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Abstract Central metabolism is organised through high‐flux, Nicotinamide Adenine Dinucleotide (NAD⁺/NADH) and NADP⁺/NADPH systems operating at near equilibrium. As oxygen is indispensable for aerobic organisms, these systems are also linked to the levels of reactive oxygen species, such as H₂O₂, and through H₂O₂to the regulation of macromolecular structures and activities, via kinetically controlled sulphur switches in the redox proteome. Dynamic changes in H₂O₂production, scavenging and transport, associated with development, growth and responses to the environment are, therefore, linked to the redox state of the cell and regulate cellular function. These basic principles form the ‘redox code’ of cells and were first defined by D. P. Jones and H. Sies in 2015. Here, we apply these principles to plants in which recent studies have shown that they can also explain cell‐to‐cell and even plant‐to‐plant signalling processes. The redox code is, therefore, an integral part of biological systems and can be used to explain multiple processes in plants at the subcellular, cellular, tissue, whole organism and perhaps even community and ecosystem levels. As the environmental conditions on our planet are worsening due to global warming, climate change and increased pollution levels, new studies are needed applying the redox code of plants to these changes. 

Abstract BackgroundCardiac pathological outcome of metabolic remodeling is difficult to model using cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) due to low metabolic maturation. MethodshiPSC-CM spheres were treated with AMP-activated protein kinase (AMPK) activators and examined for hiPSC-CM maturation features, molecular changes and the response to pathological stimuli. ResultsTreatment of hiPSC-CMs with AMPK activators increased ATP content, mitochondrial membrane potential and content, mitochondrial DNA, mitochondrial function and fatty acid uptake, indicating increased metabolic maturation. Conversely, the knockdown of AMPK inhibited mitochondrial maturation of hiPSC-CMs. In addition, AMPK activator-treated hiPSC-CMs had improved structural development and functional features—including enhanced Ca²⁺transient kinetics and increased contraction. Transcriptomic, proteomic and metabolomic profiling identified differential levels of expression of genes, proteins and metabolites associated with a molecular signature of mature cardiomyocytes in AMPK activator-treated hiPSC-CMs. In response to pathological stimuli, AMPK activator-treated hiPSC-CMs had increased glycolysis, and other pathological outcomes compared to untreated cells. ConclusionAMPK activator-treated cardiac spheres could serve as a valuable model to gain novel insights into cardiac diseases. 

Abstract Primary sclerosing cholangitis (PSC) is a complex bile duct disorder. Its etiology is incompletely understood, but environmental chemicals likely contribute to risk. Patients with PSC have an altered bile metabolome, which may be influenced by environmental chemicals. This novel study utilized state-of-the-art high-resolution mass spectrometry (HRMS) with bile samples to provide the first characterization of environmental chemicals and metabolomics (collectively, the exposome) in PSC patients located in the United States of America (USA) (n = 24) and Norway (n = 30). First, environmental chemical- and metabolome-wide association studies were conducted to assess geographic-based similarities and differences in the bile of PSC patients. Nine environmental chemicals (false discovery rate, FDR < 0.20) and 3143 metabolic features (FDR < 0.05) differed by site. Next, pathway analysis was performed to identify metabolomic pathways that were similarly and differentially enriched by the site. Fifteen pathways were differentially enriched (P < .05) in the categories of amino acid, glycan, carbohydrate, energy, and vitamin/cofactor metabolism. Finally, chemicals and pathways were integrated to derive exposure–effect correlation networks by site. These networks demonstrate the shared and differential chemical–metabolome associations by site and highlight important pathways that are likely relevant to PSC. The USA patients demonstrated higher environmental chemical bile content and increased associations between chemicals and metabolic pathways than those in Norway. Polychlorinated biphenyl (PCB)-118 and PCB-101 were identified as chemicals of interest for additional investigation in PSC given broad associations with metabolomic pathways in both the USA and Norway patients. Associated pathways include glycan degradation pathways, which play a key role in microbiome regulation and thus may be implicated in PSC pathophysiology.