Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism’s ...pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.
The search for genetic variants underlying major depressive disorder (MDD) has not yet provided firm leads to its underlying molecular biology. A complementary approach is to study gene expression in ...relation to MDD. We measured gene expression in peripheral blood from 1848 subjects from The Netherlands Study of Depression and Anxiety. Subjects were divided into current MDD (N=882), remitted MDD (N=635) and control (N=331) groups. MDD status and gene expression were measured again 2 years later in 414 subjects. The strongest gene expression differences were between the current MDD and control groups (129 genes at false-discovery rate, FDR<0.1). Gene expression differences across MDD status were largely unrelated to antidepressant use, inflammatory status and blood cell counts. Genes associated with MDD were enriched for interleukin-6 (IL-6)-signaling and natural killer (NK) cell pathways. We identified 13 gene expression clusters with specific clusters enriched for genes involved in NK cell activation (downregulated in current MDD, FDR=5.8 × 10(-5)) and IL-6 pathways (upregulated in current MDD, FDR=3.2 × 10(-3)). Longitudinal analyses largely confirmed results observed in the cross-sectional data. Comparisons of gene expression results to the Psychiatric Genomics Consortium (PGC) MDD genome-wide association study results revealed overlap with DVL3. In conclusion, multiple gene expression associations with MDD were identified and suggest a measurable impact of current MDD state on gene expression. Identified genes and gene clusters are enriched with immune pathways previously associated with the etiology of MDD, in line with the immune suppression and immune activation hypothesis of MDD.
Summary
Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated ...vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.
The morphologies and orientation relationships of Cu6Sn5 grains formed between Sn and (0 0 1), (0 1 1), (1 1 1) and (1 23) Cu single crystals under liquid- and solid-state aging conditions were ...systematically investigated. The regular prism-type Cu6Sn5 grains formed on (0 0 1) and (1 1 1) Cu single crystals are elongated either along two perpendicular directions or along three preferential directions with an angle of 60 deg between each pair of directions. The orientation relationships between Cu and Cu6Sn5 lattice structures were determined by electron backscatter diffraction and were explained in terms of their minimum misfit. However, on (0 1 1) and (1 2 3) Cu single crystal surfaces, the Cu6Sn5 grains were mainly scallop-type, with only a few regular prism-type grains. Furthermore, the regular prism-type Cu6Sn5 grains will change into scallop-type after long reflow or aging times. Meanwhile it is considered that the growth of the scallop-type grains is supplied by two fluxes: the flux of the interfacial reaction and the flux of ripening. However, the growth of the prism-type grains is only supplied by the flux of the interfacial reaction. The kinetics of IMCs growth between Sn and Cu single crystals was also investigated.
•Cr doped diamond like carbon (Cr-DLC) nanocomposite coatings were deposited by using a combined system.•The stress of the Cr-DLC coatings dramatically decreases from 0.98GPa to 0.49GPa as the Cr ...contents increases from 0at% to 9.7at%.•The results showed that Cr-DLC coating with low Cr concentration was a effective protective coating.
Cr doped diamond like carbon (Cr-DLC) coatings were deposited by using a combined system consisting of middle frequency (MF) magnetron sputtering and ion plating. The structure and properties of the undoped and Cr-doped DLC coatings were analyzed by various testing, such as Raman, XPS, hardness and temperature-dependent frictional wear testing. The results showed that Cr-DLC coatings with low Cr concentration was a effective protective coating containing Cr–C nanometer grains, whose mechanical properties were obviously improved, such as, residual stress and cohesive strength, and still kept good wear resistance at the ambient temperature of 400°C.
In the companion paper, we identified a repeatable sequence of events leading to substorm onset in THEMIS all‐sky imager observations: enhanced flows bring new plasma into the plasma sheet. The new ...plasma then moves earthward as a flow channel, bringing it to the near‐Earth plasma sheet and where it produces onset instability. New plasma entering the dusk (dawn) convection cell drifts equatorward and eastward and then around the Harang reversal, leading to pre‐midnight (near‐ and post‐midnight) onset. Here we present evidence supporting this sequence using incoherent scatter radar (ISR) ionospheric observations. Using the Sondrestrom ISR, we find that enhanced flows of new plasma commonly enter the plasma sheet from the polar cap ∼8 min prior to onset. These flows are related to poleward boundary intensification signatures, consistent with the inferences from the imagers. Using the Poker Flat ISR (PFISR), we find that shortly before onset, enhanced westward flows reach the subauroral polarization streams (SAPS) region equatorward of the Harang reversal (dusk‐cell onsets) or enhanced eastward flows enter the onset region from the poleward direction (dawn‐cell onset). PFISR proton precipitation signatures are consistent with the possibility that the enhanced flows consist of reduced‐entropy plasma sheet plasma, and that onset occurs poleward of much of the enhanced SAPS flow (dusk‐cell onsets) or equatorward of the enhanced eastward flows (dawn‐cell onsets). Consistency with reduced entropy plasma is seen only within the enhanced flows, leading us to suggest that intrusion of low‐entropy plasma may alter the radial gradient of entropy toward onset instability.
This study investigated the effects of dietary resveratrol at 0, 200, 400, or 600 mg/kg of diet on the performance, immune organ growth index, serum parameters, and expression levels of heat shock ...protein (Hsp) 27, Hsp70, and Hsp90 mRNA in the bursa of Fabricius, thymus, and spleen of 42-d-old female black-boned chickens exposed to heat stress at 37 ± 2°C for 15 d. The results showed that heat stress reduced daily feed intake and BW gain; decreased serum glutathione (GSH), growth hormone, and insulin-like growth factor-1 levels; and inhibited GSH peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities compared with birds subjected to thermo-neutral circumstances. Chickens that were fed diets supplemented with resveratrol exhibited a linear increase in feed intake and BW gain (P < 0.001); serum GSH, growth hormone, and insulin-like growth factor-1 levels (P ≤ 0.01); and GSH-Px, SOD, and CAT activities (P < 0.001) compared with chickens that were fed diets without resveratrol during heat stress. In contrast, serum malonaldehyde concentrations were decreased (P < 0.001) in the chickens fed a resveratrol-supplemented diet. Heat stress also reduced (P < 0.05) the growth index of the bursa of Fabricus and spleen; however, it had no effect on the growth index of the thymus. The growth index of the bursa of Fabricius and spleen increased (P < 0.05) upon heat stress and coincided with an increase in supplemental resveratrol levels. The expression of Hsp27, Hsp70, and Hsp90 mRNA in the bursa of Fabricius and spleen were increased (P < 0.01), but those of Hsp27 and Hsp90 mRNA in thymus were decreased (P < 0.01) under heat stress compared with no heat stress. Resveratrol attenuated the heat stress-induced overexpression of Hsp27, Hsp70, and Hsp90 mRNA in the bursa of Fabricius and spleen and increased the low expression of Hsp27 and Hsp90 mRNA in thymus upon heat stress. The results suggest that supplemental resveratrol improves growth performance and reduces oxidative stress in heat-stressed black-boned chickens by increasing serum growth hormone concentrations and modulating the expression of heat shock genes in organs of the immune system.
The poor corrosion/wear resistance of Mg alloy seriously limits its industrial application. Graphene-based anti-corrosion coatings show the excellent imperviousness, but they can provide the ...additional cathodic sites for Mg alloys, which accelerates the galvanic corrosion behaviors near the interfaces. A novel design of cerium-based intermediate layer (Ce(Ⅳ)) is reported in this study, which exhibits a synergistic effect of hydrogen/ionic bond on the graphene oxide (GO)/polyvinyl alcohol (PVA) biomimetic coating. It overcomes the problems of galvanic corrosion and low interfacial adhesion between Mg substrate and hybrid coating through a prominent barrier effect. Furthermore, the GO/PVA coating with “bricks and mortar” structure effectively blocks the permeation of electrolyte due to the reduced porosity and enhanced densification. The corrosion rate of Ce(Ⅳ)/GO/PVA coating is 11 and 19 times lower than bare Mg alloy and single GO/PVA film, respectively. The wear rate of GO/PVA and Ce(Ⅳ)/GO/PVA samples is decreased by 98.8% and 97.6%, which is ascribed to the high hardness and lubrication of GO sheets. Moreover, the relatively interlayer slipping between GO sheets can lubricate the sliding process. Compared with GO/PVA, the slightly decreased wear resistance of Ce(Ⅳ)/GO/PVA coating is resulted from the enhanced shear force.
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