Oligomeric Zinc Thiolates Tethering Multidentate Carboxylates for Nondestructive Aqueous Phase Transfer of Quantum Dots.

Functionalization of quantum dots (QDs) via ligand exchange is prone to debase their photoluminescence quantum yield (PL QY) owing to the unavoidable surface damage by excess reactants, and even worse in aqueous medium. Herein, the oligomeric zinc thiolate as the multidentate hydrophilic ligand featuring facile synthetic protocol is proposed. A simple reaction between ZnCl2 and 3-mercaptopropionic acid produces oligomeric ligands containing 3-6 zinc thiolate units, where the terminal moieties provide multidentate anchoring to the surface as well as hydrophilicity. 2D proton nuclear Overhauser effect spectroscopy (2D 1H NOESY) and X-ray photoelectron spectroscopy (XPS) reveal that the oligomeric zinc thiolate ligands adsorb on the surface via multidentate metal carboxylate bindings without destruction of molecular structure, regardless of partial dissociation of thiolate branches in aqueous phase. Enhanced binding affinity granted by the multidentate nature allows for the effective exchange of original surface ligands without considerable surface deterioration. The zinc thiolate-capped Cd-free aqueous QDs exhibit a high photoluminescence quantum yield of ≈90% and extended stability against long-term storage and photochemical stress.

Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis.

BACKGROUND: We previously identified ezetimibe, an inhibitor of Niemann-Pick C1-like intracellular cholesterol transporter 1 and European Medicines Agency-approved lipid-lowering agent, as a potent autophagy activator. However, its efficacy against pulmonary fibrosis has not yet been evaluated. This study aimed to determine whether ezetimibe has therapeutic potential against idiopathic pulmonary fibrosis. METHODS: Primary lung fibroblasts isolated from both humans and mice were employed for mechanistic in vitro experiments. mRNA sequencing of human lung fibroblasts and gene set enrichment analysis were performed to explore the therapeutic mechanism of ezetimibe. A bleomycin-induced pulmonary fibrosis mouse model was used to examine in vivo efficacy of the drug. Tandem fluorescent-tagged microtubule-associated protein 1 light chain 3 transgenic mice were used to measure autophagic flux. Finally, the medical records of patients with idiopathic pulmonary fibrosis from three different hospitals were reviewed retrospectively, and analyses on survival and lung function were conducted to determine the benefits of ezetimibe. RESULTS: Ezetimibe inhibited myofibroblast differentiation by restoring the mechanistic target of rapamycin complex 1-autophagy axis with fine control of intracellular cholesterol distribution. Serum response factor, a potential autophagic substrate, was identified as a primary downstream effector in this process. Similarly, ezetimibe ameliorated bleomycin-induced pulmonary fibrosis in mice by inhibiting mechanistic target of rapamycin complex 1 activity and increasing autophagic flux, as observed in mouse lung samples. Patients with idiopathic pulmonary fibrosis who regularly used ezetimibe showed decreased rates of all-cause mortality and lung function decline. CONCLUSION: Our study presents ezetimibe as a potential novel therapeutic for idiopathic pulmonary fibrosis.

"Nulichal" Barley Extract Suppresses Nitric Oxide and Pro-Inflammatory Cytokine Production by Lipopolysaccharides in RAW264.7 Macrophage Cell Line.

The cultivar "Nulichal," a type of naked waxy barley (Hordeum vulgare L.), was developed by the National Institute of Crop Science, Rural Development Administration, Korea, in 2010. In this study, we investigated the anti-inflammatory and antioxidant properties of the "Nulichal" ethanol extract (NRE) using various assays. The NRE exhibited a total phenolic content of 7.55±0.30 mg gallic acid equivalent/g and a flavonoid content of 1.74±0.08 mg rutin equivalent/g. Cell viability assays showed no toxicity of NRE on RAW264.7 macrophage cells up to concentrations of 500 µg/mL. The NRE (300 and 500 µg/mL) significantly reduced nitric oxide (NO) production induced by lipopolysaccharides (LPS). It also down-regulated the mRNA expression and protein levels of inducible NO synthase and cyclooxygenase-2 in a dose-dependent manner. Moreover, the NRE treatment significantly decreased the levels of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, and their mRNA expression compared to LPS treatment alone. The NRE demonstrated strong free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radicals in a dose-dependent manner. The ferric reducing antioxidant power assay also showed increased antioxidant activity with increasing NRE concentrations. These findings suggest that the NRE can be used as a functional food with anti-inflammatory and antioxidant properties.

Glutathione is an aging-related metabolic signature in the mouse kidney.

The ability to maintain systemic metabolic homeostasis through various mechanisms represents a crucial strength of kidneys in the study of metabolic syndrome or aging. Moreover, age-associated kidney failure has been widely accepted. However, efforts to demonstrate aging-dependent renal metabolic rewiring have been limited. In the present study, we investigated aging-related renal metabolic determinants by integrating metabolomic and transcriptomic data sets from kidneys of young (3 months, n = 7 and 3 for respectively) and old (24 months, n = 8 and 3 for respectively) naive C57BL/6 male mice. Metabolite profiling analysis was conducted, followed by data processing via network and pathway analyses, to identify differential metabolites. In the aged group, the levels of glutathione and oxidized glutathione were significantly increased, but the levels of gamma-glutamyl amino acids, amino acids combined with the gamma-glutamyl moiety from glutathione by membrane transpeptidases, and circulating glutathione levels were decreased. In transcriptomic analysis, differential expression of metabolic enzymes is consistent with the hypothesis of aging-dependent rewiring in renal glutathione metabolism; pathway and network analyses further revealed the increased expression of immune-related genes in the aged group. Collectively, our integrative analysis results revealed that defective renal glutathione metabolism is a signature of renal aging. Therefore, we hypothesize that restraining renal glutathione metabolism might alleviate or delay age-associated renal metabolic deterioration, and aberrant activation of the renal immune system.

High-Resolution Colloidal Quantum Dot Film Photolithography via Atomic Layer Deposition of ZnO.

High-resolution patterning of quantum dot (QD) films is one of the preconditions for the practical use of QD-based emissive display platforms. Recently, inkjet printing and transfer printing have been actively developed; however, high-resolution patterning is still limited owing to nozzle-clogging issues and coffee ring effects during the inkjet printing and kinetic parameters such as pickup and peeling speed during the transfer process. Consequently, employing direct optical lithography would be highly beneficial owing to its well-established process in the semiconductor industry; however, exposing the photoresist (PR) on top of the QD film deteriorates the QD film underneath. This is because a majority of the solvents for PR easily dissolve the pre-existing QD films. In this study, we present a conventional optical lithography process to obtain solvent resistance by reacting the QD film surface with diethylzinc (DEZ) precursors using atomic layer deposition. It was confirmed that, by reacting the QD surface with DEZ and coating PR directly on top of the QD film, a typical photolithography process can be performed to generate a red/green/blue pixel of 3000 ppi or more. QD electroluminescence devices were fabricated with all primary colors of QDs; moreover, compared to reference QD-LED devices, the patterned QD-LED devices exhibited enhanced brightness and efficiency.

The Role of Sleep in Young Children's Development: A Review.

This review article provides an overview of studies highlighting the importance of sleep in young children's development and summarizes research-based strategies for implementing healthy sleep practices. Sleep problems are common among young children and is one of the most commonly expressed concerns reported by caregivers. Insufficient sleep, poor sleep quality, and irregular sleep schedules may affect children's physical health, cognitive capacity, socioemotional processes, and behavioral functioning, with implications for children's development and well-being. Family context and factors, confounded with cultural variables, play a critical role in children's sleep behavior and practices. This article presents research-based recommendations to enhance knowledge about children's sleep and to promote appropriate practices.

Viburnum stellato-tomentosum Extract Suppresses Obesity and Hyperglycemia through Regulation of Lipid Metabolism in High-Fat Diet-Fed Mice.

The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid ß-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid ß-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.

Solvent-assisted strongly enhanced light-emitting electrochemiluminescent devices for lighting applications.

Rubrene-based electrochemiluminescence (r-ECL) cells with two different solvent systems is prepared, one in a co-solvent system with a mixture of 1,2-dichlorobenzene and propylene carbonate (DCB : PC, v/v 3 : 1) and another in a single solvent system of tetrahydrofuran (THF), as the medium to form a liquid-electrolyte (L-El). By simply changing the solvent systems, from the co-solvent DCB : PC (v/v 3 : 1) to the single solvent THF, with the same amount of electrochemiluminescent rubrene (5 mM) and Li-based salt, a dramatically enhanced brightness of over 30 cd m-2 is observed for the r-ECL cell in L-ElTHF which is approximately 7-times higher than the brightness of 5 cd m-2 observed for the r-ECL in L-ElDCB:PC(v/v 3:1).

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK-mTORC1 pathway.

Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet-induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti-adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator-activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe-mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis-related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe-mediated inhibition of adipogenesis is dependent on the AMPK-mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.

Phenolic-enriched blueberry-leaf extract attenuates glucose homeostasis, pancreatic ß-cell function, and insulin sensitivity in high-fat diet-induced diabetic mice.

Blueberry fruit exhibits strong antioxidant activity owing to the presence of anthocyanin. As blueberry-leaf extract (BLE) contains chlorogenic acid and flavonol glycosides, we hypothesized that phenolic-enriched BLE would improve glucose homeostasis and insulin sensitivity. In this study, we examined whether BLE administration decreases the glucose levels and enhances the pancreatic function in mice with high-fat diet (HFD)-induced obesity and diabetes. C57BL/6J mice were divided into the following four groups: control diet (CD), HFD (60 kcal% fat diet), BLE (HFD with 1% BLE wt/wt diet), and yerba mate extract (YME; HFD with 0.5% YME wt/wt diet). Dietary BLE and YME reduced glucose tolerance, body weight, and plasma glucose, glycated hemoglobin, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and non-esterified fatty acid levels. Compared with those of the HFD group, BLE was found to significantly reduce the pancreatic islet size and insulin content. Moreover, it increased the mRNA levels of pancreatic ß-cell proliferation-related genes, Ngn3, MafA, Pax4, Ins1, and Ins2, and pancreatic insulin signaling-related genes, IRS-1, IRS-2, PIK3ca, PDK1, PKCε, and GLUT-2, and decreased the transcriptional expression of the ß-cell apoptosis-related gene, FoxO1. Both BLE and YME improved insulin sensitivity by inhibiting TG synthesis and enhancing lipid utilization in the liver and white adipose tissue (WAT). In pancreatic MIN6 ß-cells, BLE and its main component (chlorogenic acid) increased ß-cell proliferation and promoted insulin signaling. Overall, BLE enriched with phenolic compounds has the capacity to prevent HFD-induced glucose tolerance and hyperglycemia by improving the pancreatic ß-cell function.

SQSTM1/p62 activates NFE2L2/NRF2 via ULK1-mediated autophagic KEAP1 degradation and protects mouse liver from lipotoxicity.

Lipotoxicity, induced by saturated fatty acid (SFA)-mediated cell death, plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The KEAP1 (kelch like ECH associated protein 1)-NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2) pathway is a pivotal defense mechanism against lipotoxicity. We previously reported that SQSTM1/p62 has a cytoprotective role against lipotoxicity through activation of the noncanonical KEAP1- NFE2L2 pathway in hepatocytes. However, the underlying mechanisms and physiological relevance of this pathway have not been clearly defined. Here, we demonstrate that NFE2L2-mediated induction of SQSTM1 activates the noncanonical KEAP1-NFE2L2 pathway under lipotoxic conditions. Furthermore, we identified that SQSTM1 induces ULK1 (unc-51 like autophagy activating kinase 1) phosphorylation by facilitating the interaction between AMPK (AMP-activated protein kinase) and ULK1, leading to macroautophagy/autophagy induction, followed by KEAP1 degradation and NFE2L2 activation. Accordingly, the activity of this SQSTM1-mediated noncanonical KEAP1-NFE2L2 pathway conferred hepatoprotection against lipotoxicity in the livers of conventional sqstm1- and liver-specific sqstm1-knockout mice. Moreover, this pathway activity was evident in the livers of patients with nonalcoholic fatty liver. This axis could thus represent a novel target for NAFLD treatment. Abbreviations: ACACA: acetyl-CoA carboxylase alpha; ACTB: actin beta; BafA1: bafilomycin A1; CM-H2DCFDA:5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate; CQ: chloroquine; CUL3: cullin 3; DMSO: dimethyl sulfoxide; FASN: fatty acid synthase; GSTA1: glutathione S-transferase A1; HA: hemagglutinin; Hepa1c1c7: mouse hepatoma cells; HMOX1/HO-1: heme oxygenase 1; KEAP1: kelch like ECH associated protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MTORC1: mechanistic target of rapamycin kinase complex 1; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NAC: N-acetyl-L-cysteine; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; NFE2L2/NRF2: nuclear factor, erythroid 2 like 2; NQO1: NAD(P)H quinone dehydrogenase 1; PA: palmitic acid; PARP: poly (ADP-ribose) polymerase 1; PRKAA1/2: protein kinase AMP-activated catalytic subunits alpha1/2; RBX1: ring-box 1; ROS: reactive oxygen species; SESN2: sestrin 2; SFA: saturated fatty acid; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; SREBF1: sterol regulatory element binding transcription factor 1; TBK1: TANK binding kinase 1; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; ULK1: unc-51 like autophagy activating kinase.

Decursin and decursinol angelate improve wound healing by upregulating transcription of genes encoding extracellular matrix remodeling proteins, inflammatory cytokines, and growth factors in human keratinocytes.

The coumarins decursin and decursinol angelate, which are found in Angelica gigas Nakai, have a variety of biological functions. Here, we show that treatment with these compounds improves wound healing by HaCaT human keratinocytes. Wound healing was increased by treatment with up to a threshold concentration of decursin, decursinol angelate, a mixture of both, and a nano-emulsion of these compounds, but inhibited by treatment with higher concentrations. Immunoblotting and fluorescence imaging of cells expressing an epidermal growth factor receptor (EGFR) biosensor demonstrated that these compounds did not stimulate wound healing by inducing EGFR phosphorylation. Rather, transcriptional analysis revealed that decursin and decursinol angelate improved wound healing by upregulating the expression of genes encoding extracellular matrix remodeling proteins, inflammatory cytokines, and growth factors.

Monolithic DSSC/CIGS tandem solar cell fabricated by a solution process.

Tandem architecture between organic (dye-sensitized solar cell, DSSC) and inorganic (CuInGaSe2 thin film solar cell, CIGS) single-junction solar cells was constructed particularly based on a solution process. Arc-plasma deposition was employed for the Pt interfacial layer to minimize the damage to the layers of the CIGS bottom cell. Solar cell efficiency of 13% was achieved, which is significant progress from individual single-junction solar cells (e.g., 7.25 and 6.2% for DSSC and CIGS, respectively).

The comparison of manual lymph drainage and ultrasound therapy on the leg swelling caused by wearing high heels.

One of the major symptoms when women are wearing high heels for a long time is leg swelling. The purpose of this study was to compare the effect of manual lymph drainage with ultrasound therapy. The forty-five healthy women of twenties were participated in this study and divided randomly into three groups; manual lymph drainage group (n=15), ultrasound therapy group (n=15) and control group (n=15). Swelling was measured before wearing the high heels (10 cm-height), after one-hour of wearing the high heels, wearing the high heels of one-hour after the intervention of 15 minutes. Also swelling was calculated by using a tape measure, volumeter and body composition analyzer. Statistical analysis of the comparison between the three groups was performed by one-way ANOVA. Also comparison to the mean value in swelling according to the time was performed by repeated measure ANOVA. As the result of this study, a significant changes have emerged within each of manual lymph drainage, ultrasound therapy and control group (p< 0.05). However, there were no significant differences between each group (p> 0.05). But the mean value of manual lymph drainage group showed the tendency of fast recovering before causing swelling. Therefore, we consider that the clinical treatment of manual lymph drainage and ongoing studies will be made since manual lymph drainage is very effective in releasing the leg swelling caused by wearing high heels and standing for a long time at work.

A case of propofol-induced oropharyngeal angioedema and bronchospasm.

Propofol (2,6-diisopropylphenol) is an ultrashort-acting sedative agent with sedative and amnestic effects that is used not only for anesthesia but also for sedation during minor outpatient procedures and endoscopic examinations. Rare cases of anaphylaxis following propofol administration have been reported in the medical literature. Documentation of anaphylaxis is often lacking because the cause and effect relationship is often hard to prove. Only a minority of patients get referred for allergy testing to confirm the offending drug. Here we report a 74-year-old woman who had an anaphylactic reaction with severe oropharyngeal edema and bronchospasm for a few minutes after receiving propofol during endoscopic examination. An allergy skin test was positive for both propofol and soybean. Soybean in the intralipid is one component of propofol, and we concluded that this anaphylaxis was caused by soybean.