2017 -pSS and acute pancreatitis

2017 -pSS and acute pancreatiti

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