Endocannabinoid signaling in epilepsy.

Epilepsy, characterized by recurrent abnormal neuronal discharges, can lead to severe manifestations, including prolonged seizures that may become life-threatening. Despite the availability of numerous antiseizure drugs, many patients remain refractory to existing treatments, prompting the urgent search for novel therapeutic strategies. One pivotal factor driving epileptogenesis is the disruption of the excitatory-inhibitory balance, resulting in excessive neuronal firing and hyperexcitability.

Preparation and Failure Behavior of Gel Electrolytes for Multilayer Structure Lithium Metal Solid-State Batteries.

High safety gel polymer electrolyte (GPE) is used in lithium metal solid state batteries, which has the advantages of high energy density, wide temperature range, high safety, and is considered as a subversive new generation battery technology. However, solid-state lithium batteries with multiple layers and large capacity currently have poor cycle life and a large gap between the actual output cycle capacity retention rate and the theoretical level. In this paper, polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP)/polyacrylonitrile (PAN)-lithium perchlorate (LiClO)-lithium lanthanum zirconium tantalate (LLZTO) gel polymer electrolytes was prepared by UV curing process using a UV curing machine at a speed of 0.

Understanding the structural stability and plasticity of VPS34 protein determined by selective/nonselective inhibitors: insights from molecular dynamics simulations.

Vacuolar sorting protein 34 (VPS34), a sole member of class III phosphoinositide 3-kinase (PI3K), regulates critical cellular processes, such as endosomal trafficking and autophagosome biogenesis, making it a promising target for diseases such as cancer and neurodegenerative disorders. However, developing highly selective inhibitors for VPS34 is challenging due to the structural conservation of its ATP-binding site across PI3Ks. In this study, to elucidate the structural dynamics of selective ligand recognition, we performed molecular dynamics (MD) simulations to explore the conformational landscape of VPS34 in both its apo state and in complex with selective/nonselective ligands.

Microrchidia ATPases and DNA 6mA demethylase ALKBH1 act antagonistically on PRC2 to control chromatin structure and stress tolerance.

The Microrchidia (MORC) proteins are conserved GHKL-type ATPases required for chromatin condensation and gene silencing in animals and plants. Here we show that MORC proteins function with Polycomb-Repressive Complex 2 (PRC2) to control chromatin structure, gene expression and stress responses in rice. Rice MORC6b interacts with and stabilizes PRC2 for trimethylated histone H3 lysine 27 (H3K27me3) deposition preferentially at bivalent domains marked by both H3K4me3 and H3K27me3 to repress genes enriched for stress responses.

Senkyunolide I targets CXCR4 to attenuate liver fibrosis via suppression of the NLRP3/GSDMD pathway.

Liver fibrosis is a progressive pathological disorder characterized by excessive extracellular matrix (ECM) deposition, resulting in hepatic architectural distortion and functional impairment. Despite its clinical importance, effective therapeutic options remain limited. This study evaluated the antifibrotic potential of senkyunolide I (SI), a bioactive phthalide compound derived from Ligusticum chuanxiong Hort.

A Rare t(3;15;17) in a Patient with Acute Promyelocytic Leukemia: Case Report and Review of the Literature.

We present a 48-year-old female with a past medical history of endometrioid adenocarcinoma who presented with symptoms of spontaneous gum bleeding, post-coital bleeding, and upper extremities-lower extremities-abdomen ecchymosis. Initial laboratory findings were significant for cytopenia and disseminated intravascular coagulation (DIC). Due to a suspected case of acute promyelocytic leukemia (APL), conventional karyotyping and fluorescence in situ hybridization (FISH) were performed.

AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance.

R-loops are three-stranded DNA/RNA hybrids that are essential for various cellular pathways. However, when dysregulated, they lead to genomic instability and numerous human diseases. R-loops are tightly regulated, with RNase H1 acting as a key enzyme responsible for resolving DNA/RNA hybrids.

Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae.

We previously demonstrated that a single-dose immunization with a live-attenuated Rickettsia parkeri mutant 3A2 confers complete protection against murine spotted fever rickettsioses. In this study, we investigated whether vaccination-elicited serum antibodies serve as immune correlates of protection against rickettsiae. Immunization of immunocompetent C3H/HeN mice with 3A2 induced a robust and durable level of IgG antibody response, predominantly comprising IgG2a, IgG3, and IgG2b subclasses, and was associated with a significant expansion of CD19 CD45R IgD plasma cells.

Genome-wide association study of early-stage non-small cell lung cancer prognosis: a pooled analysis in the International Lung Cancer Consortium.

Lung cancer is the leading cause of cancer mortality. To investigate genetic determinants for prognosis among patients diagnosed with early-stage non-small cell lung cancer (NSCLC), we conducted the first large-scale genome-wide association prognostic study using data from the International Lung Cancer Consortium (ILCCO) through a two-phase analysis. Phase 1 includes the discovery of genome-wide association studies analysis using a multivariable Cox PH model on 3428 NSCLC patients of European ancestry from 10 ILCCO participating studies to identify genetic variants associated with overall survival and validation analysis for genome-wide significant variants (P-value ≤5 × 10-8) using the Cancer Genome Atlas (TCGA).

Influence of local and remote ischemic preconditioning on 3-min all-out exercise performance: A randomized controlled crossover study.

Objective: This study investigated the influences of local ischemic preconditioning (LIPC) and remote ischemic preconditioning (RIPC) on muscle deoxygenation before and during a 3-min all-out cycling test (3 MT), as well as on 3 MT performance.

Methods: Fifteen male athletes completed LIPC (thighs, 220 mmHg, 4 × 5 min), RIPC (upper limbs, 30 mmHg above systolic blood pressure, 4 × 5 min), and SHAM (thighs, 20 mmHg, 4 × 5 min) interventions in a randomized crossover design, with a 4-day washout period between sessions. The 3 MT was conducted 45 min after each intervention.

The Emerging Role of Extracellular Vesicle-Derived lncRNAs and circRNAs in Tumor and Mesenchymal Stem Cells: The Biological Functions and Potential for Clinical Application.

Extracellular vesicles (EVs) are released by nearly all types of cells, and they communicate between cells by transporting bioactive molecules, including proteins, DNA, RNA, and lipids. In recent years, RNA carried by EVs, particularly the long-chain non-coding RNA (lncRNA) and circular RNA (circRNA) subtypes, has garnered interest with respect to their role in controlling tumor progression. Among them, there are increasing reports that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) maintain a recently discovered function as transporters of lncRNAs and circRNAs.

GWAS meta-analysis identifies five susceptibility loci for endometrial cancer.

Background: Endometrial cancer is the most common gynaecological cancer in high-income countries. In addition to environmental risk factors, genetic predisposition contributes towards endometrial cancer development but is still incompletely defined.

Methods: Building on genome-wide association studies (GWASs) by the Endometrial Cancer Association Consortium, we conducted a GWAS meta-analysis of 17,278 endometrial cancer cases and 289,180 controls, incorporating biobank samples from the UK, Finland, Estonia and Japan.

Characterization of Homeodomain Proteins at the Aβ Sublocus in and Their Role in Sexual Compatibility and Development.

The A mating-type locus in , which encodes homeodomain (HD) transcription factors, is essential for regulating sexual compatibility and development. While the role of the Aα sublocus and its Y-Z HD protein complex is adequality understood, the function of HD proteins at the Aβ sublocus remains unclear. In this study, we analyzed the Aβ sublocus of eight monokaryotic strains derived from the parental dikaryotic strain 20R-7-Z01 and identified four HD genes, , , , and , located at the Aβ sublocus.

LILRB4 exacerbates myocardial ischemia-reperfusion injury by promoting inflammation and pyroptosis.

Inflammation and pyroptosis are pivotal in myocardial ischemia-reperfusion injury. Although leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) modulates inflammation in conditions such as myocardial hypertrophy, its involvement in myocardial ischemia-reperfusion injury (MIRI) remains ambiguous. Recombinant adenoviral vectors were designed to induce the overexpression or knockdown of LILRB4 in H9C2 cardiomyocytes or rat myocardial tissue.

Cumulative handgrip strength and longitudinal changes in cognitive function and daily functioning among people aged 50 years and older: evidence from two longitudinal cohort studies.

Background And Purpose: Our study assesses the association between cumulative handgrip strength and longitudinal changes in cognitive function and daily functioning.

Methods: Two comparative cohort studies were used, including the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing and Retirement in Europe (SHARE). Cumulative handgrip strength was calculated using three repeated measurements of handgrip strength.

High-Quality CEST Mapping With Lorentzian-Model Informed Neural Representation.

Chemical Exchange Saturation Transfer (CEST) MRI has demonstrated its remarkable ability to enhance the detection of macromolecules and metabolites with low concentrations. While CEST mapping is essential for quantifying molecular information, conventional methods face critical limitations: model-based approaches are constrained by limited sensitivity and robustness depending heavily on parameter setups, while data-driven deep learning methods lack generalizability across heterogeneous datasets and acquisition protocols. To overcome these challenges, we propose a Lorentzian-model Informed Neural Representation (LINR) framework for high-quality CEST mapping.

Alcohol intake and pancreatic cancer risk: An analysis from 30 prospective studies across Asia, Australia, Europe, and North America.

Background: Alcohol is a known carcinogen, yet the evidence for an association with pancreatic cancer risk is considered as limited or inconclusive by international expert panels. We examined the association between alcohol intake and pancreatic cancer risk in a large consortium of prospective studies.

Methods And Findings: Population-based individual-level data was pooled from 30 cohorts across four continents, including Asia, Australia, Europe, and North America.

Genome-wide association study for lung cancer in 6531 African Americans reveals new susceptibility loci.

Despite lung cancer affecting all races and ethnicities, disparities are observed in incidence and mortality rates among different ethnic groups in the United States. Non-Hispanic African Americans had a high incidence rate of lung cancer at 55.8 per 100 000 people, as well as the highest death rate at 37.

The Role of Nitric Oxide in the Growth and Development of Under Anaerobic Conditions.

Nitric oxide (NO) is a widely recognized signaling molecule found across various organisms, yet its specific effects on fungal growth and development under anaerobic conditions remain underexplored. This study investigates how NO influences the growth and development of 20R-7-F01 under anaerobic environments. The results demonstrated an increase in endogenous NO levels during mycelial growth and basidiospore germination.

Evidence for the Existence of Mating Subtypes Within the : Mating Behavior and Genetic Divergence.

, a Basidiomycota fungus with a tetrapolar mating system, serves as a key model for studying sexual reproduction. In this study, two distinct mating subtypes (I and II) were identified in strain 20R-7-ZF01, isolated from subseafloor sediment, which exhibited eight different mating interaction phenotypes. Intra-subtypes exhibited colony-symmetric tetrapolar interactions (G1), whereas inter-subtype crosses yielded colony-asymmetric phenotypes (G2) and a reduced number of fruiting bodies.

Radiomics Analysis of Apparent Diffusion Coefficient Maps of Parotid Gland to Diagnose Morphologically Normal Sjogren Syndrome.

Objective: This study investigated novel radiomic features derived from apparent diffusion coefficient (ADC) maps for diagnosing Sjögren syndrome (SS) in patients without visible magnetic resonance morphologic changes.

Materials And Methods: This study prospectively analyzed 119 consecutive patients with SS and 95 healthy volunteers using 3.0 T magnetic resonance imaging, including diffusion-weighted imaging with b values of 0 and 1000 s/mm2.

Socioeconomic disparities in organized sports participation and physical activity among a population based sample of preschool children: a cross-sectional study.

Background: Encouraging children to participate in organized sports could increase physical activity and may promote lifelong healthy habits. There are socioeconomic disparities in organized sports participation in school-aged children and adolescents. However, it is not known if these socioeconomic disparities exist among preschool-aged children.

Effect of a three-years preventive medicine vocational education program on county-level healthcare workforce development in China: a cross-sectional study.

Background: This study aims to analyze the demand and supply of these professionals within healthcare institutions at the county level after the Chinese government launched a three-year vocational education program of preventive medicine in 2016.

Methods: A national cross-sectional design and multistage cluster sampling method were employed for this study. At the county level, a total of 132 Centers for Disease Control and Prevention (CDCs), 346 medical institutions, 20 medical colleges and 1,083 graduate students were selected.

Association between socioeconomic position and lung cancer incidence in 16 countries: a prospective cohort consortium study.

Background: Studies have reported higher lung cancer incidence among groups with lower socioeconomic position (SEP). However, it is not known how this difference in lung cancer incidence between SEP groups varies across different geographical settings. Furthermore, most prior studies that assessed the association between SEP and lung cancer incidence were conducted without detailed adjustment for smoking.

Design of humidity sensor based on poly(sodium 4-styrenesulfonate) modified SnO for visual monitoring of plant growth environments.

Organic-inorganic hybrid materials hold great application prospects in electronic devices such as humidity sensors due to their unique interfacial effects and synergistic interactions. However, relatively few studies have been conducted on the sensitization mechanism of organic-inorganic hybrid materials. Herein, we report a high performance humidity sensor based on an organic-inorganic hybrid material of poly(sodium 4-styrenesulfonate)-modified amino-functionalized SnO (PSS-SnO).