Targeting O-GlcNAcylated METTL3 impedes MDS/AML progression via diminishing SRSF1 mA modification.

N6-methyladenosine (mA) modification, primarily regulated by methyltransferase-like protein 3 (METTL3), plays a pivotal role in RNA metabolism and leukemogenesis. However, the post-translational mechanisms governing METTL3 stability and function remain incompletely understood. Given the widespread occurrence of O-GlcNAcylation on nuclear and cytosolic proteins, we hypothesized that METTL3 might undergo O-GlcNAcylation, thereby influencing its stability and oncogenic function in myeloid malignancies.

Deep learning-assisted system improves practical effect in cervical cytopathology diagnosis: A comparative study of reading modes.

Deep learning (DL) has significantly improved the diagnostic accuracy and efficiency of cytopathologists. However, current DL-assisted reading modes have yet to be fully evaluated, and there is limited evidence regarding cytopathologists' preferences and experiences. This study employs a randomized, controlled, four-way crossover design to assess the effectiveness of four different reading modes in cervical cytopathology readings.

AI-augmented prediction of high-risk PINK1 variants associated with Parkinson's disease: integrating multilayered bioinformatics, MD simulation, and deep learning.

Parkinson's disease is a prevalent neurodegenerative disease, in which genetic mutations in many genes play an important role in its pathogenesis. Among these, a mutation in the PINK1 gene, a mitochondrial-targeted serine/threonine putative kinase 1 that protects cells from stress-induced mitochondrial dysfunction, is implicated in autosomal recessive Parkinsonism. However, the exact etiology is not well understood.

Dispensing of antibiotics without prescription in community drug retail outlets of Bahir Dar city in Northwest Ethiopia: A simulated client visit before and after educational intervention.

Objectives: Non-prescription supply of antibiotics in community drug retail outlets (CDROs) significantly contributes to antibiotic resistance (ABR). This study aimed to assess the effectiveness of educational intervention for pharmacy practitioners (PPs) in reducing over-the-counter (OTC) antibiotic sales.

Methods: From August 1, 2022 to January 30, 2023 a total of 80 simulated client (SC) visits (40 pre-intervention; 40:post-intervention) were made in 40 CDROs of Bahir Dar city, to determine the baseline and post-intervention extent of OTC sale of antibiotics.

Biochar amendment improves Morchella sextelata yield by enhancing soil NO-N availability and increasing the diversity while decreasing the absolute abundance of fungal community.

Black morel (Morchella sextelata) is widely regarded as a post-fire mushroom because of its prolific fruiting in post-fire forest soils enriched with charcoal. Intriguingly, artificial cultivation of M. sextelata often incorporates biochar as a soil amendment to enhance yield, although the underlying physicochemical and ecological mechanisms remain unclear.

Facet-dependent Heterogeneous Fenton Reaction Mechanisms on Hematite Nanoparticles for (Photo)catalytic Degradation of Organic Dyes.

Although heterogeneous photo-Fenton reactions on nanoparticulate iron oxides effectively degrade organic pollutants, the underlying surface mechanisms remain debated. Here, we demonstrate how these pathways are modulated by specific hematite crystal facets. To investigate the influence of particle surface structure, methylene blue (MB) adsorption and photodegradation kinetics are examined using facet-engineered hematite nanoparticles with distinct exposed facets.

Divergent leaf water strategies in three coexisting desert shrub species: from the perspective of hydraulic, stomatal, and economic traits.

Leaves constitute a vital bottleneck in whole-plant water transport, and their water strategies are key determinants of plant competition and productivity. Nonetheless, our knowledge of leaf water strategies predominantly stems from single perspectives (i.e.

Indole-3-Lactic Acid Inhibits Keratinocyte Proliferation Through the Aryl Hydrocarbon Receptor in Psoriasis.

Psoriasis is a chronic inflammatory skin disease whose pathogenesis involves dysregulation of the skin microbiota. Multiple studies have revealed alterations in microbial community composition between psoriatic lesions and healthy skin. However, the metabolic pathways of the skin microbiota, particularly those involving tryptophan metabolism, remain poorly understood.

A multi-tissue single-cell expression atlas in cattle.

Systematic characterization of the molecular states of cells in livestock tissues is essential for understanding the cellular and genetic mechanisms underlying economically and ecologically important physiological traits. Here, as part of the Farm Animal Genotype-Tissue Expression (FarmGTEx) project, we describe a comprehensive reference map including 1,793,854 cells from 59 bovine tissues in calves and adult cattle, spanning both sexes, which reveals intra-tissue and inter-tissue cellular heterogeneity in gene expression, transcription factor regulation and intercellular communication. Integrative analysis with genetic variants that underpin bovine monogenic and complex traits uncovers cell types of relevance, such as spermatocytes, responsible for sperm motility and excitatory neurons for milk fat yield.

Naturally impaired side-chain shortening of aromatic 3-ketoacyl-CoAs reveals the biosynthetic pathway of plant acetophenones.

Acetophenones, which show scattered distribution across phylogenetically distant plants and fungi, play diverse roles in plant-plant, plant-insect, plant-microbiome and even animal-insect interactions. However, the enzymatic basis of acetophenone biosynthesis in plants remains unknown. Here we elucidate the complete biosynthetic pathway of picein (4-hydroxyacetophenone glucoside) from 4-coumaroyl-CoA using pear (Pyrus) as a study system.

A phase 2 randomized, placebo-controlled study on the efficacy and safety of AR1001, a phosphodiesterase-5 inhibitor, in patients with mild-to-moderate Alzheimer's disease.

Background: AR1001 is a phosphodiesterase-5 inhibitor that produces improved cognitive performance and reduces amyloid-β and phosphorylated tau burdens in preclinical models of Alzheimer's disease (AD).

Objectives: To evaluate the safety and efficacy of AR1001 in participants with mild-to-moderate Alzheimer's disease (AD).

Design: Randomized, double-blind, placebo-controlled phase 2 trial conducted at 21 sites in the United States.

Exercise with overdressing for heat acclimation: a multilayered approach using biophysical modeling and two randomized crossover trials.

Individuals who work in the heat, such as military personnel and athletes, are often required to rapidly transition from temperate or cooler climates to hot environments. Thus, acclimation strategies are needed for individuals lacking access to hot weather. We sought to develop and validate a practical exercise with overdressing protocol for heat acclimation.

Incidence and predictors of delirium in patients admitted to intensive care unit at comprehensive specialised hospitals in Amhara region, northwest Ethiopia: a multicentre prospective observational study.

Objective: To assess the incidence of delirium and its predictors among adult patients admitted to the intensive care units of comprehensive specialised hospitals in the Amhara region of northwest Ethiopia from 18 October 2024 to 20 February 2025.

Design: A multicentre prospective observational study was conducted.

Setting: Four comprehensive specialised hospitals in the Amhara region of northwest Ethiopia, from 18 October 2024 to 20 February 2025.

Effectiveness of silver dihydrogen citrate (SDC) and chlorine dioxide gas (ClO) as sanitation strategies for picking bags and storage bins at tree fruit production facilities.

Foodborne outbreaks and recalls within the tree fruit industry are making producers re-evaluate appropriate cleaning and sanitation practices during harvesting. Without effective sanitation, bacteria can create niches and form biofilms. This study evaluated the efficacy of silver dihydrogen citrate (SDC) and chlorine dioxide (ClO) gas to control Escherichia coli and Listeria innocua on experimentally inoculated harvesting equipment at commercial apple packinghouses within the Midwest and Pacific Northwest regions.

Quantification of carbohydrates in sugar beet roots by using ultra-fast liquid chromatography coupled with time of flight mass spectrometry.

The quantification of sucrose and other carbohydrates in sugar beet roots is essential prior to their processing to assess sugar production yield. In this study, a rapid, highly sensitive and selective ultra-fast liquid chromatography coupled with time of flight mass spectrometry (UFLC-ToFMS) method was developed and validated for the simultaneous analysis of monosaccharides (fructose, glucose-galactose), a disaccharide (sucrose), and a trisaccharide (raffinose). The method showed 1000-fold higher sensitivity, with LOD and LOQ ranging between 0.

The Fritillaria alkaloid peiminine acts as a chemosensitizer to potentiate oxaliplatin efficacy against gastric cancer.

Background: Fritillaria walujewii Regel (Xinjiang Bei-Mu), an authentic ("Dao-di") medicinal herb documented in Chinese pharmacopoeias, is traditionally used to treat respiratory disorders. Its principal steroidal alkaloid, peiminine (PMI), demonstrates significant anticancer activity. Oxaliplatin (Oxa), a first-line chemotherapeutic cornerstone for gastric cancer (GC), is limited clinically by intrinsic chemoresistance.

Efficacy of adjunctive lacosamide in children with drug-resistant epilepsy: A systematic review, meta-analysis and meta-regression.

Background: To systematically evaluate the efficacy, safety, and tolerability of adjunctive lacosamide (LCM) in children and adolescents with drug-resistant epilepsy (DRE).

Methods: A systematic review and single-arm meta-analysis was conducted in accordance with PRISMA 2020 guidelines. MEDLINE, Embase, and Cochrane Library were searched up to April 2025.

Functionalized Metal-Organic Framework Composite Electrolyte Membrane for High-Performance Solid Li Batteries.

Metal-organic frameworks (MOFs)/polymer composite electrolytes have garnered worldwide attention because of their outstanding performance in energy-related applications. Here, a highly lithiated MOF (LZM) is designed as a filler into poly(ethylene oxide) (PEO). LZM is synthesized through a postsynthetic modified strategy to obtain preeminent single-ion conducting performance.

Mesoporous Heat-Trapping and Smoke-Adsorbing Fe-MOFs Improve Fire Safety and Compression Resistance of Rigid Polyurethane Foam.

The use of highly flammable materials such as foams, resins, and plastics has led to an increase in the frequency and severity of urban fires worldwide. To address this issue, this study developed a high-specific-surface-area mesoporous metal-organic framework (Fe-MOFs) with heat trapping and smoke adsorption. The Fe-MOFs, zinc tailings (ZTs), piperazine pyrophosphate (PAPP), and sodium lignosulfonate (LS) were used to modify rigid polyurethane foam (RPUF).

TaGW2-TaVOZ1 module regulates wheat salt tolerance via both E3 ligase-dependent and -independent pathways.

Wheat production is limited by the rapid expansion of salinized arable land worldwide. Identification of the molecular mechanisms that underlie the salt stress response is of great importance. Here, we uncovered the NAC-type transcription factor, TaVOZ1, as a positive regulator of wheat salt tolerance.

variants drive chromosomal fission and accelerate speciation in zokors.

Chromosomal fissions and fusions are common, yet the molecular mechanisms and implications in speciation remain poorly understood. Here, we confirm a fission event in one zokor species through multiple-omics and functional analyses. We traced this event to a mutation in a splicing enhancer of the DNA repair gene in the fission-bearing species, which caused exon skipping and produced a truncated protein that disrupted DNA repair.

Destination authenticity as a halo? Enhancing emotional solidarity with residents in rural tourism.

Emotional interaction between tourists and hosts is a vital element of rural tourism, and tourists often seek nostalgia and authenticity in rural settings. Based on the cognition-affect-behavior (CAB) framework and the halo effect theory, this study constructs a hypothetical model to explore the antecedents and consequences of emotional solidarity between rural tourists and residents. Online responses were collected from 324 Chinese rural tourists.

Genetic and economic efficiencies of alternative breeding schemes for improvement of local breeds in low-input production systems: The case of the Farta sheep in Northwest Ethiopia.

Designing and implementing a sound breeding program is essential for sustainably improving livestock productivity. This study evaluated the efficiencies of three breeding schemes for sustainable genetic improvement of indigenous sheep in low-input production systems. The schemes were one-stage selection at six months (Scheme I) or yearling age (Scheme II) and two-stage selections with the first at six months and the second at the yearling age (Scheme III).

IntraVascular UltraSound After Below-The-Knee Endovascular Therapy: an Observational Pilot Study.

ObjectiveRestenosis limits the benefit of below-the-knee (BTK) endovascular therapy (EVT). Restenosis may be attributable to limited information from digital subtraction angiography. A promising alternative is intravascular ultrasound (IVUS).