UNASSIGNED: MecROX is a mechanistic sub-study of the UK-ROX trial which was designed to evaluate the clinical and cost-effectiveness of a conservative approach to oxygen therapy for invasively ventilated adults in intensive care. This is based on the scientific rationale that excess oxygen is harmful. Epithelial cell damage with alveolar surfactant deficiency is characteristic of hyperoxic acute lung injury. Additionally, hyperoxaemia (excess blood oxygen levels) may exacerbate whole-body oxidative stress leading to cell death, autophagy, mitochondrial dysfunction, bioenergetic failure and multi-organ failure resulting in poor clinical outcomes. However, there is a lack of in-vivo human models evaluating the mechanisms that underpin oxygen-induced organ damage in mechanically ventilated patients.
UNASSIGNED: The aim of the MecROX mechanistic sub-study is to assess lung surfactant composition and global systemic redox status to provide a mechanistic and complementary scientific rationale to the UK-ROX trial findings. The objectives are to quantify in-vivo surfactant composition, synthesis, and metabolism with markers of oxidative stress and systemic redox disequilibrium (as evidenced by alterations in the \'reactive species interactome\') to differentiate between groups of conservative and usual oxygen targets.
UNASSIGNED: After randomisation into the UK-ROX trial, 100 adult participants (50 in the conservative and 50 in usual care group) will be recruited at two trial sites. Blood and endotracheal samples will be taken at 0, 48 and 72 hours following an infusion of 3 mg/kg methyl-D 9-choline chloride. This is a non-radioactive, stable isotope of choline (vitamin), which has been extensively used to study surfactant phospholipid kinetics in humans. This study will mechanistically evaluate the in-vivo surfactant synthesis and breakdown (by hydrolysis and oxidation), oxidative stress and redox disequilibrium from sequential plasma and bronchial samples using an array of analytical platforms. We will compare conservative and usual oxygenation groups according to the amount of oxygen administered. Trial registration: ISRCTNISRCTN61929838, 27/03/2023 https://doi.org/10.1186/ISRCTN61929838.

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community-based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin-1, myomesin-2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin-2, alpha-actinin-2, and skeletal muscle alpha-actin were associated with lower leg power and strength. We also observed an unexpected correlation (R = 0.48) between a higher oxidation level of eight Cys sites in alpha-actinin-3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impairs muscle power and strength, walking speed, and cardiopulmonary fitness with aging.

The combination of the ferrocene moiety with gold(I) catalysis remains a relatively unexplored field. In this article, we delve into the synthesis, characterization, and potential catalytic activity of four complexes utilizing both monodentate and bidentate ferrocenyl diphenylphosphane ligands (ppf and dppf), coordinated with two gold(I) metal centers, linked by either chloride or pentafluorophenylthiolate bridging ligands. This leads to the formation of cationic \"self-activated\" precatalysts capable of initiating the catalytic cycle without the need for external additives. The catalytic activity of these complexes was assessed through a model reaction in gold(I) catalysis, specifically the cyclization of a N-propargylbenzamide to produce an oxazole. In addition, we studied and compared the influence exerted by both the phosphane and the bridging ligand on the performance of these catalysts.

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community-based cohort study of individuals aged 70 years and older. We tested whether levels of Cys oxidation on key muscle proteins involved in muscle structure and contraction were associated with muscle function (leg power and strength), walking speed, and fitness (VO2 peak on cardiopulmonary exercise testing) using linear regression models adjusted for age, sex, and body weight. Higher oxidation levels of select nebulin Cys sites were associated with lower VO2 peak, while greater oxidation of myomesin-1, myomesin-2, and nebulin Cys sites was associated with slower walking speed. Higher oxidation of Cys sites in key proteins such as myomesin-2, alpha-actinin-2, and skeletal muscle alpha-actin were associated with lower leg power and strength. We also observed an unexpected correlation (r = 0.48) between a higher oxidation level of 8 Cys sites in alpha-actinin-3 and stronger leg power. Despite this observation, the results generally support the hypothesis that Cys oxidation of muscle proteins impair muscle power and strength, walking speed, and cardiopulmonary fitness with aging.

The gut might play an important role in the etiopathogenesis of Alzheimer\'s disease (AD) as gastrointestinal alterations often precede the development of neuropathological changes in the brain and correlate with disease progression in animal models. The gut has an immense capacity to generate free radicals whose role in the etiopathogenesis of AD is well-known; however, it remains to be clarified whether gastrointestinal redox homeostasis is associated with the development of AD. The aim was to (i) examine gastrointestinal redox homeostasis in the presymptomatic and symptomatic Tg2576 mouse model of AD; (ii) investigate the effects of oral d-galactose previously shown to alleviate cognitive deficits and metabolic changes in animal models of AD and reduce gastrointestinal oxidative stress; and (iii) investigate the association between gastrointestinal redox biomarkers and behavioral alterations in Tg2576 mice. In the presymptomatic stage, Tg2576 mice displayed an increased gastrointestinal electrophilic tone, characterized by higher lipid peroxidation and elevated Mn/Fe-SOD activity. In the symptomatic stage, these alterations are rectified, but the total antioxidant capacity is decreased. Chronic oral d-galactose increased the antioxidant capacity and reduced lipid peroxidation in the Tg2576 but had the opposite effects in the wild-type animals. The total antioxidant capacity of the gastrointestinal tract was associated with greater spatial memory. Gut redox homeostasis might be involved in the development and progression of AD pathophysiology and should be further explored in this context.

Autoinflammatory diseases are a group of inherited and multifactorial disorders characterized by an over-activation of innate immune response. In most cases, the clinical manifestations are due to increased activity of the NLRP3 inflammasome resulting in increased IL-1β secretion. Investigating inflammatory cells from subjects affected by autoinflammatory diseases presents a number of technical difficulties related to the rarity of the diseases, to the young age of most patients, to the difficult modulation of gene expression in primary cells. However, since cell stress is involved in the pathophysiology of these diseases, the study of freshly drawn blood monocytes from patients affected by IL-1-mediated diseases strongly increases the chances that the observed phenomena is indeed pertinent to the pathogenesis of the disease and not influenced by the long-term cell culture conditions (e.g., the high O2 tension) or gene transfection in continuous cell lines that may lead to artifacts.

The ability of headwater bed and suspended sediments to mitigate non-point agricultural phosphorus (P) loads to the lower Great Lakes is recognized, but the specific biogeochemical processes promoting sediment P retention or internal P release remain poorly understood. To elucidate these mechanisms, three headwater segments located within priority watersheds of Southern Ontario, Canada, were sampled through the growing season of 2018-2020. The study employed equilibrium P assays along with novel assessments of legacy watershed nutrients, nitrogen (N) concentrations, sediment redox, and microbial community composition. 20-year data revealed elevated total P (TP) and total Nitrogen (TN) at an inorganic fertilizer and manure fertilizer-impacted site, respectively. Overall, sampled sites acted as P sinks; however, agricultural sediments exhibited significantly lower buffering capacity compared to a reference forested watershed. Collection of fine suspended sediment (<63 µm) through time-integrated sampling showed the suspended load at the inorganic-fertilized site was saturated with P, indicating a greater potential for P release into surface waters compared to bed sediments. Through vertical microsensor profiling and DNA sequencing of the sediment microbial community, site-specific factors associated with a distinct P-source event were identified. These included rapid depletion of dissolved oxygen (DO) across the sediment water interface (SWI), as well as the presence of nitrate-reducing bacterial and ammonia-oxidizing archaeal (AOA) genera. This research provides valuable insights into the dynamics of P in headwaters, shedding light on P retention and release. Understanding these processes is crucial for effective management strategies aimed at mitigating P pollution to the lower Great Lakes.

Propolis is a natural product has many biological properties of clinical interest, such as anti-inflammatory and antioxidant. Considering that people living with HIV/aids (PLWHA) on effective combined antiretroviral therapy (cART) present early aging due to an intense immune activation, inflammation, and redox imbalance, propolis consumption could offer a benefit to such patients. This double-blind longitudinal study evaluated whether Brazilian green propolis pills intake (500 mg/day for three months) would decrease the oxidative stress of virological suppressed HIV-individuals. To compare each group (propolis, n = 20 versus placebo, n = 20) in both moments (M0, before and M1, after the intervention), the following markers were assessed: plasma malondialdehyde (MDA), carbonylation, total oxide nitric, total antioxidant capacity (TAP), superoxide dismutase, catalase, and NFkB and NRF2 gene expression. Data were analyzed using Poisson, Gamma distribution and ANOVA followed by Tukey-Kramer. The groups were homogeneous regarding age, gender, time of diagnosis/ treatment, cART scheme, CD4+ T cell count, and no changes were observed in the diet food, or patients\' lifestyles. A decreased MDA concentration was seen in the propolis group (M0 = 0.24 ± 0.13, M1 = 0.20 ± 0.10 protein nmol/mg; p = 0.005) as well as a slight but non-significant increase of TAP (M0 = 49.07 ± 13.26, M1 = 52.27 ± 14.86%; p = 0.06). One may conclude that propolis promoted a lower lipid peroxidation and improved the antioxidant system, suggesting that its use may be beneficial to PLWHA in an attempt to contain the intense inflammatory and oxidant activity.

A coordination polymer has been synthesized using ferrocene-based ligand-bearing phosphinic groups of 1,1\'-ferrocene-diyl-bis(H-phosphinic acid)), and samarium (III). The coordination polymer\'s structure was studied by both single-crystal and powder XRD, TG, IR, and Raman analyses. For the first time, the Mössbauer effect studies were performed on ferrocenyl phosphinate and the polymer based on it. Additionally, the obtained polymer was studied by the method of cyclic and differential pulse voltammetry. It is shown that it has the most positive potential known among ferrocenyl phosphinate-based coordination polymers and metal-organic frameworks. Using the values of the oxidation potential, the polymer was oxidized and the ESR method verified the oxidized Fe(III) form in the solid state. Additionally, the effect of the size of the phosphorus atom substituent of the phosphinate group on the dimension of the resulting coordination compounds is shown.

The potential joint influence of metabolites on bone fragility has been rarely evaluated. We assessed the association of plasma metabolic patterns with bone fragility endpoints (primarily, incident osteoporosis-related bone fractures, and, secondarily, bone mineral density BMD) in the Hortega Study participants. Redox balance plays a key role in bone metabolism. We also assessed differential associations in participant subgroups by redox-related metal exposure levels and candidate genetic variants.
In 467 participants older than 50 years from the Hortega Study, a representative sample from a region in Spain, we estimated metabolic principal components (mPC) for 54 plasma metabolites from NMR-spectrometry. Metals biomarkers were measured in plasma by AAS and in urine by HPLC-ICPMS. Redox-related SNPs (N = 341) were measured by oligo-ligation assay.
The prospective association with incident bone fractures was inverse for mPC1 (non-essential and essential amino acids, including branched-chain, and bacterial co-metabolites, including isobutyrate, trimethylamines and phenylpropionate, versus fatty acids and VLDL) and mPC4 (HDL), but positive for mPC2 (essential amino acids, including aromatic, and bacterial co-metabolites, including isopropanol and methanol). Findings from BMD models were consistent. Participants with decreased selenium and increased antimony, arsenic and, suggestively, cadmium exposures showed higher mPC2-associated bone fractures risk. Genetic variants annotated to 19 genes, with the strongest evidence for NCF4, NOX4 and XDH, showed differential metabolic-related bone fractures risk.
Metabolic patterns reflecting amino acids, microbiota co-metabolism and lipid metabolism were associated with bone fragility endpoints. Carriers of redox-related variants may benefit from metabolic interventions to prevent the consequences of bone fragility depending on their antimony, arsenic, selenium, and, possibly, cadmium, exposure levels.