Mechanophysical Cues in Extracellular Matrix Regulation of Cell Behavior

The extracellular matrix (ECM) is a macromolecular network that can provide biochemical and structural support for cell adhesion and formation. It regulates cell behavior by influencing biochemical and physical cues. It is a dynamic structure whose components are modified, degraded, or deposited during connective tissue development, giving tissues strength and structural integrity. The physical properties of the natural ECM environment control the design of naturally or synthetically derived biomaterials to guide cell function in tissue engineering. Tissue engineering is an important field that explores physical cues of the ECM to produce new viable tissue for medical applications, such as in organ transplant and organ recovery. Understanding how the ECM exerts physical effects on cell behavior, when cells are seeded in synthetic ECM scaffolds, is of utmost importance. Herein we review recent findings in this area that report on cell behaviors in a variety of ECMs with different physical properties, i.e., topology, geometry, dimensionality, stiffness, and tension.     

Cell Sheet Comprised of Mesenchymal Stromal Cells Overexpressing Stem Cell Factor Promotes Epicardium Activation and Heart Function Improvement in a Rat Model of Myocardium Infarction

Cell therapy of the post-infarcted myocardium is still far from clinical use. Poor survival of transplanted cells, insufficient regeneration, and replacement of the damaged tissue limit the potential of currently available cell-based techniques. In this study, we generated a multilayered construct from adipose-derived mesenchymal stromal cells (MSCs) modified to secrete stem cell factor, SCF. In a rat model of myocardium infarction, we show that transplantation of SCF producing cell sheet induced activation of the epicardium and promoted the accumulation of c-kit positive cells in ischemic muscle. Morphometry showed the reduction of infarct size (16%) and a left ventricle expansion index (0.12) in the treatment group compared to controls (24–28%; 0.17–0.32). The ratio of viable myocardium was more than 1.5-fold higher, reaching 49% compared to the control (28%) or unmodified cell sheet group (30%). Finally, by day 30 after myocardium infarction, SCF-producing cell sheet transplantation increased left ventricle ejection fraction from 37% in the control sham-operated group to 53%. Our results suggest that, combining the genetic modification of MSCs and their assembly into a multilayered construct, we can provide prolonged pleiotropic effects to the damaged heart, induce endogenous regenerative processes, and improve cardiac function.     

Role of Cyclooxygenase-2 in Head and Neck Tumorigenesis

The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host’s immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis—from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.     

A distributed energy system integrating SOFC-MGT with mid-and-low temperature solar thermochemical hydrogen fuel production

Solar thermochemical hydrogen production with energy level upgraded from solar thermal to chemical energy shows great potential. By integrating mid-and-low temperature solar thermochemistry and solid oxide fuel cells, in this paper, a new distributed energy system combining power, cooling, and heating is proposed and analyzed from thermodynamic, energy and exergy viewpoints. Different from the high temperature solar thermochemistry (above 1073.15 K), the mid-and-low temperature solar thermochemistry utilizes concentrated solar thermal (473.15–573.15 K) to drive methanol decomposition reaction, reducing irreversible heat collection loss. The produced hydrogen-rich fuel is converted into power through solid oxide fuel cells and micro gas turbines successively, realizing the cascaded utilization of fuel and solar energy. Numerical simulation is conducted to investigate the system thermodynamic performances under design and off-design conditions. Promising results reveal that solar-to-hydrogen and net solar-to-electricity efficiencies reach 66.26% and 40.93%, respectively. With the solar thermochemical conversion and hydrogen-rich fuel cascade utilization, the system exergy and overall energy efficiencies reach 59.76% and 80.74%, respectively. This research may provide a pathway for efficient hydrogen-rich fuel production and power generation.     

Bond graph modeling,design and experimental validation of a photovoltaic/fuel cell/ electrolyzer/battery hybrid power system

This work presents a complete bond graph modeling of a hybrid photovoltaic-fuel cell-electrolyzer-battery system. These are multi-physics models that will take into account the influence of temperature on the electrochemical parameters. A bond graph modeling of the electrical dynamics of each source will be introduced. The bond graph models were developed to highlight the multi-physics aspect describing the interaction between hydraulic, thermal, electrochemical, thermodynamic, and electrical fields. This will involve using the most generic modeling approach possible for managing the energy flows of the system while taking into account the viability of the system. Another point treated in this work is to propose. In this work, a new strategy for the power flow management of the studied system has been proposed. This strategy aims to improve the overall efficiency of the studied system by optimizing the decisions made when starting and stopping the fuel cell and the electrolyzer. It was verified that the simulation results of the proposed system, when compared to simulation results presented in the literature, that the hydrogen demand is increased by an average of 8%. The developed management algorithm allows reducing the fuel cell degradation by 87% and the electrolyzer degradation by 65%. As for the operating time of the electrolyzer, an increment of 65% was achieved, thus improving the quality of the produced hydrogen. The Fuel Cell's running time has been decreased by 59%. With the ambition to validate the models proposed and the associated commands, the development of this study gave rise to the creation of an experimental platform. Using this high-performance experimental platform, experimental tests were carried out and the results obtained are compared with those obtained by simulation under the same metrological conditions.     

Quantifying the limits of CAR T-cell delivery in mice and men

CAR (Chimeric Antigen Receptor) T cells have demonstrated clinical success for the treatment of multiple lymphomas and leukaemias, but not for various solid tumours, despite promising data from murine models. Lower effective CAR T-cell delivery rates to human solid tumours compared to haematological malignancies in humans and solid tumours in mice might partially explain these divergent outcomes. We used anatomical and physiological data for human and rodent circulatory systems to calculate the typical perfusion of healthy and tumour tissues, and estimated the upper limits of immune cell delivery rates across different organs, tumour types and species. Estimated maximum delivery rates were up to 10 000-fold greater in mice than humans yet reported CAR T-cell doses are typically only 10–100-fold lower in mice, suggesting that the effective delivery rates of CAR T cells into tumours in clinical trials are far lower than in corresponding mouse models. Estimated delivery rates were found to be consistent with published positron emission tomography data. Results suggest that higher effective human doses may be needed to drive efficacy comparable to mouse solid tumour models, and that lower doses should be tested in mice. We posit that quantitation of species and organ-specific delivery and homing of engineered T cells will be key to unlocking their potential for solid tumours.     

基于开源技术的城市地理信息平台构建方法研究

摘 要：针对城市地理信息平台构建过程中存在的数据获取困难、研发成本较高等问题， 引入开源技术，对基于开源数据、开源开发平台与开源工具的城市地理信息平台构建技术进行 研究。所提出的城市地理信息平台由数据模块与可视化模块 2 部分组成。为构建数据模块，由 开源地理信息项目(OSM)获取了建筑与区划数据，并设计了建筑合并算法以提升数据质量。建 筑数据随之基于行政区划分级存储，通过由 ASP. NET 构建的数据接口提供给具体应用。可视 化模块则基于开源地理信息系统(GIS)项目 Cesium 实现，并设计了完善的用户界面。以北京市 为例，完成了原型系统的开发与测试，证实了该技术体系的可行性，通过开源技术降低平台研 发成本，推进城市地理信息平台的研究与应用。