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Aim: Dietary nitrate (NO3−) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO3− at rest and during exercise with a focus on skeletal muscle. Methods: In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15N‐labeled potassium nitrate (K15NO3; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1‐ and 3‐h post‐supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO3−] and [NO2−], and by mass spectrometry to determine the proportion of NO3− and NO2− that was 15N‐labeled. Results: Neither muscle [NO3−] nor [NO2−] were altered by PLA. Following NIT, muscle [NO3−] (but not [NO2−]) was elevated at 1‐h (from ~35 to 147 nmol/g, p < 0.001) and 3‐h, with almost all of the increase being 15N‐labeled. There was a significant reduction in 15N‐labeled muscle [NO3−] from pre‐ to post‐exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre‐exercise 15N‐labeled muscle [NO3−] and the magnitude of decline in 15N‐labeled muscle [NO3−] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01). Conclusion: This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO3−, the elevated muscle [NO3−] following NO3− ingestion declines during exercise, and muscle NO3− dynamics are associated with enhanced torque production during maximal intermittent muscle contractions. [ABSTRACT FROM AUTHOR]

Photocaged, activity‐based ubiquitin (Ub) probes (Ub‐ABPs) have been developed for the time‐resolved probing of deubiquitinating enzyme (DUB) activities, but many Ub‐ABPs are still challenging to photocage because their warheads (e.g. propargylamide (PA) or dehydroalanine (Dha)) are difficult to temporally block and activate. Here, we describe a new C‐terminal backbone modification strategy for the construction of photocaged Ub‐ABPs in which a light‐sensitive group is placed at the backbone amide bond of the Ub Gly75. This strategy enabled the facile generation of cell‐permeable photocaged Ub‐PA and Dha probes that could be activated to capture DUBs after photo‐irradiation, and were used to profile DUBs in cells under specially designed conditions (e.g. in cells experiencing oxidative stress) or DUBs with isopeptide linkage selectivity. This backbone modification strategy is anticipated to provide a general solution for the development of photocaged Ub ABPs bearing any warheads for DUB profiling. [ABSTRACT FROM AUTHOR]

Polymers are at the core of emerging flexible sensor and soft actuator technology. Ideal candidates not only respond to external stimuli but also have programmable response intensity and speed. Incorporating dynamic interactions into polymers has been widely studied. However, most research has focused on synthesis methods and on optical and mechanical effects of these interactions. Here, a new and tunable method of enabling environmentally adaptive polymers are introduced. Specifically, polar functionalities are "hidden" within polydimethylsiloxane (PDMS). When unveiled, these polar functionalities change the hydrophilicity of the polymer. Water is the stimulus that triggers the exposure of polar functionalities by disrupting interfacial equilibrium and driving surface reconstruction. This reversible adaptation is governed by the dynamics of a metal–ligand coordinated polymer, and therefore can be easily tailored by the choice of network structure, metal cations, and counter anions. PDMS is a particularly exciting polymer for this functionality because of the negative consequences of its intrinsically high hydrophobicity in many applications. However, this design concept is applicable to a wide range of polymers and can be expanded to other dynamic interactions such as reversible covalent bonding, hydrogen bonding, and ionic bonding, to empower programmable responsive functionality and therefore enhance material performance. [ABSTRACT FROM AUTHOR]

Aim: Dietary nitrate (NO 3 - ) supplementation increases nitric oxide bioavailability and can enhance exercise performance. We investigated the distribution and metabolic fate of ingested NO 3 - at rest and during exercise with a focus on skeletal muscle., Methods: In a randomized, crossover study, 10 healthy volunteers consumed 12.8 mmol 15 N-labeled potassium nitrate (K 15 NO 3 ; NIT) or potassium chloride placebo (PLA). Muscle biopsies were taken at baseline, at 1- and 3-h post-supplement ingestion, and immediately following the completion of 60 maximal intermittent contractions of the knee extensors. Muscle, plasma, saliva, and urine samples were analyzed using chemiluminescence to determine absolute [NO 3 - ] and [NO 2 - ], and by mass spectrometry to determine the proportion of NO 3 - and NO 2 - that was 15 N-labeled., Results: Neither muscle [NO 3 - ] nor [NO 2 - ] were altered by PLA. Following NIT, muscle [NO 3 - ] (but not [NO 2 - ]) was elevated at 1-h (from ~35 to 147 nmol/g, p < 0.001) and 3-h, with almost all of the increase being 15 N-labeled. There was a significant reduction in 15 N-labeled muscle [NO 3 - ] from pre- to post-exercise. Relative to PLA, mean muscle torque production was ~7% greater during the first 18 contractions following NIT. This improvement in torque was correlated with the pre-exercise 15 N-labeled muscle [NO 3 - ] and the magnitude of decline in 15 N-labeled muscle [NO 3 - ] during exercise (r = 0.66 and r = 0.62, respectively; p < 0.01)., Conclusion: This study shows, for the first time, that skeletal muscle rapidly takes up dietary NO 3 - , the elevated muscle [NO 3 - ] following NO 3 - ingestion declines during exercise, and muscle NO 3 - dynamics are associated with enhanced torque production during maximal intermittent muscle contractions., (© 2023 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)