Background When implantable cardioverter defibrillator (ICD) battery is depleted most patients undergo generator replacement (GR) even in the absence of persistent ICD indication. The aim of this study was to assess the incidence of ventricular arrhythmias and the overall prognosis of patients with and without persistent ICD indication undergoing GR. Predictors of 1-year mortality were also analyzed. Methods and Results Patients with structural heart disease implanted with primary prevention ICD undergoing GR were included. Patients were stratified based on the presence/absence of persistent ICD indication (left ventricular ejection fraction ≤35% at the time of GR and/or history of appropriate ICD therapies during the first generator's life). The study included 371 patients (82% male, 40% with ischemic heart disease). One third of patients (n=121) no longer met ICD indication at the time of GR. During a median follow-up of 34 months after GR patients without persistent ICD indication showed a significantly lower incidence of appropriate ICD shocks (1.9% versus 16.2%, P80 are significant predictors of 1-year mortality. Our findings enlighten the need of performing a comprehensive clinical reevaluation of ICD patients at the time of GR.Cysteine (Cys) is prone to diverse post-translational modifications in proteins, including oxidation into sulfenic acid (Cys-SOH) by reactive oxygen species generated under oxidative stress. Detection of low-concentration and metastable Cys-SOH within complex biological matrices is challenging due to the dynamic concentration range of proteins in the samples. Herein, visible laser-induced dissociation (LID) implemented in a mass spectrometer was used for streamlining the detection of Cys oxidized proteins owing to proper derivatization of Cys-SOH with a chromophore tag functionalized with a cyclohexanedione group. Once grafted, peptides undergo a high fragmentation yield under LID, leading concomitantly to informative backbone ions and to a chromophore reporter ion. Seventy-nine percent of the Cys-containing tryptic peptides derived from human serum albumin and serotransferrin tracked by parallel reaction monitoring (PRM) were detected as targets subjected to oxidation. These candidates as well as Cys-containing peptides predicted by in silico trypsin digestion of five other human plasma proteins were then tracked in real plasma samples to pinpoint the endogenous Cys-SOH subpopulation. Most of the targeted peptides were detected in all plasma samples by LID-PRM, with significant differences in their relative amounts. By eliminating the signal of interfering co-eluted compounds, LID-PRM surpasses conventional HCD (higher-energy collisional dissociation)-PRM in detecting grafted Cys-SOH-containing peptides and allows now to foresee clinical applications in large human cohorts.An efficient Cu(I)/DMAP/air system for the one-pot synthesis of 4-oxo-4H-cinnolin-2-ium-1-ides, which are often difficult to prepare by traditional routes from substituted 2-alkynylanilines and nitrosoarenes, was developed. These 4-oxo-4H-cinnolin-2-ium-1-ides have practical applications as mechanoluminescent materials. Preliminary mechanistic experiments were performed, and a plausible mechanism for this tandem process is proposed. The use of an inexpensive copper catalyst and molecular oxygen as the oxygen source and the oxidant make this an attractive green protocol with potential synthetic applications.Charge-separated states with a lifetime scale of seconds or longer not only favor studies using various steady-state analysis techniques but are important for light-energy conversion and other applications. Through a steric-hindrance-induced method, unprecedented photoinduced generation of a partially charge separated (PCS) state with a lifetime of days has been detected in the "visual" mode during the decay of excited states to a commonly observed fully charge separated (FCS) state for viologen analogues. One pale yellow 4,4'-bipyridine-based metalloviologen compound, with an interannular dihedral angle of 1.84° in 4,4'-bipyridine, directly decays to the purple FCS state after photoexcitation. The other pale yellow compound, with a similar coordination framework but a larger interannular dihedral angle (33.74°), changes first to a yellow PCS state and then relaxes slowly (in the dark in Ar, ca. 2 days; 70 °C in Ar, ca. 1 h) to the purple FCS state. The two-step coloration phenomenon is unprecedented for viologen compounds and their analogues and also rather rare for other photochromic species. EPR and Raman data reveal that photoinduced charge separation first generates univalent zinc and radicals and then the received electron in Zn(I) slowly distributes further to 4,4'-bipyridine. Reduction of π-conjugation and a direct to indirect change in band gap account for the prolongation of the relaxation process and the capture of the PCS state. These findings help to understand and control decay processes of excited states and provide a potential design strategy for multicolor photochromism, light-energy conversion with high efficiency, or other applications.Fusidic acid (FA) is a potent steroidal antibiotic that has been used in Europe for more than 60 years to treat a variety of infections caused by Gram-positive pathogens. Despite its clinical success, FA requires significantly elevated dosing (3 g on the first day, 1.2 g on subsequent days) to minimize resistance, as FA displays a high resistance frequency, and a large shift in minimum inhibitory concentration is observed for resistant bacteria. Despite efforts to improve on these aspects, all previously constructed derivatives of FA have worse antibacterial activity against Gram-positive bacteria than the parent natural product. Here, we report the creation of a novel FA analogue that has equivalent potency against clinical isolates of Staphylococcus aureus (S. aureus) and Enterococcus faecium (E. faecium) as well as an improved resistance profile in vitro when compared to FA. Importantly, this new compound displays efficacy against an FA-resistant strain of S. Brigatinib aureus in a soft-tissue murine infection model.