Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) in response to chronic hypoxia contributes to pulmonary vascular remodeling in pulmonary hypertension (PH). PH shares numerous similarities with cancer, including a metabolic shift towards glycolysis. In lung cancer, adenylate kinase 4 (AK4) promotes metabolic reprogramming and metastasis. Against this background, we show that AK4 regulates cell proliferation and energy metabolism of primary human PASMCs. We demonstrate that chronic hypoxia upregulates AK4 in PASMCs in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. RNA interference of AK4 decreases the viability and proliferation of PASMCs under both normoxia and chronic hypoxia. AK4 silencing in PASMCs augments mitochondrial respiration and reduces glycolytic metabolism. The observed effects are associated with reduced levels of phosphorylated protein kinase B (Akt) as well as HIF-1α, indicating the existence of an AK4-HIF-1α feedforward loop in hypoxic PASMCs. Finally, we show that AK4 levels are elevated in pulmonary vessels from patients with idiopathic pulmonary arterial hypertension (IPAH), and AK4 silencing decreases glycolytic metabolism of IPAH-PASMCs. We conclude that AK4 is a new metabolic regulator in PASMCs interacting with HIF-1α and Akt signaling pathways to drive the pro-proliferative and glycolytic phenotype of PH. 相似文献
A protein TRAP : The in vivo photocrosslinking of TRAP after its intracellular targeting to a binding sequence on the bait protein stabilizes protein interactions. Because the crosslinker is releasable, simple mass spectrometry can be used to identify the protein binding sites after purification.
We have studied the rate of the first destructive hydrogenation of the as-poured bulk powder and compacts of TiNi. We have established that it is determined on the whole by the rate of processes that occur on the surface of the particles and are connected with formation of catalytic sites for dissociation of hydrogen, and by the rate of processes within the volume of the particles that is controlled by the rate of hydrogen diffusion and decomposition of TiNi. The first destructive hydrogenation of bulk TiNi powders is a lengthy process that can take tens of hours. Its rate increases as the temperature and hydrogen pressure increase. The effect of particle size is nonmonotonic because of the competing action of oxygen on the particle surface. Pressing TiNi powders made it possible to shorten the time required for the first destructive hydrogenation ten-fold (down to a few hours). This is connected with formation during pressing of fresh catalytic surfaces in closed cracks and on interparticle contacts. The rate of the first destructive hydrogenation of TiNi compacts increases as the temperature rises, and does not depend on particle size.__________Translated from Poroshkovaya Metallurgiya, Nos. 1–2(441), pp. 73–79, January–February, 2005. 相似文献
The cardo polyimides and polyamides having highly nucleophilic quinuclidine groups have been synthesized with the usage of 3,3-bis(4-aminophenyl)quinuclidine as amine monomer. The latter has been obtained by the condensation of quinuclidone-3 with aniline. The characterization of such amine, including quaternization reaction, is performed. Polyimides have been derived from this monomer and various tetracarboxylic dianhydrides by one- and two-step polycyclization. Quinuclidine moieties enhance the one-step polyimide formulation leading to high molecular polymers including corresponding poly- 1,4,5,8-naphthoyleneimides even without any added catalyst. It is stated that polyamic acid formation is hindered by the side tertiary-amine-COOH salt formation. The latter reaction is eliminated by the preliminary quaternization of amine monomer. The high molecular polyamides have been prepared by low-temperature solution polycondensation of cited monomer and diacid chlorides. The obtained polymers are characterized by high thermal properties, solubility in organic solvents and represent the quite efficient catalysts for polyamic acid imidation in homo- and heterogeneous systems. 相似文献
The catalytic properties of transition metal oxides (Cr, Ce, and Co) supported on ZrO2 synthesized by various methods, as well as the effect of rhodium on the performance of the MxOy/ZrO2 oxide systems in NO reduction with hydrocarbons (methane, propane–butane mixture, and propene) were studied. Scanning electron microscopy, ammonia thermoprogrammed desorption (NH3-TPD), XPS, and IR spectroscopy were used to study the physicochemical indices of rhodium-promoted MxOy/ZrO2 oxide catalysts. The enhancement of the redox properties of the oxide catalysts upon the introduction of rhodium does not alter their bifunctional nature in SCR activity: these catalysts have both redox and strong acid Brønsted-sites. 相似文献
Milling of wear-resistant steel and titanium carbide powders is studied with an attrition mill rotation rate of 980 rpm. The physical and technological properties of powders and particle size are determined. Particle shape and the change in material chemical composition during milling are studied. It is established that steel powder cannot be milled to particle sizes less than 3.6 μm whereas a mixture of steel and titanium carbide can be milled to a fine state (0.3 μm). Powders with a size of about 1 μm neither flow nor are formable. Use of benzene as a milling medium makes it possible to prevent steel powder oxidation, but the carbon content in titanium carbide decreases. During milling of the main part of the charge to a fine state rather large steel particles (up to 50 μm) remain. 相似文献
Nano Research - Dimensionality and orientation of hexagonal boron nitride (h-BN) nanosheets are promising to create and control their unique properties for diverse applications. However,... 相似文献