The medical applications of porous Mg scaffolds are limited owing to its rapid corrosion, which dramatically decreases the mechanical strength of the scaffold. Mimicking the bone structure and ...composition can improve the mechanical and biological properties of porous Mg scaffolds. The Mg structure can also be coated with HA by an aqueous precipitation coating method to enhance both the corrosion resistance and the biocompatibility. However, due to the brittleness of HA coating layer, cracks tend to form in the HA coating layer, which may influence the corrosion and biological functionality of the scaffold. Consequently, in this study, hybrid poly(ether imide) (PEI)-SiO
layers were applied to the HA-coated biomimetic porous Mg to impart the structure with the high corrosion resistance associated with PEI and excellent bioactivity with SiO
. The porosity of the Mg was controlled by adjusting the concentration of the sodium chloride (NaCl) particles used in the fabrication via the space-holder method. The mechanical measurements showed that the compressive strength and stiffness of the biomimetic porous Mg increased as the portion of the dense region increased. In addition, following results show that HA/(PEI-SiO
) hybrid-coated biomimetic Mg is a promising biodegradable scaffold for orthopedic applications. In-vitro testing revealed that the proposed hybrid coating reduced the degradation rate and facilitated osteoblast spreading compared to HA- and HA/PEI-coating scaffolds. Moreover, in-vivo testing with a rabbit femoropatellar groove model showed improved tissue formation, reduced corrosion and degradation, and improved bone formation on the scaffold. STATEMENT OF SIGNIFICANCE: Porous Mg is a promising biodegradable scaffold for orthopedic applications. However, there are limitations in applying porous Mg for an orthopedic biomaterial due to its poor mechanical properties and susceptibility to rapid corrosion. Here, we strategically designed the structure and coating layer of porous Mg to overcome these limitations. First, porous Mg was fabricated by mimicking the bone structure which has a combined structure of dense and porous regions, thus resulting in an enhancement of mechanical properties. Furthermore, the biomimetic porous Mg was coated with HA/(PEI-SiO
) hybrid layer to improve both corrosion resistance and biocompatibility. As the final outcome, with tunable mechanical and biodegradable properties, HA/(PEI-SiO
)-coated biomimetic porous Mg could be a promising candidate material for load-bearing orthopedic applications.
Most CsPbBr3 perovskite quantum dot light‐emitting diodes (PQD‐LEDs) are fabricated with an inverted device structure where hole transport/injection layers are vacuum‐deposited on top of ITO/ZnO (as ...an electron transport layer (ETL))/PQDs. Standard device architecture of PQD‐LEDs enables a solution‐process of device fabrication; however, the spin‐coating of ZnO ETL dissolved in polar solvent results in decreasing photoluminescence (PL) of PQDs because of PQD destabilization in polar medium. Herein, CsPbBr3 PQD‐LEDs are fabricated by depositing Al2O3 and ZnO via atomic layer deposition (ALD) to avoid damages originating from the polar solvent during ZnO ETL spin‐coating. Low temperature ALD is adopted to prevent the coarsening of the CsPbBr3 PQDs. A thicker Al2O3 interlayer can prevent PL quenching, but an excessively thick interlayer hinders electron transport due to the insulating nature of Al2O3. ZnO is sequentially deposited on Al2O3 interlayer via ALD, and therefore Al2O3/ZnO bilayer structure is used because of its better electron transporting ability and higher power efficiency in PQD‐LED devices compared with Al2O3‐only devices.
Green emitting CsPbBr3 perovskite quantum dot light‐emitting diodes (PQD‐LEDs) are fabricated in a standard device structure with insertion of atomic‐layer deposited interlayer. This interlayer enables deposition of solution‐processed ZnO nanoparticles on top of CsPbBr3 PQDs directly, and successfully passivate PQD surface from polar solvent damages during ZnO spin‐casting.
Poly(lactic acid) (PLA) is the most utilized biodegradable polymer in orthopedic implant applications because of its ability to replace regenerated bone tissue via continuous degradation over time. ...However, the poor osteoblast affinity for PLA results in a high risk of early implant failure, and this issue remains one of the most difficult challenges with this technology. In this study, we demonstrate the use of a new technique in which plasma immersion ion implantation (PIII) is combined with a conventional DC magnetron sputtering. This technique, referred to as sputtering-based PIII (S-PIII), makes it possible to produce a tantalum (Ta)-implanted PLA surface within 30 s without any tangible degradation or deformation of the PLA substrate. Compared to a Ta-coated PLA surface, the Ta-implanted PLA showed twice the surface roughness and substantially enhanced adhesion stability in dry and wet conditions. The strong hydrophobic surface properties and biologically relatively inert chemical structure of PLA were ameliorated by Ta S-PIII treatment, which produced a moderate hydrophilic surface and enhanced cell–material interactions. Furthermore, in an in vivo evaluation in a rabbit distal femur implantation model, Ta-implanted PLA demonstrated significantly enhanced osseointegration and osteogenesis compared with bare PLA. These results indicate that the Ta-implanted PLA has great potential for orthopedic implant applications.
Hepatic steatosis is associated with increased insulin resistance and tricarboxylic acid (TCA) cycle flux, but decreased ketogenesis and pyruvate dehydrogenase complex (PDC) flux. This study examined ...whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities. Wild-type mice fed a high-fat diet exhibited hepatic steatosis, insulin resistance, and increased levels of pyruvate, TCA cycle intermediates, and malonyl-CoA but reduced ketogenesis and PDC activity due to PDK2 induction. Hepatic PDC activation by PDK2 inhibition attenuated hepatic steatosis, improved hepatic insulin sensitivity, reduced hepatic glucose production, increased capacity for β-oxidation and ketogenesis, and decreased the capacity for lipogenesis. These results were attributed to altered enzymatic capacities and a reduction in TCA anaplerosis that limited the availability of oxaloacetate for the TCA cycle, which promoted ketogenesis. The current study reports that increasing hepatic PDC activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease.
BACKGROUNDCeramides are associated with metabolic complications including diabetic nephropathy in patients with diabetes. Recent studies have reported that podocytes play a pivotal role in the ...progression of diabetic nephropathy. Also, mitochondrial dysfunction is known to be an early event in podocyte injury. Thus, we tested the hypothesis that ceramide accumulation in podocytes induces mitochondrial damage through reactive oxygen species (ROS) production in patients with diabetic nephropathy. METHODSWe used Otsuka Long Evans Tokushima Fatty (OLETF) rats and high-fat diet (HFD)-fed mice. We fed the animals either a control- or a myriocin-containing diet to evaluate the effects of the ceramide. Also, we assessed the effects of ceramide on intracellular ROS generation and on podocyte autophagy in cultured podocytes. RESULTSOLETF rats and HFD-fed mice showed albuminuria, histologic features of diabetic nephropathy, and podocyte injury, whereas myriocin treatment effectively treated these abnormalities. Cultured podocytes exposed to agents predicted to be risk factors (high glucose, high free fatty acid, and angiotensin II in combination GFA) showed an increase in ceramide accumulation and ROS generation in podocyte mitochondria. Pretreatment with myriocin reversed GFA-induced mitochondrial ROS generation and prevented cell death. Myriocin-pretreated cells were protected from GFA-induced disruption of mitochondrial integrity. CONCLUSIONWe showed that mitochondrial ceramide accumulation may result in podocyte damage through ROS production. Therefore, this signaling pathway could become a pharmacological target to abate the development of diabetic kidney disease.
ABSTRACT
Reactive oxygen species (ROS) derived from NADPH oxidase (Nox) has been shown to activate ADP‐ribosyl cyclase (ARC), which produces the Ca2+ mobilizing second messenger, cyclic ADP‐ribose ...(cADPR). In the present study, we examined how ROS activates cluster of differentiation (CD)38, a mammalian prototype of ARC. CD38 exists in type II and III forms with opposing membrane orientation. This study showed the coexpression of type II and III CD38 in lymphokine‐activated killer (LAK) cells. The catalytic site of the constitutively active type II CD38 faces the outside of the cell or the inside of early endosomes (EEs), whereas the basally inactive type III CD38 faces the cytosol. Type III CD38 interacted with Nox4/phosphorylated‐p22phox (p‐p22phox) in EEs of LAK cells upon IL‐8 treatment. H2O2 derived from Nox4 activated type III CD38 by forming a disulfide bond between Cys164 and Cys177, resulting in increased cADPR formation. Our study identified the mechanism by which type III CD38 is activated in an immune cell (LAK), in which H2O2 generated by Nox4 oxidizes and activates type III CD38 to generate cADPR. These findings provide a novel model of cross‐talk between ROS and Ca2+ signaling.—Park, D.‐R., Nam, T.‐S., Kim, Y.‐W., Bae, Y. S., Kim, U.‐H. Oxidative activation of type III CD38 by NADPH oxidase–derived hydrogen peroxide in Ca2+ signaling. FASEB J. 33, 3404–3419 (2019). www.fasebj.org
This study reports on the effect of a bilayer period on the growth behavior, microstructure evolution, and electrical properties of atomic layer deposition (ALD) deposited In–Zn–O (IZO) films, fixing ...the ALD cycle ratio of In–O/Zn–O as 9:1. Here, the bilayer period is defined as the total number of ALD cycles in one supercycle of In–O and Zn–O by alternately stacking Zn–O and In–O layers at a temperature of 220 °C. IZO films with a bilayer period from 10 to 40 cycles, namely, IZOIn–O/Zn–O = 9:1 to IZO36:4, result to form an amorphous phase with a resistivity of 4.94 × 10–4 Ω·cm. However, by increasing the bilayer period above 100 cycles, the IZO films begin to form a mixed amorphous–nanocrystalline microstructure, resulting from the limited intermixing at the interfaces. Concomitantly, the overall film resistivity is considerably increased with a simultaneous decrease in both the carrier mobility and the concentration. These results not only reveal the importance of the bilayer period in designing the ALD stacking sequence in the ALD-IZO, but also provide the possibility of forming various multilayered materials with different electrical properties.
Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and ...bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.
This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.
Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.
We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.
We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.
A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).
Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
The aging of ZnO nanoparticles in quantum dot light-emitting diode (QD-LED) structures was studied. Coarsening of as-synthesized ZnO nanoparticles is observed in both solution and thin film ...structures, which potentially deteriorates the performance of QD-LED devices over time. First, the temperature effect on ZnO coarsening was investigated, and it was revealed that aging of ZnO nanoparticles is faster at higher temperature due to a diffusion-controlled mechanism of nanoparticle coarsening. To observe aggregation of ZnO in the film state, the electron transporting part (ZnO/Al) of the QD-LED structure was prepared. The current density of a ZnO film and an electron-only device (QD/ZnO between two electrodes) was also measured. Resistance of the film increased as a function of aging time, which corresponded with observations of the ZnO film by optical microscopy. Aggregation of ZnO nanoparticles was directly measured by the root-mean-square value using atomic force microscopy. Ethanolamine (EA) stabilizer was added to the ZnO solution to disperse the ZnO nanoparticles without aggregation. The effect of EA on the surface passivation of the ZnO found to suppress pinhole formation, as revealed by scanning electron microscopy observations. Finally, the device lifetime was measured for QD-LEDs with EA-stabilized ZnO to understand the effect of ZnO aging on long-term QD-LED device operation.
The hepatic endocannabinoid system and cytochrome P450 2E1 (CYP2E1), a key enzyme causing alcohol-induced reactive oxygen species (ROS) generation, are major contributors to the pathogenesis of ...alcoholic liver disease. The nuclear hormone receptor oestrogen-related receptor γ (ERRγ) is a constitutively active transcriptional activator regulating gene expression.
To investigate the role of ERRγ in the alcohol-mediated regulation of CYP2E1 and to examine the possibility to control alcohol-mediated oxidative stress and liver injury through an ERRγ inverse agonist.
For chronic alcoholic hepatosteatosis study, C57BL/6J wild-type and CB1(-/-) mice were administered alcohol for 4 weeks. GSK5182 and chlormethiazole (CMZ) were given by oral gavage for the last 2 weeks of alcohol feeding. Gene expression profiles and biochemical assays were performed using the liver or blood of mice.
Hepatic ERRγ gene expression induced by alcohol-mediated activation of CB1 receptor results in induction of CYP2E1, while liver-specific ablation of ERRγ gene expression blocks alcohol-induced expression of CYP2E1 in mouse liver. An ERRγ inverse agonist significantly ameliorates chronic alcohol-induced liver injury in mice through inhibition of CYP2E1-mediated generation of ROS, while inhibition of CYP2E1 by CMZ abrogates the beneficial effects of the inverse agonist. Finally, chronic alcohol-mediated ERRγ and CYP2E1 gene expression, ROS generation and liver injury in normal mice were nearly abolished in CB1(-/-) mice.
ERRγ, as a previously unrecognised transcriptional regulator of hepatic CB1 receptor, controls alcohol-induced oxidative stress and liver injury through CYP2E1 induction, and its inverse agonist could ameliorate oxidative liver injury due to chronic alcohol exposure.
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