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1.
There is an unmet need for simplified in vitro models of malignancy and metastasis that facilitate fast, affordable and scalable gene and compound analysis. “Adherent” cancer cell lines frequently release “free-floating” cells into suspension that are viable and can reattach. This, in a simplistic way, mimics the metastatic process. We compared the gene expression profiles of naturally co-existing populations of floating and adherent cells in SW620 (colon), C33a (cervix) and HeLa (cervix) cancer cells. We found that 1227, 1367 and 1333 genes were at least 2-fold differentially expressed in the respective cell lines, of which 122 were shared among the three cell lines. As proof of principle, we focused on the anti-metastatic gene NM23-H1, which was downregulated both at the RNA and protein level in the floating cell populations of all three cell lines. Knockdown of NM23-H1 significantly increased the number of floating (and viable) cells, whereas overexpression of NM23-H1 significantly reduced the proportion of floating cells. Other potential regulators of these cellular states were identified through pathway analysis, including hypoxia, mTOR (mechanistic target of rapamycin), cell adhesion and cell polarity signal transduction pathways. Hypoxia, a condition linked to malignancy and metastasis, reduced NM23-H1 expression and significantly increased the number of free-floating cells. Inhibition of mTOR or Rho-associated protein kinase (ROCK) significantly increased cell death specifically in the floating and not the adherent cell population. In conclusion, our study suggests that dynamic subpopulations of free-floating and adherent cells is a useful model to screen and identify genes, drugs and pathways that regulate the process of cancer metastasis, such as cell detachment and anoikis.  相似文献   
2.
Extracellular vesicles (EVs) are cell-derived nanostructures that mediate intercellular communication by delivering complex signals in normal tissues and cancer. The cellular coordination required for tumor development and maintenance is mediated, in part, through EV transport of molecular cargo to resident and distant cells. Most studies on EV-mediated signaling have been performed in two-dimensional (2D) monolayer cell cultures, largely because of their simplicity and high-throughput screening capacity. Three-dimensional (3D) cell cultures can be used to study cell-to-cell and cell-to-matrix interactions, enabling the study of EV-mediated cellular communication. 3D cultures may best model the role of EVs in formation of the tumor microenvironment (TME) and cancer cell-stromal interactions that sustain tumor growth. In this review, we discuss EV biology in 3D culture correlates of the TME. This includes EV communication between cell types of the TME, differences in EV biogenesis and signaling associated with differing scaffold choices and in scaffold-free 3D cultures and cultivation of the premetastatic niche. An understanding of EV biogenesis and signaling within a 3D TME will improve culture correlates of oncogenesis, enable molecular control of the TME and aid development of drug delivery tools based on EV-mediated signaling.  相似文献   
3.
There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the role of OXT in an individual’s vulnerability or resilience with regard to developing a substance use disorder. It places specific attention on the role of social stress as a risk factor of addiction, and explores the hypothesis that OXT constitutes a homeostatic response to stress that buffers against its negative impact. For this purpose, the review summarizes preclinical and clinical literature regarding the effects of OXT in different stages of the addiction cycle. The current literature affirms that a well-functioning oxytocinergic system has protective effects such as the modulation of the initial response to drugs of abuse, the attenuation of the development of dependence, the blunting of drug reinstatement and a general anti-stress effect. However, this system is dysregulated if there is continuous drug use or chronic exposure to stress. In this context, OXT is emerging as a promising pharmacotherapy to restore its natural beneficial effects in the organism and to help rebalance the functions of the addicted brain.  相似文献   
4.
针对新能源汽车电机壳体压铸件产生粘模缺陷的问题,从模具结构设计、3D打印嵌件平衡模具温度,防止高温铝液破坏模具表面致密层等方面,在生产过程中对新能源电机壳体压铸件粘模缺陷进行改善,提出了应用3D打印嵌件的解决方案。  相似文献   
5.
文中提出了一种混合方法,将指纹识别与机器学习方法相结合,实现了IPSec VPN加密流量的识别。该方法首先基于负载特征从网络流量中筛选出IPSec VPN流量;接着,基于时间相关的流特征,利用随机森林算法建立了IPSec VPN流量分类模型,通过参数优化以及特征选择,整体流量识别的准确率达到了93%。实验结果验证了通过流特征提取的机器学习方法识别IPSec VPN流量的可行性;同时表明了该方法能够有效均衡识别精度与识别速度,达到了高效识别IPSec VPN加密流量的效果。  相似文献   
6.
基于ANSYS Workbench的RV减速器随机振动分析   总被引:1,自引:0,他引:1  
以RV减速器为研究对象,建立了RV减速器的三维模型,导入Adams中进行运动学仿真,得到了正齿轮的加速度;利用ANSYS Workbench求解得到RV减速器的固有频率,根据概率统计学分析技术推导功率谱密度函数;最后,将功率谱密度峰值提取后导入ANSYS Workbench的Random vibration模块作随机振动分析。该方法考虑了随机振动因素对机构应力以及安全裕度的影响,为处理RV减速器工作可靠性问题提供了一种新的方法。  相似文献   
7.
In this study, the anti-atherosclerotic properties of three marine phospholipids (MPLs) extracts from fishery by-products including codfish roe, squid gonad, and shrimp head are verified. Their effects on key factors involved in atherosclerosis are examined and compared to explore whether the differences in their constitutions lead to the differences in the function. All three MPLs dampen oxidation of low- density lipoproteins (LDL) in vitro. Treating RAW264.7 macrophages and HUVECs endothelial cells with each MPLs ranging 10–100 µg mL−1 does not decrease cell viability, yet ox-LDL caused cytotoxicity of both cells are alleviated by 50 or 100 µg mL−1 MPLs treatment. In addition, the three MPLs reduce ox-LDL induced macrophage foam-like transition, mainly through inhibition of lipid uptake. Of the three MPLs, the one from squid gonad exhibits the best effect. On the other hand, all three MPLs modulate inflammatory responses, equally, by inhibiting the adhesion of monocytes to endothelial cells, and decreasing secretion of pro-inflammatory cytokines IL-6 and MCP-1. Using a high-cholesterol diet induced zebrafish model, it is found that all three MPLs, especially the one from squid gonad, alleviates cholesterol accumulation in early plaques, and decreases total cholesterol as well as lipid peroxide in vivo. Practical Applications: As a way of making the best of the increasingly scarce marine resources, valuable lipid components can be recovered from by-products and wastes from the fishery industry. Here, we tested the anti-atherosclerotic effects and the mechanisms of three MPLs extracted from codfish roe, squid gonad, and shrimp head. Our study provides further evidence that marine phospholipids extracted from fishery by-products could protect against atherosclerosis, and helps to elucidate the structure-function relationship of MPLs.  相似文献   
8.
《水科学与水工程》2021,14(4):330-336
The unique structure of a dam complicates safety monitoring. Deformation can provide important information about dam evolution. In contrast to model prediction, actual dam response monitoring data can be used for diagnosis and early warning. Given the poor data mining ability of the conventional methods, it is essential to develop a method for extracting the factors influencing a dam. In this study, a data mining method and a model for evaluation of concrete dam deformation were developed using the evidence theory and a random forest. The model has the advantages of being easily understood, visualization with low complexity of training time, and accurate prediction. The model was applied to an actual concrete dam. The results indicated that the proposed random forest model could be used in analysis of concrete dams.  相似文献   
9.
为获取秸秆生物炭的离散元仿真参数,采用仿真分析与物理试验相结合的方法对生物炭接触参数进行标定。通过Placket-Burman试验筛选出生物炭离散元显著性影响参数,最陡爬坡试验确定显著性影响参数的最佳范围,Box-Behnken试验确定3个显著性影响参数分别为炭-炭滚动摩擦系数0.097、 JKR表面能0.018 J/m2、炭-钢滚动摩擦系数0.256。进行堆积角试验与其Rocky离散元仿真结果对比表明,所确定的参数误差为2.33%,满足仿真分析参数设定要求。  相似文献   
10.
The article proposes a methodological approach to the development of the tools for studying the international electro-hydrogen system creation in Northeast Asia. The term "hydrogen carrier" was introduced and its definition was given. The resource, economic and technological prerequisites for the development of the unified regional infrastructure to produce, transfer, transform and utilise both electricity and "hydrogen carriers" for consumers of energy services are considered.The author points out the need for a comprehensive consideration of technological, economic, social and political factors when developing such a complex technical system, which affects the diverse actors' interests. In order to create mutual understanding and balance the stakeholders’ interests, the tool to evaluate the efficiency of such a system is necessary. The use of mathematical models is becoming one of the most vital and widespread techniques employed for this purpose. Thereby, the article deals with the structure and the development stages of a regional electro-hydrogen model for Northeast Asia.The review of models that address the issues of hydrogen technologies and renewable energy integration into energy supply systems is given. The main types of models used to describe such technical and economic systems are identified and it is concluded that the development of a two-level modelling system is necessary. The production and transport models at the upper (international) level should be the core of the proposed models system. At the lower level (the "green hydrogen carriers" production), the models of optimal resource management are required to determine the composition and parameters of the technological equipment.Step-by-step development of the modelling system is proposed. The first stage is the simplest scenario where only solar and wind energy is considered as an energy source. At this stage, it is possible to weed out inefficient technologies and identify targeted technologies and mechanisms for multilateral regional cooperation. The second stage should balance the interests of the actors and stakeholders. Here, the traditional renewable energy (biomass, hydro and pumped storage) along with carbon (thermal) and nuclear power generation, as well as other ("carbon") hydrogen technologies will become available for consideration. The final, third stage of the research tools development, will require separate accounting of "green" and "carbon" energy to consider certification mechanisms and energy pricing when building the international hydrogen system in Northeast Asia.In conclusion, the structure of the first stage production and transport model is described. This model will allow estimating the comparative effectiveness of different electric and hydrogen technologies to deliver green energy to consumers in the Northeast Asian economies.  相似文献   
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