Peroxisomes account for ~35% of total H2O2 generation in mammalian tissues. Peroxisomal ACOX1 (acyl‐CoA oxidase 1) is the first and rate‐limiting enzyme in fatty acid β‐oxidation and a major producer ...of H2O2. ACOX1 dysfunction is linked to peroxisomal disorders and hepatocarcinogenesis. Here, we show that the deacetylase sirtuin 5 (SIRT5) is present in peroxisomes and that ACOX1 is a physiological substrate of SIRT5. Mechanistically, SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation in both cultured cells and mouse livers. Deletion of SIRT5 increases H2O2 production and oxidative DNA damage, which can be alleviated by ACOX1 knockdown. We show that SIRT5 downregulation is associated with increased succinylation and activity of ACOX1 and oxidative DNA damage response in hepatocellular carcinoma (HCC). Our study reveals a novel role of SIRT5 in inhibiting peroxisome‐induced oxidative stress, in liver protection, and in suppressing HCC development.
Synopsis
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
SIRT5 is localized in peroxisomes where it controls H2O2 metabolism.
SIRT5‐mediated desuccinylation inhibits ACOX1 activity by suppressing its active dimer formation.
SIRT5 downregulation increases ACOX1 activity and oxidative DNA damage response in HCC.
This study reveals a role for SIRT5 in regulating peroxisomal H2O2 and ROS homeostasis and indicates its potential function in liver protection and hepatocellular carcinoma suppression.
•The highest algal lipid content of 63.65% was obtained at 10 μg L−1 Tl+treatment.•Microalgae can remove 100% of Tl+at a concentration range of 0–25 μg L−1.•NO played an essential role in regulating ...lipid accumulation in microalgae.•NO was involved in antioxidant defense system to regulate the ROS level.•Extra NO donor SNP improved lipid synthesis and GSH content in microalgae.
Thallium (Tl+) is a trace metal with extreme toxicity and is highly soluble in water, posing a great risk to ecological and human safety. This work aimed to investigate the role played by Tl+ in regulating lipid accumulation in microalgae and the removal efficiency of Tl+. The effect of Tl+ on the cell growth, lipid production and Tl+ removal efficiency of Parachlorella kessleri R-3 was studied. Low concentrations of Tl+ had no significant effect on the biomass of microalgae. When the Tl+ concentration exceeded 5 μg L−1, the biomass of microalgae showed significant decrease. The highest lipid content of 63.65% and lipid productivity of 334.55 mg L−1 d−1 were obtained in microalgae treated with 10 and 5 μg L−1 Tl+, respectively. Microalgae can efficiently remove Tl+ and the Tl+ removal efficiency can reach 100% at Tl+ concentrations of 0–25 μg L−1. The maximum nitric oxide (NO) level of 470.48 fluorescence intensity (1 × 106 cells)−1 and glutathione (GSH) content of 343.51 nmol g−1 (fresh alga) were obtained under 5 μg L−1 Tl+ stress conditions. Furthermore, the exogenous donor sodium nitroprusside (SNP) supplemented with NO was induced in microalgae to obtain a high lipid content (59.99%), lipid productivity (397.99 mg L−1 d−1) and GSH content (430.22 nmol g−1 (fresh alga)). The corresponding analysis results indicated that NO could participate in the signal transduction pathway through modulation of reactive oxygen species (ROS) signaling to activate the antioxidant system by increasing the GSH content to eliminate oxidative damage induced by Tl+ stress. In addition, NO regulation of ROS signaling may enhance transcription factors associated with lipid synthesis, which stimulates the expression of genes related to lipid synthesis, leading to increased lipid biosynthesis in microalgae. Moreover, it was found that the change in Tl+ had little effect on the fatty acid components and biodiesel properties. This study showed that Tl+ stress can promote lipid accumulation in microalgae for biodiesel production and simultaneously effectively remove Tl+, which provided evidence that NO was involved in signal transduction and antioxidant defense, and improved the understanding of the interrelation between NO and ROS to regulate lipid accumulation in microalgae.
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Hydroxide exchange membrane fuel cells offer possibility of adopting platinum-group-metal-free catalysts to negotiate sluggish oxygen reduction reaction. Unfortunately, the ultrafast hydrogen ...oxidation reaction (HOR) on platinum decreases at least two orders of magnitude by switching the electrolytes from acid to base, causing high platinum-group-metal loadings. Here we show that a nickel-molybdenum nanoalloy with tetragonal MoNi
phase can catalyze the HOR efficiently in alkaline electrolytes. The catalyst exhibits a high apparent exchange current density of 3.41 milliamperes per square centimeter and operates very stable, which is 1.4 times higher than that of state-of-the-art Pt/C catalyst. With this catalyst, we further demonstrate the capability to tolerate carbon monoxide poisoning. Marked HOR activity was also observed on similarly designed WNi
catalyst. We attribute this remarkable HOR reactivity to an alloy effect that enables optimum adsorption of hydrogen on nickel and hydroxyl on molybdenum (tungsten), which synergistically promotes the Volmer reaction.
Chronic liver injury can cause cirrhosis and impaired liver regeneration, impairing organ function. Adult livers can regenerate in response to parenchymal insults, and multiple cellular sources have ...been reported to contribute to this response. In this study, we modeled human chronic liver injuries, in which such responses are blunted, without genetic manipulations, and assessed potential contributions of non-parenchymal cells (NPCs) to hepatocyte regeneration. We show that NPC-derived hepatocytes replenish a large fraction of the liver parenchyma following severe injuries induced by long-term thioacetamide (TAA) or 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) treatment. Through lineage tracing of biliary epithelial cells (BECs), we show that BECs are a source of new hepatocytes and gain an Hnf4α+CK19+ bi-phenotypic state in periportal regions and fibrotic septa. Bi-phenotypic cells were also detected in cirrhotic human livers. Together, these data provide further support for hepatocyte regeneration from BECs without genetic interventions and show their cellular plasticity during severe liver injury.
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•Non-parenchymal cells produce hepatocytes in response to severe liver injuries•Biliary epithelial cells (BECs) are a source for hepatocyte regeneration•BECs convert into hepatocytes through an Hnf4α+CK19+ bi-phenotypic state
Understanding cellular sources of hepatocyte regeneration is critical for developing effective therapies for chronic liver diseases. Xie and colleagues show that severe liver injuries can, without genetic interventions, induce biliary epithelial cells to significantly contribute to hepatocyte regeneration through direct lineage conversion.
Background & Aims
In about 20% of children with cholestasis and normal or low serum gamma‐glutamyltransferase (GGT) activity, no aetiology is identified. We sought new genes implicated in paediatric ...hepatobiliary disease.
Methods
We conducted whole‐exome sequencing in 69 children evaluated at our centre from 2011 to 2018 who had low‐GGT cholestasis and in whom homozygous/compound heterozygous predictedly pathogenic variants (PPVs) in ATP8B1, ABCB11, NR1H4, MYO5B or TJP2 were not found. Clinical records and findings on light microscopy and transmission electron microscopy of liver biopsy materials were reviewed.
Results
In seven patients from seven unrelated families, biallelic PPVs (10 in total) were found in USP53, recently associated with intrahepatic cholestasis. Seven variants were classified as pathogenic: one canonical splicing, c.569 + 2T > C, and six nonsense or frameshifting: c.169C > T (p.Arg57Ter), c.581delA (p.Arg195GlufsTer38), c.831_832insAG (p.Val279GlufsTer16), c.1012C > T (p.Arg338Ter), c.1426C > T (p.Arg476Ter) and c.1558C > T (p.Arg520Ter). Three were likely pathogenic: c.297G > T (p.Arg99Ser), c.395A > G (p.His132Arg) and c.878G > T (p.Gly293Val). In all patients, jaundice began at age <7 months. Cholestasis was transient, with documented resolution of hyperbilirubinaemia in all (oldest patient now aged 5 years) except one, who was lost to follow‐up. Light microscopy identified intralobular cholestasis, giant‐cell change of hepatocytes and perisinusoidal‐perihepatocytic and portal‐tract fibrosis. Ultrastructural study revealed elongated hepatocyte‐hepatocyte tight junctions. One patient was deaf.
Conclusion
USP53 interacts with the tight junction constituent TJP2. TJP2 mutation can cause low‐GGT intrahepatic cholestasis, with elongated hepatocyte‐hepatocyte tight junctions, as well as deafness. Our findings extend a preliminary report of USP53 disease and indicate that USP53 mutation may generate a partial phenocopy of TJP2 disease.
We report a one-step fabrication of macroscopic multifunctional graphene-based hydrogels with robust interconnected networks under the synergistic effects of the reduction of graphene oxide sheets by ...ferrous ions and in situ simultaneous deposition of nanoparticles on graphene sheets. The functional components, such as α-FeOOH nanorods and magnetic Fe3O4 nanoparticles, can be easily incorporated with graphene sheets to assemble macroscopic graphene monoliths just by control of pH value under mild conditions. Such functional graphene-based hydrogels exhibit excellent capability for removal of pollutants and, thus, could be used as promising adsorbents for water purification. The method presented here is proved to be versatile to induce macroscopic assembly of reduced graphene sheets with other functional metal oxides and thus to access a variety of graphene-based multifunctional nanocomposites in the form of macroscopic hydrogels or aerogels.
•Waste activated sludge extracts can be effectively used to produce algal lipids.•Temperature significantly affected the growth and lipid synthesis of microalgae.•The highest lipid content of 59.13 % ...was obtained at temperature of 10 °C.•Multi-omics revealed the mechanism of temperature in algal lipid synthesis.•Several genes for lipogenesis, antioxidants, and autophagy were upregulated.
Waste activated sludge (WAS) as one of the major pollutants with a significant annual production, has garnered significant attention regarding its treatment and utilization. If improperly discharged, it not only caused environmental pollution but also led to the wastage of valuable resources. In this study, the microalgae growth and lipid accumulation using waste activated sludge extracts (WASE) under different temperature conditions were investigated. The highest lipid content (59.13%) and lipid productivity (80.41 mg L−1 d−1) were obtained at cultivation temperatures of 10 and 25 °C, respectively. It was found that microalgae can effectively utilize TN/TP/NH4+-N and other nutrients of WASE. The highest utilization rates of TP, TN and NH4+-N were achieved at a cultivation temperature of 10 °C, reaching 84.97, 77.49 and 92.32%, respectively. The algal fatty acids had carbon chains predominantly ranging from C14 to C18, making them suitable for biodiesel production. Additionally, a comprehensive analysis of transcriptomics and metabolomics revealed up-regulation of genes associated with triglyceride assembly, the antioxidant system of algal cells, and cellular autophagy, as well as the accumulation of metabolites related to the tricarboxylic acid (TCA) cycle and lipids. This study offers novel insights into the microscopic mechanisms of microalgae culture using WASE and approaches for the resource utilization of sludge.
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Microalgae have been proposed as a potential renewable energy source for biofuel production. However, owing to the low biomass concentration and lipid productivity, the sustainable and industrialized ...production of microalgae biofuels is still limited. New lipid improvement strategies have appeared at the technology forefront to overcome the bottlenecks. This review comprehensively illustrates the stress-induced strategies of recent studies and achievements in promoting the lipid accumulation of microalgae. Different stress-induced strategies for improving lipid production such as the use of phytohormone, change of cultivation strategies, combined chemical additives and abiotic stresses (nutrient stress, metal ions and wastewater, etc.) are addressed. After a comprehensive analysis, it is shown that the use of phytohormone combined with abiotic stress under two-stage culture condition is a promising stress-induced strategy to promote the microalgae lipid accumulation. Furthermore, the possible mechanisms of using phytohormone and abiotic stress to enhance the microalgae lipid biosynthesis are discussed. This review is dedicated to further accelerate the sustainable development and practical application of microalgae-based biofuel production.
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