Cobalt-Catalyzed Biaryl Couplings via C–F Bond Activation in the Absence of Phosphine or NHC Ligands

A highly general and selective Co-catalyzed biaryl coupling through C–F cleavage under phosphine or NHC-free conditions was described. A broad range of aryl fluorides including unactivated fluorides as well as those with sensitive functionalities could couple with various Ti­(OEt)₄-mediated aryl Grignard reagents with high selectivity under the catalysis of CoCl₂/DMPU. Importantly, selective C–F bond activation couplings between two types of fluorines (difluorinated aromatics and on two different coupling partners) and in the presence of C–Cl or C–Br bonds could also be achieved

Characterization of Glutamine Deamidation by Long-Length Electrostatic Repulsion-Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry (LERLIC-MS/MS) in Shotgun Proteomics

Deamidation of glutamine (Gln) residues is a spontaneous or enzymatic process with significant implications in aging and human pathology. Although some methods are available to identify the γ/α-glutamyl products of deamidation, none of these methods allows the characterization of this post-translational modification (PTM) from complex biological samples by shotgun proteomics. Here we present LERLIC-MS/MS, a chromatographic strategy that uses a long (50 cm) anion-exchange capillary column operating in the electrostatic repulsion-hydrophilic interaction mode (ERLIC) and coupled directly to tandem mass spectrometry (MS/MS) for proteome analysis in a single injection. Profiling of soluble extracts of brain tissues by LERLIC-MS/MS distinguished for the first time γ/α-glutamyl isomers of deamidation, encountering a 1.7 γ/α-glutamyl ratio for most Gln deamidation products. A detailed analysis of any deviation from that observed ratio allowed the identification of transglutaminase-mediated γ-glutamyl isomers as intermediate products of transamidation. Furthermore, LERLIC-MS/MS was able to simultaneously separate Gln and asparagine (Asn) deamidation products even for those peptides showing multiple deamidated proteoforms. The characterization of Asn deamidated residues by LERLIC-MS/MS also uncovered novel PIMT (protein L-isoaspartyl methyltransferase) substrate proteins in human brain tissues that deviated from the expected 3:1 isoAsp/Asp ratio. Taken together, our results demonstrate that LERLIC-MS/MS can be used to perform an in-depth study of protein deamidation on a global proteome scale. This new strategy should help to elucidate the biological implications of deamidation in aging and disease conditions

Characterization of Glutamine Deamidation by Long-Length Electrostatic Repulsion-Hydrophilic Interaction Chromatography-Tandem Mass Spectrometry (LERLIC-MS/MS) in Shotgun Proteomics

Deamidation of glutamine (Gln) residues is a spontaneous or enzymatic process with significant implications in aging and human pathology. Although some methods are available to identify the γ/α-glutamyl products of deamidation, none of these methods allows the characterization of this post-translational modification (PTM) from complex biological samples by shotgun proteomics. Here we present LERLIC-MS/MS, a chromatographic strategy that uses a long (50 cm) anion-exchange capillary column operating in the electrostatic repulsion-hydrophilic interaction mode (ERLIC) and coupled directly to tandem mass spectrometry (MS/MS) for proteome analysis in a single injection. Profiling of soluble extracts of brain tissues by LERLIC-MS/MS distinguished for the first time γ/α-glutamyl isomers of deamidation, encountering a 1.7 γ/α-glutamyl ratio for most Gln deamidation products. A detailed analysis of any deviation from that observed ratio allowed the identification of transglutaminase-mediated γ-glutamyl isomers as intermediate products of transamidation. Furthermore, LERLIC-MS/MS was able to simultaneously separate Gln and asparagine (Asn) deamidation products even for those peptides showing multiple deamidated proteoforms. The characterization of Asn deamidated residues by LERLIC-MS/MS also uncovered novel PIMT (protein L-isoaspartyl methyltransferase) substrate proteins in human brain tissues that deviated from the expected 3:1 isoAsp/Asp ratio. Taken together, our results demonstrate that LERLIC-MS/MS can be used to perform an in-depth study of protein deamidation on a global proteome scale. This new strategy should help to elucidate the biological implications of deamidation in aging and disease conditions

DataSheet_1_Construction and validation of nomograms based on the log odds of positive lymph nodes to predict the prognosis of lung neuroendocrine tumors.docx

BackgroundThis research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs).MethodsWe collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell’s concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses.ResultsThe Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDSConclusionsWe created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.</p

Ultrasensitive and Ultraselective Impedimetric Detection of Cr(VI) Using Crown Ethers as High-Affinity Targeting Receptors

Detection of Cr­(VI) by electrochemical methods generally focuses on noble-metal-modified electrodes in strong acid solution using voltammetric techniques. In this work, we report a new strategy to detect Cr­(VI) as HCrO₄^– at pH 5.0 in drinking water using electrochemical impedance spectroscopy. The strategy is based on the high-affinity and specific binding of crown ethers (i.e., azacrown) to HCrO₄^–, which forms sandwich complexes between them via hydrogen bonds and moiety interactions with K⁺ captured by azacrown on its self-assembled Au electrode surface. This then blocks the access of redox probes (Fe­(CN)₆^3–/4–) to the self-assembled Au electrode, further resulting in an increase in the electron transfer resistance. This method offers a detection limit of 0.0014 ppb Cr­(VI) with a sensitivity of 4575.28 kΩ [log <i>c</i> (ppb)]⁻¹ over the linear range of 1–100 ppb (<i>R</i>² = 0.994) at pH 5.0. In addition, the azacrown self-assembled Au electrode has good selectivity for Cr­(VI) with good stability and low interferences. This approach can be performed on spiked Cr­(VI) as well as real samples. To the best of our knowledge, this is the first example of electrochemical impedimetric sensing that allows ultrasensitive and ultraselective detection of Cr­(VI)

Adsorbent Assisted <i>in Situ</i> Electrocatalysis: An Ultra-Sensitive Detection of As(III) in Water at Fe₃O₄ Nanosphere Densely Decorated with Au Nanoparticles

Most gold nanoparticle-based electrodes have been utilized for the analysis of highly toxic As­(III), while nano-Fe₃O₄ materials are currently attracting considerable interest as an adsorbent for the removal of As­(III). However, the combination of gold nanoparticles with Fe₃O₄ nanoadsorbents for stripping voltammetry is, to the best of our knowledge, unexplored. Here, a sensing interface for ultrasensitive detection of As­(III) is designed and constructed by abundantly dispersing Au nanoparticles (Au NPs) on the surface of the Fe₃O₄ nanosphere. The Au@Fe₃O₄ nanospheres are covered by the room temperature ionic liquid (RTIL) and then modified on the screen-printed carbon electrode (SPCE). By combining the excellent catalytic properties of the Au nanoparticles (∼3–9 nm in diameter) with the good adsorption capacity of Fe₃O₄ nanospheres toward As­(III), as well as the good conductivity of RTIL, the Au@Fe₃O₄-RTIL shows excellent performance in the detection of arsenic under nearly neutral conditions without modifying the morphology of the sensing interface. Through optimization of the experimental conditions, an ultrahigh sensitivity of 458.66 μA ppb^–1 cm^–2 from 0.1 to 1 ppb with a detection limit (3σ method) of 0.0022 ppb was obtained. The reproducibility and reliability of the Au@Fe₃O₄-RTIL sensing interface was also evaluated with good results. Finally, we used this platform to analyze real samples

Schematic representation of the artificial neural network developed to distinguish malignancy of thyroid nodules.

<p>Schematic representation of the artificial neural network developed to distinguish malignancy of thyroid nodules.</p

Classification Accuracy of ANN in Training and Validation Groups (561 nodules).

<p><i>ANN</i> artificial neural network; <i>PPV</i> positive predictive value; <i>NPV</i> negative predictive value.</p

Receiver operating characteristic curve analysis of the predictive accuracy of the models to predict malignancy of thyroid nodules in the training and validation cohorts.

<p>Receiver operating characteristic curve analysis of the predictive accuracy of the models to predict malignancy of thyroid nodules in the training and validation cohorts.</p

Classification Accuracy of ANN in Training and Validation Groups (689 nodules).

<p><i>ANN</i> artificial neural network; <i>PPV</i> positive predictive value; <i>NPV</i> negative predictive value.</p