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.     

Tailoring the electron-blocking layer by addition of YSZ to Ba-containing anode for improvement of ceria-based solid oxide fuel cell

The in-situ fabrication of an electron-blocking layer between the Ba-containing anode and the ceria-based electrolyte is an effective approach in suppressing the internal electronic leakage in ceria-based solid oxide fuel cell (SOFC). To improve the thickness of the electron-blocking layer and to research the effect of the layer thickness on the improvement of SOFC, a Ba-containing compound (0.6NiO-0.4BaZr_0.1Ce_0.7Y_0.2O_3-δ) modified by Y stabilized zirconia (YSZ) was employed as a composite anode in this research. SEM analyses demonstrated that the thickness of the interlayer can be simply controlled by regulating the proportion of YSZ at anode. The in-situ formed interlayer in the cell with the anode modified by 20?mol% YSZ possesses a thickness of 0.9?µm which is more suitable for the cell achieving an enhanced performance.     

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.     

Evaluation of microbial toxins,trace elements and sensory properties of a high-theabrownins instant Pu-erh tea produced using Aspergillus tubingensis via submerged fermentation

Theabrownins (TB) are polymeric phenolic compounds associated with the multiple bioactivities of Pu-erh tea, a post-fermented Chinese dark tea. High-TB instant Pu-erh tea was produced via a novel submerged fermentation (SF) using Aspergillus tubingensis and compared with samples produced commercially via the conventional solid-state fermentation (SSF). Viable microorganisms and microbial toxins, especially aflatoxins B₁, G₁, B₂, G₂, cyclopiazonic acid, fumonisins B₁, B₂, B₃ and ochratoxin A, were below the detection limit in all samples. Fewer microbial metabolites were found in SF instant tea compared with the SSF teas. Based on an adult consuming 1 g of instant Pu-erh tea daily, the dietary intake of investigated elements was below the safe limits recommended by various authorities. Tasters viewed the instant tea infusions as very mild, smooth, mellow and full. This suggested that submerged fermentation using A. tubingensis offers a speedy and safe alternative to commercial production of instant Pu-erh tea.     

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.     

Nutrient digestibility and endogenous protein losses in the foregut and small intestine of weaned dairy calves fed calf starters with conventional or enzyme-treated soybean meal

The aims of this experiment were (1) to compare the effects of a soybean meal with an enzymatic treatment (ESBM) to reduce the concentration of antinutritional factors versus a standard soybean meal (SBM) on foregut and small intestine digestion in weaned dairy calves and (2) to estimate the endogenous losses of crude protein (CP) in the small intestine. Our hypothesis was that a diet containing ESBM instead of SBM would improve ruminal and small intestine digestion and absorption of nutrients. A T-cannula was placed in the duodenum, and a second T-cannula was installed in the distal ileum of 12 Holstein calves at approximately 3 wk of age. Calves were weaned on d 42, and on d 50 they were assigned randomly to a quadruplicated 3 × 3 Latin square with 10-d periods. Digesta samples were collected on d 7 and 8 from the ileum and d 9 and 10 from the duodenum. The diets were fed for ad libitum intake and consisted of a calf starter (CS) of 20% CP with SBM as the main source of protein (CTRL), and an isonitrogenous CS with an ESBM instead of SBM (ENZT). A third diet with a low content of CP (10%) and no soy protein was fed to estimate endogenous N losses and digestibilities of test ingredients. Flows and digestibilities of nutrients were compared between CTRL and ENZT and their test ingredients (SBM vs. ESBM, respectively). Duodenal net flows of CP and total AA as well as ruminal microbial protein synthesis per kilogram of digested CP were greater, and flow of nonprotein N and CP true (corrected by endogenous and microbial flows) foregut digestibility were lower with ENZT than CTRL. The apparent small intestine digestibilities of CP and total AA were greater for ESBM than SBM, but there were no differences between the CTRL and ENZT diets. We observed no differences in digestibilities at the duodenum or ileum of starch or NDF, but true small intestine digestibilities of CP and all AA were greater with ENZT than CTRL. Total endogenous protein losses in the small intestine estimated from calves fed the low-CP with no soy protein diet were 37 ± 1.5 g of CP and 29 ± 1.4 g of AA/kg of DMI. These values may be considered the basal endogenous losses as they are similar to values obtained with the regression method, which estimates N losses when dietary N is null. Our results indicated that the inclusion of an ESBM improved the efficiency of ruminal microbial protein synthesis per digested kilogram of organic matter and CP, and increased CP and AA absorption in the small intestine despite a greater proportion of undigested dietary protein entering the duodenum.