Low-Temperature Production of Genuinely Amorphous Carbon from Highly Reactive Nanoacetylide Precursors

Copper acetylide is a well-known explosive compound. However, when the size of it crystals is reduced to the nanoscale, its explosive nature is lost, owing to a much lower thermal conductance that inhibits explosive chain reactions. This less explosive character can be exploited for the production of new carbon materials. Generally, amorphous carbon is prepared by carbonization of organic compounds exposed to high temperature, which can induce partial crystallization in graphite. In this work, we present a new method in which the carbonization reaction can proceed at a lower annealing temperature (under 150°C) owing to the highly reactive nature of copper acetylide, thus avoiding crystallization processes and enabling the production of genuinely amorphous carbon materials

Identification of DJ-1-Associated Regions on Human Genes from SH-SY5Y Cells using Chromatin Immunoprecipitation Sequence Technique

DJ-1, a cancer- and Parkinson’s disease-associated protein, works as a coactivator to various transcription factors. In this study, DNA fragments that bind to DJ-1 complexes were obtained by a chromatin immunoprecipitation sequencing with an anti-human DJ-1 antibody using chromatin from SH-SY5Y cells. We identified 60 different sequences as potential DJ-1 complex-binding sites in genes. Of sequences identified, expression levels of DJ-1-associated sitecontaining genes for DNA polymerase N, estrogen receptor α and S-adenosylhomocysteine hydrolase like-2 were decreased in DJ-1-knockdown cells and in 6-OHDA-treated cells. These studies suggest that DJ-1 regulates the expression of versatile genes at the transcriptional level and that some of the genes are regulated by DJ-1 in an oxidative status-dependent manne

Co-occurrence of Estrogenic and Antiestrogenic Activities in Wastewater: Quantitative Evaluation of Balance by <i>in Vitro</i> ERα Reporter Gene Assay and Chemical Analysis

Endocrine-disrupting chemicals are exogenous substances that alter the function of the endocrine system, with adverse health effects on organisms or their progeny. <i>In vitro</i> estrogen receptor (ER) reporter gene assays have long been used to measure estrogenic activity in wastewater. Nevertheless, there is still uncertainty about their usefulness in environmental monitoring on account of a discrepancy between the estrogenic response of the <i>in vitro</i> assay and concentrations of estrogenic compounds determined by chemical analysis. Here, we measured estrogenic and antiestrogenic activities in wastewater by ERα reporter gene assay. All samples were simultaneously analyzed for estrone, 17β-estradiol, estriol, and 17α-ethynylestradiol, and the concentrations were used to predict estrogenic activity. All samples in which measured estrogenic activity was significantly lower than predicted showed strong antiestrogenic activity. In addition, we confirmed that the fraction that did not have antiestrogenic activity showed stronger estrogenic activity than the unfractionated wastewater extract. These results indicate that antiestrogenic compounds in wastewater suppress the activity of natural estrogens, and the reporter gene assay represents the net activity

Evaluation of Estrogenic Activity of Wastewater: Comparison Among In Vitro ERα Reporter Gene Assay, In Vivo Vitellogenin Induction, and Chemical Analysis

The in vitro estrogen receptor (ER) reporter gene assay has long been used to measure estrogenic activity in wastewater. In a previous study, we demonstrated that the assay represents net estrogenic activity in the balance between estrogenic and antiestrogenic activities in wastewater. However, it remained unclear whether the net estrogenic activity measured by the in vitro ERα reporter gene assay can predict the in vivo estrogenic effect of wastewater. To determine this, we measured the following: estrogenic and antiestrogenic activities of wastewater and reclaimed water by the in vitro ERα reporter gene assay, expression of <i>vitellogenin-1</i> (<i>vtg1</i>) and <i>choriogenin-H</i> (<i>chgH</i>) in male medaka (<i>Oryzias latipes</i>) by quantitative real-time PCR, and estrone, 17β-estradiol, estriol, and 17α-ethynylestradiol concentrations chemically to predict estrogenic activity. The net estrogenic activity measured by the in vitro medaka ERα reporter gene assay predicted the in vivo <i>vtg1</i>/<i>chgH</i> expression in male medaka more accurately than the concentrations of estrogens. These results also mean that in vivo <i>vtg1</i>/<i>chgH</i> expression in male medaka is determined by the balance between estrogenic and antiestrogenic activities. The in vitro medaka ERα reporter gene assay also predicted in vivo <i>vtg1</i>/<i>chgH</i> expression on male medaka better than the human ERα reporter gene assay

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (&gt;90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting