BACKGROUND: Polymorphism rs1049434 characterizes the nonsynonymous exchange of adenosine (A) by thymidine (T) in the gene for monocarboxylate transporter 1 (MCT1). We tested whether T-allele carriers of rs1049434 demonstrate increased accumulation of markers of metabolic strain.
METHODS: Physically active, healthy, young male subjects (n = 22) conducted a power-matched one-legged cycling exercise to exhaustion. Metabolic substrates in capillary blood, selected metabolic compounds, and indices for the slow oxidative phenotype of vastus lateralis muscle were quantified in samples collected before and after exercise. The genotypes of the rs1049434 polymorphism were determined with polymerase chain reactions.
RESULTS: One-legged exercise affected the concentration of muscle metabolites entering the tricarboxylic acid cycle, such as acetyl-co-enzyme A (+448%) and acetyl-L-carnitine (+548%), muscle glycogen (-59%), and adenosine monophosphate (-39%), 30 min post-exercise. Exercise-related variability in the muscular concentration of glycogen, long-chain acyl co-enzyme As and a triglyceride, nicotinamide adenine dinucleotide (NADH), and adenosine monophosphate (AMP) interacted with rs1049434. T-allele carriers demonstrated a 39% lesser reduction in glycogen after exercise than non-carriers when NADH increased only in the non-carriers. Muscle lactate concentration was 150% higher, blood triacyl-glyceride concentration was 53% lower, and slow fiber percentage was 20% lower in T-allele carriers.
CONCLUSIONS: The observations suggest a higher anaerobic glycolytic strain during exhaustive exercise and a lowered lipid handling in T-allele non-carriers.

Human carbonic anhydrase II (hCAII) naturally catalyzes the reaction between two achiral molecules - water and carbon dioxide - to yield the achiral product carbonic acid through a zinc hydroxide intermediate. We have previously shown that a zinc hydride, instead of a hydroxide, can be generated in this enzyme to create a catalyst for the reduction of aryl ketones. Dialkyl ketones are more challenging to reduce, and the enantioselective reduction of dialkyl ketones with two alkyl groups that are similar in size and electronic properties, is a particularly challenging transformation to achieve with high activity and selectivity. Here, we show that hCAII, as well as a double variant of it, catalyzes the enantioselective reduction of dialkyl ketones with high yields and enantioselectivities, even when the two alkyl groups are similar in size. We also show that variants of hCAII catalyze the site-selective reduction of one ketone over the other in an unsymmetrical aliphatic diketone. Computational docking of a dialkyl ketone to the double variant containing the zinc hydride provides insights into the origins of the reactivity of various substrates and the high enantioselectivity of the transformations and show how a confined environment can control the enantioselectivity of an abiological intermediate.

Introduction Diagnosing a concussion is challenging because of complex and variable symptoms. Establishing a viable biomarker of injury may rely on physiologic measurements rather than symptomology. Volatile organic compounds (VOCs) such as breath acetone have been identified as potential physiological markers that can capture changes in the utilization of energy substrates post-concussion. Here, we aimed to explore whether differences in VOCs exist between concussed and non-concussed athletes at the initial and later stages of injury recovery. Methods Six (N=6) non-concussed athletes were enrolled as control participants prior to the competitive season. Control participants\' breath acetone, heart rate, and anthropometric measures were obtained at rest and throughout a single exercise challenge by breathalyzer. Six (N=6) athletes diagnosed with concussion during the competitive season had breath acetone measured daily until cleared to return to activity or approximately four weeks following enrollment where they participated in an exit exercise challenge having breath acetone, heart rate, and anthropometric measures obtained. Comparisons were made between at-rest measures of concussed and non-concussed participants at multiple time points during the recovery period. Paired t-test comparisons with individuals serving as their own control were used to determine individual differences in recovery. Visual graphs were used to demonstrate differences in obtained measures amongst individuals and between groups during the exercise challenges. Results Results demonstrated statistically significant differences in breath acetone between concussed and control participants when the highest day measured during the first week of concussion was compared to the control participant\'s resting values (P=0.017). Additionally, when the concussed participants served as their own control and their highest measured day of the first week post-concussion was compared to values when cleared to return to activity or at 26 days post-concussion, there was a significant difference in breath acetone (P=0.028). Comparing breath acetone during exercise between non-concussed and cleared concussed participants or four weeks post-injury, demonstrated no significant differences throughout the challenge or at rest prior. Visual graph comparisons in a single participant before and after concussion suggest differences may appear following exercise during the recovery period. Discussion These results suggest VOCs, particularly breath acetone, have the potential to serve as diagnostic markers of concussion. However, longitudinal research within larger cohorts and with equipment able to expel VOCs other than acetone from measures are needed to make informed recommendations.

Calorie restriction (CR) and fasting affect lifespan, disease susceptibility and response to acute injury across multiple animal models, including ischaemic injuries such as myocardial infarction or kidney hypoxia. The cargo and function of circulating extracellular vesicles (EV) respond to changes in host physiology, including exercise, injury, and other interventions. Thus, we hypothesised that EVs induced following CR may reflect some of the beneficial properties of CR itself. In a pilot study, EVs were isolated from mice following 21 days of 30 % CR, and from eight human donors after 72 h water-only fasting. EV size, concentration and morphology were profiled by NTA, western blot and cryoEM, and their function was assessed using multiple assays related to ischaemic diseases. We found that EVs from post-fasting samples better protected cardiac cells from hypoxia/reperfusion (H/R) injury compared to pre-fasting EVs. However, there was no difference when used to treat H/R-injured kidney epithelial cells. Post-fasting derived EVs slowed the rate of fibroblast migration and slightly reduced macrophage inflammatory gene expression compared to pre-fasting derived EVs. Lastly, we compared miRNA cargos of pre- and post-fasting human serum EVs and found significant changes in a small number of miRNAs. We conclude that fasting appears to influence EV cargo and function, with varied effects worthy of further exploration.

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation-reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C-N bond. This method selectively oxidatively cleaves the C-N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

The ketogenic diet is an effective treatment for drug-resistant epilepsy, but the therapeutic mechanisms are poorly understood. Although ketones are able to fuel the brain, it is not known whether ketones are directly metabolized by neurons on a time scale sufficiently rapid to fuel the bioenergetic demands of sustained synaptic transmission. Here, we show that nerve terminals can use the ketone β-hydroxybutyrate in a cell- autonomous fashion to support neurotransmission in both excitatory and inhibitory nerve terminals and that this flexibility relies on Ca2+ dependent upregulation of mitochondrial metabolism. Using a genetically encoded ATP sensor, we show that inhibitory axons fueled by ketones sustain much higher ATP levels under steady state conditions than excitatory axons, but that the kinetics of ATP production following activity are slower when using ketones as fuel compared to lactate/pyruvate for both excitatory and inhibitory neurons.

Polyetheretherketone (PEEK) is a polymer that has a comprehensive range of possible uses in dental treatment. The goal of this study was to compile research findings on the substance of dental claims and highlight the upcoming predictions of PEEK in clinical dentistry. PEEK is a novel polymeric material that is yet in its preliminary stage of evolution. Biomolecules are elastic materials with remarkable mechanical strength, barrier properties, and heat resistance compared to other matrix materials. The efficacy of PEEK in clinical dentistry has been acknowledged. Polyetherketone (PEKK) and PEEK are the most commonly mentioned members of the polyaryletherketone (PAEK) family. PEEK has also found significant use in dentistry, notably in prosthodontics and implant dentistry. It also offers exceptional mechanical qualities, including high strength and toughness, making it ideal for dental implants and prostheses. It can endure the stresses of chewing and grinding, resulting in long-lasting restorations. PEEK\'s tooth-colored look and ability to simulate natural tooth translucency make it suitable for use in dental prostheses such as crowns and bridges. This makes it a more esthetically acceptable alternative to standard metal-based repairs.

The chiral aziridine-containing vicinal iminophenol tridentate ligands (named salazins) are a class of readily prepared chiral ligands from enantiopure aziridines and salicylaldehydes. Their scandium and yttrium triflate complexes show excellent reactivity and enantioselectivities in the catalytic asymmetric aldol condensation of electron-deficient aromatic aldehydes and ketones, including acetone and cycloalkanones. The stereoselectivity is rationalized to the strong π-stacking interaction between aromatic aldehydes and the vicinal iminophenol group in the chiral ligands.

Lignin is continuously investigated by various techniques for valorization due to its high content of oxygen-containing functional groups. Catalytic systems employing hydrolysis‑hydrogenolysis, leveraging the synergistic effect of redox metal sites and acid sites, exhibit efficient degradation of lignin. The predominance of either hydrolysis or hydrogenolysis reactions hinges upon the relative activity of acid and metal sites, as well as the intensity of the reductive atmosphere. In this study, the Pd-MoOx/TiO2 catalyst was found to primarily catalyze hydrolysis in the lignin depolymerization process, attributed to the abundance of moderate acidic sites on Pd and the redox-assisted catalysis of MoOx under inert conditions. After subjecting the reaction to 240 °C for 30 h, a yield of 48.22 wt% of total phenolic monomers, with 5.90 wt% consisting of diphenols, was achieved. Investigation into the conversion of 4-propylguaiacol (4-PG), a major depolymerized monomer of corncob lignin, revealed the production of ketone intermediates, a phenomenon closely linked to the unique properties of MoOx. Dehydrogenation of the propyl is a key step in initiating the reaction, and 4-PG could be almost completely transformed, accompanied by an over 97 % of 4-propylcatechol selectivity. This distinctive system lays a new theoretical groundwork for the eco-friendly valorization of lignin.

BACKGROUND: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined.
RESULTS: Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-[11C]3-OHB and L-[11C]3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (P<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (P<0.003). D-3-OHB increased CO nonsignificantly (P=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (P<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-[11C]3-OHB showed rapid cardiac uptake and metabolism, whereas L-[11C]3-OHB demonstrated much slower pharmacokinetics.
CONCLUSIONS: 3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.