Metabolic Signatures of Lung Cancer in Biofluids: NMR-Based Metabonomics of Blood Plasma

In this work, the variations in the metabolic profile of blood plasma from lung cancer patients and healthy controls were investigated through NMR-based metabonomics, to assess the potential of this approach for lung cancer screening and diagnosis. PLS-DA modeling of CPMG spectra from plasma, subjected to Monte Carlo Cross Validation, allowed cancer patients to be discriminated from controls with sensitivity and specificity levels of about 90%. Relatively lower HDL and higher VLDL + LDL in the patients' plasma, together with increased lactate and pyruvate and decreased levels of glucose, citrate, formate, acetate, several amino acids (alanine, glutamine, histidine, tyrosine, valine), and methanol, could be detected. These changes were found to be present at initial disease stages and could be related to known cancer biochemical hallmarks, such as enhanced glycolysis, glutaminolysis, and gluconeogenesis, together with suppressed Krebs cycle and reduced lipid catabolism, thus supporting the hypothesis of a systemic metabolic signature for lung cancer. Despite the possible confounding influence of age, smoking habits, and other uncontrolled factors, these results indicate that NMR-based metabonomics of blood plasma can be useful as a screening tool to identify suspicious cases for subsequent, more specific radiological tests, thus contributing to improved disease management.ERDF - Competitive Factors Thematic Operational ProgrammeFCT/PTDC/ QUI/68017/2006FCOMP-01-0124-FEDER-007439SFRH/BD/ 63430/2009National UNESCO Committee - L'Oréal Medals of Honor for Women in Science 200Portuguese National NMR Network - RNRM

Molecular Structure, Infrared Spectra, Photochemistry, and Thermal Properties of 1‑Methylhydantoin

The structural, vibrational, and photochemical study of 1-methylhydantoin (1-MH, C₄H₆N₂O₂) was undertaken by matrix isolation infrared spectroscopy (in argon matrix; 10 K), complemented by quantum chemical calculations performed at the DFT­(B3LYP)/6-311++G­(d,p) level of approximation. The theoretical calculations yielded the <i>C_s</i> symmetry structure, with planar heavy atom skeleton, as the minimum energy structure on the potential energy surface of the molecule. The electronic structure of this minimum energy structure of 1-MH was then studied in detail by means of the natural bond orbital (NBO) and atoms in molecules (AIM) approaches, allowing for the elucidation of specific characteristics of the molecule’s σ and π electronic systems. The infrared spectrum of the matrix-isolated 1-MH was fully assigned, also with the help of the theoretically predicted spectrum of the compound, and its UV-induced unimolecular photochemistry (λ ≥ 230 nm) was investigated. The compound was found to fragment to CO, isocyanic acid, methylenimine, and <i>N</i>-methyl–methylenimine. Finally, a thermal behavior investigation on 1-MH samples was carried out using infrared spectroscopy (10 K until melting), differential scanning calorimetry and polarized light thermal microscopy. A new polymorph of 1-MH was identified. The IR spectra of the different observed phases were recorded and interpreted

Statistical Analysis of Photoluminescence Decay Kinetics in Quantum Dot Ensembles: Effects of Inorganic Shell Composition and Environment

Discerning the kinetics of photoluminescence (PL) decay of packed quantum dots (QDs) and QD-based hybrid materials is of crucial importance for achieving their promising potential. However, the interpretation of the decay kinetics of QD-based systems, which usually are not single-exponential, remains challenging. Here, we present a method for analyzing photoluminescence (PL) decay curves of fluorophores by studying their statistical moments. A certain combination of such moments, named as the n-th order moments’ ratio, Rn, is studied for several theoretical decay curves and experimental PL kinetics of CdSe quantum dots (QDs) acquired by time-correlated single photon counting (TCSPC). For the latter, three different case studies using the Rn ratio analysis are presented, namely, (i) the effect of the inorganic shell composition and thickness of the core–shell QDs, (ii) QD systems with Förster resonance energy transfer (FRET) decay channels, and (iii) system of QDs near a layer of plasmonic nanoparticles. The proposed method is shown to be efficient for the detection of slight changes in the PL kinetics, being time-efficient and requiring low computing power for performing the analysis. It can also be a powerful tool to identify the most appropriate physically meaningful theoretical decay function, which best describes the systems under study

Cationic Half-Sandwich Iron(II) and Iron(III) Complexes with N‑Heterocyclic Carbene Ligands

The cationic piano-stool iron complexes containing the N-heterocyclic carbene ligand tethered to a tetramethylcyclopentadienyl ring [(Cp*-NHC)­Fe­(CO)­(L)]­[X] (L = NCMe, DMSO; X = BF₄, OTf) have been prepared and analyzed by spectroscopic, electrochemical, and crystallographic methods. Oxidation reactions of the cationic complex [(Cp*-NHC)­Fe­(CO)­(NCMe)]­[BF₄] (<b>2</b>) with silver tetrafluoroborate and <i>tert</i>-butyl hydroperoxide in acetonitrile yield the dicationic iron­(III) complexes [(Cp*-NHC)­Fe­(NCMe)₂]­[BF₄]₂ and [(Cp*-NHC)­Fe­(H₂O)]­[BF₄]₂, respectively. When the reaction of <b>2</b> with AgBF₄ is performed in dichloromethane, the cationic complex [(Cp*-NHC)­FeCl]­[BF₄] is obtained. These new iron­(III) complexes have been characterized by Mössbauer spectroscopy and in one case by X-ray diffraction studies. DFT calculations were used to rationalize experimental results. The cationic complex [(Cp*-NHC)­Fe­(CO)­(NCMe)]­[OTf] is catalytically active toward the reduction of benzaldehyde and acetophenone using phenylsilane under neat conditions and in the absence of visible light irradiation

Experimental Study on the Solubility of Carbon Dioxide in Systems Containing Ethane-1,2-diol + Water + Salt (Sodium Chloride or Calcium Carbonate)

The influence of salt concentration on the solubility of gases in aqueous solutions is of interest in many processes of the oil and gas processing industry. Here, we show the influence of the presence of different concentrations of sodium chloride or calcium carbonate on the solubility of carbon dioxide (CO₂) in mixtures of monoethylene glycol (MEG) and water by using a gas expansion method. From the experimental data, the solubility and Henry’s constant were measured as a function of pressure (from 0.1 to 0.5 MPa) and temperature (from 298 to 333 K), in pure water, pure MEG and in its equimolar mixture, using concentrations of salt up to saturation for all the studied solvents. The experimental data indicate that the increase in temperature decreases the CO₂ solubility in the liquid mixture, whereas pressure shows a positive linear influence on the dissolution of gas. The addition of salt reduced the CO₂ solubility in all mixtures due to the salting-out effect

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale &amp; Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting &amp; Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (&lt;60, 60-69, and &gt;_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 &amp; PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages &lt;60, 60-69, and &gt;_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791