5 research outputs found
Baseline characteristics of the ARD patient group and age- and sex-matched comparison group.
<p>Baseline characteristics of the ARD patient group and age- and sex-matched comparison group.</p
Incidence of dementia and Cox model results for the ARD patient group and the comparison group.
<p>Incidence of dementia and Cox model results for the ARD patient group and the comparison group.</p
Cumulative incidence plot of dementia among ARD and non-ARD patient group.
<p>(a) presents a comparison of the cumulative incidence of dementia for the ARD and non-ARD patient groups. (b) presents a comparison of the cumulative incidence of dementia for RA and non-ARD cohorts. (c) presents a comparison of the cumulative incidence of dementia for SS (primary SS and secondary SS) and non-ARD cohorts. (d) presents a comparison of the cumulative incidence of dementia for SLE and non-ARD cohorts.</p
Chemical Inhibition of Human Thymidylate Kinase and Structural Insights into the Phosphate Binding Loop and Ligand-Induced Degradation
Targeting thymidylate
kinase (TMPK) that catalyzes the phosphotransfer
reaction for formation of dTDP from dTMP is a new strategy for anticancer
treatment. This study is to understand the inhibitory mechanism of
a previously identified human TMPK (hTMPK) inhibitor YMU1 (<b>1a</b>) by molecular docking, isothermal titration calorimetry, and photoaffinity
labeling. The molecular dynamics simulation suggests that <b>1a</b> prefers binding at the catalytic site of hTMPK, whereas the hTMPK
inhibitors that bear pyridino[<i>d</i>]isothiazolone or
benzo[<i>d</i>]isothiazolone core structure in lieu of the
dimethylpyridine-fused isothiazolone moiety in <b>1a</b> can
have access to both the ATP-binding and catalytic sites. The binding
sites of hTMPK inhibitors were validated by photoaffinity labeling
and mass spectrometric studies. Taking together, <b>1a</b> and
its analogues stabilize the conformation of ligand-induced degradation
(LID) region of hTMPK and block the catalytic site or ATP-binding
site, thus attenuating the ATP binding-induced closed conformation
that is required for phosphorylation of dTMP