Mycobacterium abscessus (MAB) is a rapidly growing mycobacterium (RGM), and infections with this pathogen have been increasing worldwide. Recently, we reported that rough type (MAB-R) but not smooth ...type (MAB-S) strains enhanced type 1 interferon (IFN-I) secretion via bacterial phagosome escape, contributing to increased virulence. Here, we sought to investigate the role of mitochondrial oxidative stress in bacterial survival, IFN-I secretion and NLRP3 inflammasome activation in MAB-infected murine macrophages. We found that live but not heat-killed (HK) MAB-R strains increased mitochondrial ROS (mtROS) and increased release of oxidized mitochondrial DNA (mtDNA) into the cytosol of murine macrophages compared to the effects of live MAB-S strains, resulting in enhanced NLRP3 inflammasome-mediated IL-1β and cGAS-STING-dependent IFN-I production. Treatment of the infected macrophages with mtROS-modulating agents such as mito-TEMPO or cyclosporin A reduced cytosolic oxidized mtDNA, which inhibited the MAB-R strain-induced production of IL-1β and IFN-I. The reduced cytosolic oxidized mtDNA also inhibited intracellular growth of MAB-R strains via cytosolic escape following phagosomal rupture and via IFN-I-mediated cell-to-cell spreading. Moreover, our data showed that mtROS-dependent IFN-I production inhibited IL-1β production, further contributing to MAB-R intracellular survival in murine macrophages. In conclusion, our data indicated that MAB-R strains enhanced IFN-I and IL-1β production by inducing mtROS as a pathogen-associated molecular pattern (PAMP). These events also enhance bacterial survival in macrophages and dampen inflammation, which contribute to the pathogenesis of MAB-R strains.
Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic ...polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (
⁻
) were isolated from the seeds of
Medikus (Fabaceae) and tested for their DPP-IV⁻inhibitory activity. We demonstrated for the first time, that compounds
⁻
inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds
⁻
within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV.
The effective production and usage of ginsenosides, given their distinct pharmacological effects, are receiving increasing amounts of attention. As the ginsenosides content differs in different parts ...of Panax ginseng, we wanted to assess and compare the ginsenosides content in the ginseng roots, leave, stems, and berries. To extract the ginsenosides, 70% (v/v) methanol was used. The optimal ultra-performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) method was used to profile various ginsenosides from the different parts of P. ginseng. The datasets were then subjected to multivariate analysis including principal component analysis (PCA) and hierarchical clustering analysis (HCA). A UPLC-QTOF/MS method with an in-house library was constructed to profile 58 ginsenosides. With this method, a total of 39 ginsenosides were successfully identified and quantified in the ginseng roots, leave, stem, and berries. PCA and HCA characterized the different ginsenosides compositions from the different parts. The quantitative ginsenoside contents were also characterized from each plant part. The results of this study indicate that the UPLC-QTOF/MS method can be an effective tool to characterize various ginsenosides from the different parts of P. ginseng.
In situ exsolution for nanoscale electrode design has attracted considerable attention because of its promising activity and high stability. However, fundamental research on the mechanisms underlying ...particle growth remains insufficient. Herein, cation‐diffusion‐determined exsolution is presented using an analytical model based on classical nucleation and diffusion. In the designed perovskite system, the exsolution trend for particle growth is consistent with this diffusion model, which strongly depends on the initial cation concentration and reduction conditions. Based on the experimental and theoretical results, a highly Ni‐doped anode and an electrochemical switching technique are employed to promote exsolution and overcome growth limitations. The optimal cell exhibits an outstanding maximum power density of 1.7 W cm−2 at 900 °C and shows no evident degradation when operating at 800 °C for 240 h under wet H2. This study provides crucial insights into the developing and tuning of heterogeneous catalysts for energy‐conversion applications.
Diffusion‐determined exsolution behavior and its mechanism are demonstrated by controlling and modeling particle growth. Following this model, a highly active and durable nanostructured electrode for solid oxide fuel cells using an in situ exsolution method is developed. The particle growth of the exsolved Ni nanoparticles is enhanced by electrochemical switching,leading to a drastic improvement in cell performance.
Recently, with scaling down of semiconductor devices, need for nanotechnology has increased enormously. For nanoscale devices especially, each of the layers should be as thin and as perfect as ...possible. Thus, the application of atomic layer deposition (ALD) to nanofabrication strategies and emerging nanodevices has sparked a good deal of interest due to its inherent benefits compared to other thin film deposition techniques. Since the ALD process is intrinsically atomic in nature and results in the controlled deposition of films at the atomic scale, ALD produces layers with nanometer scale thickness control and excellent conformality. In this report, we review current research trends in ALD processes, focusing on the application of ALD to emerging nanodevices utilizing fabrication through nanotechnology.
Chronic neuroinflammation is a common feature of the aged brain, and its association with the major neurodegenerative changes involved in cognitive impairment and motor dysfunction is well ...established. One of the most potent antiaging interventions tested so far is dietary restriction (DR), which extends the lifespan in various organisms. Microglia and astrocytes are two major types of glial cells involved in the regulation of neuroinflammation. Accumulating evidence suggests that the age-related proinflammatory activation of astrocytes and microglia is attenuated under DR. However, the molecular mechanisms underlying DR-mediated regulation of neuroinflammation are not well understood. Here, we review the current understanding of the effects of DR on neuroinflammation and suggest an underlying mechanistic link between DR and neuroinflammation that may provide novel insights into the role of DR in aging and age-associated brain disorders.
Despite the record power conversion efficiencies, inverted perovskite solar cells (PSCs) are still looking to overcome the challenge of moisture instability. This is mitigated by introducing 2D ...perovskite at the base of a 3D perovskite via coating of ethylenediamine bications on top of the hole transport layer of p–i–n planar configured devices. The cations induce thin 2D perovskite growth beneath the 3D perovskite to create a 2D/3D hybrid active layer. This 2D layer in turn acts as a template for the growth of relatively large grains compared to that of pure 3D perovskite films. This stems from the merging of grain boundaries. The hydrophobicity of the 2D/3D perovskite film consequently improves, as evidenced by a large contact angle of 93.1°, compared to 68.9° for the 3D perovskite film. Because there are fewer defects sourced from grain boundaries, the air‐processed 2D/3D perovskite devices yield a high power conversion efficiency of 15.02%, compared to 13.10% from 3D perovskite devices. When stored in moderately humid environment of 55% relative humidity, the 2D/3D devices exhibit longer stabilities, with 75% of their power conversion efficiencies maintained after 150 h, compared to a total loss in efficiency for 3D device in the same time frame.
When introduced beneath the 3D perovskite layer, the 2D perovskite seeding layer acts as a template for growth in the planar direction, resulting in an increase in perovskite grains with less and narrow grain boundaries. As a result, the hydrophobicity of the film increases resulting in better stability and improved efficiency when the films are processed in air.
Lentil (
; Fabaceae), one of the major pulse crops in the world, is an important source of proteins, prebiotics, lipids, and essential minerals as well as functional components such as flavonoids, ...polyphenols, and phenolic acids. To improve crop nutritional and medicinal traits, hybridization and mutation are widely used in plant breeding research. In this study, mutant lentil populations were generated by γ-irradiation for the development of new cultivars by inducing genetic diversity. Molecular networking via Global Natural Product Social Molecular Networking web platform and dipeptidyl peptide-IV inhibitor screening assay were utilized as tools for structure-based discovery of active components in active mutant lines selected among the lentil population. The bioactivity-based molecular networking analysis resulted in the annotation of the molecular class of phosphatidylcholine (PC) from the most active mutant line. Among PCs, 1-stearoyl-2-hydroxy-
-glycero-3-phosphocholine (18:0 Lyso PC) was selected for further in vivo study of anti-obesity effect in a high-fat diet (HFD)-induced obese mouse model. The administration of 18:0 Lyso PC not only prevented body weight gain and decreased relative gonadal adipose tissue weight, but also attenuated the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and leptin in the sera of HFD-induced obese mice. Additionally, 18:0 Lyso PC treatment inhibited the increase of adipocyte area and crown-like structures in adipose tissue. Therefore, these results suggest that 18:0 Lyso PC is a potential compound to have protective effects against obesity, improving obese phenotype induced by HFD.
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