Effect of GDM Pairing on PEMFC Performance in Flow-Through and Dead-Ended Anode Mode.

Asymmetric gas diffusion media (GDM) pairing, which feature distinct GDM at the anode and cathode of the proton electrolyte membrane fuel cell (PEMFC), enhance water management compared to symmetric pairing of GDM (anode and cathode GDM are identical). An asymmetric pairing of Freudenberg GDM (H24C3 at anode and H23C2 at cathode) reduces ohmic resistances by up to 40% and oxygen transport resistances by 14% en route to 25% higher current density in dry gas flows. The asymmetric GDM pairing effectively hydrates the membrane electrode assembly (MEA) while minimizing liquid water saturation in the cathode compared to a commonly used symmetric GDM pairing of SGL 29BC at the anode and cathode. Superior water management observed with asymmetric GDM in flow-through mode is also realized in dead-ended anode (DEA) mode. Compared to the symmetric GDM pairing, the asymmetric GDM pairing with Freudenberg GDM increases cell voltage at all current densities, extends and stabilizes steady-state voltage behavior, slows voltage decay, and vastly reduces the frequency of anode purge events. These results support that the asymmetric Freudenberg GDM combination renders the PEMFC less prone to anode water saturation and performance loss from the anticipated increase in water back-diffusion during DEA mode operation.

Fabrication Method for Laboratory-Scale High-Performance Membrane Electrode Assemblies for Fuel Cells.

Custom catalyst-coated membranes (CCMs) and membrane electrode assemblies (MEAs) are necessary for the evaluation of advanced electrocatalysts, gas diffusion media (GDM), ionomers, polymer electrolyte membranes (PEMs), and electrode structures designed for use in next-generation fuel cells, electrolyzers, or flow batteries. This Feature provides a reliable and reproducible fabrication protocol for laboratory scale (10 cm2) fuel cells based on ultrasonic spray deposition of a standard Pt/carbon electrocatalyst directly onto a perfluorosulfonic acid PEM.

Autophagic signaling promotes systems-wide remodeling in skeletal muscle upon oncometabolic stress by D2-HG.

OBJECTIVES: Cachexia is a metabolic disorder and comorbidity with cancer and heart failure. The syndrome impacts more than thirty million people worldwide, accounting for 20% of all cancer deaths. In acute myeloid leukemia, somatic mutations of the metabolic enzyme isocitrate dehydrogenase 1 and 2 cause the production of the oncometabolite D2-hydroxyglutarate (D2-HG). Increased production of D2-HG is associated with heart and skeletal muscle atrophy, but the mechanistic links between metabolic and proteomic remodeling remain poorly understood. Therefore, we assessed how oncometabolic stress by D2-HG activates autophagy and drives skeletal muscle loss. METHODS: We quantified genomic, metabolomic, and proteomic changes in cultured skeletal muscle cells and mouse models of IDH-mutant leukemia using RNA sequencing, mass spectrometry, and computational modeling. RESULTS: D2-HG impairs NADH redox homeostasis in myotubes. Increased NAD+ levels drive activation of nuclear deacetylase Sirt1, which causes deacetylation and activation of LC3, a key regulator of autophagy. Using LC3 mutants, we confirm that deacetylation of LC3 by Sirt1 shifts its distribution from the nucleus into the cytosol, where it can undergo lipidation at pre-autophagic membranes. Sirt1 silencing or p300 overexpression attenuated autophagy activation in myotubes. In vivo, we identified increased muscle atrophy and reduced grip strength in response to D2-HG in male vs. female mice. In male mice, glycolytic intermediates accumulated, and protein expression of oxidative phosphorylation machinery was reduced. In contrast, female animals upregulated the same proteins, attenuating the phenotype in vivo. Network modeling and machine learning algorithms allowed us to identify candidate proteins essential for regulating oncometabolic adaptation in mouse skeletal muscle. CONCLUSIONS: Our multi-omics approach exposes new metabolic vulnerabilities in response to D2-HG in skeletal muscle and provides a conceptual framework for identifying therapeutic targets in cachexia.

ATP-dependent citrate lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling of the Heart.

Background: Metabolic remodeling is a hallmark of the failing heart. Oncometabolic stress during cancer increases the activity and abundance of the ATP-dependent citrate lyase (ACL, Acly ), which promotes histone acetylation and cardiac adaptation. ACL is critical for the de novo synthesis of lipids, but how these metabolic alterations contribute to cardiac structural and functional changes remains unclear. Methods: We utilized human heart tissue samples from healthy donor hearts and patients with hypertrophic cardiomyopathy. Further, we used CRISPR/Cas9 gene editing to inactivate Acly in cardiomyocytes of MyH6-Cas9 mice. In vivo, positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to the loss of ACL. We conducted a multi-omics analysis using RNA-sequencing and mass spectrometry-based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. Results: Here, we show that in mice, ACL drives metabolic adaptation in the heart to sustain contractile function, histone acetylation, and lipid modulation. Notably, we show that loss of ACL increases glucose oxidation while maintaining fatty acid oxidation. Ex vivo isotope tracing experiments revealed a reduced efflux of glucose-derived citrate from the mitochondria into the cytosol, confirming that citrate is required for reductive metabolism in the heart. We demonstrate that YAP inactivation facilitates ACL deficiency. Computational flux analysis and integrative multi-omics analysis indicate that loss of ACL induces alternative isocitrate dehydrogenase 1 flux to compensate. Conclusions: This study mechanistically delineates how cardiac metabolism compensates for suppressed citrate metabolism in response to ACL loss and uncovers metabolic vulnerabilities in the heart.

Products of SO2 adsorption on fuel cell electrocatalysts by combination of sulfur K-edge XANES and electrochemistry.

Electrochemical adsorption of SO(2) on platinum is complicated by the change in sulfur oxidation state with potential. Here, we attempt to identify SO(2) adsorption products on catalyst coated membranes (CCMs) at different electrode potentials using a combination of in situ sulfur K-edge XANES (X-ray absorption near-edge structure) spectroscopy and electrochemical techniques. CCMs employed platinum nanoparticles supported on Vulcan carbon (Pt/VC). SO(2) was adsorbed from a SO(2)/N(2) gas mixture while holding the Pt/VC-electrode potential at 0.1, 0.5, 0.7, and 0.9 V vs a reversible hydrogen electrode (RHE). Sulfur adatoms (S(0)) are identified as the SO(2) adsorption products at 0.1 V, while mixtures of S(0), SO(2), and sulfate/bisulfate ((bi)sulfate) ions are suggested as SO(2) adsorption products at 0.5 and 0.7 V. At 0.9 V, SO(2) is completely oxidized to (bi)sulfate ions. The identity of adsorbed SO(2) species on Pt/VC catalysts at different electrode potentials is confirmed by modeling of XANES spectra using FEFF8 and a linear combination of experimental spectra from sulfur standards. Results on SO(2) speciation gained from XANES are used to compare platinum-sulfur electronic interactions for Pt(3)Co/VC versus Pt/VC catalysts in order to understand the difference between the two catalysts in terms of SO(2) contamination.