Tolstrupsejersen5276

Persistent activation of mTOR (mammalian target of rapamycin) in diabetes increases the vulnerability of the heart to ischemia/reperfusion (I/R) injury. We show here that infusion of rapamycin (mTOR inhibitor) at reperfusion following ischemia reduced myocardial infarct size and apoptosis with restoration of cardiac function in type 1 diabetic rabbits. Likewise, treatment with rapamycin protected hyperglycemic human-pluripotent-stem-cells-derived cardiomyocytes (HG-hiPSC-CMs) following simulated ischemia (SI) and reoxygenation (RO). Phosphorylation of S6 (mTORC1 marker) was increased, whereas AKT phosphorylation (mTORC2 marker) and microRNA-302a were reduced with concomitant increase of its target, PTEN, following I/R injury in diabetic heart and HG-hiPSC-CMs. Rapamycin inhibited mTORC1 and PTEN, but augmented mTORC2 with restoration of miRNA-302a under diabetic conditions. Inhibition of miRNA-302a blocked mTORC2 and abolished rapamycin-induced protection against SI/RO injury in HG-hiPSC-CMs. We conclude that rapamycin attenuates reperfusion injury in diabetic heart through inhibition of PTEN and mTORC1 with restoration of miR-302a-mTORC2 signaling.Bacterial ParB partitioning proteins involved in chromosomes and low-copy-number plasmid segregation are cytosine triphosphate (CTP)-dependent molecular switches. CTP-binding converts ParB dimers to DNA clamps, allowing unidimensional diffusion along the DNA. This sliding property has been proposed to explain the ParB spreading over large distances from parS centromere sites where ParB is specifically loaded. We modeled such a "clamping and sliding" mechanism as a typical reaction-diffusion system, compared it to the F plasmid ParB DNA binding pattern, and found that it can account neither for the long range of ParB binding to DNA nor for the rapid assembly kinetics observed in vivo after parS duplication. Also, it predicts a strong effect on the F plasmid ParB binding pattern from the presence of a roadblock that is not observed in ChIP-sequencing (ChIP-seq). We conclude that although "clamping and sliding" can occur at short distances from parS, another mechanism must apply for ParB recruitment at larger genomic distances.Vascular smooth muscle cells (VSMCs) represent the prevailing cell type of arterial vessels and are essential for blood vessel structure and homeostasis. find more They have substantial potential for phenotypic plasticity when exposed to various stimuli in their local microenvironment. How VSMCs maintain their differentiated contractile phenotype is still poorly understood. Here we demonstrate that the Hippo pathway effectors YAP and TAZ play a critical role in maintaining the differentiated contractile phenotype of VSMCs. In the absence of YAP/TAZ, VSMCs lose their differentiated phenotype and undergo osteogenic differentiation, which results in vascular calcification. Osteogenic transdifferentiation was accompanied by the upregulation of Wnt target genes. The absence of YAP/TAZ in VSMCs led to Disheveled 3 (DVL3) nuclear translocation and upregulation of osteogenesis-associated genes independent of canonical Wnt/β-catenin signaling activation. Our data indicate that cytoplasmic YAP/TAZ interact with DVL3 to avoid its nuclear translocation and osteogenic differentiation, thereby maintaining the differentiated phenotype of VSMCs.In this work, we introduce HI-Light, a surface-engineered glass-waveguide-based "shell-and-tube" type photothermal reactor which is both scalable in diameter and length. We examine the effect of temperature, light irradiation, and residence time on its photo-thermocatalytic performance for CO2 hydrogenation to form CO, with a cubic phase defect-laden indium oxide, In2O3-x(OH)y, catalyst. We demonstrate the light enhancement effect under a variety of reaction conditions. Notably, the light-on performance for the cubic nanocrystal photocatalyst exhibits a CO evolution rate at 15.40 mmol gcat-1 hr-1 at 300°C and atmospheric pressure. This is 20 times higher conversion rate per unit catalyst mass per unit time beyond previously reported In2O3-x(OH)y catalyst in the cubic form under comparable operation conditions and more than 5 times higher than that of its rhombohedral polymorph. This result underscores that improvement in photo-thermocatalytic reactor design enables uniform light distribution and better reactant/catalyst mixing, thus significantly improving catalyst utilization.Tumors comprised a tightly surrounded tumor microenvironment, made up of non-cellular extracellular matrix (ECM) and stromal cells. Although treatment response is often attributed to tumor heterogeneity, progression and malignancy are profoundly influenced by tumor cell interactions with the surrounding ECM. Here, we used a tumor organoid model, consisting of hepatic stellate cells (HSCs) embedded in collagen type 1 (Col1) and colorectal cancer cell (HCT-116) spheroids, to determine the relationship between the ECM architecture, cancer cell malignancy, and chemoresistance. Exogenous transforming growth factor beta (TGF-β) used to activate the HSCs increased the remodeling and bundling of Col1 in the ECM around the cancer spheroid. A dense ECM architecture inhibited tumor cell growth, reversed their mesenchymal phenotype, preserved stem cell population, and reduced chemotherapy response. Overall, our results demonstrate that controlled biofabrication and manipulation of the ECM in tumor organoids results enables studying tumor cell-ECM interactions and better understand tumor cell response to chemotherapies.The emerging triboelectric nanogenerator (TENG) network shows great potential in harvesting the ocean wave energy, which can help to achieve large-scale clean wave power generation. However, due to the lack of an effective networking strategy and theoretical guidance, the practicability of the TENG network is heavily restricted. In this paper, based on the typical spherical TENG, we investigated the networking design of TENGs. Four fundamental forms of electrical networking topology are proposed for large-scale TENG networks, and the influences of cable resistance and output phase asynchrony of each unit to the network output were systematically investigated. The research results show that the forms of electrical networking topology can produce an important influence on the output power of large-scale TENG networks. This is the first strategy analysis for the TENG network, which provides a theoretical basis and a universal method for the optimization design of large-scale power networks.