Disruption of islet architecture and function.

<p>(A) Hematoxylin and Eosin (H&E) staining and (B) immunofluorescent staining for insulin (red) and glucagon (green) were performed to analyze histopathological changes in the pancreatic islets at the end of study. (C) Islet area was determined from at least 5 different islets per pancreas stained with H&E (n = 4). (D) Pancreatic insulin concentration measured by ELISA (n = 6). V, vehicle; BGE, black ginseng extract; RGE, red ginseng extract. Values represent means ± SEM. *<i>P</i> < 0.05; **<i>P</i> < 0.01.</p

Cytokine-induced toxic signaling in β-cells.

<p>(A) Pancreatic protein expressions of glucose transporter 2 (GLUT2), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor-κB p65 (NF-κB p65), phospho-NF-κB p65 (p-NF-κB p65) and inducible nitric oxide synthase (iNOS) were measured by western blotting (n = 4). (B) Pancreatic mRNA expressions of <i>TNF-α</i>, <i>IL-1β</i>, <i>p65</i> and <i>iNOS</i> (n = 6). (C) Nitrite and (D) thiobarbituric acid reactive substances (TBARS) concentrations in serum (n = 6). TBARS was expressed in terms of malondialdehyde (MDA) equivalents. (E) A potential inhibitory mechanism of STZ-induced β-cell apoptosis by BGE. STZ is taken up by β-cells via GLUT2 and promotes cytokine-initiated apoptotic signaling. BGE may suppress the expressions of IFN-γ, TNF-α and IL-1β, leading to inhibition of the NF-κB pathway and caspase-3 activation, which ultimately protects the β-cells. Solid lines indicate the stimulatory actions by STZ. Dashed lines indicate the inhibitory actions by BGE. V, vehicle; BGE, black ginseng extract; RGE, red ginseng extract. Values represent means ± SEM. *<i>P</i> < 0.05; **<i>P</i> < 0.01.</p

STZ-induced β-cell apoptosis.

<p>(A) TUNEL (green) and (B) active caspase (red) immunofluorescent staining were performed to measure apoptosis in pancreatic islets at the end of study. Arrows indicate cells with positive signals. At least five different islets per pancreas section were counted to calculate the percentage of (C) TUNEL-positive cells or (D) cleaved caspase-3 positive area. (E) Pancreatic protein expressions of total caspase-3 and cleaved caspase-3 were measured by western blotting. V, vehicle; BGE, black ginseng extract; RGE, red ginseng extract. Values represent means ± SEM (n = 4). *<i>P</i> < 0.05; ***<i>P</i> < 0.001.</p

Physiological changes of glucose homeostasis.

<p>Mice received the indicated sample treatments for 5 weeks. Diabetes was induced by multiple (for 5 consecutive days) low-dose (50 mg/kg) intraperitoneal injections of STZ. (A) Time line of the study. (B) Body weights and (C) fed blood glucose during the experimental period. (D) Cumulative incidence of diabetes was calculated as a percentage of hyperglycemic mice (glucose level ≥ 300 mg/dL) at each time point. (E) The ratio of fasting insulin (pg/mL) and glucose (mg/dL) at day 32 was used as an index of insulin deficiency in mice. (F) Glucose concentrations during an oral glucose tolerance test (OGTT), (G) area under the curve (AUC) for glucose, (H) insulin concentrations during OGTT and (I) AUC for insulin. V, vehicle; BGE, black ginseng extract; RGE, red ginseng extract. Values represent means ± SEM (n = 6). *<i>P</i> < 0.05.</p

Defect-Free Copolymer Gate Dielectrics for Gating MoS₂ Transistors

In this study, the poly­(2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane-<i>co</i>-cyclohexyl methacrylate) [p­(V4D4-<i>co</i>-CHMA)] copolymer was developed for use as a gate dielectric in molybdenum disulfide (MoS₂) field-effect transistors (FETs). The p­(V4D4-<i>co</i>-CHMA) copolymer was synthesized via the initiated chemical vapor deposition (<i>i</i>CVD) of two types of monomers: 2,4,6,8-tetramethyl-2,4,6,8-tetravinylcyclotetrasiloxane (V4D4) and cyclohexyl methacrylate (CHMA). Four vinyl groups of V4D4 monomers and cyclohexyl groups of CHMA monomers were introduced to enhance the electrical strength of gate dielectrics through the formation of a highly crosslinked network and to reduce the charge trap densities at the MoS₂–dielectric interface, respectively. The <i>i</i>CVD-grown p­(V4D4-<i>co</i>-CHMA) copolymer films yielded a dielectric constant of 2.3 and a leakage current of 3.8 × 10^–11 A/cm² at 1 MV/cm. The resulting MoS₂ FETs with p­(V4D4-<i>co</i>-CHMA) gate dielectrics exhibited excellent electrical properties, including an electron mobility of 35.1 cm²/V s, a subthreshold swing of 0.2 V/dec, and an on–off current ratio of 2.6 × 10⁶. In addition, the environmental and operational stabilities of MoS₂ FETs with p­(V4D4-<i>co</i>-CHMA) top-gate dielectrics were superior to those of devices with SiO₂ back-gate dielectrics. The use of <i>i</i>CVD-grown copolymer gate dielectrics as demonstrated in this study provides a novel approach to realizing next-generation two-dimensional electronics

Decellularized Matrix Produced by Mesenchymal Stem Cells Modulates Growth and Metabolic Activity of Hepatic Cell Cluster

Miniature organlike three-dimensional cell clusters often called organoids have emerged as a useful tool for both fundamental and applied bioscience studies. However, there is still a great need to improve the quality of organoids to a level where they exhibit similar biological functionality to an organ. To this end, we hypothesized that a decellularized matrix derived from mesenchymal stem cell (MSC) could regulate the phenotypic and metabolic activity of organoids. This hypothesis was examined by culturing cells of interest in the decellularized matrix of MSCs cultured on a 2D substrate at confluency or in the form of spheroids. The decellularized matrix prepared with MSC spheroids showed a 3D porous structure with a higher content of extracellular matrix molecules than the decellularized matrix derived from MSCs cultured on a 2D substrate. HepG2 hepatocarcinoma cells, which retain the metabolic activity of hepatocytes, were cultured in these decellularized matrices. Interestingly, the decellularized matrix from the MSC spheroids served to develop the hepatic cell clusters with higher levels of E-cadherin-mediated cell–cell adhesion and detoxification activity than the decellularized matrix from the MSCs cultured on a 2D substrate. Overall, the results of this study are useful in improving biological functionality of a wide array of organoids

DataSheet_1_Investigating the endocrine disruption effects of four disinfection byproducts on zebrafish estrogen receptor-α.docx

Reports have shown an increase in the use of disinfectants in wastewater treatment plants, prompted by the detection of residual viruses in sewage. However, the release of disinfection byproducts (DBPs) in final effluents has raised concerns about their potential adverse effects, such as endocrine disruption, on aquatic environments. Despite these concerns, few studies have examined the endocrine-disrupting effects of DBPs on fish, which may be vulnerable to DBPs. The aim of this case study was to investigate the endocrine-disrupting properties of four commonly formed DBPs: chloroiodomethane (CIM), dibromochloromethane (DBCM), bromodichloromethane (BDCM), and trichloroacetic acid (TCA) on the estrogen receptor-α in zebrafish (zERα). The results indicated that all four DBPs have high anti-estrogenic activity against zERα; with CIM, BDCM, DBCM, and TCA yielding 80.8%, 78.4%, 49.0%, and 64.1% anti-estrogenic effects on zERα, respectively. Moreover, all DBPs demonstrated negligible estrogenic effects on zERα. Our study sheds new light on the adverse effects of DBPs, particularly the endocrine-disrupting activity of CIM, which, as part of the dihalomethanes group, has received limited research attention in the past. This study shows the molecular interactions in terms of the endocrine disruption of DBP on zERα, warranting further studies to understand the overall impact of fish in affected aquatic ecosystems.</p

Crystal Structure of Human Myotubularin-Related Protein 1 Provides Insight into the Structural Basis of Substrate Specificity

<div><p>Myotubularin-related protein 1 (MTMR1) is a phosphatase that belongs to the tyrosine/dual-specificity phosphatase superfamily. MTMR1 has been shown to use phosphatidylinositol 3-monophosphate (PI(3)P) and/or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P₂) as substrates. Here, we determined the crystal structure of human MTMR1. The refined model consists of the Pleckstrin homology (PH)-GRAM and phosphatase (PTP) domains. The overall structure was highly similar to the previously reported MTMR2 structure. Interestingly, two phosphate molecules were coordinated by strictly conserved residues located in the C(X)₅R motif of the active site. Additionally, our biochemical studies confirmed the substrate specificity of MTMR1 for PI(3)P and PI(3,5)P₂ over other phosphatidylinositol phosphates. Our structural and enzymatic analyses provide insight into the catalytic mechanism and biochemical properties of MTMR1.</p></div

RUE decreases the level of alcohol-induced liver damage markers.

<p>(A) Representative images of hematoxylin & eosin (H&E) staining of liver (200× magnification); (B) Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. All data are presented as the mean ± SEM. (**<i>P</i> < 0.01 vs. control).</p

RUE attenuates alcohol-induced oxidative damages through its antioxidant activity and proposed molecular pathway in liver.

<p>(A) Representative images of 3,3’-diaminobenzidine (DAB) and nitro-tyrosine in the liver tissue (40× magnification). DAB and nitro-tyrosine were used to measure the level of reactive oxygen species (ROS) and reactive nitrogen species, respectively; (B) Representative images of DNA damages measured by Avidin-TRITC staining in the liver tissue (250× magnification). Avidin-TRITC-stained nucleus can be recognized as 8-OH-dG and nucleus were stained with 4’,6-diamino-2-phenylindole (DAPI). Histograms represent the quantification of avidin stained nucleus over the total number of nucleus. Data are presented as the mean ± SEM. (*<i>P</i> < 0.05; ***<i>P</i><0.001 vs. control); (C, D) Representative images of immunohistochemical and immunoblot analyses of lipid peroxidation adducts, 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) (40× magnification). A graph depicting the quantification of the relative abundance of the genes is shown. Data are presented as the mean ± SEM. (*<i>P</i> < 0.05; **<i>P</i><0.01 vs. control); (E) Immunoblot analysis of glutathione disulfide (GSSG); (F) Proposed molecular pathways for the preventive effect of RUE against alcohol-induced liver injury through ROS scavenging.</p