Does ownership concentration affect corporate environmental responsibility engagement? The mediating role of corporate leverage

This paper examines the effect of ownership concentration on engagement in corporate environmental responsibility (CER) in time and spatial dimensions. The time dimension focuses on the macroeconomic environment, in particular, periods of rapid and moderate-speed economic growth. The spatial dimension focuses on industry characteristics and different types of ownership (state or private). Further, it explores the mediating role of corporate leverage using panel regression models and stepwise regression with a sample of Chinese A-share listed companies over the period 2008–2016. The results show that ownership concentration has a significantly negative effect on CER. In addition, when we consider the macroeconomic growth rate, ownership type, and industry characteristics, the effect is heterogeneous. In periods with rapid economic growth, ownership concentration has a significantly negative effect on CER whereas it is not significant in a period with moderate economic growth. Further, the negative effect exists at state-owned and non-state-owned companies and at non-heavy-polluting industries. Corporate leverage has a partial mediating effect between ownership concentration and engagement in CER

GABA Coordinates with Insulin in Regulating Secretory Function in Pancreatic INS-1 β-Cells

Pancreatic islet β-cells produce large amounts of γ-aminobutyric acid (GABA), which is co-released with insulin. GABA inhibits glucagon secretion by hyperpolarizing α-cells via type-A GABA receptors (GABAARs). We and others recently reported that islet β-cells also express GABAARs and that activation of GABAARs increases insulin release. Here we investigate the effects of insulin on the GABA-GABAAR system in the pancreatic INS-1 cells using perforated-patch recording. The results showed that GABA produces a rapid inward current and depolarizes INS-1 cells. However, pre-treatment of the cell with regular insulin (1 µM) suppressed the GABA-induced current (IGABA) by 43%. Zinc-free insulin also suppressed IGABA to the same extent of inhibition by regular insulin. The inhibition of IGABA occurs within 30 seconds after application of insulin. The insulin-induced inhibition of IGABA persisted in the presence of PI3-kinase inhibitor, but was abolished upon inhibition of ERK, indicating that insulin suppresses GABAARs through a mechanism that involves ERK activation. Radioimmunoassay revealed that the secretion of C-peptide was enhanced by GABA, which was blocked by pre-incubating the cells with picrotoxin (50 µM, p<0.01) and insulin (1 µM, p<0.01), respectively. Together, these data suggest that autocrine GABA, via activation of GABAARs, depolarizes the pancreatic β-cells and enhances insulin secretion. On the other hand, insulin down-regulates GABA-GABAAR signaling presenting a feedback mechanism for fine-tuning β-cell secretion

Role of Organic Cation Transporter 1, OCT1 in the Pharmacokinetics and Toxicity of cis-Diammine(pyridine)chloroplatinum(II) and Oxaliplatin in Mice

PurposeThe goal of this study was to test the hypothesis that by controlling intracellular uptake, organic cation transporter 1, Oct1 is a key determinant of the disposition and toxicity of cis-diammine(pyridine)chloroplatinum(II)(CDPCP) and oxaliplatin.MethodsPharmacokinetics, tissue accumulation and toxicity of CDPCP and oxaliplatin were compared between Oct1-/- and wild-type mice.ResultsAfter intravenous administration, hepatic and intestinal accumulation of CDPCP was 2.7-fold and 3.9-fold greater in Oct1 wild-type mice (p &lt; 0.001). Deletion of Oct1 resulted in a significantly decreased clearance (0.444 ± 0.0391 ml/min*kg versus 0.649 ± 0.0807 ml/min*kg in wild-type mice, p &lt; 0.05) and volume distribution (1.90 ± 0.161 L/kg versus 3.37 ± 0.196 L/kg in wild-type mice, p &lt; 0.001). Moreover, Oct1 deletion resulted in more severe off-target toxicities in CDPCP-treated mice. Histologic examination of the liver and measurements of liver function indicated that the level of hepatic toxicity was mild and reversible, but was more apparent in the wild-type mice. In contrast, the effect of Oct1 on the pharmacokinetics and toxicity of oxaliplatin in the mice was minimal.ConclusionsOur study suggests that Oct1 plays an important role in the pharmacokinetics, tissue distribution and toxicity of CDPCP, but not oxaliplatin

Impact of Oil Financialization on Oil Price Fluctuation: A Perspective of Heterogeneity

A large number of studies have confirmed that oil speculation has played a vital role in oil price fluctuation in recent years. However, the heterogeneous impact of oil financialization on oil price fluctuation has not received enough attention. Based on time series data from January 1990 to October 2021, this paper adopts the Time-Varying Parameter Vector Auto-Regression (TVP-VAR) model and the Ensemble Empirical Mode Decomposition (EEMD) method to study the heterogeneous impact of oil financialization on oil price fluctuation from three perspectives: different periods, different frequencies, and different time points of major events. The research results are as follows. First, the impact of oil financialization on oil price fluctuation in different periods is heterogeneous in terms of fluctuation amplitude and intensity. During major events such as the financial crisis or the COVID pandemic, the impact of oil financialization on oil price fluctuation is volatile and intense. Second, the impact of oil financialization on the oil price fluctuation of different frequencies is mainly reflected in the direction and duration. Oil financialization mainly promotes high-frequency oil price fluctuation in the short term, and it mainly suppresses low-frequency oil price fluctuation in the long term. Third, the impact of oil financialization on oil price fluctuation is heterogeneous in terms of duration, intensity, and transmission speed at different time points of major events

Impact of Oil Financialization on Oil Price Fluctuation: A Perspective of Heterogeneity

A large number of studies have confirmed that oil speculation has played a vital role in oil price fluctuation in recent years. However, the heterogeneous impact of oil financialization on oil price fluctuation has not received enough attention. Based on time series data from January 1990 to October 2021, this paper adopts the Time-Varying Parameter Vector Auto-Regression (TVP-VAR) model and the Ensemble Empirical Mode Decomposition (EEMD) method to study the heterogeneous impact of oil financialization on oil price fluctuation from three perspectives: different periods, different frequencies, and different time points of major events. The research results are as follows. First, the impact of oil financialization on oil price fluctuation in different periods is heterogeneous in terms of fluctuation amplitude and intensity. During major events such as the financial crisis or the COVID pandemic, the impact of oil financialization on oil price fluctuation is volatile and intense. Second, the impact of oil financialization on the oil price fluctuation of different frequencies is mainly reflected in the direction and duration. Oil financialization mainly promotes high-frequency oil price fluctuation in the short term, and it mainly suppresses low-frequency oil price fluctuation in the long term. Third, the impact of oil financialization on oil price fluctuation is heterogeneous in terms of duration, intensity, and transmission speed at different time points of major events

Synthesis and antiproliferative activities of thioxoflavonoids on three human cancer cells

<p>Two series of fifteen novel thioxoflavonoids <b>2a-2h</b> and <b>4a-4g</b> were synthesized from corresponding flavonoids <b>1a-1h</b> and <b>3a-3g</b> by reacting with Lawesson’s reagent, respectively. Their <i>in vitro</i> antiproliferative activities were evaluated on a panel of three human cancer cell lines (Hela, HCC1954 and SK-OV-3) using cell counting kit-8 (CCK-8) assay. The results showed that most of the target compounds exhibited moderate to good antiproliferative activities against the three human cancer cell lines. In particular, thioxoflavonoids <b>2f</b> and <b>2g</b> showed the strongest antiproliferative activity on all three human cancer cell lines with IC₅₀ values ranging from 3.34 to 4.67 μM, <b>4f</b> showed the best antiproliferative activity on Hela cells (IC₅₀ 2.30 μM), <b>2e</b> showed the best antiproliferative activity on HCC1954 cells (IC₅₀ 2.13 μM) and SK-OV-3 cells (IC₅₀ 2.33 μM). The antiproliferative activities may be involved in their antioxidant activity, which can be speculated by their ability to scavenge free radicals and by their capacity of affecting key redox enzymes.</p

Procyanidin improves experimental colitis by regulating macrophage polarization

Background: Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. Purpose: Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. Methods: In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. Results: The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. Conclusions: This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases