Exploring the influence of women's leadership and corporate governance on operational liquidity: The glass cliff effect.

This research investigates the glass cliff effect and the positions held by women in leadership roles, focusing on their impact on operational liquidity. The study delves into the relationship between corporate governance attributes and operational liquidity in 60 non-financial companies listed on the Pakistan Stock Exchange during Covid-19. Utilizing Quine-McCluskey technique and fuzzy set Qualitative Comparative Analysis (fsQCA), it examines the combined effect of Women on the Board, Board Size, Ownership by Blockholders, Board Qualifications and Busy Directors on Operational Liquidity. The necessary condition analysis (NCA) emphasises that firms can operate without reliance on any particular variable taken in the study. The sufficiency analysis provided an expanded understanding of the three conditions leading to the same outcome both before and during the pandemic. This research highlights the significance of the glass cliff effect and emphasizes the pivotal role of women in effectively managing liquidity during times of crisis. Additionally, it provides valuable insights for policymakers regarding the impact of Covid-19 on the interplay between corporate governance characteristics and operational liquidity.

Physicochemical characterization, rheological properties, and hypolipidemic and antioxidant activities of compound polysaccharides in Chinese herbal medicines by fractional precipitation.

This study aimed to investigate the effects of different compound polysaccharides (CPs) extracted from Folium nelumbinis, Fructus crataegi, Fagopyrum tataricum, Lycium barbarum, Semen cassiae, and Poria cocos (w/w, 2:4:2:1:1.5:1) by gradient ethanol precipitation on the physicochemical properties and biological activities. Three CPs (CP50, CP70, and CP80) were obtained and comprised rhamnose, arabinose, xylose, mannose, glucose, and galactose in different proportions. The CPs contained different amounts of total sugar, uronic acid, and proteins. These also exhibited different physical properties, including particle size, molecular weight, microstructure, and apparent viscosity. Scavenging abilities of 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), 1,1'-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and superoxide radicals of CP80 were more potent compared to those of the other two CPs. Furthermore, CP80 significantly increased serum levels of high-density lipoprotein cholesterol (HDL-C) and lipoprotein lipase (LPL), and hepatic lipase (HL) activity in the liver, while decreasing the serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C), along with LPS activity. Therefore, CP80 may serve as a natural novel lipid regulator in the field of medicinal and functional food.

Monitoring and risk assessment of perchlorate in tea samples produced in China.

Accumulation of potentially perchlorate in tea is a new concern for tea consumers. The information on perchlorate contamination in tea is highly limited. This study aimed to investigate the occurrence and accumulation of perchlorate in tea samples from China and to assess human exposure risks. A total of 288 tea samples collected from 16 provinces of China were tested, and nearly 94.8% of the samples were found to have detectable perchlorate contamination. Concentrations of perchlorate ranged from below LOQ to 1274.3 µg/kg, with a mean value of 294.6 µg/kg. Tea samples collected from Central China had the highest mean perchlorate concentration (403.4 µg/kg). The mean and median perchlorate levels in the dark and black samples were much higher than that of other types of tea samples. After brewing tea, the dissolution rates of perchlorate from the dried tea ranged from 58.9% to 89.2%. For the worst-case scenario, the estimated daily intakes (EDIs) of tea samples in 16 investigated provinces ranged from 25.9 to 157.8 ng/kg bw/day and 29.7-180.7 ng/kg bw/day for male and female respectively, indicating no significant health risks to local residents via tea consumption.

Aflatoxin B1: metabolism, toxicology, and its involvement in oxidative stress and cancer development.

Aflatoxins are a class of carcinogenic mycotoxins produced by Aspergillus fungi, which are widely distributed in nature. Aflatoxin B1 (AFB1) is the most toxic of these compounds and its metabolites have a variety of biological activities, including acute toxicity, teratogenicity, mutagenicity and carcinogenicity, which has been well-characterized to lead to the development of hepatocellular carcinoma (HCC) in humans and animals. This review focuses on the metabolism of AFB1, including epoxidation and DNA adduction, as it concerns the initiation of cancer and the underlying mechanisms. In addition to DNA adduction, inflammation and oxidative stress caused by AFB1 can also participate in the occurrence of cancer. Therefore, the main carcinogenic mechanism of AFB1 related ROS is summarized. This review also describes recent reports of AFB1 exposures in occupational settings. It is hoped that people will pay more attention to occupational health, in order to reduce the incidence of cancer caused by occupational exposure.

An overview of autophagy: Mechanism, regulation and research progress.

Autophagy refers to the formation of autophagosomes by membrane wrapping part of the cytoplasm and the organelles and proteins that need to be degraded in the cells. Autophagosomes are fused with lysosomes to form autophagolysosome, which degrade the contents of the inclusions, to achieve cell homeostasis and organelle renewal. The regulatory mechanism of autophagy is complex, and its upstream signaling pathway mainly involves mTOR dependent pathway and mTOR independent pathway (AMPK, PI3K, Ras-MAPK, p53, PTEN, endoplasmic reticulum stress). Autophagy is a phenomenon of "self-eating" in cells. Apoptosis is a phenomenon of "self-killing". Both of them share the same stimulating factors and regulatory proteins, but the threshold of induction is different. How to transform and coordinate is not clear at present. This paper summarizes the history of autophagy discovery, the structure and function of related molecules, the biological function of autophagy, the regulatory mechanism and the research results of the relationship between autophagy and apoptosis.

IFN-gamma down-regulates ABCA1 expression by inhibiting LXRalpha in a JAK/STAT signaling pathway-dependent manner.

Interferon gamma (IFN-gamma) is an immunomodulatory and anti-microbial cytokine, which has a variety of proatherogenic effects. It has been reported that IFN-gamma can down-regulate ABCA1 expression. However, its mechanism is elusive. In the present study, we have investigated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux in THP-1 macrophage-derived foam cells. IFN-gamma decreased ABCA1 expression at both transcriptional and translational levels in a dose-dependent manner. Cellular cholesterol content was increased while cholesterol efflux was decreased by IFN-gamma treatment. Liver X receptor alpha (LXRalpha), which can regulate the expression of ABCA1, was also down-regulated by IFN-gamma treatment. LXRalpha-specific activation by LXRalpha agonist almost compensated the down-regulation of ABCA1 expression by IFN-gamma, while siRNA of LXRalpha led to down-regulation of ABCA1 expression more significantly than IFN-gamma. IFN-gamma induced phosphorylation of STAT1 and expression of STAT1alpha in the nucleus, which was inhibited by a JAK inhibitor AG-490. Treatment with STAT1 siRNA further enhanced down-regulation of LXRalpha mRNA by IFN-gamma. Furthermore, AG-490 and STAT1 siRNA almost compensated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux. In conclusion, IFN-gamma may first down-regulate expression of LXRalpha through the JAK/STAT1 signaling pathway and then decrease expression of ABCA1 and cholesterol efflux in THP-1 macrophage-derived foam cells. Therefore, our study may be useful in understanding the critical effect of IFN-gamma in pathogenesis of atherosclerosis.

Liver X receptor agonist T0901317 reduces atherosclerotic lesions in apoE-/- mice by up-regulating NPC1 expression.

In this study, we studied the effect of liver X receptor (LXR) agonist T0901317 on Niemann-Pick C1 protein (NPC1) expression in apoE-/- mice. Male apoE-/- mice were randomized into 4 groups, baseline group (n=10), control group (n = 14), treatment group (n = 14) and prevention group (n = 14). All of the mice were fed with a high-fat/high-cholesterol (HFHC) diet containing 15% fat and 0.25% cholesterol. The baseline group treated with vehicle was sacrificed after 8 weeks of the diet. The control group and the prevention group were treated with either vehicle or T0901317 daily by oral gavage for 14 weeks. The treatment group was treated with vehicle for 8 weeks, and then was treated with the agonist T0901317 for additional 6 weeks. Gene and protein expression was analyzed by real-time quantitative PCR, immunohistochemistry and Western blotting, respectively. Plasma lipid concentrations were measured by commercially enzymatic methods. We used RNA interference technology to silence NPC1 gene expression in THP-1 macrophage-derived foam cells and then detected the effect of LXR agonist T0901317 on cholesterol efflux. Plasma triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and apoA-I concentrations were markedly increased in T0901317-treated groups. T0901317 treatment reduced the aortic atherosclerotic lesion area by 64.2% in the prevention group and 58.3% in the treatment group. LXR agonist treatment increased NPC1 mRNA expression and protein levels in the small intestine, liver and aorta of apoE-/- mice. Compared with the normal cells, cholesterol efflux of siRNA THP-1 macrophage-derived foam cells was significantly decreased, whereas cholesterol efflux of LXR agonist T0901317-treated THP-1 macrophage-derived foam cells was significantly increased. Our results suggest that LXR agonist T0901317 inhibits atherosclerosis development in apoE-/- mice, which is related to up-regulating NPC1 expression.

The effect of T0901317 on ATP-binding cassette transporter A1 and Niemann-Pick type C1 in apoE-/- mice.

Although a range of studies indicated Liver X receptor (LXR) activation inhibited the development of atherosclerosis in animal models, the mechanism of this effect for LXR agonists has not been fully understood. A recent study has suggested LXR activators increased the amount of free cholesterol in the plasma membrane of human macrophages by inducing Niemann-Pick type C1 (NPC1) gene expression. Therefore, we hypothesize that LXRs may also promote NPC1 expression in vivo. Here we investigated the effect of a synthetic LXR agonist T0901317 on ATP-binding cassette transporter A1 (ABCA1) and NPC1 in apolipoprotein E knockout (apoE-/-) mice. Male apoE-/- mice were randomized into four groups: baseline group (n = 10), vehicle group (n = 14), prevention group (n = 14), and treatment group (n = 14). En face analysis and Oil red O staining were used to examine the aortic atherosclerotic lesions. Macrophage content of aortic root atherosclerotic lesions and cholesterol efflux form peritoneal macrophages were measured. Gene and protein expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting, respectively. T0901317 treatment reduced aortic atherosclerotic lesion area by 64.2% in prevention group (P < 0.001) and 58.3% in treatment group (P < 0.001) and resulted in a reduction in macrophage content. Plasma triglyceride, total cholesterol, high-density lipoprotein cholesterol, and apoA-I concentrations were markedly increased in T0901317-treated groups. T0901317 also promoted ABCA1 and NPC1 gene and protein levels in the aorta, liver, and small intestine of apoE-/- mice and significantly increased cholesterol efflux from peritoneal macrophages. T0901317 upregulates ABCA1 and NPC1. This study gives us a new insight into the mechanism for antiatherogenic effect of LXR synthetic agonists.

Synthetic liver X receptor agonist T0901317 inhibits semicarbazide-sensitive amine oxidase gene expression and activity in apolipoprotein E knockout mice.

Semicarbazide-sensitive amine oxidase (SSAO) catalyzes oxidative deamination of primary aromatic and aliphatic amines. Increased SSAO activity has been found in atherosclerosis and diabetes mellitus. We hypothesize that the anti-atherogenic effect of liver X receptors (LXRs) might be related to the inhibition of SSAO gene expression and its activity. In this study, we investigated the effect of LXR agonist T0901317 on SSAO gene expression and its activity in apolipoprotein E knockout (apoE(-/-)) mice. Male apoE(-/-) mice (8 weeks old) were randomly divided into four groups: basal control group; vehicle group; prevention group; and treatment group. SSAO gene expression was analyzed by real-time quantitative polymerase chain reaction and its activity was determined. The activity of superoxide dismutase and content of malondialdehyde in the aorta and liver were also determined. In T0901317-treated mice, SSAO gene expression was significantly decreased in the aorta, liver, small intestine, and brain. SSAO activities in serum and in these tissues were also inhibited. The amount of superoxide dismutase in the aorta and liver of the prevention group and treatment group was significantly higher compared with the vehicle group (P<0.05). Malondialdehyde in the tissues of these two groups was significantly lower compared with the vehicle group (P<0.05). Our results showed that T0901317 inhibits SSAO gene expression and its activity in atherogenic apoE(-/-) mice. The atheroprotective effect of LXR agonist T0901317 is related to the inhibition of SSAO gene expression and its activity.

Effect of T0901317 on hepatic proinflammatory gene expression in apoE-/- mice fed a high-fat/high-cholesterol diet.

OBJECTIVE: In present study, we employed cDNA-based microarray technique to investigate the effect of a synthetic LXR ligand T0901317 on hepatic gene expression of proinflammatory cytokines in apolipoprotein E knockout mice fed an atherogenic diet. METHODS AND RESULTS: Male 8-week-old apoE-/- mice were randomly divided into four groups, baseline group, vehicle group, prevention group and treatment group. All of the mice were fed a high-fat/high-cholesterol diet with or without LXR agonist T0901317 for 8 or 14 weeks. Gene array analysis found 17 atherosclerosis-related genes with a 2- to 8-fold difference in expression level between vehicle-treated group and T0901317-treated group. It induced mRNA expression of proinflammatory cytokine tumor necrosis factor (TNF), but inhibited gene expression of several other proinflammatory cytokines including interleukin (IL)-1alpha, IL-6, and IL-7 in the liver. C-reactive protein, TNF, matrix metalloproteinase-9, IL-1alpha, IL-6, and IL-7 were verified by real-time quantitative PCR. Next, enzyme-linked immunosorbent assay analyses showed up-regulation of TNFalpha levels and down-regulation of IL-alpha, IL-6, IL-7 levels in plasma sample. CONCLUSION: The synthetic LXR agonist T0901317 has paradoxical roles in hepatic gene expression of proinflammatory cytokines in apoE-/- mice.