Development of Potent and Selective Inhibitors of Methylenetetrahydrofolate Dehydrogenase 2 for Targeting Acute Myeloid Leukemia: SAR, Structural Insights, and Biological Characterization.

Methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2), a pivotal mitochondrial enzyme in one-carbon metabolism, is significantly upregulated in various cancers but minimally expressed in normal proliferating cells. In contrast, MTHFD1, which performs similar functions, is predominantly expressed in normal cells. Therefore, targeting MTHFD2 with selective inhibitors holds promise for a broader therapeutic window with reduced toxicity and fewer side effects.

Evaluating the Efficacy and Safety of Botulinum Toxin in Treating Overactive Bladder in the Elderly: A Meta-Analysis with Trial Sequential Analysis of Randomized Controlled Trials.

Overactive bladder (OAB) significantly impairs quality of life in the elderly. Although the intradetrusor injection of botulinum toxin type A (BoNT-A) is a treatment option, its effects on older adults remain uncertain. This study aimed to evaluate the efficacy and safety of BoNT-A intradetrusor injections in elderly OAB patients through a systematic review and meta-analysis.

The levels of pattern-triggered immunity in the root and stembase of tomato cultivars positively correlate with the resistance to Ralstonia solanacearum.

Background: Bacterial wilt (BW), caused by Ralstonia solanacearum (Rs), is one of the most destructive diseases impacting a wide range of crops globally. The infection process is complex involving intricate interactions between the plant and Rs. Managing BW is challenging, and crop breeding remains the most effective strategy for disease control.

Adverse birth and obstetric outcomes in the offspring of male adolescent and young adult cancer survivors: A nationwide population-based study.

Background The growing population of male adolescent and young adult (AYA, 15-40 years old) cancer survivors has heightened interest in their reproductive health. However, studies have reported conflicting findings on the potential risks of cancer and its treatments on birth and obstetric outcomes. Methods We utilized encrypted identification numbers for both fathers and mothers to link three nationwide Taiwan datasets from 2004 to 2019, identifying 3,785 births with a paternal history of AYA cancer.

Versatile Strategy for the Chemoenzymatic Synthesis of Branched Human Milk Oligosaccharides Containing the Lacto-N-Biose Motif.

Human milk oligosaccharides (HMOs) exhibit prebiotic, antimicrobial, and immunomodulatory properties and confer significant benefits to infants. Branched HMOs are constructed through diverse glycosidic linkages and prominently feature the lacto-N-biose (LNB, Gal-β1,3-GlcNAc) motif with fucose and/or sialic acid modifications, displaying structural complexity that surpasses that of N- and O-glycans. However, synthesizing comprehensive libraries of branched HMO is challenging due to this complexity.

Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions.

The burgeoning field of microbiome research has profoundly reshaped our comprehension of human health, particularly highlighting the potential of probiotics and fecal microbiota transplantation (FMT) as therapeutic interventions. While the benefits of traditional probiotics are well-recognized, the efficacy and mechanisms remain ambiguous, and FMT's long-term effects are still being investigated. Recent advancements in high-throughput sequencing have identified gut microbes with significant health benefits, paving the way for next-generation probiotics (NGPs).

Garbage In, Garbage Out? Negative Impact of Physiological Waveform Artifacts in a Hospital Clinical Data Warehouse.

Hospitals around the world are deploying increasingly advanced systems to collect and store high-resolution physiological patient data for quality improvement and research. However, data accuracy, completeness, consistency, and contextual validity remain issues. This report highlights a data artifact known as waveform clipping in our hospital's physiological data capture system that went unnoticed for years, limiting data analysis and delaying several research projects.

Tetrabromobisphenol A induced p38-MAPK/AMPKα activation downstream-triggered CHOP signal contributing to neuronal apoptosis and death.

Tetrabromobisphenol A (TBBPA), a brominated flame retardant (BFR), has been implicated as the neurotoxic effects in mammalian. However, the exact mechanisms underlying TBBPA-induced neurotoxicity remain unclear. In the present study, Neuro-2a cells, a mouse neural crest-derived cell line, were used to examine the mechanism of TBBPA-induced neuronal cytotoxicity.

A Comparison of Scoring Systems to Identify Patients at Increased Risk From Traumatic Rib Fractures.

Introduction: Patients with rib fractures from traumatic injuries may suffer increased morbidity, an increased hospital stay, an increased length of time in the intensive care unit (ICU), pulmonary complications resulting in the need for mechanical ventilation, and increased mortality. Some studies have focused on developing specific scoring systems to triage and to help identify patients most at risk for the most severe complications. One such protocol is the RibScore.

Efficient synthesis of porous triazine-based macrocycles with 22-carbon and 6-nitrogen ring atoms and their adsorption/desorption of non-volatile organic compounds.

Porous triazine-based macrocycles with 22-carbon and 6-nitrogen ring atoms were efficiently synthesized and used for adsorbing bisphenol A, sulfamethoxazole, sodium dodecyl sulfate, and polyoxyethylene laural ether from aqueous media; after adsorption, simple extraction to desorb the guests from these porous macrocycles demonstrates a facile and efficient approach for porous materials to adsorb and desorb non-volatile organic compounds, thus being potentially applied to other surfactants or antibiotics.

Satisfaction with bladder management in community-dwelling patients with chronic spinal cord injury.

Background/purpose: This study aimed to assess the satisfaction of community-dwelling patients with chronic spinal cord injury (SCI) regarding bladder management and urological treatments.

Methods: A survey was conducted among patients with chronic SCI undergoing community health examinations in Taiwan. A total of 1275 patients with chronic SCI were surveyed to collect data on their initial bladder management, urological treatments, changes in bladder management, and satisfaction with current bladder management.

Enhancing indoor air quality and cardiopulmonary health in patients with asthma by photocatalytic oxidation and filters air cleaner.

Background: Air purifiers can enhance indoor air quality and health outcomes, and studies have primarily focused on filters and particulate matter (PM) in households. Photocatalytic oxidation (PCO) is a promising technique for eliminating gaseous pollutants and bioaerosols. However, no field study was conducted in household.

FZD5 controls intestinal crypt homeostasis and colonic Wnt surrogate agonist response.

The rapidly regenerating intestinal epithelium requires crypt intestinal stem cells (ISCs). Wnt/β-catenin signaling maintains crypt homeostasis and Lgr5+ ISCs, and WNT ligands bind Frizzled receptors (FZD1-10). Identifying specific FZD(s) essential for intestinal homeostasis has been elusive; however, bioengineered antagonists blocking Wnt binding to FZD5 and FZD8 deplete the gut epithelium in vivo, highlighting potential roles.

Expression of Viral DNA Polymerase in Synthetic Recombinant Adeno-Associated Virus Producer Cell Line Enhances Full Particle Productivity.

Recombinant adeno-associated virus (rAAV) is a widely used viral vector in gene therapy. To meet the growing clinical demand, a scalable production technology which can efficiently produce high-quality products is required. We have developed a synthetic biology strategy to generate HEK293-based cell lines which have integrated essential AAV and adenoviral helper genes and are capable of producing rAAV upon induction.

Corticosteroid effects on IL-10 and IL-1β in U937-derived macrophages: A model for Kawasaki disease-associated inflammation.

Background: Kawasaki disease (KD) is a pediatric vasculitis that has a predilection for coronary artery involvement. Activated macrophages play an important role in the destruction of the coronary arteries in KD. Although intravenous immunoglobulin (IVIG) is standard therapy, corticosteroids are sometimes given to patients at a higher risk of IVIG non-responsiveness.

Search for Soft Unclustered Energy Patterns in Proton-Proton Collisions at 13 TeV.

The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.

Environmental Effects on the Interfacial Chemical Reactions at RTV Silicone-Silica Interfaces.

Silicone sealants and adhesives are extensively used in construction, automotive, industrial, and electronic applications because they exhibit excellent mechanical properties, strong adhesion, and good weather resistance. Room-temperature vulcanized (RTV) silicones develop good adhesion to many substrates and do not require heat for curing, which leads to flexible use in many applications. Although it is known that various factors such as relative humidity and temperature affect the curing of the RTV silicone adhesives, the interfacial chemistry that occurs during the curing process is still poorly understood but critical for success in adhesive applications.

Correlation Between mRNA Expression of Activated Eosinophils and Air Pollutant Exposure in Patients With Asthma.

Background: Eosinophil activation is associated with asthma. Whether air pollution affects the activation of blood eosinophils in patients with asthma remains unknown. In this study, we investigated the correlation between transcriptional activity in eosinophils and air pollutant exposure in patients receiving different levels of Global Initiative for Asthma (GINA) treatment.

Enhanced performance of GaN-based thin-film flip-chip LEDs with reflective current blocking layers.

To further enhance the performance of GaN-based thin-film flip-chip light-emitting diodes (TFFC-LEDs), we designed and fabricated two sets of high-power blue chips with conventional and reflective current-blocking layers (CBL) The conventional CBL is composed of SiO, whereas the reflective CBL consists of SiO and a distributed Bragg reflector (DBR). We systematically characterized their optoelectronic performance. The results indicate that at an injection current of 350 mA, the light output power (LOP) and external quantum efficiency (EQE) of the TFFC-LEDs with a reflective CBL increased by 4.

Fast and slow waves in a chain of superconducting split-ring resonators with staggered coupling strengths.

The transmission and reflection spectra of a linear chain comprising superconducting split-ring resonators operating at 6 GHz, with staggered coupling strength are investigated. The collective mode and the associated transmission and reflection on resonances can be fully analyzed by employing finite-element simulations focused on the unit cell structure and an effective hopping model. Robust coupling energies, equivalent to approximately 4% of the resonant frequency, enable significant transmission through the collective modes.