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51.
    
Mitochondrial proteins are encoded by both nuclear and mitochondrial DNA. While some of the essential subunits of the oxidative phosphorylation (OXPHOS) complexes responsible for cellular ATP production are synthesized directly in the mitochondria, most mitochondrial proteins are first translated in the cytosol and then imported into the organelle using a sophisticated transport system. These proteins are directed mainly by targeting presequences at their N-termini. These presequences need to be cleaved to allow the proper folding and assembly of the pre-proteins into functional protein complexes. In the mitochondria, the presequences are removed by several processing peptidases, including the mitochondrial processing peptidase (MPP), the inner membrane processing peptidase (IMP), the inter-membrane processing peptidase (MIP), and the mitochondrial rhomboid protease (Pcp1/PARL). Their proper functioning is essential for mitochondrial homeostasis as the disruption of any of them is lethal in yeast and severely impacts the lifespan and survival in humans. In this review, we focus on characterizing the structure, function, and substrate specificities of mitochondrial processing peptidases, as well as the connection of their malfunctions to severe human diseases.  相似文献   
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Among the multitude of polymers with carbon-based macromolecular architectures that easily ignite in certain applications where short circuits may occur, polyimide has evolved as a class of polymers with high thermal stability while exhibiting intrinsic flame retardancy at elevated temperatures via a char-forming mechanism. However, high amounts of aromatic rings in the macromolecular backbone are required for these results, which may affect other properties such as film-forming capacity or mechanical properties; thus, much work has been done to structurally derivatize or make hybrid polyimide systems. In this respect, flexible polyimide films (PI(1–4)) containing bulky 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) units have been developed starting from commercial dianhydrides and an aromatic diamine containing two side chain bulky DOPO groups. The chemical structure of PI(1–4)) was characterized by 1H NMR, 13C NMR and 31P NMR spectroscopy. The optical properties, including absorption and luminescence spectra of these polymers, were analyzed. All polyimides containing DOPO derivatives emitted blue light with an emission maxima in the range of 340–445 nm, in solvents such as N,N-dimethylformamide, N-methyl-2-pyrrolidone, chloroform, and N,N-dimethylacetamide, while green light emission (λem = 487 nm for PI-4) was evidenced in a thin-film state. The thermal decomposition mechanism and flame-retardant behavior of the resulting materials were investigated by pyrolysis-gas-chromatography spectrometry (Py-GC), scanning electron microscopy (SEM), EDX maps and FTIR spectroscopy. The residues resulting from the TGA experiments were examined by SEM microscopy images and FTIR spectra to understand the pyrolysis mechanism.  相似文献   
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Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3′5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3′5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3′5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-β1. Furthermore, 3′5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3′5-DMBA may be a promising candidate for IPF treatment.  相似文献   
54.
    
In a prospective study, 48 fetuses were evaluated with Doppler ultrasound after 34 weeks and classified, according to the cerebroplacental ratio (CPR) and estimated fetal weight (EFW), into fetuses with normal growth and fetuses with late-onset fetal growth restriction (LO-FGR). Overexpression of miRNAs from neonatal cord blood belonging to LO-FGR fetuses, was validated by real-time PCR. In addition, functional characterization of overexpressed miRNAs was performed by analyzing overrepresented pathways, gene ontologies, and prioritization of synergistically working miRNAs. Three miRNAs: miR-25-3p, miR-185-5p and miR-132-3p, were significantly overexpressed in cord blood of LO-FGR fetuses. Pathway and gene ontology analysis revealed over-representation of certain molecular pathways associated with cardiac development and neuron death. In addition, prioritization of synergistically working miRNAs highlighted the importance of miR-185-5p and miR-25-3p in cholesterol efflux and starvation responses associated with LO-FGR phenotypes. Evaluation of miR-25-3p; miR-132-3p and miR-185-5p might serve as molecular biomarkers for the diagnosis and management of LO-FGR; improving the understanding of its influence on adult disease.  相似文献   
55.
    
Alzheimer’s disease (AD) is a multifactorial pathology characterized by β-amyloid (Aβ) deposits, Tau hyperphosphorylation, neuroinflammatory response, and cognitive deficit. Changes in the bacterial gut microbiota (BGM) have been reported as a possible etiological factor of AD. We assessed in offspring (F1) 3xTg, the effect of BGM dysbiosisdysbiosis in mothers (F0) at gestation and F1 from lactation up to the age of 5 months on Aβ and Tau levels in the hippocampus, as well as on spatial memory at the early symptomatic stage of AD. We found that BGM dysbiosisdysbiosis with antibiotics (Abx) treatment in F0 was vertically transferred to their F1 3xTg mice, as observed on postnatal day (PD) 30 and 150. On PD150, we observed a delay in spatial memory impairment and Aβ deposits, but not in Tau and pTau protein in the hippocampus at the early symptomatic stage of AD. These effects are correlated with relative abundance of bacteria and alpha diversity, and are specific to bacterial consortia. Our results suggest that this specific BGM could reduce neuroinflammatory responses related to cerebral amyloidosis and cognitive deficit and activate metabolic pathways associated with the biosynthesis of triggering or protective molecules for AD.  相似文献   
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57.
    
Aquaporins (AQPs) are small transmembrane tetrameric proteins that facilitate water, solute and gas exchange. Their presence has been extensively reported in the biological membranes of almost all living organisms. Although their discovery is much more recent than ion transport systems, different biophysical approaches have contributed to confirm that permeation through each monomer is consistent with closed and open states, introducing the term gating mechanism into the field. The study of AQPs in their native membrane or overexpressed in heterologous systems have experimentally demonstrated that water membrane permeability can be reversibly modified in response to specific modulators. For some regulation mechanisms, such as pH changes, evidence for gating is also supported by high-resolution structures of the water channel in different configurations as well as molecular dynamics simulation. Both experimental and simulation approaches sustain that the rearrangement of conserved residues contributes to occlude the cavity of the channel restricting water permeation. Interestingly, specific charged and conserved residues are present in the environment of the pore and, thus, the tetrameric structure can be subjected to alter the positions of these charges to sustain gating. Thus, is it possible to explore whether the displacement of these charges (gating current) leads to conformational changes? To our knowledge, this question has not yet been addressed at all. In this review, we intend to analyze the suitability of this proposal for the first time.  相似文献   
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59.
In the present work, Pt/γ-Al2O3 catalysts with high metal dispersion were prepared and characterized using chloroplatinic acid and platinum acetylacetonate as metal precursors. The activity and selectivity of the catalysts were evaluated in the hydrogenation of sunflower oil. A comprehensive analysis of the effects of key operational parameters on catalytic performance was carried out. The experimental variables were hydrogen pressure (275.8–551.6 kPa), temperature (160–200°C), and catalyst loading (0.005–0.015 kg Ptexp/m3oil). Platinum catalysts were active, with a double bond conversion of 28% at 2 h. The metal precursor affected catalyst selectivity. The catalyst prepared with chloroplatinic acid exhibited a lower formation of trans-isomers compared with Pt acetylacetonate. The γ-Al2O3 supported platinum catalyst with a metal loading of 0.51 wt.% and a metal dispersion of 98% maintained its initial catalyst activity and selectivity after 10 consecutive uses (1200 min accumulate operation time), without changes in its catalytic properties. The obtained results suggested that Pt catalysts are an attractive alternative to conventional nickel catalysts for the hydrogenation of vegetable oil.  相似文献   
60.
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