Defective Mammary Epithelial Outgrowth in Transgenic EKAREV-NLS Mice: Correction via Estrogen Supplementation and Genetic Background Modification.

Fluorescent biosensors offer a powerful tool for tracking and quantifying protein activity in living systems with high temporospatial resolution. However, the expression of genetically encoded fluorescent proteins can interfere with endogenous signaling pathways, potentially leading to developmental and physiological abnormalities. The EKAREV-NLS mouse model, which carries a FRET-based biosensor for monitoring extracellular signal-regulated kinase (ERK) activity, has been widely utilized both in vivo and in vitro across various cell types and organs.

Target-regulated AgS/FeOOH heterojunction activity: a direct label-free photoelectrochemical immunosensor.

Myoglobin (Mb), an important cardiac marker, plays a crucial role in diagnosing, monitoring, and evaluating the condition of patients with cardiovascular diseases. Here, we propose a label-free photoelectrochemical (PEC) sensor for the detection of Mb through target regulated the photoactivity of AgS/FeOOH heterojunction. The AgS/FeOOH nanospindles were synthesized and served as a sensing platform for the fabrication of bio-recognized process for Mb.

Simultaneous multislice diffusion imaging using navigator-free multishot spiral acquisitions.

Purpose: This work aims to raise a novel design for navigator-free multiband (MB) multishot uniform-density spiral (UDS) acquisition and reconstruction, and to demonstrate its utility for high-efficiency, high-resolution diffusion imaging.

Theory And Methods: Our design focuses on the acquisition and reconstruction of navigator-free MB multishot UDS diffusion imaging. For acquisition, radiofrequency-pulse encoding was used to achieve controlled aliasing in parallel imaging in MB imaging.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Functionally-informed fine-mapping identifies genetic variants linking increased CHD1L expression and HIV restriction in monocytes.

Human Immunodeficiency Virus Type 1 (HIV) set-point viral load is a strong predictor of disease progression and transmission risk. A recent genome-wide association study in individuals of African ancestries identified a region on chromosome 1 significantly associated with decreased HIV set-point viral load. Knockout of the closest gene, CHD1L, enhanced HIV replication in vitro in myeloid cells.

Rapid Development of High Concentration Protein Formulation Driven by High-Throughput Technologies.

Background: High concentration protein formulation (HCPF) development needs to balance protein stability attributes such as conformational/colloidal stability, chemical stability, and solution properties such as viscosity and osmolality.

Methodology: A three-phase design is established in this work. In Phase 1, conformational and colloidal stability are measured by 384-well-based high-throughput (HT) biophysical screening while viscosity reduction screening is performed with HT viscosity screening.

Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

The Canadian Experience With Magnetic Esophageal Anastomosis: A Report From the Canadian Consortium for Research in Pediatric Surgery Study (CanCORPS).

Objective: Magnetic anastomosis is an innovative technique for establishing esophageal continuity in infants born with esophageal atresia. Few case series featuring this technology have been published, with even fewer reports on complications. We present the entire Canadian experience with this approach.

Diabetic foot ulcer in the Western Pacific Region: Current data on ulceration rates and microbial profiles, gaps and charting strategies.

The Western Pacific Region hosts the largest proportion of people with diabetes. Despite being a key diabetes-related complication, diabetic foot ulcer has been neglected in both prevention and treatment efforts. This narrative review highlights available data on the burden (either prevalence or incidence), as well as microbial profiles of diabetic foot ulcers in the Western Pacific Region, identifies data gaps, and discusses strategies to address these gaps.

Ex vivo assessment of human neutrophil motility and migration.

Neutrophils are pivotal in orchestrating tumor-induced systemic inflammation and are increasingly recognized for their critical involvement in both the initiation and progression of cancer. A fundamental facet of neutrophil biology is their migratory capacity, which enables them to extravasate and infiltrate tumors in other tissues, where they carry out essential effector functions. Unraveling the intricate mechanisms of neutrophil motility and migration is crucial for comprehending immune responses and inflammatory processes, shedding light on their substantial contribution to cancer progression.

The New Niche: Transcatheter Aortic Valve Explantation and the Key Issues Concerning the Heart Team.

The volume of transcatheter aortic valve implantation (TAVI) for treatment of isolated aortic stenosis has far surpassed surgical aortic valve replacement (SAVR). There has been a consequent increase in TAVI explantation, now the fastest growing cardiac surgical procedure. Transcatheter heart valve explantation can be technically complex, with higher perioperative morbidity and mortality than routine SAVR or valve-in-valve TAVI.

Bio-fabrication of chitosan-stabilized magnesium oxide nanomaterials: Investigation of photocatalytic, in vitro cytotoxicity activities and apoptosis in oral squamous carcinoma cells.

A bio-fabrication approach is a novel way to develop chitosan-stabilized magnesium oxide nanomaterials (cMgO-NMs). The process involves utilizing polymeric chitosan as the reducing and stabilizing agent. The characteristics of the developed cMgO-NMs were determined using various spectroscopical techniques.

Persistent pollutant exposure impacts metabolomic profiles in polar bears and ringed seals from the High Arctic and Hudson Bay, Canada.

Metabolomics measures low molecular weight endogenous metabolites and changes linked to contaminant exposure in biota. Few studies have explored the relationship between metabolomics and contaminants in Arctic wildlife. We analyzed 239 endogenous metabolites and ∼150 persistent organic pollutants (POPs), including total mercury (THg), in the liver of polar bears and their ringed seal prey harvested from low Canadian Arctic (western Hudson Bay; WHB) and high Arctic (HA) locations during 2015-2016.

MoS nanoflowers surface decorated with CuS nanorods and carbon dots for fluorescent and ultrasound imaging in cancer therapy.

In recent years, the design of various ultrasound responsive echogenic nanomaterials offers many advantages such as deep tissue penetration, high signal intensity, colloidal stability, biocompatibility and less expensive for ultrasound-based cancer cell imaging while providing the option to monitor the progress of tumor volume during the treatment. Further, the ability of nanomaterials to combine photo-thermal therapy (PTT) and chemotherapy has opened a new avenue in the development of cancer theranostics for synergistic cancer therapy. Herein, we report MoS nanoflowers (NFs) surface decorated with CuS nanorods (NRs) and folic acid-derived carbon dots (FACDs) using cystine-polyethyleneimine (PEI) linker for PTT-chemotherapy.

Actionable Gene Alterations Identified in Patients With Malignant Melanoma by Targeted Sequencing in Japan.

Purpose: Precision medicine plays an important role in the treatment of patients with advanced melanoma. Despite its high incidence in White patients, advanced melanoma is rare in Asian countries, hampering prospective clinical trials targeting the Asian population. This retrospective study aimed to elucidate the real-world molecular diagnoses and outcomes of Japanese patients with melanoma using comprehensive genome profiling (CGP).

A Dual-Channel Fluorescence Probe for Early Diagnosis and Treatment Monitoring of Acute Kidney Injury by Detecting HOCl and Cys with Different Fluorescence Signals.

The pathogenesis of acute kidney injury (AKI) is a multifaceted process involving various mechanisms, with oxidative stress playing a crucial role in its development. Hypochlorite (HOCl) and cysteine (Cys) are indicators of oxidative stress in AKI pathophysiology, directly reflecting the degree of oxidative stress and disease severity. However, their exact mechanism of action in AKI pathophysiology remains unknown.

Biomarkers of RV Dysfunction in HFrEF Identified by Direct Tissue Proteomics: Extracellular Proteins Fibromodulin and Fibulin-5.

Background: Right ventricular dysfunction (RVD) is common in patients with heart failure with reduced ejection fraction, and it is associated with poor prognosis. However, no biomarker reflecting RVD is available for routine clinical use.

Methods: Proteomic analysis of myocardium from the left ventricle and right ventricle (RV) of patients with heart failure with reduced ejection fraction with (n=10) and without RVD (n=10) who underwent heart transplantation was performed.

Structure-activity relationship expansion and microsomal stability assessment of the 2-morpholinobenzoic acid scaffold as antiproliferative phosphatidylcholine-specific phospholipase C inhibitors.

Dysregulation of choline phospholipid metabolism and overexpression of phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in various cancers. Current known enzyme inhibitors include compounds based on a 2-morpholino-5--benzylamino benzoic acid, or hydroxamic acid, scaffold. In this work, 81 compounds were made by modifying this core structure to explore the pharmacophore.

Absence of Cysteine and Iron Chelation Induces Ferroptosis in Triple-Negative Breast Cancer Cells.

Background: Ferroptosis is a recently studied form of programmed cell death characterized by lipid peroxides accumulation in the cells. This process occurs when a cell's antioxidant capacity is disturbed resulting in the inability of the cell to detoxify the toxic peroxides. Two major components that regulate ferroptosis are cysteine and iron.

Prevalence of "weak B" phenotypes and their evaluation and differentiation in healthy blood donor population in Eastern India.

Background: Examples of group B red cells that react weakly or not at all with anti-B have been described. Subgroups of B such as B, B, B, and B are rare and are less frequently reported. We studied the frequency of subgroups of B in our healthy blood donor population and serologically characterized and differentiated these subgroups.

Incident thrombocytopenia and bleeding risk in elderly patients with atrial fibrillation on direct oral anticoagulants: insights from the ATHEROsclerosis in Atrial Fibrillation study.

Background: The bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated.

Defects Calculation and Accelerated Interfacial Charge Transfer in a Photoactive MOF-Based Heterojunction.

Photocatalytic hydrogen production is currently considered a clean and sustainable route to meet the energy and environmental issues. Among, heterojunction photocatalysts have been developed to improve their photocatalytic efficiency. Defect engineering of heterojunction photocatalysts is attractive due to it can perform as electron trap and change the band structure to optimize the interfacial separation rate of photogenerated electron-hole pairs.

Dietary flaxseed: Cardiometabolic benefits and its role in promoting healthy aging.

Flaxseed, a rich source of omega-3 polyunsaturated fatty acid alpha-linolenic acid (ALA), lignans, and soluble fiber, has attracted attention for its potential to improve multiple cardiometabolic risk factors. While its benefits are well-recognized, comprehensive evaluations of its direct impact on clinical outcomes, such as the prevention or progression of cardiometabolic diseases, remain limited. Additionally, its potential to support healthy aging and longevity through fundamental biological mechanisms has not been fully elucidated.