Effects of CEO water shortage experience and power intensity on corporate water performance - Evidence from China.

Corporate water performance and sustainable development are currently vital focus areas for scholars. Therefore, this paper investigates the experience of Chief Executive Officers (CEOs) with water shortage influences corporate water performance by focusing on listed companies in water-intensive and high-water-risk industries in China between 2014 and 2019. This paper manually collected information relative to the cities and provinces where CEOs grew up to evaluate their early exposure to water shortages. Furthermore, this paper develops an evaluation scale, based on the Enterprise Water Conservation Evaluation Guide (GB/T 7119-2006), to compute the enterprise water management practices scores. These results will constitute the enterprise water performance evaluation score. Moreover, this paper focuses on CEOs who have experienced water resource shortages through a positive impact on the water resource performance of their companies. As for the findings, they demonstrate that CEOs who grew up in regions with higher water scarcity have a more pronounced positive effect on their water shortage experience through corporate water performance. Furthermore, CEO power intensity positively moderates the relationship between the CEO's water shortage experience and corporate water resource performance. Further investigation reveals generational differences in the impact of CEO water shortage experience on company water performance. CEOs, who grew up during periods with a higher incidence of droughts, demonstrate a more significant promoting effect on corporate water performance. To sum up, this study expands the understanding of factors influencing corporate water resource performance and deepens the knowledge of the early life experiences of CEOs.

Study on the Metabolic Transformation Rule of Enrofloxacin Combined with Tilmicosin in Laying Hens.

There is often abuse of drugs in livestock and poultry production, and the improper use of drugs leads to the existence of a low level of residues in eggs, which is a potential threat to human safety. Enrofloxacin (EF) and tilmicosin (TIM) are regularly combined for the prevention and treatment of poultry diseases. The current studies on EF or TIM mainly focus on a single drug, and the effects of the combined application of these two antibiotics on EF metabolism in laying hens are rarely reported. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the residual EF and TIM in laying hens and to investigate the effect of TIM on the EF metabolism in laying hens. In this paper, we first establish a method that can detect EF and TIM simultaneously. Secondly, the results showed that the highest concentration of EF in the egg samples was 974.92 ± 441.71 µg/kg on the 5th day of treatment. The highest concentration of EF in the egg samples of the combined administration group was 1256.41 ± 226.10 µg/kg on the 5th day of administration. The results showed that when EF and TIM were used in combination, the residue of EF in the eggs was increased, the elimination rate of EF was decreased, and the half-life of EF was increased. Therefore, the use of EF and TIM in combination should be treated with greater care and supervision should be strengthened to avoid risks to human health.

NRF-2α and mitophagy underlie enhanced mitochondrial functions and biogenesis induced by T-2 toxin in GH3 cells.

T-2 toxin is a natural contaminant in grain cereals produced by species of Fusarium. Studies indicate that T-2 toxin can positively affect mitochondrial function, but the underlying mechanism is unclear. In this study, we examined the role of nuclear respiratory factor 2α (NRF-2α) in T-2 toxin-activated mitochondrial biogenesis and the direct target genes of NRF-2α. Furthermore, we investigated T-2 toxin-induced autophagy and mitophagy, and the role of mitophagy in changes in mitochondrial function and apoptosis. It was found that T-2 toxin significantly increased NRF-2α levels and nuclear localization of NRF-2α was induced. NRF-2α deletion significantly increased the production of reactive oxygen species (ROS), abrogated T-2 toxin-induced increases in ATP and mitochondrial complex I activity, and inhibited the mitochondrial DNA copy number. Meanwhile, With chromatin immunoprecipitation sequencing (ChIP-Seq), various novel NRF-2α target genes were identified, such as mitochondrial iron-sulphur subunits (Ndufs 3,7) and mitochondrial transcription factors (Tfam, Tfb1m, and Tfb2m). Some target genes were also involved in mitochondrial fusion and fission (Drp1), mitochondrial translation (Yars2) and splicing (Ddx55), and mitophagy. Further studies showed that T-2 toxin induced Atg5 dependent autophagy and Atg5/PINK1-dependent mitophagy. In addition, mitophagy defects increase ROS production, inhibit ATP levels and the expression of genes related to mitochondrial dynamics, and promote apoptosis in the presence of T-2 toxins. Altogether, these results suggest that NRF-2α plays a critical role in promoting mitochondrial function and biogenesis through regulation of mitochondrial genes, and, interestingly, mitophagy caused by T-2 toxin positively affected mitochondrial function and protected cell survival against T-2 toxin.

Cytochrome P450 enzymes mediated by DNA methylation is involved in deoxynivalenol-induced hepatoxicity in piglets.

Deoxynivalenol (DON) is an inevitable contaminant in animal feed and can lead to liver damage, then decreasing appetite and causing growth retardation in piglets. Although many molecular mechanisms are related to hepatoxicity caused by DON, few studies have been done on cytochrome P450 (CYP450) enzymes and DNA methylation. To explore the role of CYP450 enzymes and DNA methylation in DON-induced liver injury, male piglets were fed a control diet, or diet containing 1.0 or 3.0 mg/kg DON for 4 weeks. DON significantly raised the activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamyl transpeptidase (GGT) (P < 0.01), leading to liver injury. In vivo study found that DON exposure increased the expression of CYP450 enzymes (such as CYP1A1, CYP2E1, CYP3A29) (P < 0.05), and disturbed the expression of nicotinamide N-methyltransferase (NNMT), galanin-like peptide (GALP) and insulin-like growth factor 1 (IGF-1) (P < 0.05), in which DNA methylation affected the expression of these genes. In vitro study (human normal hepatocytes L02) further proved that DON elevated the expression of CYP1A1, CYP2E1 and CYP3A4 (P < 0.05), and inhibited cell growth in a dose-dependent manner, resulting in cell necrosis. More importantly, knockdown of CYP1A1 or CYP2E1 could alleviate DON-induced growth inhibition by promoting IGF-1 expression. Taken together, increased CYP450 enzymes expression was one of the mechanisms of hepatoxicity and growth inhibition induced by DON, suggesting that the decrease of CYP450 enzymes can antagonize the hepatoxicity in animals, which provides some value for animal feed safety.

Oxidative Stress and Metabolism: A Mechanistic Insight for Glyphosate Toxicology.

Glyphosate (GLYP) is a widely used pesticide; it is considered to be a safe herbicide for animals and humans because it targets 5-enolpyruvylshikimate-3-phosphate synthase. However, there has been increasing evidence that GLYP causes varying degrees of toxicity. Moreover, oxidative stress and metabolism are highly correlated with toxicity. This review provides a comprehensive introduction to the toxicity of GLYP and, for the first time, systematically summarizes the toxicity mechanism of GLYP from the perspective of oxidative stress, including GLYP-mediated oxidative damage, changes in antioxidant status, altered signaling pathways, and the regulation of oxidative stress by exogenous substances. In addition, the metabolism of GLYP is discussed, including metabolites,metabolic pathways, metabolic enzymes, and the toxicity of metabolites. This review provides new ideas for the toxicity mechanism of GLYP and proposes effective strategies for reducing its toxicity.

Metabolic Disposition and Elimination of Tritum-Labeled Sulfamethoxazole in Pigs, Chickens and Rats.

Sulfamethoxazole (SMZ), as a sulfa antibiotic, is often used in the treatment of various infectious diseases in animal husbandry. At present, SMZ still has many unresolved problems in the material balance, metabolic pathways, and residual target tissues in food animals. Therefore, in order to solve these problems, the metabolism, distribution, and elimination of SMZ is investigated in pigs, chickens, and rats by radioactive tracing methods, and the residue marker and target tissue of SMZ in food animals were determined, providing a reliable basis for food safety. After a single administration of [3H]-SMZ (rats and pigs by intramuscular injection and chickens by oral gavage), the total radioactivity was rapidly excreted, with more than 93% of the dose excreted within 14 days in the three species. Pigs and rats had more than 75% of the administered volume recovered by urine. After 7 days of continuous administration, within the first 6 h, radioactivity was found in almost all tissues. The highest radioactivity and longest persistence in pigs was in the liver, while in chickens it was in the liver and kidneys, most of which was removed within 14 days. A total of six, three and three metabolites were found in chickens, rats and pigs, respectively. N4-acetyl-sulfamethoxazole (S1) was the main metabolite of SMZ in rats, pigs and chickens. The radioactive substance with the longest elimination half-life is sulfamethoxazole (S0), so S0 was suggested to be the marker residue in pigs and chickens.

Metabolism and Mechanism of Human Cytochrome P450 Enzyme 1A2.

Human cytochrome P450 enzyme 1A2 (CYP1A2) is one of the most important cytochrome P450 (CYP) enzymes in the liver, accounting for 13% to 15% of hepatic CYP enzymes. CYP1A2 metabolises many clinical drugs, such as phenacetin, caffeine, clozapine, tacrine, propranolol, and mexiletine. CYP1A2 also metabolises certain precarcinogens such as aflatoxins, mycotoxins, nitrosamines, and endogenous substances such as steroids. The regulation of CYP1A2 is influenced by many factors. The transcription of CYP1A2 involves not only the aromatic hydrocarbon receptor pathway but also many additional transcription factors, and CYP1A2 expression may be affected by transcription coactivators and compression factors. Degradation of CYP1A2 mRNA and protein, alternative splicing, RNA stability, regulatory microRNAs, and DNA methylation are also known to affect the regulation of CYP1A2. Many factors can lead to changes in the activity of CYP1A2. Smoking, polycyclic aromatic hydrocarbon ingestion, and certain drugs (e.g., omeprazole) increase its activity, while many clinical drugs such as theophylline, fluvoxamine, quinolone antibiotics, verapamil, cimetidine, and oral contraceptives can inhibit CYP1A2 activity. Here, we review the drugs metabolised by CYP1A2, the metabolic mechanism of CYP1A2, and various factors that influence CYP1A2 metabolism. The metabolic mechanism of CYP1A2 is of great significance in the development of personalised medicine and CYP1A2 target-based drugs.

Targeting peroxisome proliferator-activated receptors: A new strategy for the treatment of cardiac fibrosis.

Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life, and health and causes huge economic losses. Increasing evidence has shown that peroxisome proliferator-activated receptors (PPARs) can regulate the progression of cardiac fibrosis. For the first time, this review systematically summarizes the literature on cardiac fibrosis from the perspective of PPARs from 2010 to 2020. Moreover, the role of each PPARs in cardiac fibrosis was clarified in this scientific revision from the perspectives of pharmacologically active substances, known agonists, natural extract compounds, and nucleic-acid-based drugs in different CVD models. Furthermore, the combination of multiple PPARs on the treatment of cardiac fibrosis is discussed. This scientific review provides new ideas for targeting PPARs in the treatment of cardiac fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against cardiac fibrosis based on PPAR activity.

Mequindox induces apoptosis, DNA damage, and carcinogenicity in Wistar rats.

Mequindox (MEQ) is a synthetic antibacterial agent. Recent studies showed that MEQ and its primary metabolites exhibit strong genotoxicity to mammalian cells, and MEQ induced carcinogenicity in mice. These findings suggest that chronic exposure to MEQ could lead to an increased risk of cancer later in life. In the present study, four groups of Wistar rats (55 rats/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for 2 years. The results showed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive systems, were the main targets for MEQ. Liver toxicity mediated by MEQ was associated with apoptosis and the nuclear factor κB (NF-κB) signaling pathway. In addition, MEQ increased the incidence of tumors in rats. Phosphorylated histone H2AX (γ-H2AX) is identified as a biomarker of cellular response to DNA double-strand breaks (DSB). Our data demonstrated that γ-H2AX expression was significantly increased in tumors. Thus, high levels of DSB might be responsible for carcinogenesis in rats, and further investigation is absolutely required to clarify the exact molecular mechanisms for carcinogenicity caused by MEQ in vivo.

Statins: Adverse reactions, oxidative stress and metabolic interactions.

Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, are currently the most effective lipid-lowering drugs, effectively reducing the plasma total cholesterol and low-density lipoprotein, while also decreasing three triacylglycerols and increasing plasma high-density lipoprotein to a certain extent. However, the excessive or long-term use of statins can cause in vitro cytotoxicity, in vivo liver injury, liver necrosis, kidney damage, and myopathy in both human beings and animals. Many studies indicate that oxidative stress is involved in the various toxicities associated with statins, and various antioxidants have been evaluated to investigate their protective roles against statin-induced liver, kidney, and muscle toxicities. Widespread attention has been given to statin-induced oxidative stress, with and without the use of other drugs. Much of the information about the mechanism for this reduction comes from cell culture and in experimental animal studies. The primary focus of this article is to summarize the research progress associated with oxidative stress as a plausible mechanism for statin-induced toxicity, as well as its metabolic interactions. This review summarizes the research conducted over the past five years into the production of reactive oxygen species, oxidative stress as a result of statin treatments, and their correlation with statin-induced toxicity and metabolism. Statin-induced metabolism involves various CYP450 enzymes, which provide potential sites for statin-induced oxidative stress, and these metabolic factors are also reviewed. The therapeutics of a variety of compounds against statin-induced organ damage based on their anti-oxidative effects is also discussed to further understand the role of oxidative stress in statin-induced toxicity. This review sheds new light on the critical roles of oxidative stress in statin-induced toxicity and prevention of this oxidative damage, as well as on the contradictions and unknowns that still exist regarding statin toxicity and the cellular effects in terms of organ injury and cell signaling pathways.

Mequindox-Induced Kidney Toxicity Is Associated With Oxidative Stress and Apoptosis in the Mouse.

Mequindox (MEQ), belonging to quinoxaline-di-N-oxides (QdNOs), is a synthetic antimicrobial agent widely used in China. Previous studies found that the kidney was one of the main toxic target organs of the QdNOs. However, the mechanisms underlying the kidney toxicity caused by QdNOs in vivo still remains unclear. The present study aimed to explore the molecular mechanism of kidney toxicity in mice after chronic exposure to MEQ. MEQ led to the oxidative stress, apoptosis, and mitochondrial damage in the kidney of mice. Meanwhile, MEQ upregulated Bax/Bcl-2 ratio, disrupted mitochondrial permeability transition pores, caused cytochrome c release, and a cascade activation of caspase, eventually induced apoptosis. The oxidative stress mediated by MEQ might led to mitochondria damage and apoptosis in a mitochondrial-dependent apoptotic pathway. Furthermore, upregulation of the Nrf2-Keap1 signaling pathway was also observed. Our findings revealed that the oxidative stress, mitochondrial dysfunction, and the Nrf2-Keap1 signaling pathway were associated with the kidney apoptosis induced by MEQ in vivo.

The implications of dust ice nuclei effect on cloud top temperature in a complex mesoscale convective system.

Mineral dust is the most important natural source of atmospheric ice nuclei (IN) which may significantly mediate the properties of ice cloud through heterogeneous nucleation and lead to crucial impacts on hydrological and energy cycle. The potential dust IN effect on cloud top temperature (CTT) in a well-developed mesoscale convective system (MCS) was studied using both satellite observations and cloud resolving model (CRM) simulations. We combined satellite observations from passive spectrometer, active cloud radar, lidar, and wind field simulations from CRM to identify the place where ice cloud mixed with dust particles. For given ice water path, the CTT of dust-mixed cloud is warmer than that in relatively pristine cloud. The probability distribution function (PDF) of CTT for dust-mixed clouds shifted to the warmer end and showed two peaks at about -45 °C and -25 °C. The PDF for relatively pristine cloud only show one peak at -55 °C. Cloud simulations with different microphysical schemes agreed well with each other and showed better agreement with satellite observations in pristine clouds, but they showed large discrepancies in dust-mixed clouds. Some microphysical schemes failed to predict the warm peak of CTT related to heterogeneous ice formation.