High-carbohydrate diets (HCD) can induce the occurrence of nonalcoholic fatty liver disease (NAFLD), characterized by dramatic accumulation of hepatic lipid droplets (LDs). However, the potential ...molecular mechanisms are still largely unknown. In this study, we investigated the role of autophagy in the process of HCD-induced changes of hepatic lipid metabolism, and to examine the process of underlying mechanisms during these molecular contexts. We found that HCD significantly increased hepatic lipid accumulation and activated autophagy. Using primary hepatocytes, we found that HG increased lipid accumulation and stimulated the release of NEFA by autophagy-mediated lipophagy, and that lipophagy significantly alleviated high glucose (HG)-induced lipid accumulation. Oxidative and endoplasmic reticulum (ER) stress pathways played crucial regulatory roles in HG-induced lipophagy activation and HG-induced changes of lipid metabolism. Further investigation found that HG-activated lipophagy and HG-induced changes of lipid metabolism were via enhancing carbohydrate response element-binding protein (ChREBP) DNA binding capacity at PPARγ promoter region, which in turn induced transcriptional activation of the key genes related to lipogenesis and autophagy. The present study, for the first time, revealed the novel mechanism for lipophagy mediating HCD-induced changes of lipid metabolism by oxidative stress and ER stress, and ChREBP/PPARγ pathways. Our study provided innovative evidence for the direct relationship between carbohydrate and lipid metabolism via ChREBP/PPARγ pathway.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Oxytetracycline (OTC) and Cu are prevalent in aquatic ecosystems and their pollution are issues of serious concern. The present working hypothesis is that the toxicity of Cu and OTC mixture on ...physiological activity of fish was different from single OTC and Cu alone. The present study indicated that, compared to single OTC or Cu alone, Cu+OTC mixture reduced growth performance and feed utilization of grass carp, escalated the contents of Cu, OTC and TG, increased lipogenesis, induced oxidative stress, damaged the mitochondrial structure and functions and inhibited the lipolysis in the liver tissues and hepatocytes of grass carp. Cu+OTC co-treatment significantly increased the mRNA abundances and protein expression of Nrf2. Moreover, we found that Cu+OTC mixture-induced oxidative stress promoted Nrf2 recruitment to the SREBP-1 promoter and increased SREBP-1-mediated lipogenesis; Nrf2 sited at the crossroads of oxidative stress and lipid metabolism, and mediated the regulation of oxidative stress and lipid metabolism. Our findings clearly indicated that OTC and Cu mixture differed in environmental risks from single antibiotic or metal element itself, and thus posed different toxicological responses to aquatic animals. Moreover, our findings suggested that Nrf2 functioned as an important antioxidant regulator linking oxidative stress to lipogenic metabolism, and thus elucidated a novel regulatory mechanism for lipid metabolism.
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•Cu+OTC escalated TG content by up-regulating lipogenesis and inhibiting lipolysis.•Cu+OTC induced oxidative stress, damaged mitochondrial structure and functions.•Cu+OTC increased Nrf2 expression and promoted Nrf2 recruitment to SREBP-1 promoter.•Cu+OTC increased TG content via Nrf2-SREBP-1 pathway activated by oxidative stress.•Nrf2 sited at crossroad of oxidative stress and lipid metabolism induced by Cu+OTC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A simple and efficient visible‐light‐promoted selenylation/cyclization of enaminones have been realized for the practical synthesis of 3‐selanyl‐4H‐chromen‐4‐ones. This reaction is performed in the ...mild conditions, no transition metal catalyst or photocatalysts and no additional oxidants are required. In addition, the 3‐selanyl‐4H‐chromen‐4‐ones could be easily converted to selanyl‐functionalized pyrimidines by reacting with benzamidine substrates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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•Berberine was timely and comprehensively reviewed against five metabolic diseases.•Graphically displayed the main targets and signaling pathways of berberine therapy.•Detailed ...summary of clinical trials of berberine in treating five metabolic diseases.•Berberine has demonstrated good therapeutic effects on five metabolic diseases.
The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds to treat metabolic diseases. Berberine (BBR), an important quaternary benzylisoquinoline alkaloid, exists in many traditional medicinal plants. In recent years, BBR has received widespread attention due to its good potential in the treatment of metabolic diseases. In order to promote the basic research and clinical application of BBR, this review provides a timely and comprehensive summary of the pharmacological and clinical advances of BBR in the treatment of five metabolic diseases, including type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease, hyperlipidemia, and gout. Both animal and clinical studies have proved that BBR has good therapeutic effects on these five metabolic diseases. The therapeutic effects of BBR are based on regulating various metabolic aspects and pathophysiological procedures. For example, it can promote insulin secretion, improve insulin resistance, inhibit lipogenesis, alleviate adipose tissue fibrosis, reduce hepatic steatosis, and improve gut microbiota disorders. Collectively, BBR may be a good and promising drug candidate for the treatment of metabolic diseases. More studies, especially clinical trials, are needed to further confirm its molecular mechanisms and targets. In addition, large-scale, long-term and multi-center clinical trials are necessary to evaluate the efficacy and safety of BBR in the treatment of these metabolic diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The study was conducted to determine the effects of three dietary Se sources, such as sodium-selenite (S-S), seleno-yeast (S-Y) and seleno-methionine (S-M), on Se concentration, glutathione ...peroxidase (GPX) and TXNRD activities, and mRNA expression of fifteen representative selenoproteins, and protein expression of four endoplasmic reticulum-resided selenoproteins in a wide range of tissues of yellow catfish. Compared with S-S and S-M groups, dietary S-Y significantly decreased growth performance and feed utilisation of yellow catfish. Dietary Se sources significantly influenced Se contents in the spleen, dorsal muscle and the kidney, GPX activities in spleen, kidney, intestine, muscle and mesenteric fat, and TXNRD activities in the heart, intestine and mesenteric fat. Among ten tested tissues, dietary Se sources influenced mRNA expression of GPX4 and SELENOK in three tissues; GPX3, SELENOS and TXNRD2 in four tissues; SELENOF, SELENON and DIO2 in five tissues; SELENOM, GPX1/2 and TXNRD3 in six tissues; SELENOW in seven tissue and SELENOP and SELENOT in eight tissues. Based on these observations above, S-S and S-M seem to be suitable Se sources for improving growth performance and feed utilisation of yellow catfish. Dietary Se sources differentially influence the expression of selenoproteins in various tissues of yellow catfish. For the first time, we determined the expression of selenoproteins in fish in responses to dietary Se sources, which contributes to a better understanding of the functions and regulatory mechanisms of selenoporteins.
Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one ...important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α (accα), fatty acid synthase (fas) and stearoyl-CoA desaturase 1 (scd1)) in a freshwater teleost, grass carp Ctenopharyngodon idella. We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp-1, accα, scd1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp-1 promoter activity, increased scd1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp-1, fas and scd1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp-1 mRNA expression and up-regulated miR-29 mRNA expression. The 3'UTR of srebp-1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp-1 3'UTR and srebp-1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.
The wide use of perfluorooctane sulfonate (PFOS) has led to increasing concern about its human health risks over the past decade. In vivo and in vitro studies are important and effective means to ...ascertain the toxic effects of PFOS on humans and its toxic mechanisms. This article systematically reviews the human health risks of PFOS based on the currently known facts found by in vivo and in vitro studies from 2008 to 2018. Exposure to PFOS has caused hepatotoxicity, neurotoxicity, reproductive toxicity, immunotoxicity, thyroid disruption, cardiovascular toxicity, pulmonary toxicity, and renal toxicity in laboratory animals and many in vitro human systems. These results and related epidemiological studies confirmed the human health risks of PFOS, especially for exposure via food and drinking water. Oxidative stress and physiological process disruption based on fatty acid similarity were widely studied mechanisms of PFOS toxicity. Future research for assessing the human health risks of PFOS is recommended in the chronic toxicity and molecular mechanisms, the application of various omics, and the integration of toxicological and epidemiological data.
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•Assessing human health risks of PFOS by in vivo and in vitro studies are reviewed.•Exposure to PFOS can cause significant human health risks.•The chronic toxicity and molecular mechanisms need further study.•Integration of the toxicological and epidemiological data is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lipid metabolism could be used as a biomarker for environmental monitoring of metal pollution, including Cu. Given the potential role of the Wnt/β-catenin signaling pathway and acetylation in lipid ...metabolism, the aim of this study was to investigate the mechanism of Wnt signaling and acetylation mediating Cu-induced lipogenesis. Grass carp Ctenopharyngodon idella, widely distributed freshwater teleost, were used as the model. We found that waterborne Cu exposure increased the accumulation of Cu and lipid, up-regulated lipogenesis, suppressed Wnt signaling, reduced β-catenin protein level and its nuclear location, reduced the sirt1 mRNA levels and up-regulated the β-catenin acetylation level. Further investigation found that Cu up-regulated lipogenesis through Wnt/β-catenin pathway; Cu regulated the β-catenin acetylation, and K311 was the key acetylated residue after Cu incubation. SIRT1 mediated Cu-induced changes of acetylated β-catenin and played an essential role in nuclear accumulation of β-catenin and Cu-induced lipogenesis. Cu facilitated lipid accumulation via the regulation of Wnt pathway by SIRT1. For the first time, our study uncovered the novel mechanism for Wnt/β-catenin pathway and β-catenin acetylation levels mediating Cu-induced lipid deposition, which provided insights into the association between Cu exposure and lipid metabolism in fish and had important environmental implications for monitoring metal pollution in the water by using new biomarkers involved in lipid metabolism.
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•Cu exposure increased lipid deposition and up-regulated lipogenesis of grass carp.•Wnt/β-catenin signal and its acetylation mediated Cu-induced change of lipogenesis.•SIRT1 mediated Cu-induced change of β-catenin acetylation and its localization.•Cu facilitated lipid accumulation via the regulation of Wnt signaling by SIRT1.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
As a newly emerging class of porous materials, covalent organic frameworks (COFs) have attracted much attention due to their intriguing structural merits (
e.g.
, total organic backbone, tunable ...porosity and predictable structure). However, the insoluble and unprocessable features of bulk COF powder limit their applications. To overcome these limitations, considerable efforts have been devoted to exploring the fabrication of COF thin films with controllable architectures, which open the door for their novel applications. In this critical review, we aim to provide the recent advances in the fabrication of COF thin films not only supported on substrates but also as free-standing nanosheets
via
both bottom-up and top-down strategies. The bottom-up strategy involves solvothermal synthesis, interfacial polymerization, room temperature vapor-assisted conversion, and synthesis under continuous flow conditions; whereas, the top-down strategy involves solvent-assisted exfoliation, self-exfoliation, mechanical delamination, and chemical exfoliation. In addition, the applications of COF thin films including energy storage, semiconductor devices, membrane-separation, sensors, and drug delivery are summarized. Finally, to accelerate further research, a personal perspective covering their synthetic strategies, mechanisms and applications is presented.
This review presents a comprehensive summary of the synthesis and applications of covalent organic framework thin films.
To increase the energy density of supercapacitors to approach that of batteries, the current research is always directed towards the cathode materials, whereas the anode materials are rarely studied. ...In the present work, single-crystalline Fe2O3 nanoparticles directly grown on graphene hydrogels are investigated as high performance anode materials for supercapacitors. During the formation of the graphene/Fe2O3 composite hydrogels, flexible graphene sheets decorated with Fe2O3 particles are self-assembled to form interconnected porous microstructures with high specific surface area, which strongly facilitate charge and ion transport in the full electrode. Infrared spectra show that hydrogen bond is formed between C–OH on graphene hydrogels and Fe2O3. Benefits from the combined graphene hydrogels and Fe2O3 particles in such a unique structure are that the graphene/Fe2O3 composite electrode exhibits an ultrahigh specific capacitance of 908Fg−1 at 2Ag−1 within the potential range from −1.05 to −0.3V, and an outstanding rate capability (69% capacity retention at 50Ag−1). Furthermore, the cycling performance is clearly much better for the graphene/Fe2O3 composite hydrogels than that for pure Fe2O3 sample. These findings open a new pathway to the design and fabrication of three-dimensional graphene hydrogel composites as anode materials in the development of high-performance energy-storage systems.
Three-dimensional graphene/Fe2O3 composite hydrogels show ultrahigh specific capacitance and outstanding rate capability. Display omitted
•Flexible graphene sheets decorated with Fe2O3 particles are self-assembled to form interconnected porous microstructures.•IR spectra show intramolecular hydrogen bonding is formed in grapheme/Fe2O3 composite hydrogels.•Graphene/Fe2O3 composite electrode exhibits ultrahigh specific capacitance of 908Fg−1 at 2Ag−1 within the potential range from −1.05 to −0.3V, and outstanding rate capability (69% capacity retention at 50Ag−1).•Cycling performance is clearly much better for the graphene/Fe2O3 composite hydrogels than for pure Fe2O3 sample.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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