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.

Transcriptional regulation of miR528-PPO module by miR156 targeted SPLs orchestrates chilling response in banana.

Banana is sensitive to cold stress and often suffers from chilling injury with browning peel and failure to normal ripening. We have previously reported that banana chilling injury is accompanied by a reduction of miR528 accumulation, alleviating the degradation of its target gene MaPPO and raising ROS levels that cause peel browning. Here, we further revealed that the miR528-MaPPO cold-responsive module was regulated by miR156-targeted SPL transcription factors, and the miR156c-MaSPL4 module was also responsive to cold stress in banana.

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.

Evolving Paradigms in Spinal Surgery: A Systematic Review of the Learning Curves in Minimally Invasive Spine Techniques.

Our research examines the learning curves of various minimally invasive lumbar surgeries to determine the benefits and challenges they pose to both surgeons and patients. The advent of microsurgical techniques since the 1960s, including advances in fluoroscopic navigation and intraoperative computed tomography, has significantly shifted spinal surgery from open to minimally invasive methods. This study critically evaluates surgical duration, intraoperative conversions to open surgery, and complications as primary parameters to gauge these learning curves.

Effect of composite yeast culture on the jejunal barrier function, inflammatory response, and microbial community structure of laying hens during the late stage of egg production.

During the late laying period, the intestinal barrier of laying hens is susceptible to damage, resulting in enteric infections and even systemic inflammatory responses, posing a major challenge for the poultry industry. Therefore, it is crucial to investigate methods for addressing intestinal inflammation in late laying hens. In order to maximize the production potential of egg laying chickens, farmers usually use various feed additives to prevent damage to the intestinal barrier.