Targeting the ERα DBD-LBD interface with mitoxantrone disrupts receptor function through proteasomal degradation.

The estrogen receptor (ER or ERα) remains the primary therapeutic target for luminal breast cancer, with current treatments centered on competitive antagonists, receptor down-regulators, and aromatase inhibitors. Despite these options, resistance frequently emerges, highlighting the need for alternative targeting strategies. We discovered a novel mechanism of ER inhibition that targets the previously unexplored interface between the DNA-binding domain (DBD) and ligand-binding domain (LBD) of the receptor.

Age-Dependent Contributions of Rare and Common Genetic Variation in Atrial Fibrillation.

Background: Genetic variation contributes to atrial fibrillation (AF), but its impact may vary with age. The Research Program contains whole-genome sequencing of data from 100 574 adult participants with linked electronic health records.

Methods: We assessed clinical, monogenic, and polygenic associations with AF in a cross-sectional analysis, stratified by age: <45 years (n=22 290), 45 to 60 years (n=26 805), and >60 years (n=51 659).

Robotic mitral annuloplasty using a semi-continuous three-suture technique with a flexible band.

Robotic mitral repair is often associated with longer ischaemic and cardiopulmonary bypass times, particularly early in the learning curve. We demonstrate a semi-continuous, three-suture technique for robotic annuloplasty that retains the mechanical principles of traditional interrupted sutures while leveraging the advantages of robotic precision and exposure. The use of pre-knotted sutures minimizes intra-cardiac knot tying, further enhancing procedural efficiency.

AtGH3.10 and JAR1 Produce 12-Hydroxyjasmonoyl-l-isoleucine from 12-Hydroxyjasmonic Acid in Arabidopsis thaliana.

Jasmonates are plant hormones that regulate plant defense and development. 7-iso-Jasmonoyl-l-isoleucine (JA-Ile) is a representative active jasmonate which is biosynthesized from 7-iso-jasmonic acid (JA) by the jasmonoyl-amido synthases JASMONATE RESISTANT 1 (JAR1) and AtGH3.10 in Arabidopsis thaliana.

Parental emotion socialization and internalizing problems in childhood and adolescence: A meta-analytic review.

Anxiety and depression symptoms and disorders are the leading child mental health problems in western societies. This systematic review evaluated how parental emotion socialization (ES) relates to children's internalizing problems (from birth to age 18 years). Three meta-analyses, evaluating supportive ( = 50, = 10,698), nonsupportive ES behaviors ( = 47, = 10,970), and elaboration ( = 6, = 867) were conducted.

Standardising cardiac CT-based personalised surgical planning and execution in congenital aortic valvar disease.

Background: Congenital aortic valvar disease represents a heterogeneous population with suboptimal surgical repair or replacement outcomes. We assess our approach and short-term outcomes in this population using cardiac CT evaluation for personalised surgical planning and execution.

Methods: We assessed patients who underwent aortic valvar surgery from February 2022 to August 2024.

Eplet mismatch analysis in kidney transplantation: from concept to clinical practice.

Eplet mismatch analysis offers a refined approach to assessing donor-recipient compatibility in kidney transplantation, surpassing conventional antigen-level human leukocyte antigen (HLA) matching in predicting immunologic outcomes. By identifying polymorphic amino acid residues on HLA molecules recognized by B cell receptors, this method quantifies immunologic risk. Clinical studies demonstrate that high eplet mismatch loads, particularly at HLA-DQ, are strongly associated with donor-specific antibody development, antibody-mediated rejection, and reduced graft survival.

A clinical practice review: management strategies and emerging approaches for anastomotic leakage following radical surgery for esophageal cancer.

Radical esophagectomy remains the cornerstone of curative treatment for esophageal cancer, but is frequently complicated by postoperative events, most notably anastomotic leakage. Anastomotic leakage, occurring in up to 30% of cases, is multifactorial in origin and significantly increases morbidity and mortality. This review aims to summarize current management strategies, highlight emerging therapies, and identify persistent clinical challenges related to this complication.

An Amino Acid-Based Self-Shrinking Supramolecular Bioactive Hydrogel - A Sustainable Platform for Wastewater Treatment and Water Purification.

This study investigates the unique syneresis (self-shrinking) behavior of N-Terminally Fmoc-protected amino acid, Fmoc-hPhe-OH (Fmoc-homo-L-phenylalanine, abbreviated in this work as hF)-based hydrogel, and its potential in environmental remediation applications. Fmoc-hPhe-OH (hF) forms a hydrogel in 50 mM phosphate buffer (PB) of pH 7.4.

High-Performance Anion Exchange Membranes with π-π Stacking and Hydrogen Bonding Bifunctional Units.

Strong intermolecular interactions facilitate the formation of efficient ion transport channels, which, in turn, significantly boost the performance of anion exchange membranes (AEMs). Herein, 9-anthracene methanol with both π-π stacking and hydrogen bonding intermolecular forces is used as a bifunctional unit to synthesize high-performance AEMs through the Friedel-Crafts superacid catalytic reaction for the first time. The π-π stacking in the bifunctional units can induce hydrophilic pyridine cations to aggregate, and the hydrogen bonding can provide transport sites for OH and water molecules in the hydrophobic component.

A Uniquely Structured Heteronuclear Cluster Cage with Anion-Templated Pentagons and Hexagons.

Constructing structurally sophisticated molecules with interesting properties is the goal of supramolecular chemistry. Herein, two heterometallic clusters, formulated respectively as [GdNi(μ-CO)(μ-NO)(μ-OH)(μ-OH)(μ-CO)(HO)]Cl·49HO·90MeOH (, H = -methyliminodiacetic acid) and [TbNi(μ-CO)(μ-NO)(μ-OH)(μ-OH)(HO)]Cl·50HO·130MeOH (), were obtained by the cohydrolysis of Ln (Ln = Gd, Tb) and Ni in the presence of H and triethylamine. The essentially isostructural cationic cluster cages are constructed by coexisting pentagons and hexagons whose formation is respectively templated by nitrate and oxalate ions.

A Sensitive and Comprehensive LC-MS/MS Method for the Analysis of Hallucinogens, Synthetic Cathinones, and Synthetic Cannabinoids in Urine Samples.

The laboratory analysis of new psychoactive substances and related drugs is crucial for accurate clinical and forensic diagnosis of poisonings. Given this, a new LC-MS/MS method for analyzing hallucinogens, synthetic cathinones, and synthetic cannabinoids in urine was developed. Urine samples were extracted using a liquid-liquid extraction protocol optimized via a multivariate experimental design.

Harnessing CoO/AgMoO/CeO ternary nanocomposites for solar light-induced degradation of anthropogenic dye contaminants.

A CoO/AgMoO/CeOternary nanocomposites photocatalyst was successfully synthesized through a straightforward ethanol-assisted chemical method. Comprehensive characterization of its structural and optical properties was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), UV-Vis diffuse reflectance spectroscopy (UV-DRS), and photoluminescence (PL) analysis. XRD analysis confirmed the presence of CoO, AgMoO and CeO in the ternary composite sample.

Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.

Dysregulated spine morphology is a common feature in the pathology of many neurodevelopmental and neuropsychiatric disorders. Overabundant immature dendritic spines in the hippocampus are causally related to cognitive deficits of Fragile X syndrome (FXS), the most common form of heritable intellectual disability. Recent findings from us and others indicate autophagy plays important roles in synaptic stability and morphology, and autophagy is downregulated in FXS neurons.

Acute kidney injury and subsequent risk of late-onset infection among extremely low gestational age newborns.

Objective: Determine whether acute kidney injury (AKI) is associated with subsequent late-onset infection (LOI) among extremely low gestational age newborns (ELGAN).

Study Design: Secondary analysis of participants in the Preterm Erythropoietin for Neuroprotection Trial. Infants surviving ≥7 days with sufficient serum creatinine data were included.

Prelude to the perfect storm: the many triggers of secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is an increasingly recognized disorder of immune hyperactivity that often leads to multiorgan failure and death. In adults, HLH is usually triggered by infection, malignancy, or an autoimmune/autoinflammatory disorder that precipitates a destructive cytokine storm. Treatment aims to deescalate the hyperimmunity by treating the triggers while interfering with the immune pathways that cause the morbidity.

Association of intraoperative end-tidal CO levels with postoperative outcomes: a patient-level analysis of two randomised clinical trials.

Background: The relationship between intraoperative end-tidal CO (etCO) levels and postoperative outcomes remains unclear. We conducted a post hoc analysis of two randomised trials in adults undergoing major surgery under general anaesthesia.

Methods: We re-analysed individual participant data comparing high or low positive end-expiratory pressure with low tidal volume intraoperative ventilation using a merged database derived from two randomised trials in non-obese (PROVHILO: ISRCTN70332574) and obese (PROBESE: NCT02148692) patients.

Off-label underdosing of edoxaban antithrombotic therapy for patients with atrial fibrillation and stable coronary artery disease: findings from the EPIC-CAD trial.

Objective: The impact of off-label underdosing of direct oral anticoagulants (DOACs) on clinical outcomes in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) remains unclear.

Methods: The EPIC-CAD trial (Edoxaban vs Edoxaban with antiPlatelet agent In patients with atrial fibrillation and Chronic stable Coronary Artery Disease) randomised patients with AF and stable CAD to receive either edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus single antiplatelet agent). Off-label underdosing was defined as low-dose edoxaban (30 mg once daily) without standard criteria for dose reduction.

Associations of body mass index, waist circumference, and weight-adjusted waist index with body composition and biomarkers: A multinational pooled analysis.

Background: The widely-used anthropometric indices, such as body mass index (BMI) and waist circumference (WC), have limitations in their use as indicators of body composition. Recent studies proposed weight-adjusted waist index (WWI=WC/√(body weight)) as an alternative index for body composition but it is unclear whether WWI reflects body composition in different racial/ethnic groups.

Objective: We examined the associations of WWI, BMI, and WC with dual-energy x-ray absorptiometry (DEXA)-measured body composition, biomarkers (fasting blood glucose, HDL-cholestrol, LDL-cholestrol, triglyceride), and handgrip strength.

Lonicera caerulea var. edulis in acute lung injury therapy: integrated chemical composition, anti-inflammation, antioxidation, and NF-κB cascades based on bioactivity-guided fractionation.

Ethnopharmacological Relevance: Lonicera caerulea var. edulis is an Oroqen medicine with fever relief, detoxification, and anti-inflammatory activities. However, pharmacological and chemical research on its leaves is limited.

Construction of melem/BiVO/g-CN photocatalyst with a conjugated S-scheme charge transfer pathway for boosting photocatalytic activity under LED light irradiation.

The development of novel multijunction heterostructure photocatalysts is critical for the efficient degradation of organic pollutants, attributed to their ability to enhance the separation of photogenerated electron-hole pairs. In our study, a ternary composite, melem/BiVO/g-CN (BVO/CNMH), was synthesized via an acid-soaking method followed by calcination, using g-CN as a sacrificial precursor in the presence of BiVO. This approach yielded a porous, interconnected architecture in BVO/CNMH.

Clinical outcomes following TAVR for patients with low and very low gradient aortic stenosis.

Objectives: This study explores the impact of lower baseline aortic valve (AV) mean gradients on the clinical outcomes of patients with low-gradient aortic stenosis (LG AS) post-transcatheter aortic valve replacement (TAVR). Additionally, the study aims to understand the predictors of a lower baseline AV mean gradient (MG).

Background: Reduced left ventricular ejection fraction (LVEF) and low-flow states are known to correlate with worse clinical outcomes.