8 research outputs found

    Comparison between different baseline correction methods.

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    <p>Good (a) and bad (b) trial samples after preprocessing of fNIRS data. Solid cyan curves: the time window for RDSs viewing and black screen (28s for each trial). Black curves: subjective assessments and shut-eye rests (13.3s). The averaged response of good (c) and bad (e) trial samples using traditional time-course analysis (zero order baseline corrections). The averaged response of good (d) and bad (f) trial samples using curvilinear fitting baseline corrections.</p

    The correlation between subjective assessments and fNIRS data at group level (n = 11).

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    <p>The correlation between subjective assessments and fNIRS data at group level (n = 11).</p

    Illustration of the data processing.

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    <p>(a): a bad trial sample with large background noise; (b): extracted brain activity from the raw data; (c): fitting the data by two normal distribution functions.</p

    Quantification of Hemoglobin and White Blood Cell DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9<i>H</i>‑pyrido[2,3‑<i>b</i>]indole and 4‑Aminobiphenyl Formed in Humans by Nanoflow Liquid Chromatography/Ion Trap Multistage Mass Spectrometry

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    Aromatic amines covalently bound to hemoglobin (Hb) as sulfinamide adducts at the cysteine 93 residue of the Hb β chain have served as biomarkers to assess exposure to this class of human carcinogens for the past 30 years. In this study, we report that 2-amino-9<i>H</i>-pyrido­[2,3-<i>b</i>]­indole (AαC), an abundant carcinogenic heterocyclic aromatic amine formed in tobacco smoke and charred cooked meats, also reacts with Hb to form a sulfinamide adduct. A novel nanoflow liquid chromatography/ion trap multistage mass spectrometry (nanoLC-IT/MS<sup>3</sup>) method was established to assess exposure to AαC and the tobacco-associated bladder carcinogen 4-aminobiphenyl (4-ABP) through their Hb sulfinamide adducts. Following mild acid hydrolysis of Hb <i>in vitro</i>, the liberated AαC and 4-ABP were derivatized with acetic anhydride to form the <i>N</i>-acetylated amines, which were measured by nanoLC-IT/MS<sup>3</sup>. The limits of quantification (LOQ) for AαC- and 4-ABP-Hb sulfinamide adducts were ≤7.1 pg/g Hb. In a pilot study, the mean level of Hb sulfinamide adducts of AαC and 4-ABP were, respectively, 3.4-fold and 4.8-fold higher in smokers (>20 cigarettes/day) than nonsmokers. In contrast, the major DNA adducts of 4-ABP, <i>N</i>-(2′-deoxyguanosin-8-yl)-4-aminobiphenyl, and AαC, <i>N</i>-(2′-deoxyguanosin-8-yl)-2-amino-9<i>H</i>-pyrido­[2,3-<i>b</i>]­indole, were below the LOQ (3 adducts per 10<sup>9</sup> bases) in white blood cell (WBC) DNA of smokers and nonsmokers. These findings reaffirm that tobacco smoke is a major source of exposure to AαC. Hb sulfinamide adducts are suitable biomarkers to biomonitor 4-ABP and AαC; however, neither carcinogen binds to DNA in WBC, even in heavy smokers, at levels sufficient for biomonitoring

    Stability and Characteristics of the Halogen Bonding Interaction in an Anion–Anion Complex: A Computational Chemistry Study

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    Halogen bonding is the noncovalent interaction between the positively charged σ-hole of organohalogens and nucleophiles. In reality, both the organohalogen and nucleophile could be deprotonated to form anions, which may lead to the vanishing of the σ-hole and possible repulsion between the two anions. However, our database survey in this study revealed that there are halogen bonding-like interactions between two anions. Quantum mechanics calculations with small model complexes composed of halobenzoates and propiolate indicated that the anion–anion halogen bonding is unstable in vacuum but attractive in solvents. Impressively, the QM optimized halogen bonding distance between the two anions is shorter than that in a neutral system, indicating a possibly stronger halogen bonding interaction, which is verified by the calculated binding energies. Furthermore, natural bond orbital and quantum theory of atoms in molecule analyses also suggested stronger anion–anion halogen bonding than that of the neutral one. Energy decomposition by symmetry adapted perturbation theory revealed that the strong binding might be attributed to large induction energy. The calculations on 4 protein–ligand complexes from PDB by the QM/MM method demonstrated that the anion–anion halogen bonding could contribute to the ligands’ binding affinity up to ∼3 kcal/mol. Therefore, anion–anion halogen bonding is stable and applicable in reality

    Like-Charge Guanidinium Pairing between Ligand and Receptor: An Unusual Interaction for Drug Discovery and Design?

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    A database survey in this study revealed for the first time that there are 227 counterintuitive like-charge guanidinium pairings (Gdm<sup>+</sup>–Arg pairings) between ligands and receptors in the Protein Data Bank, implying the potential guanidinium–arginine binding between guanidine-containing drugs and their target proteins. Furthermore, there are 145 guanidine-containing molecules in the DrugBank, showing the prevalence of guanidinium groups in drugs. It has also been reported that the introduction of a guanidinium group forming Gdm<sup>+</sup>–Arg pairing improved the potency of the drug by more than 8-fold in a typical case. On the basis of the survey, six ligand–protein complexes with typical Gdm<sup>+</sup>–Arg pairings were chosen for QM/MM calculations. The calculations at the B97-D/6-311++g­(d,p) level revealed that the interaction could be as strong as −1.0 to −2.5 kcal/mol in DMSO and water, comparable to common intermolecular interactions. The calculations also unveiled that the Gdm<sup>+</sup>–Arg pairing interactions change from repulsive to attractive with the increase of dielectric constant, suggesting that the dielectric constant has a general stabilization effect on the Gdm<sup>+</sup>–Arg pairing. This study suggested that the like-charge guanidinium pairing interaction could be used not only for tuning the physical and chemical properties of drug leads but also for improving ligand binding affinity
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