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Atherosclerosis and nonalcoholic fatty liver disease are leading causes of morbidity and mortality in the Western countries. The renin–angiotensin system (RAS) with its two main opposing effectors, i.e., angiotensin II (Ang II) and Ang-(1–7), is widely recognized as a major regulator of cardiovascular function and body metabolic processes. Angiotensin-converting enzyme 2 (ACE2) by breaking-down Ang II forms Ang-(1–7) and thus favors Ang-(1–7) actions. Therefore, the aim of our study was to comprehensively evaluate the influence of prolonged treatment with ACE2 activator, diminazene aceturate (DIZE) on the development of atherosclerotic lesions and hepatic steatosis in apoE−/− mice fed a high-fat diet (HFD). We have shown that DIZE stabilized atherosclerotic lesions and attenuated hepatic steatosis in apoE−/− mice fed an HFD. Such effects were associated with decreased total macrophages content and increased α-smooth muscle actin levels in atherosclerotic plaques. Moreover, DIZE changed polarization of macrophages towards increased amount of anti-inflammatory M2 macrophages in the atherosclerotic lesions. Interestingly, the anti-steatotic action of DIZE in the liver was related to the elevated levels of HDL in the plasma, decreased levels of triglycerides, and increased biosynthesis and concentration of taurine in the liver of apoE−/− mice. However, exact molecular mechanisms of both anti-atherosclerotic and anti-steatotic actions of DIZE require further investigations.  相似文献   
63.

Squeeze casting and powder metallurgy techniques were employed to fabricate AlSi12/Al2O3 composites, which are lightweight structural materials with potential applications in the automotive industry. The impact of the processing route on the material properties was studied. Comparative analyses were conducted for the Vickers hardness, flexural strength, fracture toughness, thermal conductivity, thermal residual stresses, and frictional wear. Our results show that the squeeze cast composite exhibits superior properties to those obtained using powder metallurgy.

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Somatostatin analogues are useful pharmaceuticals in peptide receptor radionuclide therapy. In previous studies, we analyzed a new bicyclic somatostatin analogue (BCS) in connection with Cu(II) ions. Two characteristic sites were present in the peptide chain: the receptor- and the metal-binding site. We have already shown that this ligand can form very stable imidazole complexes with the metal ion. In this work, our aim was to characterize the intramolecular interaction that occurs in the peptide molecule. Therefore, we analyzed the coordination abilities of two cyclic ligands, i.e., P1 only with the metal binding site and P2 with both sites, but without the disulfide bond. Furthermore, we used magnetic circular dichroism (MCD) spectroscopy to better understand the coordination process. We applied this method to analyze spectra of P1, P2, and BCS, which we have described previously. Additionally, we analyzed the MCD spectra of P3 ligand, which has only the receptor binding site in its structure. We have unequivocally shown that the presence of the Phe-Trp-Lys-Thr motif and the disulfide bond significantly increases the metal binding efficiency.  相似文献   
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Highly tunable properties of materials used for the construction of electrochemical capacitors make them a perfect choice for a broad scope of applications with high power demand. The ability to design the system according to the expected power/energy profile allows them being considered as powerful alternatives to conventional capacitors and batteries. Carbon materials with the developed specific surface area are the most common electrode components of electrochemical capacitors because of their cost, versatile form, availability, easiness of processing, and eco-friendly character. Biomass is frequently used for carbon production, however, among many natural organic materials, only some of them should be regarded as a useful precursor. Ongoing research brings many novel concepts of using bio-derived materials in high-performance electrochemical capacitors. This review article summarizes the progress on the applications of abundant biomaterials and materials derived from biomass in the field. Various ‘green’ resources have been used as precursors for activated carbons, as binders, or as gel (gelating) agents for solid-state electrolytes. The authors attempt to critically evaluate a commercial potential of these materials upon ongoing trends in research & development of electrochemical capacitors. Pros and cons of utilizing the selected biomass materials are provided and perspectives for their advanced processing are discussed.  相似文献   
68.
A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.  相似文献   
69.
Air plasma spray (APS) thermal barrier coatings (TBCs) contain pores, cracks and splat interfaces that are preferentially aligned normal to the heat flux direction. These significantly reduce (by as much as 50%) the thermal conductivity over a fully dense coating. Here the microstructures of APS thermal barrier coatings (TBCs) have been characterized in 3D using X‐ray microcomputed tomography (μ‐CT). Pores larger than 2.8 μm3 are resolved and their contribution to thermal conductivity reduction is evaluated using image‐based microstructurally realistic numerical models. However, the models overestimate (by almost 50%) the measured thermal conductivity of the as‐deposited TBC sample. It is shown that this discrepancy is due to very fine (micrometer and submicrometer) cracks which readily sinter after short‐term exposure to temperatures representative of TBC operating conditions causing the measured thermal conductivity to rise to within 15% of that predicted. This suggests that under the realistic service conditions, the 3D image‐based models based on CT images provide a good indicator of the likely long‐term TBC performance. Virtual experiments showed that for the retained pores, the larger pores which are flatter and more oriented in the plane of the APS splats, contribute disproportionately to the beneficial reduction in thermal conductivity. Our results demonstrate that X‐ray imaging is a useful tool in establishing APS process conditions that give rise to a beneficial distribution of such pores.  相似文献   
70.
Wireless Networks - Integrated process planning and scheduling in networked manufacturing systems plays a crucial role nowadays and in the forthcoming context of Industry 4.0 to enable effective...  相似文献   
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