Electron Transport Pathways Research Articles

Oxidation of Biogenic U(IV) in the Presence of Bioreduced Clay Minerals and Organic Ligands.

Bioreduction of soluble U(VI) to sparingly soluble U(IV) is proposed as an effective approach to remediating uranium contamination. However, the stability of biogenic U(IV) in natural environments remains unclear. We conducted U(IV) reoxidation experiments following U(VI) bioreduction in the presence of ubiquitous clay minerals and organic ligands. Bioreduced Fe-rich nontronite (rNAu-2) and Fe-poor montmorillonite (rSWy-2) enhanced U(IV) oxidation through shuttling electrons between oxygen and U(IV). Ethylenediaminetetraacetic acid (EDTA), citrate, and siderophore desferrioxamine B (DFOB) promoted U(IV) oxidation via complexation with U(IV). In the presence of both rNAu-2 and EDTA, the rate of U(IV) oxidation was between those in the presence of rNAu-2 and EDTA, due to a clay/ligand-induced change of U(IV) speciation. However, the rate of U(IV) oxidation in other combinations of reduced clay and ligands was higher than their individual ones because both promoted U(IV) oxidation. Unexpectedly, the copresence of rNAu-2/rSWy-2 and DFOB inhibited U(IV) oxidation, possibly due to (1) blockage of the electron transport pathway by DFOB, (2) inability of DFOB-complexed Fe(III) to oxidize U(IV), and (3) stability of the U(IV)-DFOB complex in the clay interlayers. These findings provide novel insights into the stability of U(IV) in the environment and have important implications for the remediation of uranium contamination.

VO2/CNTs thick cathode electrode with multi-dimensional electron transport pathways enabled by rolling for high energy thermal batteries

Increasing the thickness of cathode electrodes is a promising strategy for improving the specific energy of thermal batteries. However, this approach also introduces challenges related to electron transfer kinetics and discharge performance due to the extended electron transport distance. In this study, a novel approach combining the rolling process and carbon thermal reduction was employed to construct the VO2/CNTs cathode powders with multi-dimensional electron transport pathways. A quasi-two-dimensional structure inside VO2/CNTs electrode materials is constructed by the rolling process, enabling the formation of additional electronic transmission channels, and enhancing the structural stability during discharge. As a result, VO2/CNTs thick electrodes with 0.4 g have a remarkable specific capacity with 350.96 mAh g−1, which is the highest value in contrast to the thick electrodes with grinding and ball milling. Even the electrode mass is increased to 1.0 g, it still exhibits a high specific capacity with 316.89 mAh g−1. This approach holds promise for the development of low-cost, sustainable thick electrodes with increased specific energy for thermal batteries, and can be extended to other electrode materials.

Jianpi-Yangxue-Jiedu decoction improves the energy metabolism of psoriasis mice by regulating the electron transfer of oxidative phosphorylation

Ethnopharmacological relevanceThe inflammatory skin condition psoriasis is immune-related. The decoction of Jianpi-Yangxue-Jiiedu (JPYX) is a useful medication for psoriasis. However, the underlying mechanics of JPYX have not yet been clarified. Aim of the studyThe objective of this study was to investigate the mechanism underlying the efficacy of JPYX in the treatment of psoriasis in the context of a high-fat diet. Materials and methodsThis work generated a high-fat feeding model of imiquimod (IMQ)-induced psoriasis-like lesion mice. The blood composition of JPYX was examined using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The mechanism of JPYX decoction for treating psoriasis was predicted using methods of network pharmacology, metabolomics, and transcriptomics. ResultsJPYX prevented the release of inflammatory cytokines, decreased keratinocyte proliferation, enhanced the percentage of Treg cells in the skin, lymph nodes, and thymus, and greatly alleviated psoriatic lesions. Network pharmacology predicted that IL-1β, TNF, STAT3, and EGFR may be potential targets, and KEGG results showed that PI3K-AKT-mTOR may be a potential mechanism of action. Verification of experimental data demonstrated that the JPYX decoction dramatically decreased mTOR and AKT phosphorylation. According to metabolomics analysis, amino acids and their metabolites, benzene and its substitutes, aldehyde ketone esters, heterocyclic compounds, etc. were the primary metabolites regulated by JPYX. KEGG enrichment analysis of differential metabolites was performed. Fatty acid biosynthesis, Type I polyketide structures, Steroid hormone biosynthesis, Biosynthesis of unsaturated fatty acid, etc. Transcriptomic results showed that JPYX significantly regulated skin development, keratinocyte differentiation, and oxidative phosphorylation. Further experimental data verification showed that JPYX decoction significantly reduced the mRNA levels of mt-Nd4, mt-Nd5, mt-Nd1, Ifi205, Ifi211, and mt-Atp8. ConclusionsJPYX may improve psoriasis by regulating the metabolic pathways of fatty acids and electron transport of oxidative phosphorylation.

Simultaneous suppression of As mobilization and N2O emission from NH4+/As-rich paddy soils by combined nitrate and birnessite amendment

The environmental impacts of As mobilization and nitrous oxide (N2O) emission in flooded paddy soils are serious issues for food safety and agricultural greenhouse gas emissions. Several As immobilization strategies utilizing microbially-mediated nitrate reducing-As(III) oxidation (NRAO) and birnessite (δ-MnO2)-induced oxidation/adsorption have proven effective for mitigating As bioavailability in flooded paddy soils. However, several inefficiency and unsustainability issues still exist in these remediation approaches. In this study, the effects of a combined treatment of nitrate and birnessite were assessed for the simultaneous suppression of As(III) mobilization and N2O emission from flooded paddy soils. Microcosm incubations confirmed that the combined treatment achieved an effective suppression of As(III) mobilization and N2O emission, with virtually no As(T) released and at least a 87% decrease in N2O emission compared to nitrate treatment alone after incubating for 8 days. When nitrate and birnessite are co-amended to flooded paddy soils, the activities of denitrifying enzymes within the denitrification electron transport pathway were suppressed by MnO2. As a result, the majority of applied nitrate participated in nitrate-dependent microbial Mn(II) oxidation. The regenerated biogenetic MnO2 was available to facilitate subsequent cycles of As(III) immobilization and concomitant N2O emission suppression, sustainable remediation strategy. Moreover, the combined nitrate-birnessite amendment promoted the enrichment of Pseudomonas, Achromobacter and Cupriavidu, which are known to participate in the oxidation of As(III)/Mn(II). Our findings document strong efficacy for the combined nitrate/birnessite treatment as a remediation strategy to simultaneously mitigate As-pollution and N2O emission, thereby improving food safety and reducing greenhouse gas emissions from flooded paddy soils enriched with NH4+ and As.

Electrochemical elucidation of phosphorus-doped and 3D graphene aerogel surface-modified SiOx porous nanocomposite electrode material for high-performance lithium-ion batteries

Silicon oxide (SiOx) is promising as an earth abundant eco-friendly cost-effective anode material for lithium-ion batteries (LIBs), boasts a higher capacity compared to commercial graphite, garnering significant interest. Nevertheless, its practical application is hindered by issues related to poor cycling performance and low electronic conductivity. In this investigation, graphene aerogel-wrapped (GA) red phosphorus (P) doped SiOx (P-SiOx@GA) composite material is successfully constructed through ball-milling followed by freeze-drying and thermal treatment processes. The prepared materials are characterized the physico-chemical properties. The electrochemical performance is evaluated through Li-ion half and full (LiFePO4//P-SiOx@GA) cells configuration. The synthesized P-SiOx@GA electrode exhibits outstanding cyclic performance, demonstrating a specific capacity of 1094 mAh g−1 at 0.5C with a capacity retention of 80.3 % over 200 cycles in half-cell test. Furthermore, it demonstrates superior rate capability and delivers a reversible rate capacity of 754 mAh g−1 at 2C. Besides, the Li-ion punch cell configuration of LiFePO4//P-SiOx@GA shows good reversible capacity of 1.4 mAh at 0.5C over 300 cycles. The doping of P and porous 3D structure of GA forms an SiOx matrix network is facilitate the establishment of a 3D conductive pathway for electron transport and Li+ diffusion but also acts as a flexible matrix to accommodate the volume changes of SiOx. Therefore, the results and way of preparation promotes a practical feasibility of high-performance Si-based Li-ion batteries applications.

Rational construction of visible-light-driven perylene diimides/Fe2O3@C derived from MIL-88A (Fe) heterojunction with S-scheme electron transfer pathway to activate peroxymonosulfate for degradation of antibiotics

The novel composite photocatalytic material perylene diimides/Fe2O3@C (PDIs/Fe2O3@C) was constructed by a simple hydrothermal-calcination method and an oil bath method. 20 % PDIs/Fe2O3@C displayed a 16.4-fold increase in the rate of tetracycline (TC) removal over Fe2O3@C at 8 min. The main factor that enhanced photocatalytic performance was due to the combination of PDIs with Fe2O3@C, which effectively improved the phenomenon during the self-assembly of highly agglomerative PDIs, increased the specific surface area of Fe2O3@C, exposed more reaction sites, and promoted the activation of peroxymonosulfate (PMS) by Fe2+/Fe3+; and secondly, the composite of two different materials, both organic and inorganic, which effectively promoted the photogenerated electron transfer and the separation of electron-hole pairs, the a new S-scheme electron transport pathway is formed, which effectively promoted the photogenerated electron transfer as well as the e−-h+ separation, which was more favorable for the activation of PMS. The whole reaction pathway and product toxicity were thoroughly evaluated by Fukui function calculations, Liquid Chromatograph Mass Spectrometer (LC-MS), and Toxicity Estimation Software Tool (T.E.S.T.) simulation results, which demonstrated the rationality of the degradation pathway and the greatly reduced product toxicity. Moreover, the composites were effective and versatile for all other antibiotics (chlortetracycline (CTC), ciprofloxacin (CIP) and sulfadiazine (SDZ)). As an advanced oxidation process, the activation of PDIs/Fe2O3@C under visible light shows its potential application in pollutant degradation, which provides new perspectives and ideas for further effective treatment of real wastewater.

Construction of a redox pathway through a polyoxometalate and covalent organic framework for H2O2 photosynthesis.

A novel type of electron donor-acceptor system was built from a nitrogen-rich covalent organic framework (PC) and a polyoxometalate (BW12), fabricating a composite material (BW12@PC-250), which shows significantly improved photocatalytic H2O2 yield (56.4 μM h-1) under full spectrum illumination in pure water, being about 30 times higher than that of PC. This is due to the opening of the electron and proton transport pathway between PC and BW12, which paves a new way for POMs to modulate the photocatalytic reactions of COFs.

Improved lithium-ion battery cathode rate performance via carbon black functionalization

Chemical modification of carbon black (CB) is proposed to improve rate performance of lithium-ion battery cathode. The study demonstrates the role of oxygen groups at the interface (cathode–CB–electrolyte) originating from chemical interactions.

The effect of weak π-π interactions on single-molecule electron transport properties of the tetraphenylethene molecule and its derivatives: a first-principles study.

Intramolecular π-π interactions are a significant research focus in fields such as chemistry, biology, and materials science. Different configurations of benzene-benzene moieties within a molecule can affect the magnitude of their π-π interactions, consequently influencing the electronic transport capabilities of the molecule. In this study, we designed three π-conjugated molecules, TPEM, TPEEM, and TEEPM, based on tetraphenylethene (TPE). These three molecules exhibit three distinct π-conjugated structures: linear cis-π-conjugation, linear trans-π-conjugation, and cross-π-conjugation. Thereinto, TPEM and TPEEM molecules share the same TPE core, with identical π-π interaction distances, while the TEEPM molecule has acetylene groups between the TPE units, thereby increasing the π-π interaction distances between the benzene moieties. Using density functional theory calculations combined with non-equilibrium Green's function (DFT+NEGF), our results reveal that the conductance order of different π-conjugated structures in TPEM and TPEEM molecules is as follows: cis > cross ≈ trans. Through analysis of transmission spectra, transmission pathways, and the innermost π orbitals, we find that in TPEM and TPEEM molecules, the cis- and cross-π-conjugated structures exhibit π-π interactions between benzene moieties and provide special through-space electron transport pathways, enhancing their electronic transport capabilities in coordination with the bonded molecular framework, whereas their trans-conjugated structures only allow electron transport along the molecular backbone. In contrast, in TEEPM molecule, due to the absence of π-π interactions, the conductance of different π-conjugated structures is primarily determined by the molecular backbone and follows the order: trans > cis > cross. These findings provide a theoretical basis for designing single-molecule electronic devices with multiple electron channels based on intramolecular π-π interactions.

Dual roles in interspecies electron transfer of carbon-based materials for accelerating anaerobic digestion of food waste

Food waste is tremendously generated and leads to serious environmental pollution if it is improperly disposed. Anaerobic digestion is recognized as an effective biotechnology to treat food waste. In order to improve the conversion efficiency, the effect of carbon-based materials on anaerobic digestion of food waste was investigated, and the microbial communities and electron transport pathways were also analyzed. The results showed that adding biochar improved the performance of anaerobic digestion of food waste, but adding graphite had no significant effect. The maximum daily methane yield of 67.79 ± 6.37 and 72.78 ± 6.17 mL/g VS·d were obtained with 1.250 (BC10) and 1.875 (BC15) g biochar/g VS raw material added, increased by 13.27% and 21.61% in comparison with the control system. Meanwhile, the systems reached 80% of cumulative methane yield on day 10, and the increase of 13.50% (423.66 ± 13.74 mL/g VS) and 13.57% (423.96 ± 20.33 mL/g VS) were obtained for the methane yield. Adding biochar selectively increased the relative abundance of Syntrophomonas, Clostridium sensu stricto, Petrimonas, Clostridium XlVb, Comamonas, Acinetobacter, Methanothrix and Methanobacterium. The interaction between Methanobacterium and Syntrophomonas was also promoted due to biochar acted as an electron carrier. Therefore, biochar had complex regulation on electron transport pathway of anaerobic digestion and promoted the conversion efficiency of food waste.

DIET-like and MIET-like mutualism of S. oneidensis MR-1 and metal-reducing function microflora boosts Cr(VI) reduction

Microbial treatment of Cr(VI) is an environmentally friendly and low-cost approach. However, the mechanism of mutualism and the role of interspecies electron transfer in Cr(VI) reducing microflora are unclear. Herein, we constructed an intersymbiotic microbial association flora to augment interspecies electron transfer via functionalizing electroactive Shewanella oneidensis MR-1 with metal-reducing microflora, and thus the efficiency of Cr(VI) reduction. The findings suggest that the metal-reducing active microflora could converts glucose into lactic acid and riboflavin for S. oneidensis MR-1 to act as a carbon source and electron mediator. Thus, when adding initial 25 mg/L Cr (VI), this microflora exhibited an outstanding Cr (VI) removal efficiency (100%) at 12 h and elevated Cr (III) immobilization efficiency (80%) at 60 h with the assistance of 25 mg/L Cu(II). A series of electrochemical experiments proved this remarkable removal efficiency were ascribed to the improved interspecies electron transfer efficiency through direct interspecies electron transfer and riboflavin through mediated interspecies electron transfer. Furthermore, the metagenomic analysis revealed the expression level of the electron transport pathway was promoted. Intriguing high abundance of genes participating in the bio-reduction and biotransformation of Cr(VI) was also observed in functional microflora. These outcomes give a novel strategy for enhancing the reduction and fixation of harmful heavy metals by coculturing function microflora with electrogenic microorganisms.

Understanding Porous Transport Layer Structure-Property-Performance Relationships in PEM Water Electrolyzers

Low temperature electrolysis (LTE) is a very promising technology to help with the decarbonization of the energy sector through the production of green hydrogen from renewable energy sources. The DOE has recently launched the first Energy Earthshot targeting the reduction of clean hydrogen cost by 80% to $1 per 1 kg H2 produced in 1 decade. To reach such ambitious targets the technology development needs to consider both capital expenditures (CAPEX) such as material and component costs and their lifetimes, as well as operational expenditures (OPEX) such as cell performance and efficiency. One component that touches on either expenditure is the porous transport layer (PTL). The PTL provides various key functions within an electrolysis cell/stack. It provides transport pathways for electrons, water and gas, and mechanical support for the membrane. Its interface with the catalyst layer is crucial with regards to the limitation of ohmic overpotentials, but also heat transport within the cell. PTLs are currently fabricated from sintered Ti materials that are required to be coated with a PGM material when operated with low loading catalyst layers. Multi-layer PTL materials may further improve cell performance and enable the thrifting of catalyst loadings and the utilization of thin membrane materials. This presentation will introduce the various functionalities of the PTL and highlight research and development efforts including those of DOE’s H2New Consortium and NREL. Specifically impacts of PTL morphology, PTL coatings, and PTL/catalyst layer interactions will be discussed.

Exacerbation of drought-induced physiological and biochemical changes in leaves of Pisum sativum upon restriction of COX and AOX pathways of mitochondrial oxidative electron transport

Exacerbation of drought-induced physiological and biochemical changes in leaves of Pisum sativum upon restriction of COX and AOX pathways of mitochondrial oxidative electron transport

Donor-acceptor moiety functionalized covalent organic frameworks for boosting charge separation and H2 photogeneration

Covalent organic frameworks (COFs) have a broad prospect to be used as a photocatalytic platform to convert solar energy into valuable chemicals due to their tunable structures and rich active catalytic sites. However, constructing COFs with tuned sp2-carbon donor-acceptor moiety remains an enormous challenge. Herein, we synthesized two new fully π-conjugated cyano-ethylene-linked COFs containing benzotrithiophene as functional group by Knoevenagel polycondensation reaction. The accetpor 2,2′-bipyridine unit in BTT-BpyDAN-COF skeleton favored the formation of a intermolecular specific electron transport pathway with the donor benzotrithiophene, and thereby promoted charge separation and transfer efficiency. Specifically, a donor-acceptor (D-A) type BTT-BpyDAN-COF exhibited high hydrogen evolution rate of 10.1 mmol g-1h−1 and an excellent apparent quantum efficiency of 4.83 % under visible light irradiation.

Photocatalytic degradation of antibiotics using a Li-C3N4/ZnO/BiOI: Insights on the electron transport pathways

Photocatalytic degradation of antibiotics using a Li-C3N4/ZnO/BiOI: Insights on the electron transport pathways

Long-term stability of lithium–sulfur batteries via synergistic integration of nitrogen-doped graphitic carbon-coated cobalt selenide nanocrystals within porous three-dimensional graphene-carbon nanotube microspheres

Three-dimensional porous microspheres consist of highly conductive reduced graphene oxide-carbon nanotube (rGO‒CNT) framework with well-embedded cobalt selenide (CoSe2) nanocrystals coated with N-doped graphitic carbon (NGC) were synthesized (referred as “P–CoSe2@NGC/rGO‒CNT” microspheres) and utilized as an electrocatalytic interlayer to enhance the performance of lithium-sulfur (Li–S) batteries. The incorporation of the NGC layer and rGO‒CNT framework not only enhances the electronic conductivity significantly but also offers numerous conductive pathways (primary and secondary) for efficient electron transport. Macropores (φ = 100 nm) formed by the decomposition of PS nanobeads (φ = 200 nm) guarantee effective electrolyte penetration and short diffusion pathways. Moreover, the CoSe2 nanocrystals offer a multitude of polar active sites that effectively anchor polysulfide intermediates, reducing the loss of active material. Benefiting from the nanostructure merits, Li–S cells featuring a P–CoSe2@NGC/rGO‒CNT-coated separator and a conventional sulfur electrode demonstrated outstanding rate capability (up to 2.0 C) and remarkable cycling stability (1000 cycles at 2.0 C). Even under more demanding cell conditions, such as high sulfur content (71 %), high sulfur loading (4.6 mg cm−2), and low E/S (5.6 μL mg−1) ratio, the cell exhibits impressive cycling stability with 420 cycles at 0.1 C, along with feasible rate performance up to 0.3 C.

Wood shavings combined with polyaniline and carbon nanotube film for flexible high-performance energy storage devices

Wood, as a uniquely ordered porous material, plays an indispensable role in energy storage devices. Here, wood shavings (WS) are utilized as a flexible substrate to form an electrode material with excellent flexibility. A conductive coating material made of spinnable carbon nanotube (CNT) film is applied onto the wood shavings, while polyaniline (PANI) nanoparticles are chemically polymerized in situ and deposited onto the CNT film to create flexible electrodes. CNTs offer optimal pathways for electron transport and establish stable connections among PANI particles. Furthermore, the incorporation of the CNT film causes an augmentation of the conductivity of WS substrate. The PANI/CNT@WS exhibits an outstanding specific capacity of 152.81 F g−1 at 0.2 A g−1. The flexible supercapacitor (FSC) presents a high specific capacitance of 45.89 F g−1 at 0.2 A g−1, and capacity rate is as high as 98.98 % after 1000 charge–discharge cycles. Even when bent to 120°, the capacity remains 62.9 %. Therefore, the composite electrode demonstrates exceptional flexibility and excellent electrochemical performance.

Defect-Engineering-Mediated Long-Lived Charge-Transfer Excited-State in Fe-Gallate Complex Improves Iron Cycle and Enables Sustainable Fenton-Like Reaction.

Fenton reactions are inefficient because the Fe(II) catalyst cannot be recycled in time due to the lack of a rapid electron transport pathway. This results in huge H2 O2 wastage in industrial applications. Here, it is shown that a sustainable heterogeneous Fenton system is attainable by enhancing the ligand-to-metal charge-transfer (LMCT) excited-state lifetime in Fe-gallate complex. By engineering oxygen defects in the complex, the lifetime is improved from 10-90 ps. The lengthened lifetime ensures sufficient concentrations of excited-states for an efficient Fe cycle, realizing previously unattainable H2 O2 activation kinetics and hydroxyl radical (• OH) productivity. Spectroscopic and electrochemical studies show the cyclic reaction mechanism involves in situ Fe(II) regeneration and synchronous supply of oxygen atoms from water to recover dissociated Fe─O bonds. Trace amounts of this catalyst effectively destroy two drug-resistant bacteria even after eight reaction cycles. This work reveals the link among LMCT excited-state lifetime, Fe cycle, and catalytic activity and stability, with implications for de novo design of efficient and sustainable Fenton-like processes.

Construction of Z-scheme NiO/BiOBr heterojunction for facilitating photocatalytic degradation of oxytetracycline and 2-mercaptobenzothiazole

Z-scheme NiO/BiOBr heterojunction was prepared by mechanical ball milling method and applied for the photodegradation removal of oxytetracycline (OTC) and 2-mercaptobenzothiazole (MBT). The Z-scheme electron transport pathway optimizes the separation of photogenerated carriers, thereby significantly increasing the generation capacity of reactive oxygen species (ROS). The photocatalytic degradation experiments demonstrate that the optimized OTC and MBT removal efficiency of NiO/BiOBr (NBOB) composites could reach 72.6% (120 min) and 97.7% (9 min), respectively. Photoluminescence (PL) spectra and PL decay curves indicate that NBOB-2 composites exhibit low photoinduced electron-hole recombination rate and accelerated electron separation efficiency. In addition, ESR spectra confirm that the Z-scheme NiO/BiOBr heterojunction can generate a larger quantity of ROS species. The possible photodegradation pathways and toxicity analysis for the OTC and MTB photodegradation intermediates are elucidated by HPLC-MS measurement and T.E.S.T. application. The manuscript provides a reference for the macro-preparation of bismuth-based photocatalysts with superior performance and high stability.

Abstract 15515: SGLT2 Inhibitor Empagliflozin Increases Fatty Acid Oxidation, Coupling Between Glycolysis and Glucose Oxidation, and Decreases Left Ventricular Hypertrophy in Mice With Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation

Background: A metabolic switch from fatty acid oxidation (FAO) to glycolysis associates with LV hypertrophy (LVH). Glucagon signaling increases FAO in the heart and sodium-glucose co-transporter 2 inhibitors (SGLT2i) raise glucagon/insulin ratio (GIR) in patients. We have shown that SGLT2i reprogram cardiac metabolic genes favoring FAO, yet the mechanism is unknown. Hypothesis: SGLT2i increases GIR, thereby increasing FAO and glycolysis/glucose oxidation coupling (GGC), which in turn attenuates LVH and fibrosis in a murine model of HCM (R403Q myosin mutation). Methods: Mice 9 weeks of age were treated ± SGLT2i empagliflozin (EMPA, 0.15 mg/g chow). After 2 weeks, prior to LVH onset, myocardial transcriptomic analysis was performed. After 16 weeks, echocardiography, proteomics, fasted GIR, and histology were obtained. Glucose fluxes, energetics and 13 C substrate oxidation were measured in isolated beating hearts by 31 P and 13 C NMR spectroscopy. Results: R403Q mice had ↓GIR which was normalized by EMPA. Transcriptomics (2 weeks) and proteomics (16 weeks) confirmed downregulation of electron transport and FAO pathways, and upregulation of LVH and fibrosis pathways. At 16 weeks, R403Q hearts exhibited LVH, fibrosis, ↓diastolic function and ↓contractile reserve (rate pressure product increase between low and high workload). Metabolically, R403Q had ↑glucose uptake and ↓GGC with ↑lactate production; ↓FAO and impaired energetics (↓free energy of ATP hydrolysis, ΔG ~ATP , at both workloads). The HCM phenotype and all measures of metabolic dysfunction were partially or completely prevented by EMPA. Conclusion: R403Q hearts display marked metabolic reprogramming that appears early in the disease process and leads to energetic dysfunction. SGLT2i corrects GIR, attenuates metabolic reprogramming and the energetic, structural and functional features of HCM. SGLT2i and possibly other measures to modulate glucagon signaling hold therapeutic potential in HCM.