Methotrexate resistance and its regulatory mechanisms in pediatric tumors and beyond.

Methotrexate (MTX) is a critical antimetabolite drug in treating various pediatric diseases, including acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), brain tumors, osteosarcoma, inflammatory myofibroblastic tumor (IMT), juvenile scleroderma (JS), and juvenile idiopathic arthritis (JIA). MTX acts as a folate antagonist by inhibiting dihydrofolate reductase (DHFR), an enzyme essential for the synthesis of tetrahydrofolate. This disruption impairs DNA synthesis, repair, and cellular replication, particularly affecting rapidly dividing cells.

Large-scale genomic and phenomic analyses of modern cultivars empower future rice breeding design.

Modern cultivated rice plays a pivotal role in global food security. China accounts for nearly 30% of the world's rice production and has bred numerous cultivated varieties over the last decades that are well adapted to diverse growing regions. However, the genomic bases that underlie the phenotypes of modern cultivars are poorly characterized, limiting access to this vast resource for breeding of specialized, regionally adapted cultivars.

Uniform Spray Dried Loxapine Microparticles Potentially for Nasal Delivery: Exploring Discriminatory In Vitro Release Evaluation Methods.

This study aimed to develop suitable in vitro evaluation methods for the release behavior of nasal powders (NPs). We synthesized a range of standardized microparticles with adjustable size and morphology by co-spray-drying loxapine succinate (LOX) and gelatin (GEL) using an ethanol/water solvent mixture in a self-designed micro-fluidic jet spray dryer (MFJSD). The influence of the LOX/GEL mass ratio and solvent composition on particle characteristics, including size, morphology, and crystalline properties, was systematically investigated.

Dissemination strategies of clinical practice guidelines-mixed methods evidence synthesis protocol.

Clinical practice guidelines (CPGs) are shared through various dissemination strategies using a range of dissemination products and channels. However, users may have different needs for accessing and understanding them. Patients and carers from low- and middle-income countries might face challenges in accessing CPGs such as inadequate systems for printed book distribution and insufficient and substandard photocopies.

Metabolic Activation of -Anethole Plays a Role in Hepatic Cytotoxicity in Mice.

-Anethole (1-methoxy-4-[1()-propenyl]benzene, tAT) is the main ingredient in the essential oil extracted from star anise fruits. The double bonds in the side chain of tAT are a type of alert structure that can be metabolized into epoxides possibly causing liver damage. This work investigated and identified the reactive metabolites of tAT that are chemically reactive to biothiols, such glutathione (GSH), -acetyl-l-cysteine (NAC), and cysteine residues of proteins.

SP1 regulates porcine primary adipocyte differentiation by modulating BAMBI transcriptional activity.

Obesity is a critical metabolic disorder in modern society, necessitating urgent research and intervention. Compared to mice, pigs are increasingly been recognized as valuable model organisms for such studied due to their closer genetic similarity to humans. The BAMBI gene plays a pivotal role in adipocyte differentiation and adipose tissue development, rendering it a potent target for exploring the mechanisms of obesity and related metabolic disorders.

Pseudomembranous Aspergillus tracheobronchitis: A Rare Manifestation of Invasive Aspergillosis in a Immunocompetent Patient.

Purpose: Pseudomembranous Aspergillus tracheobronchitis (PMATB), an uncommon clinical form of invasive aspergillosis, is mainly occurs in patients who are moderate to severely immunocompromised. There are some case reports of immunocompetent individuals developing invasive aspergillosis after occupational exposure (Primarily observed in farmers, sawmill workers, waste collectors, mushroom processing workers, or those who handle grain, hay, or straw), including allergic bronchopulmonary aspergillosis (ABPA), severe asthma with fungal sensitization, hypersensitivity pneumonitis, and invasive pulmonary aspergillosis. To our knowledge, there are no published case reports in the literature with PMATB as the main presentation in construction worker after occupational exposure.

A novel 3D lightweight model for COVID-19 lung CT Lesion Segmentation.

3D-based medical image segmentation, offering enhanced spatial information compared to 2D slice-based methods, encounters challenges arising from factors such as a restricted clinical sample size, imbalanced foreground-background pixel distribution, and suboptimal generalization performance. To address these challenges, we propose a lightweight segmentation model tailored to 3D medical images. Employing the K-means algorithm, our approach efficiently extracts the Region of Interest (ROI) from medical images, facilitating lung area segmentation while minimizing interference from background pixels.

TAL-SRX: an intelligent typing evaluation method for KASP primers based on multi-model fusion.

Intelligent and accurate evaluation of KASP primer typing effect is crucial for large-scale screening of excellent markers in molecular marker-assisted breeding. However, the efficiency of both manual discrimination methods and existing algorithms is limited and cannot match the development speed of molecular markers. To address the above problems, we proposed a typing evaluation method for KASP primers by integrating deep learning and traditional machine learning algorithms, called TAL-SRX.

Transcriptomic analysis reveals the mechanisms underlying the differential effects of caffeine, theophylline, and theobromine in regulating hepatic fat accumulation.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by excessive fat accumulation in the liver. Caffeine, theophylline, and theobromine are the primary naturally occurring methylxanthines found in various foods and beverages such as coffee, tea, and chocolate. They exhibit diverse pharmacological effects.

Identification of 13 natural antioxidants in green calyx plum using AAPH, ABTS, and FRAP-coupled HPLC-DAD via QTOF-MS/MS.

The novel application of a combined screening method, utilizing AAPH, ABTS, and FRAP assays with HPLC, is first used for screening natural antioxidants in Green Calyx plums (GCP). This method was assumed that the peak areas of compounds with antioxidant activity in HPLC chromatograms would be significantly reduced or disappeared after incubating with the AAPH, ABTS, and FRAP. The thirteen screened antioxidants can be identified by Q-TOF-MS/MS.

Observation of metal-organic interphase in Cu-based electrochemical CO-to-ethanol conversion.

Interphases are critical in electrochemical systems, influencing performance by controlling ion transport and stability. This study explores a metal-organic interphase in the electrocatalytic reduction of CO (CORR) on Cu, extending the concept of interphases to CO conversion. Investigating organic modifications on CuO, we discover metal-organic interphases over 10 nm thick in highly ethanol-selective systems, contrary to the expected monolayer adsorption.

Methamphetamine and traumatic brain injury outcomes: an analysis of 29,416 patients from the national trauma data bank.

Background: Methamphetamine (Meth) use is rising in the US. Most research focuses on severe TBI, neglecting milder cases. We evaluated Meth's impact on patient outcomes and hospital resource use across all TBI severities.

Molecular dynamics simulation-driven focused virtual screening and experimental validation of Fisetin as an inhibitor of Helicobacter pylori HtrA protease.

Helicobacter pylori (H. pylori, Hp) is a primary contributor to various stomach diseases, including gastritis and gastric cancer. This bacterium can colonize gastric epithelial cells, compromising their integrity and leading to the development of these conditions.

Risk of All-Cause Mortality in US Adults With Preserved Ratio Impaired Spirometry: An Observational Study.

Background: Preserved ratio impaired spirometry (PRISm) is defined as forced expiratory volume in one second (FEV)/forced vital capacity (FVC)≥0.70 and FEV<80% predicted. Previous studies have shown that individuals with PRISm may develop airflow obstruction and have an increased mortality risk.

Expression of Serum Ferritin, Human neutrophil lipocalin, Procalcitonin, and inflammatory factors in children with Kawasaki disease and their relationship to coronary artery lesions.

Objective: To investigate the levels of serum ferritin (SF), human neutrophil lipocalin (HNL), procalcitonin (PCT), and inflammatory cytokines (IL-6, IL-10, IL-17, IL-18, TNF-α, INF-γ, and sCD25) in Kawasaki disease (KD) and their relationship with coronary artery lesions (CAL).

Methods: A retrospective analysis was conducted on 76 children with KD treated from May 2022 to May 2024. Participants were classified into a lesion group (n=48) and a no-lesion group (n=28) based on CAL status.

The polarization of macrophages participates in the repair after folic acid-induced acute kidney injury.

Acute kidney injury (AKI) remains a major public health challenge, posing serious threats to human health. Increasing evidence indicates that renal cells undergo significant metabolic alterations following AKI, with inflammatory responses persisting throughout both injury and repair phases. Our previous research has demonstrated that heightened aerobic glycolysis after AKI leads to increased secretion of metabolic byproducts such as lactate, which plays a critical role in tissue repair.

Adaptation and validation of a condom-related stigma scale for older adults in China.

Background: Condom use has long been recommended as an effective method for preventing HIV/AIDS. However, a large proportion of older adults in China reported not using condoms, leading to an alarming increase in HIV prevalence among this population. Negative attitudes, especially condom-related stigma, have been identified as the main barrier.

Natural compound PEITC inhibits gain of function of p53 mutants in cancer cells by switching YAP-binding partners between p53 and p73.

Phenethyl isothiocyanate (PEITC) derived from cruciferous vegetables has shown anticancer activities by modulating apoptosis, cell cycle arrest, drug-metabolizing enzymes and even preferentially restoring a 'WT-like' conformation to p53. But its molecular anti-cancer mechanisms are not well understood. Evidence shows that switching YAP-binding partners from pro-tumorigenic to pro-apoptotic proteins might hold great potential for the treatment of human cancers harboring mtp53.

Metabolic Activation of Stiripentol Correlates with Cytotoxicity.

Stiripentol (SRP) is an antiepileptic agent utilized in managing seizures related to Dravet syndrome. Long-term safety studies have highlighted significant adverse effects in patients including drowsiness, reduced appetite, ataxia, and elevated levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The present study aimed at identifying the reactive metabolite of SRP and defining the potential correlation between its cytotoxicity and metabolic activation.

Glucokinase Regulatory Protein as a Putative Target for Gestational Diabetes Mellitus and Related Complications: Evidence From the Mendelian Randomization Study.

Background: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and is highly associated with adverse perinatal outcomes and long-term health problems for the mother and offspring. However, there are respective limitations in the pharmacological strategies for the current treatment of GDM. Glucokinase regulatory protein (GCKR) has been associated with GDM in observational studies and animal experiments and thus represents a potential drug target of interest for investigation.

MtCro: multi-task deep learning framework improves multi-trait genomic prediction of crops.

Genomic Selection (GS) predicts traits using genome-wide markers, speeding up genetic progress and enhancing breeding efficiency. Recent emphasis has been placed on deep learning models to enhance prediction accuracy. However, current deep learning models focus on learning specific phenotypes for the given task, overlooking the inter-correlations among different phenotypes.

Transarterial Chemoembolization With or Without Systemic Therapy for Unresectable Hepatocellular Carcinoma: A Retrospective Comparative Study.

Introduction: Standard treatments provide limited benefits for patients with intermediate- or advanced-stage hepatocellular carcinoma (HCC). This retrospective observational study aimed to assess the potential improvements in outcomes associated with systemic therapies in patients receiving transarterial chemoembolization (TACE) for initially unresectable HCC.

Methods: Between February 2019 and March 2023, we reviewed patients diagnosed with intermediate-to-advanced HCC who were treated with either TACE or TACE combined with antiangiogenic agents and immune checkpoint inhibitors (combination therapy) as their initial treatment.

JMJD6 Rewires ATF4-Dependent Glutathione Metabolism to Confer Ferroptosis Resistance in SPOP-Mutated Prostate Cancer.

Ferroptosis inducers have shown therapeutic potential in prostate cancer (PCa), but tumor heterogeneity poses a barrier to their efficacy. Distinguishing the regulators orchestrating metabolic crosstalk between cancer cells could shed light on therapeutic strategies to more robustly activate ferroptosis. Here, we found that aberrant accumulation of jumonji domain containing 6 (JMJD6) proteins correlated with poorer prognosis of PCa patients.

Progress on long non-coding RNAs in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a common cardiovascular condition in the elderly population. The aortic valve, influenced by factors such as endothelial dysfunction, inflammation, oxidative stress, lipid metabolism disorders, calcium deposition, and extracellular matrix remodeling, undergoes fibrosis and calcification, ultimately leading to stenosis. In recent years, long non-coding RNAs (lncRNAs) have emerged as significant regulators of gene expression, playing crucial roles in the occurrence and progression of various diseases.