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.

Genetic insights into therapeutic targets for gout: evidence from a multi-omics mendelian randomization study.

Background: Considering that the treatment of gout is poor, we performed a Mendelian randomization (MR) study to identify candidate biomarkers and therapeutic targets for gout.

Methods: A drug-targeted MR study was performed for gout by integrating the gout genome-wide association studies (GWAS) summary data and cis expression quantitative trait loci of 2,633 druggable genes from multiple cohorts. Summary data-based Mendelian randomization (SMR) analyses based on transcript and protein levels were further implemented to validate the reliability of the identified potential therapeutic targets for gout.

Calibration verification for stochastic agent-based disease spread models.

Accurate disease spread modeling is crucial for identifying the severity of outbreaks and planning effective mitigation efforts. To be reliable when applied to new outbreaks, model calibration techniques must be robust. However, current methods frequently forgo calibration verification (a stand-alone process evaluating the calibration procedure) and instead use overall model validation (a process comparing calibrated model results to data) to check calibration processes, which may conceal errors in calibration.

Neuronal diversity and stereotypy at multiple scales through whole brain morphometry.

We conducted a large-scale whole-brain morphometry study by analyzing 3.7 peta-voxels of mouse brain images at the single-cell resolution, producing one of the largest multi-morphometry databases of mammalian brains to date. We registered 204 mouse brains of three major imaging modalities to the Allen Common Coordinate Framework (CCF) atlas, annotated 182,497 neuronal cell bodies, modeled 15,441 dendritic microenvironments, characterized the full morphology of 1876 neurons along with their axonal motifs, and detected 2.

Research on the simulation method of a BP neural network PID control for stellar spectrum.

This study investigated the multiple correlations among spectral simulation units based on digital micromirror device (DMD) spectral simulation, which leads to the problem that conventional spectral simulation methods such as PID control exhibit a low fitting accuracy or long fitting time in the spectral simulation of various targets. In this paper, a method of stellar spectrum simulation based on back propagation neural network-based PID (BP-PID) control is proposed to achieve high efficiency and high precision simulation of various spectral targets. The topology of the BP neural network was constructed based on the spectral modulation model of a DMD stellar spectrum simulation system, and the algorithm of the BP-PID control was designed.

Exploring causal associations between dietary intake and liver diseases: A bidirectional Mendelian randomization study.

Previous evidence suggests that dietary intake can affect liver diseases; However, the causal relationship between dietary intake and liver diseases remains unclear. To investigate this, we conducted a bidirectional Mendelian randomization (MR) analysis to comprehensively assess the potential causal relationship between dietary intake and liver diseases. Two-sample bidirectional MR was performed based on genome-wide association studies summary data from the UK Biobank and FinnGen database.

Comparative transcriptome analysis of maize ( L.) seedlings in response to copper stress.

Copper (Cu) is considered one of the major heavy metal pollutants in agriculture, leading to reductions in crop yield. To reveal the molecular mechanisms of resistance to copper stress in maize ( L.) seedlings, transcriptome analysis was conducted on the hybrid variety Zhengdan 958 exposed to 0 (control), 5, and 10 mM Cu stress using RNA-seq.

Spatial transcriptomic sequencing reveals immune microenvironment features of granulomas in lung and omentum.

Granulomas are a key pathological feature of tuberculosis (TB), characterized by cell heterogeneity, spatial composition, and cellular interactions, which play crucial roles in granuloma progression and host prognosis. This study aims to analyze the transcriptome profiles of cell populations based on their spatial location and to understand the core transcriptome characteristics of granuloma formation and development. In this study, we collected four clinical biopsy samples including (Mtb) infected lung (MTB-L) and omentum tissues (MTB-O), as well as two lung and omentum biopsies from non-TB patients.

A UAV Thermal Imaging Format Conversion System and Its Application in Mosaic Surface Microthermal Environment Analysis.

UAV thermal infrared remote sensing technology, with its high flexibility and high temporal and spatial resolution, is crucial for understanding surface microthermal environments. Despite DJI Drones' industry-leading position, the JPG format of their thermal images limits direct image stitching and further analysis, hindering their broad application. To address this, a format conversion system, ThermoSwitcher, was developed for DJI thermal JPG images, and this system was applied to surface microthermal environment analysis, taking two regions with various local zones in Nanjing as the research area.

Clinical value of modified Shenling Baizhu powder in treating targeted therapy-induced diarrhea in non-small cell lung cancer.

Objective: To assess clinical value of modified Shenling Baizhu powder (, SBP) in intervening targeted therapy-induced diarrhea.

Methods: This study was a prospective randomized controlled study. Eighty-five non-small cell lung cancer (NSCLC) patients with diarrhea who took targeted drugs were randomly divided into two groups.

Identification of HEPACAM2 as a novel and specific marker of small cell carcinoma.

Background: Small cell lung cancer (SCLC) is the most aggressive neuroendocrine lung cancer, with a dismal 5-year survival rate. No reliable biomarkers or imaging are available for early SCLC detection. In a search for a specific marker of SCLC, this study identified that hepatocyte cell adhesion molecule 2 (HEPACAM2), a member of the immunoglobulin-like superfamily, is highly and specifically expressed in SCLC.

HER2 status results in an unstable switch from primary to recurrent breast cancer.

Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression.

Investigation of the Mechanical Properties of Composite Honeycomb Sandwich Panels after Fatigue in Hygrothermal Environments.

Since carbon fibre composite sandwich structures have high specific strength and specific modulus, which can meet the requirements for the development of aircraft technology, more and more extensive attention has been paid to their residual mechanical properties after subjecting them to fatigue loading in hygrothermal environments. In this paper, the compression and shear characteristics of carbon fibre-reinforced epoxy composite honeycomb sandwich wall panels after fatigue in hygrothermal environments are investigated through experiments. The experimental results show that under compressive loading, the load required for the buckling of composite honeycomb sandwich wall panels after fatigue loading in hygrothermal environments decreases by 25.

Machine learning-based model for worsening heart failure risk in Chinese chronic heart failure patients.

Aims: This study aims to develop and validate an optimal model for predicting worsening heart failure (WHF). Multiple machine learning (ML) algorithms were compared, and the results were interpreted using SHapley Additive exPlanations (SHAP). A clinical risk calculation tool was subsequently developed based on these findings.

An Experimental Study on the Thermomechanical Coupling Effects of Carbon-Fiber-Reinforced Polyetheretherketone under Dynamic Impact.

Carbon-fiber-reinforced polyetheretherketone (CF/PEEK) composites are widely utilized in aerospace, medical devices, and automotive industries, renowned for their superior mechanical properties and high-temperature resistance. Despite these advantages, the thermomechanical coupling behavior of CF/PEEK under dynamic loading conditions is not well understood. This study aims to explore the thermomechanical coupling effects of CF/PEEK at elevated strain rates, employing Hopkinson bar impact tests and scanning electron microscopy (SEM) for detailed characterization.

Thyroid dysfunction and risk of different types of dementia: A systematic review and meta-analysis.

Background: The impact of thyroid function on the risk of various types of dementia, including Alzheimer's disease (AD) and vascular dementia (VD), remains unclear. This meta-analysis investigates the association between thyroid dysfunction and the risk of these dementia types, aiming to inform strategies for dementia prevention.

Methods: A comprehensive search was conducted in PubMed, Embase, and the Cochrane Library for studies published up to February 2023, focusing on the risk of thyroid dysfunction in dementia.

Platelet-rich plasma-derived exosomes promote blood-spinal cord barrier repair and attenuate neuroinflammation after spinal cord injury.

Spinal cord injury (SCI) compromises the blood-spinal cord barrier (BSCB) and induces neuroinflammation, potentially exacerbating neuronal damage. This underscores the importance of maintaining BSCB integrity and mitigating neuroinflammation in SCI treatment. Our study explores an innovative approach to treating SCI by utilizing platelet-rich plasma-derived exosomes (PRP-Exos) to stabilize BSCB function and alleviate neuroinflammation.