Azo-Sulforhodamine Dyes: A Novel Class of Broad Spectrum Dark Quenchers

A rapid access to a novel class of water-soluble dark quencher dyes was achieved using an azo-coupling reaction between a fluorescent primary arylamine derived from a sulforhodamine 101 scaffold and a tertiary aniline equipped with different bioconjugatable groups. The thus obtained nonfluorescent azo-sulforhodamine hybrids display a broad quenching range spanning the visible to NIR regions. This was demonstrated through the preparation and enzymatic activation of FRET-based fluorogenic substrates of urokinase

Universal Dark Quencher Based on “Clicked” Spectrally Distinct Azo Dyes

The first synthesis of an heterotrifunctional molecular scaffold derived from the popular DABCYL azo dye quencher has been achieved. The sequential derviatization of this trivalent azobenzene derivative with two other nonfluorescent azo dyes (Black Hole Quencher BHQ-1 and BHQ-3) and through effective reactions from the “bioconjugation chemistry” repertoire has led to an universal dark quencher (UDQ). This “clicked” poly azo dye is able to turn off an array of fluorophores covering the UV/NIR (300–750 nm) spectral range

Selective Functionalization of Antimycin A Through an <i>N</i>‑Transacylation Reaction

Acylation of 3-(<i>N</i>-formylamino)­salicylic acids resulted in transacylation with loss of the formyl moiety. The reaction proceeds through a bis-<i>N</i>-acylated intermediate, which undergoes facile deformylation. This transacylation reaction has been employed for the site-specific functionalization of the mitochondrial poison antimycin A, affording several novel derivatives. The selective cytotoxicity of some of these derivatives toward cultured A549 human lung epithelial adenocarcinoma cells, in comparison with WI-38 normal human lung fibroblasts, illustrates one application of this transacylation reaction

Selective Functionalization of Antimycin A Through an <i>N</i>‑Transacylation Reaction

Acylation of 3-(<i>N</i>-formylamino)­salicylic acids resulted in transacylation with loss of the formyl moiety. The reaction proceeds through a bis-<i>N</i>-acylated intermediate, which undergoes facile deformylation. This transacylation reaction has been employed for the site-specific functionalization of the mitochondrial poison antimycin A, affording several novel derivatives. The selective cytotoxicity of some of these derivatives toward cultured A549 human lung epithelial adenocarcinoma cells, in comparison with WI-38 normal human lung fibroblasts, illustrates one application of this transacylation reaction

Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting

Nitroreductase (NTR) activities have been known for decades, studied extensively in bacteria and also in systems as diverse as yeast, trypanosomes, and hypoxic tumors. The putative bacterial origin of mito­chondria prompted us to explore the possible existence of NTR activity within this organelle and to probe its behavior in a cellular context. Presently, by using a profluorescent near-infrared (NIR) dye, we characterize the nature of NTR activity localized in mammalian cell mito­chondria. Further, we demonstrate that this mito­chondrially localized enzymatic activity can be exploited both for selective NIR imaging of mito­chondria and for mito­chondrial targeting by activating a mito­chondrial poison specifically within that organelle. This constitutes a new mechanism for mito­chondrial imaging and targeting. These findings represent the first use of mito­chondrial enzyme activity to unmask agents for mito­chondrial fluorescent imaging and therapy, which may prove to be more broadly applicable

Is the EuroSCORE II reliable to estimate operative mortality among octogenarians?

<div><p>Objectives</p><p>Concerns have been raised about the predictive performance (PP) of the EuroSCORE I (ES I) to estimate operative mortality (OM) of patients aged ≥80. The EuroSCORE II (ES II) has been described to have better PP of OM but external validations are scarce. Furthermore, the PP of ES II has not been investigated among the octogenarians. The goal of the study was to compare the PP of ES II and ES I among the overall population and patients ≥ 80.</p><p>Methods</p><p>The ES I and ES II were computed for 7161 consecutive patients who underwent major cardiac surgery in a 7-year period. Discrimination was assessed by using the c- index and calibration with the Hosmer-Lemeshow (HL) and calibration plot by comparing predicted and observed mortality.</p><p>Results</p><p>From the global cohort of 7161 patients, 832 (12%) were ≥80. The mean values of ES I and ES II were 7.4±9.4 and 5.2±9.1 respectively for the whole cohort, 6.3±8.6 and 4.7±8.5 for the patients <80, 15.1±11.8 and 8.5±11.0 for the patients ≥80. The mortality was 9.38% (≥80) versus 5.18% (<80). The discriminatory power was good for the two algorithms among the whole population and the <80 but less satisfying among the ≥80 (AUC 0.64 [0.58–0.71] for ES I and 0.67 [0.60–0.73] for the ES II without significant differences (p = 0.35) between the two scores. For the octogenarians, the ES II had a fair calibration until 10%-predicted values and over-predicted beyond.</p><p>Conclusions</p><p>The ES II has a better PP than the ES I among patients <80. Its discrimination and calibration are less satisfying in patients ≥80, showing an overestimation in the elderly at very high-surgical risk. Nevertheless, it shows an acceptable calibration until 10%- predicted mortality.</p></div

Calibration of ES I and ES II for in-hospital mortality among the overall population and according to age.

<p>Calibration of ES I and ES II for in-hospital mortality among the overall population and according to age.</p

Characteristics for the whole population and for both age groups.

<p>Characteristics for the whole population and for both age groups.</p

Observed and predicted mortality of the study population.

<p>Observed and predicted mortality of the study population.</p

Discrimination for in-hospital mortality among the overall population and according to age.

<p>Discrimination for in-hospital mortality among the overall population and according to age.</p