In Vitro Inhibition of Voltage-Dependent Sodium Currents by the Antifungal Drug Amorolfine.

Voltage-gated sodium (Nav) channels are critical for electrical signaling, and their pharmacological modulation can be leveraged for the development of therapeutic agents targeting various disorders. The local anesthetic (LA) site on Nav channels is particularly important, as it is a common target for many clinically used inhibitors, including anticonvulsants and antiarrhythmics. Our goal was to identify novel Nav channel inhibitors by leveraging physicochemical criteria, focusing on potential LA site binding candidates.

In vitro reconstitution reveals substrate selectivity of protein S-acyltransferases.

Protein S-acylation, commonly known as protein palmitoylation, is the most prevalent form of protein lipidation with ∼6000 target proteins and in humans, is catalyzed by 23 integral membrane enzymes of the zDHHC family. Recognition of its importance in cellular physiology as well as human diseases has undergone an explosive growth in recent years. Yet, the nature of zDHHC-substrate interactions has remained poorly understood for most zDHHC enzymes.

Utility of F-FDG PET/CT and Cardiac MRI in Early Cardiac Sarcoidosis.

Background And Aims: Although F-FDG-PET/CT and CMR are commonly used to diagnose cardiac sarcoidosis(CS), their clinical utility in early- vs. late-stage disease is unclear. The objective of this study was to compare the diagnostic utility of 18-fluorodeoxyglucose positron emission tomography/computed tomography(F-FDG-PET/CT) and cardiac magnetic resonance imaging(CMR) in patients with early- and late-stage CS.

CircRUNX1 enhances the Warburg effect and immune evasion in non-small cell lung cancer through the miR-145/HK2 pathway.

Non-small cell lung cancer (NSCLC) is acknowledged as the primary subtype of lung cancer. The Warburg effect, marked by elevated glucose consumption and lactate fermentation, is a prevalent characteristic of NSCLC. The mechanisms by which circRNA mediates the regulation of the Warburg effect and immune evasion in NSCLC remain unclear.

Designing the next generation of clinical trials in intermediate AMD- a consensus driven, pragmatic, proof of concept early intervention study.

A greater understanding of the pathophysiology of AMD has yielded potential therapeutic strategies for slowing vision loss. Structural imaging biomarkers and novel functional outcomes, both under intensive study as surrogate endpoints in AMD clinical trials, are new granular tools needed to assess disease progression and follow response to therapy. These advances have created, for the first time, the possibility to intervene early in AMD, and to measure success in a time frame feasible for clinical trials.

Retinal Imaging in an Era of Open Science and Privacy Protection.

Artificial intelligence (AI) holds great promise for analyzing complex data to advance patient care and disease research. For example, AI interpretation of retinal imaging may enable the development of noninvasive retinal biomarkers of systemic disease. One potential limitation, however, is government regulation regarding retinal imaging as biometric data, which has been recently under debate in the United States.

Prosocial Helping Behavior: Conceptual Issues and Neural Mechanisms.

Prosocial helping behavior, characterized by voluntary actions taken to benefit others, plays a vital role in promoting cooperation and maintaining social bonds across human and animal social groups. In this review, we examine key conceptual issues surrounding prosocial behavior, focusing specifically on targeted helping and comforting actions. We outline the behavioral paradigms used to study these two types of prosocial behaviors and summarize recent insights into their underlying neural mechanisms.

Temporal regulation of endoderm convergence and extension by the BMP activity gradient through mesoderm-dependent and independent mechanisms.

One hundred years ago, Spemann and Mangold identified the organizer, a critical embryonic region that establishes vertebrate body axes by directing cell fate and morphogenesis. A conserved vertebrate mechanism involves the regulation of a ventral-to-dorsal BMP activity gradient during gastrulation by the organizer-expressed molecules. In zebrafish, BMP signaling controls mesodermal cell convergence and extension (C&E) by inhibiting Planar Cell Polarity (PCP) signaling and regulating cell adhesion.

Psychiatric morbidities and Quality of Life Among Surgically Treated Noma Survivors. Preliminary observations in Nigerian cohorts.

Introduction: Facial disfigurement, a sequelae of Noma, has the potential to impact the mental and social well-being of survivors, predisposing them to psychiatric morbidities and low health-related quality of life (HRQoL). The aim of the study is to determine the psychiatric morbidities and QoL among Noma patients in Nigeria.

Material And Methods: A total of 41 participants were recruited and sociodemographic data were collected.

Safety and effectiveness of self-expanding TAVR in Japanese Dialysis patients with severe aortic stenosis: 1-year outcomes.

Background: In Japan, transcatheter aortic valve replacement (TAVR) with self-expanding valves (SEV) was approved for patients with severe aortic stenosis (AS) and on chronic maintenance dialysis in May 2023. This study assessed the safety and efficacy of TAVR with SEVs in this patient population.

Methods: This prospective, non-randomized, single-center study evaluated the safety and effectiveness of TAVR using a supra-annular SEV in Japanese patients with severe AS on chronic maintenance dialysis.

Tedizolid for osteoarticular infections: evaluation of the published evidence.

Introduction: Tedizolid phosphate, an oxazolidinone antibiotic, has been approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). However, its off-label use has been reported in various infections, including osteoarticular infections.

Methods: A systematic review of data from PubMed, Scopus, and Web of Science was conducted to evaluate the antimicrobial activity, safety, and effectiveness of tedizolid in patients with bone and joint infections, including prosthetic joint infections, osteomyelitis, and septic arthritis.

Orthopaedic Musculoskeletal Biologics Research Impacts Patient Care: The 3rd Annual Journal of Arthroscopy Orthobiologics Virtual Special Issue.

Orthobiologics represent a rapidly advancing field of research in musculoskeletal care, providing novel therapies to modify symptoms and potentially augment tissue regeneration when used in the clinical or operative setting. These treatments are derived from autologous cells, tissues, and blood components, yielding bioactive elements that may promote healing, reduce symptoms and be associated with improved patient outcomes. Biologic therapies such as platelet-rich plasma, bone marrow aspirate concentrate, adipose-derived products, and amniotic allograft tissues have demonstrated favorable clinical outcomes.

Metabolic reprogramming and synergistic cytotoxicity of genistein and chemotherapy in human breast cancer cells.

Breast cancer (BCa) is a heterogeneous disease, initially responsive to hormone therapy but often developing resistance to both hormonal and chemotherapy treatments. Novel therapeutic strategies are needed for drug-resistant BCa. Genistein, a phytoestrogen structurally similar to estrogen, competes with estrogen for receptor binding and exhibits anti-cancer effects.

Repeated Loading and Damage Progression in Cerebral Arteries.

Traumatic brain injury poses a major public health challenge with significant immediate and long-term effects. Repetitive head trauma is an ongoing area of research, and little is known about the response of cerebral blood vessels to such loading. This study investigated the mechanical response of cerebral arteries to repetitive overstretch, hypothesizing that repeated overstretch leads to cumulative damage.

Dual RNA-Seq Reveals Strain-Specific Transcriptional Adaptations of Trypanosoma cruzi in Host Cells Infected with Isolates from Acute and Chronic Cases.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health issue, particularly in Latin America, and is traditionally transmitted by triatomine bugs. Chagas disease progresses through two phases: an acute phase characterized by high parasitemia and a chronic phase, which may remain asymptomatic or develop into severe complications. This study utilized dual-RNAseq technology to analyze gene expression in mice fibroblast host cells infected with the strain JJ21 isolated from an acute Chagas disease case of presumptive oral transmission, comparing it with the MG strain isolated from a chronic Chagas disease human case.

Isolation and characterization a novel Acinetobacter bacteriophage with activity against several multidrug-resistant gram-negative bacteria.

Acinetobacter baumannii (A. baumannii) is a notorious nosocomial pathogen that is frequently associated with multidrug resistance around the world. Endolysin is a bacteriophage-produced hydrolytic enzyme.

A chemical-recovery-free ammonium sulfite-based alkali pretreatment of corn stover for low-cost sugar production via fertilizer use of waste liquor.

The production of cellulosic sugars is a pivotal strategy for advancing biomass bioconversion. This study evaluated the pretreatment of corn stover using ammonium sulfite and potassium hydroxide to develop comprehensive data on sugar, lignin, chemicals, and overall mass recovery profiles in a batch reactor at 80 °C. The results indicated significant improvements in delignification, deacetylation, enzymatic digestibility, and overall sugar yield.

Shared decision-making in FPIES.

Food protein induced enterocolitis syndrome (FPIES) is a non IgE-mediated food allergy presenting with profuse vomiting, lethargy and potential progression to severe dehydration and hypotension. Delayed-onset bloody diarrhea may also be a feature, though generally in neonates. FPIES can be misdiagnosed due to non-specific symptoms and the fact that there is no laboratory test specific for the disease.

Multi-Agent Large Language Model Frameworks: Unlocking New Possibilities for Optimizing Wastewater Treatment Operation.

Wastewater treatment plants (WWTPs) are highly complex systems where biological, chemical, and physical processes interact dynamically, creating significant operational challenges. Traditional modeling approaches, such as Activated Sludge Models (ASMs) and machine learning algorithms (MLAs), struggle to process the unstructured and multimodal data generated in WWTPs, limiting their effectiveness. Large Language Models (LLMs) offer a promising solution by integrating diverse data sources, recognizing patterns, and enabling human-in-the-loop interactions for informed decision-making.

Photobiomodulation therapy facilitates transplantation of dental pulp stem cells for spinal cord injury.

Background: While dental pulp stem cells (DPSCs) show therapeutic potential for spinal cord injury (SCI), post-traumatic oxidative stress and mitochondrial dysfunction critically compromise grafted cell survival. Photobiomodulation therapy (PBMT) is a noninvasive approach that may enhance regenerative efficacy. This study investigates whether PBMT improves the survival and neural differentiation of transplanted DPSCs in SCI models.

Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy.

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment.

Evaluation of oil and grease from roadway runoff in sediment from detention basins and swales within the Edwards Aquifer recharge zone, Central Texas, U.S.A.

In this study, we evaluated the oil and grease concentrations in sediment from roadway runoff in detention basins and swales following rain events. The study was conducted in three swales and two detention basins within the Edwards Aquifer recharge zone in San Antonio, Texas and one swale located in the contributing zone. The Edwards Aquifer is the primary source of municipal water for Bexar and surrounding counties and being a karst aquifer makes it susceptible to pollution.

Epidemiology, Natural History and Treatment of IBD in Africa: A Scoping Review.

Background: Inflammatory bowel diseases (IBD); Crohn's disease (CD), ulcerative colitis (UC)) are global diseases. There is a paucity of knowledge about the burden and epidemiology of IBD in Africa. We performed a scoping review of the published literature on IBD in Africa to identify burden, risk factors, and outcomes as well as knowledge gaps.

IRF2BP2 Deficiency: An important form of common variable immunodeficiency with inflammation.

Background: Interferon regulatory factor-2 binding protein-2 (IRF2BP2) is a transcription factor that plays an important role in regulating immune pathways, angiogenesis, apoptosis, and cell differentiation. Defects in this gene have been implicated in immunodeficiency.

Objective: To deepen the understanding of the clinical implications of IRF2BP2 variants, we sought to clinically characterize and functionally test thirty-four individuals with IRF2BP2 variants.