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An open computational toolbox to analyze multi- and single-unit sympathetic nerve activity in microneurography 用于分析微神经图中多单位和单单位交感神经活动的开放式计算工具箱
Pub Date : 2024-06-01 DOI: 10.1063/5.0202385
G. D'Alesio, Lars Ingmar Stumpp, P. Sciarrone, Alessandro Navari, Francesco Gentile, C. Borrelli, Sara Ballanti, Eleonora Degl'Innocenti, Adrian Carrasco, Ana Catarina Costa, Alexandre Andrade, A. Mannini, Vaughan G. Macefield, Michele Emdin, C. Passino, Alberto Mazzoni, A. Giannoni, C. Oddo
Microelectrode recordings from human peripheral and cranial nerves provide a means to study both afferent and efferent axonal signals at different levels of detail, from multi- to single-unit activity. Their analysis can lead to advancements both in diagnostic and in the understanding of the genesis of neural disorders. However, most of the existing computational toolboxes for the analysis of microneurographic recordings are limited in scope or not open-source. Additionally, conventional burst-based metrics are not suited to analyze pathological conditions and are highly sensitive to distance of the microelectrode tip from the active axons. To address these challenges, we developed an open-source toolbox that offers advanced analysis capabilities for studying neuronal reflexes and physiological responses to peripheral nerve activity. Our toolbox leverages the observation of temporal sequences of action potentials within inherently cyclic signals, introducing innovative methods and indices to enhance analysis accuracy. Importantly, we have designed our computational toolbox to be accessible to novices in biomedical signal processing. This may include researchers and professionals in healthcare domains, such as clinical medicine, life sciences, and related fields. By prioritizing user-friendliness, our software application serves as a valuable resource for the scientific community, allowing to extract advanced metrics of neural activity in short time and evaluate their impact on other physiological variables in a consistent and standardized manner, with the final aim to widen the use of microneurography among researchers and clinicians.
人体周围神经和颅神经的微电极记录为研究传入和传出轴突信号提供了从多单元活动到单单元活动等不同层次的详细资料。对这些信号的分析可促进诊断和了解神经疾病的成因。然而,用于分析微神经记录的现有计算工具箱大多范围有限或未开源。此外,传统的基于突发性的指标并不适合分析病理情况,而且对微电极尖端与活动轴突的距离非常敏感。为了应对这些挑战,我们开发了一个开源工具箱,为研究神经元反射和周围神经活动的生理反应提供先进的分析功能。我们的工具箱利用了对固有周期信号中动作电位时间序列的观察,引入了创新方法和指数来提高分析的准确性。重要的是,我们设计的计算工具箱便于生物医学信号处理新手使用。这可能包括医疗保健领域的研究人员和专业人员,如临床医学、生命科学和相关领域。通过优先考虑用户友好性,我们的软件应用程序成为科学界的宝贵资源,可以在短时间内提取神经活动的高级指标,并以一致和标准化的方式评估它们对其他生理变量的影响,最终目的是在研究人员和临床医生中扩大微神经描记术的使用范围。
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引用次数: 0
Design approaches for 3D cell culture and 3D bioprinting platforms 三维细胞培养和三维生物打印平台的设计方法
Pub Date : 2024-05-16 DOI: 10.1063/5.0188268
M Sreepadmanabh, Ashitha B. Arun, Tapomoy Bhattacharjee
The natural habitat of most cells consists of complex and disordered 3D microenvironments with spatiotemporally dynamic material properties. However, prevalent methods of in vitro culture study cells under poorly biomimetic 2D confinement or homogeneous conditions that often neglect critical topographical cues and mechanical stimuli. It has also become increasingly apparent that cells in a 3D conformation exhibit dramatically altered morphological and phenotypical states. In response, efforts toward designing biomaterial platforms for 3D cell culture have taken centerstage over the past few decades. Herein, we present a broad overview of biomaterials for 3D cell culture and 3D bioprinting, spanning both monolithic and granular systems. We first critically evaluate conventional monolithic hydrogel networks, with an emphasis on specific experimental requirements. Building on this, we document the recent emergence of microgel-based 3D growth media as a promising biomaterial platform enabling interrogation of cells within porous and granular scaffolds. We also explore how jammed microgel systems have been leveraged to spatially design and manipulate cellular structures using 3D bioprinting. The advent of these techniques heralds an unprecedented ability to experimentally model complex physiological niches, with important implications for tissue bioengineering and biomedical applications.
大多数细胞的自然栖息地由复杂无序的三维微环境组成,具有时空动态的材料特性。然而,目前流行的体外培养方法是在生物仿真度较低的二维封闭或均质条件下研究细胞,往往忽略了关键的地形线索和机械刺激。此外,越来越明显的是,三维构象中的细胞表现出显著变化的形态和表型状态。因此,在过去几十年中,设计用于三维细胞培养的生物材料平台的工作占据了中心位置。在此,我们将广泛介绍用于三维细胞培养和三维生物打印的生物材料,包括整体和颗粒系统。我们首先对传统的单片水凝胶网络进行了批判性评估,重点关注特定的实验要求。在此基础上,我们记录了最近出现的基于微凝胶的三维生长介质,它是一种前景广阔的生物材料平台,能够在多孔和颗粒支架内对细胞进行检测。我们还探讨了如何利用干扰微凝胶系统,通过三维生物打印技术在空间上设计和操纵细胞结构。这些技术的出现预示着一种前所未有的能力,可以在实验中模拟复杂的生理龛位,对组织生物工程和生物医学应用具有重要意义。
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引用次数: 0
Subcellular mechano-regulation of cell migration in confined extracellular microenvironment 细胞在封闭的细胞外微环境中迁移的亚细胞机械调节作用
Pub Date : 2023-12-01 DOI: 10.1063/5.0185377
Daesan Kim, Dong-Hwee Kim
Cell migration is a highly coordinated cellular event that determines diverse physiological and pathological processes in which the continuous interaction of a migrating cell with neighboring cells or the extracellular matrix is regulated by the physical setting of the extracellular microenvironment. In confined spaces, cell migration occurs differently compared to unconfined open spaces owing to the additional forces that limit cell motility, which create a driving bias for cells to invade the confined space, resulting in a distinct cell motility process compared to what is expected in open spaces. Moreover, cells in confined environments can be subjected to elevated mechanical compression, which causes physical stimuli and activates the damage repair cycle in the cell, including the DNA in the nucleus. Although cells have a self-restoring system to repair damage from the cell membrane to the genetic components of the nucleus, this process may result in genetic and/or epigenetic alterations that can increase the risk of the progression of diverse diseases, such as cancer and immune disorders. Furthermore, there has been a shift in the paradigm of bioengineering from the development of new biomaterials to controlling biophysical cues and fine-tuning cell behaviors to cure damaged/diseased tissues. The external physical cues perceived by cells are transduced along the mechanosensitive machinery, which is further channeled into the nucleus through subcellular molecular linkages of the nucleoskeleton and cytoskeleton or the biochemical translocation of transcription factors. Thus, external cues can directly or indirectly regulate genetic transcriptional processes and nuclear mechanics, ultimately determining cell fate. In this review, we discuss the importance of the biophysical cues, response mechanisms, and mechanical models of cell migration in confined environments. We also discuss the effect of force-dependent deformation of subcellular components, specifically focusing on subnuclear organelles, such as nuclear membranes and chromosomal organization. This review will provide a biophysical perspective on cancer progression and metastasis as well as abnormal cellular proliferation.
细胞迁移是一种高度协调的细胞活动,它决定着各种生理和病理过程,其中迁移细胞与邻近细胞或细胞外基质的持续互动受细胞外基质微环境物理环境的调节。在密闭空间中,细胞迁移的发生与非密闭的开放空间不同,这是因为限制细胞运动的额外力量导致细胞偏向于侵入密闭空间,从而形成了与开放空间中不同的细胞运动过程。此外,密闭环境中的细胞会受到高强度的机械挤压,从而造成物理刺激,激活细胞(包括细胞核中的 DNA)的损伤修复周期。虽然细胞有一个自我修复系统来修复从细胞膜到细胞核中遗传成分的损伤,但这一过程可能会导致遗传和/或表观遗传的改变,从而增加癌症和免疫紊乱等多种疾病恶化的风险。此外,生物工程的范式已从开发新的生物材料转向控制生物物理线索和微调细胞行为,以治疗受损/患病组织。细胞感知到的外部物理线索通过机械敏感机制传递,再通过核骨架和细胞骨架的亚细胞分子连接或转录因子的生化转位进入细胞核。因此,外部线索可以直接或间接调控基因转录过程和核机械,最终决定细胞的命运。在这篇综述中,我们将讨论细胞在封闭环境中迁移的生物物理线索、反应机制和力学模型的重要性。我们还讨论了亚细胞成分受力变形的影响,特别关注核下细胞器,如核膜和染色体组织。本综述将从生物物理角度探讨癌症进展和转移以及异常细胞增殖。
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引用次数: 0
The multivalency game ruling the biology of immunity 统治免疫生物学的多价游戏
Pub Date : 2023-12-01 DOI: 10.1063/5.0166165
Lara Victoria Aiassa, Giuseppe Battaglia, L. Rizzello
Macrophages play a crucial role in our immune system, preserving tissue health and defending against harmful pathogens. This article examines the diversity of macrophages influenced by tissue-specific functions and developmental origins, both in normal and disease conditions. Understanding the spectrum of macrophage activation states, especially in pathological situations where they contribute significantly to disease progression, is essential to develop targeted therapies effectively. These states are characterized by unique receptor compositions and phenotypes, but they share commonalities. Traditional drugs that target individual entities are often insufficient. A promising approach involves using multivalent systems adorned with multiple ligands to selectively target specific macrophage populations based on their phenotype. Achieving this requires constructing supramolecular structures, typically at the nanoscale. This review explores the theoretical foundation of engineered multivalent nanosystems, dissecting the key parameters governing specific interactions. The goal is to design targeting systems based on distinct cell phenotypes, providing a pragmatic approach to navigating macrophage heterogeneity's complexities for more effective therapeutic interventions.
巨噬细胞在我们的免疫系统中发挥着至关重要的作用,它能维护组织健康并抵御有害病原体。本文探讨了巨噬细胞在正常和疾病情况下受组织特异性功能和发育起源影响的多样性。了解巨噬细胞活化状态的范围,尤其是在病理情况下它们对疾病的进展有重大影响,对于有效开发靶向疗法至关重要。这些状态以独特的受体组成和表型为特征,但也有共性。针对单个实体的传统药物往往是不够的。一种很有前景的方法是使用缀有多种配体的多价系统,根据表型选择性地靶向特定的巨噬细胞群。实现这一目标需要构建超分子结构,通常是纳米级结构。本综述探讨了工程多价纳米系统的理论基础,剖析了影响特定相互作用的关键参数。其目的是根据不同的细胞表型设计靶向系统,为驾驭巨噬细胞异质性的复杂性提供实用方法,以实现更有效的治疗干预。
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引用次数: 0
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