Mitoxantrone inhibits and downregulates ER through binding at the DBD-LBD interface.

Targeting the estrogen receptor (ER or ERα) through competitive antagonists, receptor downregulators, or estrogen synthesis inhibition remains the primary therapeutic strategy for luminal breast cancer. We have identified a novel mechanism of ER inhibition by targeting the critical interface between its DNA-binding domain (DBD) and ligand-binding domain (LBD). We demonstrate that mitoxantrone (MTO), a topoisomerase II inhibitor, binds at this previously unexplored DBD-LBD interface.

Reoperations as an Outcome Indicator for Developmental Dysplasia of the Hip Treated at Walking Age.

Background: Reoperation is a major adverse event following surgical treatment but has yet to be used as a primary outcome measure in population studies to assess current treatments for developmental dysplasia of the hip (DDH). The purpose of the present study was to explore the risk factors associated with reoperations following procedures under anesthesia ("operations") for DDH in patients between the ages of 1 and 3.00 years, with the goal of deriving treatment recommendations.

The Potential for High-Priority Care Based on Pain Through Facial Expression Detection with Patients Experiencing Chest Pain.

Background And Objective: Cardiovascular disease (CVD), one of the chronic non-communicable diseases (NCDs), is defined as a cardiac and vascular disorder that includes coronary heart disease, heart failure, peripheral arterial disease, cerebrovascular disease (stroke), congenital heart disease, rheumatic heart disease, and elevated blood pressure (hypertension). Having CVD increases the mortality rate. Emotional stress, an indirect indicator associated with CVD, can often manifest through facial expressions.

The sequence-structure-function relationship of intrinsic ERα disorder.

The oestrogen receptor (ER or ERα), a nuclear hormone receptor that drives most breast cancer, is commonly activated by phosphorylation at serine 118 within its intrinsically disordered N-terminal transactivation domain. Although this modification enables oestrogen-independent ER function, its mechanism has remained unclear despite ongoing clinical trials of kinase inhibitors targeting this region. By integration of small-angle X-ray scattering and nuclear magnetic resonance spectroscopy with functional studies, we show that serine 118 phosphorylation triggers an unexpected expansion of the disordered domain and disrupts specific hydrophobic clustering between two aromatic-rich regions.

The Development of a System for Elbow Joint Range of Motion Measurement Based on Image Recognition and Myoelectric Signals.

After a fracture, patients have reduced willingness to bend and extend their elbow joint due to pain, resulting in muscle atrophy, contracture, and stiffness around the elbow. Moreover, this may lead to progressive atrophy of the muscles around the elbow, resulting in permanent functional loss. Currently, a goniometer is used to measure the range of motion, ROM, to evaluate the recovery of the affected limb.