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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.
海南小型露天采石场矿山数量多且呈遍地开花式分布,且不规范的开采对环境造成较大的破坏,与绿色矿山之路背道而行,相对大型矿山规范化的治理,小型矿山治理比较滞后,本文以日富采石场地质环境治理为例,通过摸清当地的地质环境条件,结合矿山现状,因地制宜地制定出日富采石场地质环境治理的具体措施,通过治理可获得林地2.6hm2,矿山安全隐患及地貌景观等矿山地质环境问题得到有效地防治,有效解决农业灌溉及周边虾塘养殖用水缺乏问题,实现较好的社会经济效益,为今后治理类似矿山提供参考。  相似文献   
5.
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   
6.
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   
7.
刘强  郝文辉  郭巨  张恒 《中州煤炭》2022,(11):1-5,11
士元水泥灰岩矿位于燕山山脉的东部的河北省境内,长时间的矿石开采造成了当地生态环境的严重破坏。经过勘查,发现矿区内存在4个采坑,对各个采坑进行了稳定性评价。矿山治理主要为采坑边坡顶部防护及植被恢复,并对采坑平台的破坏区域进行重点治理,主要范围分2个平台及3、4号采坑底部进行治理,治理对象包括渣堆、采面、平台等。通过清除危岩、修筑挡土墙以及覆土绿化,消除了地质灾害隐患,极大地改善了矿区的生态环境和空气质量,提升了人们的生活质量和政府的对外形象。  相似文献   
8.
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   
9.
针对某海上风电项目,基于ABAQUS三维数值软件定量分析桩坑与复合筒型基础的距离、桩坑尺寸及深度等参数变化对复合筒型基础结构泥面倾斜率的影响,引入可反映桩坑充盈固结程度的系数γ与切线斜率K。结果表明:随着桩坑尺寸增加,复合筒型基础泥面倾斜率呈非线性增长,且均向桩坑所在方向倾斜;桩坑深度大于复合筒型基础入土深度时,基础倾斜率增长较快;研究表明筒型基础泥面倾斜率对大深度、近距离桩坑内部土体强度尤为敏感,拟通过该文研究为复合筒型基础风电机组安装船舶选型及布置提供理论依据。  相似文献   
10.
针对基于惯容的结构控制装置(IDVA)最优作用位置问题,建立基于拉格朗日方程的风力机动力学模型,给出装置参数优化方法。优化问题考虑IDVA系统安装在塔架不同位置对减振性能的影响,以及塔架位移与IDVA相对位移之间的相互影响。结果表明:IDVA系统安装在塔架的位置越高减振效果越好。不考虑IDVA行程时,IDVA系统可极大提升减振性能;考虑IDVA行程时,IDVA系统减振性能有所下降,在该优化问题条件下,塔顶位移与IDVA行程存在冲突,无法同时得到改善。  相似文献   
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