空的模拟过程。高温(150℃)挤压处理后,EHT具有最高的各向异性指数(HHL/H44%=1.90)和理想的肉样结构。发现在胃消化的早期阶段,EHT的推注中同时发生颗粒崩解和溶胀,但在未经挤压处理(HLT)的样品中却没有。这种差异可能归因于挤压产生的EHT的紧凑和排列良好的各向异性结构。并导致难以酶促水解,除非颗粒溶胀和展开聚合物链。胃消化过程中EHT中颗粒崩解的困难是胃排空速率相对较慢和蛋白质降解减少的结果。因此,在高温下进行挤压处理并具有最佳各向异性纤维结构的EHT表现出最慢的胃消化。这种新型固体食物显示出良好的潜力,可作为饮食人群所需的营养食品。
    Plant-based meat analogs have increasingly attracted the attention of the food industry in recent years. However, the digestion behavior of this innovative solid food in human stomach is poorly understood. In this study, plant-based meat analogs with different internal structures were prepared with/without high-moisture extrusion technology and at different temperatures. A semi-dynamic gastric digestion system which involves the mimic processes of the secretion of gastric juice and the gastric emptying was applied. After extrusion treatment at high temperature (150 ℃), the EHT had the highest anisotropic index (H⊥/H∥=1.90) and an ideal meat-like structure. It was found that particle disintegration and swelling simultaneously occurred in the bolus of the EHT but not in the sample without extrusion treatment (the HLT) in the early stage of gastric digestion. This difference might be attributed to the compact and well-arranged anisotropic structure of the EHT resulting from the extrusion, and leads to difficult enzymatic hydrolyzation unless the particles swell and unfold the polymer chains. The difficulty in particle disintegration in the EHT during gastric digestion is the consequence of the relatively slow gastric emptying rate and the decrease of protein degradation. As a result, the EHT which underwent extrusion treatment at high temperature and possessed the best anisotropic fibrous structure exhibited the slowest gastric digestion. This novel solid food shows good potential as a desired nutritional food for people on diet.
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  • 文章类型: Journal Article
    了解机械力对组织养分运输的作用至关重要,因为持续的力量可能会影响椎间盘内的营养水平并引发椎间盘退变。这项研究旨在评估不同压缩力幅度以及拉力对椎间盘内葡萄糖浓度和细胞活力的时间依赖性影响。基于机械-电化学混合理论,建立了腰椎间盘的多相有限元模型。对于不同的压缩力幅度,预测正常和退化椎间盘中的最小葡萄糖浓度和最小细胞密度。拉力,和相应的蠕变时间。在高压缩力下,在正常椎间盘中,最低葡萄糖浓度随蠕变时间呈现先升高后降低的趋势,而退化盘的增加,然后减少,最后又增加了。在稳定状态下,较高的压缩力伴随较低的葡萄糖浓度分布。在退化的光盘中,最小细胞密度与蠕变时间呈负相关,在更高的压缩力下,受影响的组织范围更大。对于拉力,退化椎间盘的最低葡萄糖浓度随时间升高。这项研究强调了蠕变时间的重要性,力大小,和影响营养素浓度和细胞活力的力类型。持续的负重活动会使退化盘的营养环境恶化,而拉力在有效改善退化椎间盘内的营养水平方面可能具有不可忽视的作用。
    Understanding the role of mechanical force on tissue nutrient transport is essential, as sustained force may affect nutrient levels within the disc and initiate disc degeneration. This study aims to evaluate the time-dependent effects of different compressive force amplitudes as well as tensile force on glucose concentration and cell viability within the disc. Based on the mechano-electrochemical mixture theory, a multiphasic finite element model of the lumbar intervertebral disc was developed. The minimum glucose concentration and minimum cell density in both normal and degenerated discs were predicted for different compressive force amplitudes, tensile force, and corresponding creep time. Under high compressive force, the minimum glucose concentration exhibited an increasing and then decreasing trend with creep time in the normal disc, whereas that of the degenerated disc increased, then decreased, and finally increased again. At steady state, a higher compressive force was accompanied by a lower glucose concentration distribution. In the degenerated disc, the minimum cell density was negatively correlated with creep time, with a greater range of affected tissue under a higher compressive force. For tensile force, the minimum glucose concentration of the degenerated disc raised over time. This study highlighted the importance of creep time, force magnitude, and force type in affecting nutrient concentration and cell viability. Sustained weight-bearing activities could deteriorate the nutrient environment of the degenerated disc, while tensile force might have a nonnegligible role in effectively improving nutrient levels within the degenerated disc.
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  • 文章类型: Journal Article
    现代解剖学中的双袋理论表明,具有涂层的结构在人体中普遍存在于各种长度尺度,例如被细胞周围基质(PCM)覆盖的骨细胞过程和被肌肉组织覆盖的骨骼。为了了解这种生物结构的力学行为和生理反应,我们开发了一个分析模型,以量化表面效应对弹性基质中涂覆的圆柱形可压缩液体夹杂物的变形的影响。我们的分析解决方案表明,涂层可以放大或减弱夹杂物的体积应变,根据夹杂物的相对弹性模量,涂层,和矩阵。为了说明,我们利用这个解决方案来探索肌肉骨骼系统中体积应变的放大/衰减,神经细胞,和血管组织。我们证明,涂层通常在人体组织和细胞发育和修复的机械调节中起着至关重要的作用。我们的模型提供了涂层液体夹杂物的跨尺度力学响应的定性分析,有助于构建细胞的机械微环境。 .
    The double-bag theory in modern anatomy suggests that structures with coatings are commonly found in human body at various length scales, such as osteocyte processes covered by pericellular matrix and bones covered by muscle tissue. To understand the mechanical behaviors and physiological responses of such biological structures, we develop an analytical model to quantify surface effects on the deformation of a coated cylindrical compressible liquid inclusion in an elastic matrix subjected to remote loading. Our analytical solution reveals that coating can either amplify or attenuate the volumetric strain of the inclusion, depending on the relative elastic moduli of inclusion, coating, and matrix. For illustration, we utilize this solution to explore amplification/attenuation of volumetric strain in musculoskeletal systems, nerve cells, and vascular tissues. We demonstrate that coating often plays a crucial role in mechanical regulation of the development and repair of human tissues and cells. Our model provides qualitative analysis of cross-scale mechanical response of coated liquid inclusions, helpful for constructing mechanical microenvironment of cells.
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  • 文章类型: Journal Article
    在边界表面附近截留细菌具有生物学和实际意义,然而,基本的物理学还没有得到很好的理解。我们证明,包括与流体动力学相互作用的空间变化有关的通常被忽视的热力学效应至关重要。通过一个模型,提供了两个无量纲参数的细菌截留的分析解释:α_{1}热能与自我推进的比率,α_{2}是一个内在形状因子。对于在室温下与大肠杆菌相匹配的α_{1}和α_{2},我们的模型定量再现了现有的实验观察结果,包括两个以前尚未解决的关键功能:细菌“鼻子向下”配置,以及俯仰角和摆动角之间的反相关性。此外,我们的模型分析地预测了由{α_{1}定义的参数空间中截留区的存在,α_{2}}。
    The entrapment of bacteria near boundary surfaces is of biological and practical importance, yet the underlying physics is not well understood. We demonstrate that it is crucial to include a commonly neglected thermodynamic effect related to the spatial variation of hydrodynamic interactions, through a model that provides analytic explanation of bacterial entrapment in two dimensionless parameters: α_{1} the ratio of thermal energy to self-propulsion, and α_{2} an intrinsic shape factor. For α_{1} and α_{2} that match an Escherichia coli at room temperature, our model quantitatively reproduces existing experimental observations, including two key features that have not been previously resolved: The bacterial \"nose-down\" configuration, and the anticorrelation between the pitch angle and the wobbling angle. Furthermore, our model analytically predicts the existence of an entrapment zone in the parameter space defined by {α_{1},α_{2}}.
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  • 文章类型: Journal Article
    手性在生物学中起着至关重要的作用,因为它是高度保守的,在发展过程中至关重要。为了更好地理解单个细胞的手性与组织和生物体的手性之间的关系,我们建立了手性极化粒子的广义力学模型,以研究基质上细胞群的旋流动力学。我们的分析表明,具有相同手性的细胞可以在环形或矩形基底上形成不同的手性模式。有趣的是,我们的研究表明,过强或过弱的单个细胞手性阻碍了这种手性模式的形成。我们的研究还表明,手性模式中存在底物边界的影响距离。当细胞-细胞相互作用较弱时,观察到较小的影响距离。相反,当细胞间的相互作用太强时,多个细胞倾向于堆叠在一起,在我们的分析中防止在底物上形成手性模式。此外,我们证明了细胞与底物边界之间的相互作用有效地控制了细胞取向在环形底物上的手性分布。本研究突出了协调边界特征的意义,个体细胞手性,和细胞-细胞相互作用在控制细胞群体的手性运动中,并为理解单细胞的手性与组织和生物体的手性之间的复杂联系提供了有价值的力学见解。
    Chirality plays a crucial role in biology, as it is highly conserved and fundamentally important in the developmental process. To better understand the relationship between the chirality of individual cells and that of tissues and organisms, we develop a generalized mechanics model of chiral polarized particles to investigate the swirling dynamics of cell populations on substrates. Our analysis reveals that cells with the same chirality can form distinct chiral patterns on ring-shaped or rectangular substrates. Interestingly, our studies indicate that an excessively strong or weak individual cellular chirality hinders the formation of such chiral patterns. Our studies also indicate that there exists the influence distance of substrate boundaries in chiral patterns. Smaller influence distances are observed when cell-cell interactions are weaker. Conversely, when cell-cell interactions are too strong, multiple cells tend to be stacked together, preventing the formation of chiral patterns on substrates in our analysis. Additionally, we demonstrate that the interaction between cells and substrate boundaries effectively controls the chiral distribution of cellular orientations on ring-shaped substrates. This research highlights the significance of coordinating boundary features, individual cellular chirality, and cell-cell interactions in governing the chiral movement of cell populations and provides valuable mechanics insights into comprehending the intricate connection between the chirality of single cells and that of tissues and organisms.
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  • 文章类型: Journal Article
    在本文中,我们考虑了具有修改Leslie-Gower的随机两物种捕食者-食饵系统。同时,我们假设捕食者中发生了狩猎合作。通过运用IT公式构造一个合适的Lyapunov函数,我们首先证明,对于任何给定的正初始值,都有一个唯一的全局正解。此外,基于切比雪夫不等式,讨论了随机最终有界性和随机持久性。然后,在某些条件下,我们证明了系统的均值和灭绝的持久性。最后,我们通过数值模拟验证了我们的结果。
    In this paper, we consider a stochastic two-species predator-prey system with modified Leslie-Gower. Meanwhile, we assume that hunting cooperation occurs in the predators. By using Itô formula and constructing a proper Lyapunov function, we first show that there is a unique global positive solution for any given positive initial value. Furthermore, based on Chebyshev inequality, the stochastic ultimate boundedness and stochastic permanence are discussed. Then, under some conditions, we prove the persistence in mean and extinction of system. Finally, we verify our results by numerical simulations.
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  • 文章类型: Journal Article
    视网膜细胞代谢活动过程中产生的过氧化氢(H2O2)过多会导致视网膜色素上皮(RPE)组织氧化变性,涉及导致失明的各种视网膜疾病的特定病理过程,这可以通过饮食抗氧化剂来减轻,以防止炎症和受损的细胞功能障碍。这项研究检验了以下假设:在H2O2挑战的模型中,叶黄素可以减轻氧化应激引起的损害。这是基于在三维(3D)打印的纤维支架上培养的ARPE-19细胞单层。用叶黄素(0.5μM)预处理这些模型24小时可以显着降低氧化应激并维持吞噬作用和屏障功能。此外,叶黄素可以调节NLRP3炎性体,导致促炎细胞因子(IL-1β和IL-18)水平下降40%。总的来说,本研究提示3DRPE模型是检测叶黄素调节细胞功能和调节NLRP3炎症能力的有效工具.
    Excessive hydrogen peroxide (H2O2) generated during retinal cell metabolic activity could lead to oxidative degeneration of retinal pigment epithelium (RPE) tissue, a specific pathological process implicated in various retinal diseases resulting in blindness, which can be mitigated by taking dietary antioxidants to prevent inflammation and impaired cellular dysfunction. This study tested the hypothesis that damages induced by oxidative stresses can be mitigated by lutein in a H2O2-challenged model, which was based on an ARPE-19 cell monolayer cultured on three-dimensional (3D)-printed fibrous scaffolds. Pretreating these models with lutein (0.5 μM) for 24 h can significantly lower the oxidative stress and maintain phagocytosis and barrier function. Moreover, lutein can modulate the NLRP3 inflammasome, leading to a ∼40% decrease in the pro-inflammatory cytokine (IL-1β and IL-18) levels. Collectively, this study suggests that the 3D RPE model is an effective tool to examine the capability of lutein to modulate cellular functionalities and regulate NLRP3 inflammation.
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  • 文章类型: Journal Article
    时间序列实验对于理解生物现象的瞬态和动态性质至关重要。这些实验,利用先进的分类和聚类算法,允许深入了解细胞过程。然而,虽然这些方法有效地识别数据中的模式和趋势,他们经常需要改进阐明这些变化背后的因果机制。建立在这个基础上,我们的研究介绍了一种用于时间因果信号建模的新算法,整合已建立的知识网络与序列基因表达数据,以阐明随着时间的推移信号转导途径。专注于大肠杆菌(E.大肠杆菌)需氧到厌氧过渡(AAT),这项研究标志着在理解生物体的代谢变化方面的重大飞跃。通过将我们的算法应用于全面的大肠杆菌调控网络和时间序列微阵列数据集,我们构建了大肠杆菌AAT的跨时间点核心信号和调控过程。通过基因表达分析,我们验证了支配这一过程的主要调控相互作用.我们确定了一种新的调控方案,其中环境响应基因,soxR和oxyR,激活毛皮,调节氮代谢调节剂fnr和nac。这种调节级联控制应力调节剂ompR和lrhA,最终影响细胞运动基因flhD,揭示了一个新颖的监管轴,阐明了AAT过程中复杂的监管动态。我们的方法,将经验数据与先验知识合并,代表了细胞信号过程建模的重大进步,对微生物生理学及其在生物技术中的应用有更深入的了解。
    Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli\'s (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism\'s metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli\'s AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.
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  • 文章类型: Journal Article
    在本文中,提出了一种多斑块和多组媒介传播疾病模型,以研究宿主通勤(拉格朗日方法)和/或媒介迁移(欧拉方法)对疾病传播的影响。我们首先定义模型的基本再现数,R0,这完全决定了模型系统的全局动态。即,如果R0≤1,那么无病均衡是全局渐近稳定的,如果R0>1,那么就存在一个全局渐近稳定的特有均衡。然后,我们表明,基本繁殖数具有下界和上界,这与宿主停留时间矩阵和矢量迁移矩阵无关。特别是,在均匀环境中,宿主和矢量的非均匀混合通常会增加疾病的持久性,并且当宿主和矢量的分布成比例时,模型的基本繁殖数达到最小值。此外,如果环境是同质的,R0也可以通过断开的补丁的基本再现数量来估计。针对特殊场景,获得了最优矢量控制策略。在两个补丁和两个小组的情况下,我们数值分析了基本繁殖数和总感染人数对宿主停留时间矩阵的依赖性,并说明了在同质和异质环境中的最优矢量控制策略。
    In this paper, a multi-patch and multi-group vector-borne disease model is proposed to study the effects of host commuting (Lagrangian approach) and/or vector migration (Eulerian approach) on disease spread. We first define the basic reproduction number of the model, R 0 , which completely determines the global dynamics of the model system. Namely, if R 0 ≤ 1 , then the disease-free equilibrium is globally asymptotically stable, and if R 0 > 1 , then there exists a unique endemic equilibrium which is globally asymptotically stable. Then, we show that the basic reproduction number has lower and upper bounds which are independent of the host residence times matrix and the vector migration matrix. In particular, nonhomogeneous mixing of hosts and vectors in a homogeneous environment generally increases disease persistence and the basic reproduction number of the model attains its minimum when the distributions of hosts and vectors are proportional. Moreover, R 0 can also be estimated by the basic reproduction numbers of disconnected patches if the environment is homogeneous. The optimal vector control strategy is obtained for a special scenario. In the two-patch and two-group case, we numerically analyze the dependence of the basic reproduction number and the total number of infected people on the host residence times matrix and illustrate the optimal vector control strategy in homogeneous and heterogeneous environments.
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