Naive pluripotent stem cells (nPSCs) frequently undergo pathological loss of DNA methylation at imprinted gene loci, posing a hurdle for biomedical applications and underscoring the need to identify underlying causes. We show that nPSCs from inbred mouse strains exhibit strain-specific susceptibility to locus-specific deregulation of imprinting marks during reprogramming and upon exposure to a mitogen-activated protein kinase (MAPK) inhibitor, a common approach to maintain naive pluripotency. Analysis of genetically diverse nPSCs from the Diversity Outbred (DO) stock confirms the impact of genetic variation on epigenome stability, which we leverage to identify trans-acting quantitative trait loci (QTLs) that modulate DNA methylation levels at specific targets or genome-wide.
View Article and Find Full Text PDFPlastic pollution is an increasing stressor adding pressure on coral reefs. Microplastic (MP) affects photosynthetic performance and growth of corals and may lead to bleaching. When corals are bleached and autotrophy is impaired, corals are more dependent on heterotrophic feeding to complement energy acquisition.
View Article and Find Full Text PDFThis study investigates the anatomy and biomechanics of the scapholunate ligament in Vietnamese cadavers. Measurements reveal population-specific dimensions and tensile strength, providing valuable insights for clinical management of wrist instability and guiding future research in orthopedic applications.
View Article and Find Full Text PDFObjectives: Evaluate the surgical results of cerebellopontine angle (CPA) meningiomas via a retrosigmoid approach.
Methods: This study investigated the outcomes of the retrosigmoid approach for CPA meningiomas in 36 patients. Demographic characteristics and surgical outcomes were recorded on admission, post-operation for 3-month, and 12-month follow-up.
Background: This subanalysis of BENEFIT-KOREA cohort assessed the impact of baseline pulse rate (PR) and posttreatment PR reduction on the blood pressure (BP)-lowering efficacy of nebivolol in patients with hypertension.
Methods: South Korean patients with hypertension were enrolled in the BENEFIT-KOREA study; 3,011 patients received nebivolol as monotherapy/add-on therapy. Time-averaged BP, calculated by sum of the product of BPs at weeks 12 and 24 corrected for number of participants at these timepoints, was evaluated with/without adjustment for baseline BP.
Background: Receptor-activated SMADs trimerize with SMAD4 to regulate context-dependent target gene expression. However, the presence of a single SMAD1/5/8 binding motif in cis-regulatory elements alone does not trigger transcription in native contexts. We hypothesize that binding to composite motifs in which at least two SMAD binding sites are in close proximity would be enough to induce transcription as this scenario allows the simultaneous interaction of at least two SMAD proteins, thereby increasing specificity and affinity.
View Article and Find Full Text PDFOptical microcavities are widely used to confine photons for exciton-polariton formation. However, their compact design often imposes limitations on spatial freedom, particularly in controlling the cavity length with the nanometer precision required for effective coupling with excitons. Existing methods for tuning resonances by integrating cavities with dynamic structures often lack sufficient resolution or a complex operation.
View Article and Find Full Text PDFThe enhancement magnitude of the electromagnetic effects has consistently ranked among the highest research priorities in Surface-enhanced Raman scattering (SERS). This study introduces a novel facile synthesis method for zinc oxide nanorice (ZnONR) decorated with small silver particles (ZnONR-Ag). The semiconductor-noble nanomaterial is designed to enhance sensitivity and reproducibility when detecting isoprocarb (IPC) and crystal violet (CV) at trace levels using SERS.
View Article and Find Full Text PDFEctopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of bone marrow (BM). Although bone morphogenetic protein (BMP)-2 has been reported to induce eBM formation, it remains unproven whether BMP-2 induced eBM (BMP-eBM) can provide a functional BM niche that is comparable to native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate for the first time that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM.
View Article and Find Full Text PDFBackground And Aims: Despite being a major cause of hospitalisations, there is limited literature on the trends in diabetes-related foot disease (DFD) in Victoria, Australia. The aim of this study was to assess the incidence of DFD admissions and outcomes in inpatients with DM at a major Victorian health service.
Methods: Inpatients aged >18 years with DM and DFD between 2013 and 2022 were identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) codes.
Conformational flexibility allows macrocyclic peptides like cyclosporine A (CycA) to cross membranes, yet drug design leveraging this property has largely failed. A key challenge is linking specific conformers to function, as different conformers govern permeability versus target binding. We reveal a mechanism that enhances CycA and alisporivir (ALI) permeability: -to- isomerization at MeVal11-MeBmt1 creates conformers that remain "soluble" in both membrane-like and aqueous environments.
View Article and Find Full Text PDFPhysical activities in childhood are important. However, a lack of exercise among children and adolescents is becoming a global reality. Moreover, following the coronavirus disease 2019 pandemic, the increase in time spent at home has led to qualitative changes, such as at-home exercises and the use of YouTube content.
View Article and Find Full Text PDFConjugated polymers (CPs) are considered one of the most important gas-sensing materials due to their unique features, combining the benefits of both metals and semiconductors, along with their outstanding mechanical properties and excellent processability. However, CPs with conventional morphological structures, such as largely amorphous and bulky matrices, face limitations in practical applications because of their inferior charge transport characteristics, low surface area, and insufficient sensitivity. Therefore, the design and development of novel morphological nanostructures in CPs have attracted significant attention as a promising strategy for improving morphological and electrical characteristics, thereby enabling a considerable increase in the sensing performance of corresponding gas sensors.
View Article and Find Full Text PDFInterstitial lung disease (ILD) consists of a group of immune-mediated disorders that can cause inflammation and progressive fibrosis of the lungs, representing an area of unmet medical need given the lack of disease-modifying therapies and toxicities associated with current treatment options. Tissue-specific splice variants (SVs) of human aminoacyl-tRNA synthetases (aaRSs) are catalytic nulls thought to confer regulatory functions. One example from human histidyl-tRNA synthetase (HARS), termed HARS because the splicing event resulted in a protein encompassing the WHEP-TRS domain of HARS (a structurally conserved domain found in multiple aaRSs), is enriched in human lung and up-regulated by inflammatory cytokines in lung and immune cells.
View Article and Find Full Text PDFObjective: Concurrent use of alcohol and cigarettes is well-documented in the literature. However, it is unclear how e-cigarette regulations in a growing number of localities impact the use of tobacco and alcohol in the US. This study aims to evaluate the impacts of excise taxes, tobacco use restrictions in restaurants/bars, and availability of alcohol flavor in e-cigarettes on tobacco consumption, and their cross impacts on alcohol consumption.
View Article and Find Full Text PDFBackground: Hypocalcemia is the most frequent complication of thyroid surgeries. Hypocalcemia is the most common complication following thyroid surgeries and is crucial in managing patients with thyroid cancer.
Objectives: This study aimed to describe hypocalcemia after thyroidectomy and evaluate the factors associated with postoperative hypocalcemia.
Background: Novel strategies that account for population-level changes in dominant variants, immunity, testing practices and changes in individual risk profiles are needed to identify patients who remain at high risk of severe COVID-19. The aim of this study was to develop and prospectively validate a tool to predict absolute risk of severe COVID-19 incorporating dynamic parameters at the patient and population levels that could be used to inform clinical care.
Methods: A retrospective cohort of vaccinated US Veterans with SARS-CoV-2 from July 1, 2021, through August 25, 2023 was created.
Genotoxic estrogen metabolites generate various DNA lesions; however, their target genes and carcinogenic mechanisms remain unexplored. Here, genome-wide sequencing using click probe enrichment coupled with liquid chromatography-tandem mass spectrometry (Click-Probe-Seq/LC-MS) is developed to identify damaged genes and characterize the released and stable adducts induced by 4-hydroxy-17β-estradiol (4OHE2) in MCF-7 cell chromatin. The data reveal that guanine nucleobases in the GC-rich transcription-relevant domain are the main target sites.
View Article and Find Full Text PDFThis study aims to develop fouling-resistant membranes utilizing zwitterionic polymers for an integrated electrocoagulation (EC) and nanofiltration (NF) process to effectively remove microcystin-LR (MC-LR). The fabricated membranes were thoroughly characterized through contact angle measurements, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The efficacy of these modified membranes was investigated for synthetic microcystin removal, employing both commercial NF 270 membranes and modified NF 270 with zwitterionic polymers.
View Article and Find Full Text PDFExperimental constraints and sample limitations can preclude ideal measurements of electrical transport properties of materials. In such situations, AC electrical transport methods are often employed due to a significant increase in signal-to-noise ratio they can provide. However, dynamic effects that are not often accounted for may be present that may modify the signals in these measurements.
View Article and Find Full Text PDFPhys Chem Chem Phys
March 2025
The discovery that ATP can prevent the aggregation of proteins and enhance their stability sparked significant interest in understanding the interactions between ATP and proteins. All-atom molecular dynamics simulations provide detailed insight into the underlying mechanism, while an appropriate force field must be developed. Existing force fields accurately describe the conformations of polyphosphates, but are not suitable for simulations at high ATP concentrations, because excessive self-aggregation occurs.
View Article and Find Full Text PDFA critical challenge in the structural characterization of metal complexes in apolar environments is distinguishing transient structural isomers within an ensemble of lower- and higher-order assemblies. These structural variations arise from subtle changes in ligand architecture and metal coordination chemistry, which are often difficult to deconvolute. Here, we utilize ion activation in both drift-tube and cyclic ion mobility spectrometry-mass spectrometry (IMS-MS) to resolve ligand conformational isomerism and metal coordination isomerism in metal sandwich complexes of cyclic depsipeptide ligands known for selective metal ion transport.
View Article and Find Full Text PDFBackground: Muscle proteins of the obscurin protein family play important roles in sarcomere organization and sarcoplasmic reticulum and T-tubule architecture and function. However, their precise molecular functions and redundancies between protein family members as well as their involvement in cardiac diseases remain to be fully understood.
Methods: To investigate the functional roles of Obsc (obscurin) and its close homolog Obsl1 (obscurin-like 1) in the heart, we generated and analyzed knockout mice for , , as well as double knockouts.
Introduction: The Nijmegen Questionnaire assesses hyperventilation syndrome (HVS), but a validated Vietnamese version is lacking. This study investigates the cross-culture validity, structural validity, and reliability of the Vietnamese Nijmegen questionnaire (VNQ) for screening HVS in primary healthcare settings.
Methods: Following Beaton's guidelines, translation and adaptation involved two independent expert panels for content validity.
Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19.
Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose.
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