Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy.

Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity.

A novel vector for magnetic resonance imaging-guided chemo-photothermal therapy for cancer.

As an effective strategy for oncotherapy, developing efficacious drug delivery systems for cancer combination therapy remains a major challenge. To improve nanodrug biocompatibility and composite function facilitating their clinical conversion application, a novel nanocarrier was presented by a facile method through conjugating humic acid with gadolinium ions to synthesize HA-Gd with good biocompatibility and dispersity. HA-Gd exhibited high photothermal conversion efficiency up to 38%, excellent photothermal stability, and high doxorubicin (DOX) loading capacity (93%) with pH-responsive release properties.

Simultaneous Maximum Likelihood Estimation for Piecewise Linear Instrumental Variable Models.

Analysis of instrumental variables is an effective approach to dealing with endogenous variables and unmeasured confounding issue in causal inference. We propose using the piecewise linear model to fit the relationship between the continuous instrumental variable and the continuous explanatory variable, as well as the relationship between the continuous explanatory variable and the outcome variable, which generalizes the traditional linear instrumental variable models. The two-stage least square and limited information maximum likelihood methods are used for the simultaneous estimation of the regression coefficients and the threshold parameters.