Unconventional ratiometric-enhanced optical sensing of oxygen by mixed-phase TiO2

We show that mixed-phase titanium dioxide (TiO2) can be effectively employed as an unconventional, inorganic, dual-emitting and ratiometric optical sensor of O2. Simultaneous availability of rutile and anatase TiO2 PL and their peculiar anti-correlated PL responses to O2 allow using their ratio as measurement parameter associated to O2 concentration, leading to an experimental responsivity being by construction larger than the one obtainable for single-phase PL detection. A proof of this concept in given, showing a two-fold enhancement of the optical responsivity provided by the ratiometric approach. Besides the peculiar ratiometric-enhanced responsivity, other characteristics of mixed phase TiO2 can be envisaged as favorable for O2 optical probing, namely: a) low production costs, b) absence of heterogeneous components, c) self-supporting properties. These characteristics encourage experimenting its use for applications requiring high indicator quantities at competitive price, possibly also tackling the need to develop supporting matrixes that carry the luminescent probes and avoiding issues related to the use of different components for ratiometric sensing.Comment: 12 pages, 5 figure

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: analysis by the Pharmachild Safety Adjudication Committee

Background To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies

Mitochondrial ATP synthase: architecture, function and pathology

Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions

Sarcopenia; Aging-related loss of muscle mass and function

Sarcopenia is a loss of muscle mass and function in the elderly that reduces mobility, diminishes quality of life, and can lead to fall-related injuries, which require costly hospitalization and extended rehabilitation. This review focuses on the aging-related structural changes and mechanisms at cellular and subcellular levels underlying changes in the individual motor unit: specifically, the perikaryon of -motoneuron, its neuromuscular junction(s), and the muscle fibers that it innervates. Loss of muscle mass with aging, which is largely due to the progressive loss of motoneurons, is associated with reduced muscle fiber number and size. Muscle function progressively declines because motoneuron loss is not adequately compensated by reinnervation of muscle fibers by the remaining motoneurons. At the intracellular level, key factors are qualitative changes in posttranslational modifications of muscle proteins and the loss of coordinated control between contractile, mitochondrial, and sarcoplasmic reticulum protein expression. Quantitative and qualitative changes in skeletal muscle during the process of aging also have been implicated in the pathogenesis of acquired and hereditary neuromuscular disorders. In experimental models, specific intervention strategies have shown encouraging results on limiting deterioration of motor unit structure and function under conditions of impaired innervation. Translated to the clinic, if these or similar interventions, by saving muscle and improving mobility, could help alleviate sarcopenia in the elderly, there would be both great humanitarian benefits and large cost savings for health care systems

Unconventional use of mixed-phase TiO2 as optical gauge of molecular oxygen with ratiometric-enhanced responsivity

We show that mixed-phase (MP) titanium dioxide (TiO2) can be effectively employed as an unconventional, inorganic, dual-emitting and ratiometric optical sensor of O2. Thanks to the peculiar “anti-correlated” photoluminescence of the two TiO2 crystal phases, MP-TiO2 exhibits an unusual ratiometric-enhanced responsivity. Simultaneous availability of rutile and anatase TiO2 PL allows using their ratio as measurement parameter associated to O2 concentration, leading to larger experimental responsivity compared to the one obtainable for single-phase PL detection. A proof of this concept is given, showing a two-fold enhancement of the optical responsivity. Additional characteristics of mixed phase TiO2 can be envisaged as favorable for O2 optical probing, namely: (a) low production costs, (b) absence of heterogeneous components, (c) self-supporting properties. These characteristics promote testing mixed phase TiO2 use for applications requiring high indicator quantities at competitive price, possibly also tackling the need to develop supporting matrixes that carry the luminescent probes and avoiding issues related to the use of different components for ratiometric sensing

Laser ablation and deposition of titanium dioxide with ultrashort pulses at 527 nm

We report an experimental analysis on laser ablation and deposition of TiO2 with ≈300-fs, 527-nm ultrashort laser pulses. We particularly address the following: (1) the dependence of the deposition rate on the laser fluence, in high-vacuum conditions; (2) the effect of an oxygen background gas pressure on the expansion of the ablated species and on the deposition rate. Two different regimes are observed for the dependence of the deposition rate in high vacuum: The first one governed by two-photon absorption occurring close to the ablation threshold is, then, followed by the second, thermal dependence at larger fluences. The propagation of the atomic and nanoparticulate plumes produced in ultrashort laser ablation are influenced in a quite different way by the background gas pressure, which eventually reflects on the variation of the deposition rate with pressure. Moreover, it is observed that the ablated material is predominantly composed of nanoparticles (≈70 %), similar to what was reported before in the case of elemental metallic targets. Finally, plume deposition results in the formation of nanoparticle-assembled films with a variation of the characteristics morphology with the background gas pressure