Joint effects of household ventilation and indoor air pollutants on lung cancer risk.

a<p>High-temperature cooking oil and coal used for cooking were included in kitchen ventilation, solid fuels used for heating was included in bedroom ventilation while ever smoking and secondhand smoke at home were included in both kitchen and bedroom ventilation.</p>b<p>Adjusted for age (continuous), gender, education level (illiterate/primary school/middle school/high school/college), income 10 years ago (Yuan/year, continuous), body mass index (kg/m², continuous), family history of lung cancer (yes/no), pack-years of smoking (continuous), ethanol consumption (ml/week, continuous), and study area (Dafeng/Ganyu).</p>c<p>The joint effects category for further estimation of additive interaction.</p>d<p>The reference category for measures of interaction on additive scale.</p

Characteristics of cases and controls.

a<p>Based on Chi-squared tests.</p>b<p>Chinese recommend standard was used for the cut-off points of overweight and obesity: underweight (BMI <18.5), normal weight (BMI 18.5–23.9), overweight (BMI 24.0–27.9), obese (BMI≥28.0).</p

Distribution of factors related to indoor air pollution and their associations with lung cancer risk.

a<p>Adjusted for age (continuous), gender, education level (illiterate/primary school/middle school/high school/college), income 10 years ago (Yuan/year, continuous), body mass index (kg/m², continuous), family history of lung cancer (yes/no), pack-years of smoking (continuous), ethanol consumption (ml/week, continuous), and study area (Dafeng/Ganyu).</p

Joint effects of household ventilation and number of pollutant sources on lung cancer risk.

a<p>Adjusted for age (continuous), gender, education level (illiterate/primary school/middle school/high school/college), income 10 years ago (Yuan/year, continuous), body mass index (kg/m2, continuous), family history of lung cancer (yes/no), pack-years of smoking (continuous), ethanol consumption (ml/week, continuous), and study area (Dafeng/Ganyu).</p>b<p>The joint effects category for further estimation of additive interaction.</p>c<p>The reference category for measures of interaction on additive scale.</p

Discovery of (1<i>S</i>,2<i>R</i>,3<i>S</i>,4<i>S</i>,5<i>R</i>,6<i>R</i>)‑2-Amino-3-[(3,4-difluorophenyl)sulfanylmethyl]-4-hydroxy-bicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY3020371·HCl): A Potent, Metabotropic Glutamate 2/3 Receptor Antagonist with Antidepressant-Like Activity

As part of our ongoing efforts to identify novel ligands for the metabotropic glutamate 2 and 3 (mGlu_2/3) receptors, we have incorporated substitution at the C3 and C4 positions of the (1<i>S</i>,2<i>R</i>,5<i>R</i>,6<i>R</i>)-2-amino-bicyclo­[3.1.0]­hexane-2,6-dicarboxylic acid scaffold to generate mGlu_2/3 antagonists. Exploration of this structure–activity relationship (SAR) led to the identification of (1<i>S</i>,2<i>R</i>,3<i>S</i>,4<i>S</i>,5<i>R</i>,6<i>R</i>)-2-amino-3-[(3,4-difluorophenyl)­sulfanylmethyl]-4-hydroxy-bicyclo­[3.1.0]­hexane-2,6-dicarboxylic acid hydrochloride (LY3020371·HCl, <b>19f</b>), a potent, selective, and maximally efficacious mGlu_2/3 antagonist. Further characterization of compound <b>19f</b> binding to the human metabotropic 2 glutamate (hmGlu₂) site was established by cocrystallization of this molecule with the amino terminal domain (ATD) of the hmGlu₂ receptor protein. The resulting cocrystal structure revealed the specific ligand–protein interactions, which likely explain the high affinity of <b>19f</b> for this site and support its functional mGlu₂ antagonist pharmacology. Further characterization of <b>19f</b> in vivo demonstrated an antidepressant-like signature in the mouse forced-swim test (mFST) assay when brain levels of this compound exceeded the cellular mGlu₂ IC₅₀ value