Super-Enhancer-Mediated DLX5 Activation Defines Regulatory Mechanisms in Human Embryonic Stem Cell-Derived Osteoblasts.

Osteoblast differentiation is essential for skeletal development and homeostasis. Although bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) are commonly used to study osteoblast differentiation in the context of bone homeostasis, their relevance to osteoblast differentiation during human skeletal development remains unclear. To understand the regulatory mechanisms underlying osteoblast differentiation in a human developmental context, we performed Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) and RNA-seq analyses on osteoblasts isolated from an in vivo implantation system using induced sclerotome derived from Col2.

Evaluation of the Glucocorticoid-Sparing Effect of Adding Methotrexate in Polymyalgia Rheumatica: A Single-Center Retrospective Study.

Objective This study assessed whether the addition of methotrexate (MTX) to glucocorticoid therapy reduces overall glucocorticoid usage in patients with polymyalgia rheumatica (PMR), focusing particularly on those exhibiting glucocorticoid-resistant disease.  Methods This retrospective study included 82 patients with PMR treated with glucocorticoids. After applying matching weights, outcomes were compared between weighted populations of 18 patients receiving MTX and 18 receiving glucocorticoid monotherapy.

Polymorphism and Thermally Induced Structural Transformation in Semiconducting Cd(II) Coordination Polymers.

Three polymorphs of a semiconducting Cd(II)-thiolate coordination polymer with the formula [Cd(2-SNPh)] (2-HSNPh = 2-naphthalenethiol) have been reported. Single-crystal X-ray structural analysis revealed that adopts a one-dimensional (1D) structure composed of single-strand (-Cd-S-) ladder chains, whereas adopts a 1D architecture with double-strand (-Cd-S-) chains assembled through S···S interactions. In contrast, microcrystal electron diffraction analysis demonstrated that , obtained through thermal treatment of and , exhibits the formation of a 1D structure comprising triple-strand (-Cd-S-) chains, also formed via S···S interactions.

Enhancement of Emission Efficiency and Color Tuning by Mixing Platinum(II) and Palladium(II) Complexes in a One-dimensional Chain.

A series of mixed metal crystals comprising square-planar platinum(II) and palladium(II) complexes, K[M(CN)(dFppy)]·HO (M = Pt, Pd; dFppy = 2-(4,6-difluorophenyl)pyridinate), were prepared, and their unique luminescence properties-emerging upon mixing-were revealed. Seven mixed crystals with Pt/Pd ratios of 1:0.5, 1:1, 1:1.

Association between plasma mid-regional pro-adrenomedullin levels and muscle properties.

Aim: Adrenomedullin exerts a vasodilative effect and is thought to be associated with skeletal muscle properties by regulating microcirculation. This cross-sectional study aimed to clarify the possible association in older adults aged ≥65 years.

Methods: The study population included 978 community residents (mean age 71.

Correspondence of high dimensional emotion structures elicited from video clips between humans and multimodal LLMs.

Recent studies have revealed that human emotions exhibit a high-dimensional, complex structure. A full capturing of this complexity requires new approaches, as conventional models that disregard high dimensionality risk overlooking key nuances of human emotions. Here, we examined the extent to which the latest generation of rapidly evolving Multimodal Large Language Models (MLLMs) capture these high-dimensional, intricate emotion structures, including capabilities and limitations.

Epidermal growth factor receptor inhibitor-related skin toxicities: a review of management and possible preventive and therapeutic approaches for Asian patients by the Japanese Pharmacist-led Oncodermatology Study Team.

Epidermal growth factor receptor antibodies and tyrosine kinase inhibitors cause various skin toxicities. Acneiform rash, paronychia, and pruritus are the major side effects, and their incidence is high, especially in Asian patients. These skin disorders greatly reduce the patients' quality of life and can affect treatment intensity.

Developing Methods for the Synthesis of Ligand-Oligonucleotide Conjugates for Drug Discovery Applications.

Recently, oligonucleotide-based drug discovery has attracted considerable amounts of attention. As oligonucleotide therapeutics have evolved into practical use, research into the development of functional artificial nucleic acids has been vigorously conducted worldwide. However, the synthesis of artificial nucleic acids generally requires long sequences from starting materials; hence, structurally optimizing oligonucleotide therapeutics is extremely difficult.

Degradation of azo dyes using laccase immobilized on mechanically ground silk fibroin nanofibers.

The extensive use of azo dyes in the textile industry poses serious environmental and health hazards due to their carcinogenic and mutagenic properties, largely stemming from the stability of their azo bonds (-NN-) which resist natural degradation. Enzymatic azo dye degradation using laccases offers an eco-friendly solution. However, the limited operational stability and reusability of free (non-immobilized) laccases in continuous degradation systems hinders their industrial application.

Evidence that mitochondria in macrophages are destroyed by microautophagy.

Microautophagy is an intracellular degradation process in which degradatory organelles, such as the lysosome, directly take up substrates by invagination and/or protrusion of their membranes. Here, we provide evidence that Rab32-positive, lysosome-related organelles in macrophages incorporate various other organelles, including endosomes and mitochondria. Our data indicates that, upon exposure to a mitochondria-damaging reagent, mitochondria can be directly engulfed by the lysosome-like organelles independently of macroautophagy or ESCRT machinery.

Selective TLR ligand stimulation enhances in vivo mosquito-borne flavivirus pathogenicity.

Mosquito saliva facilitates pathogen transmission and enhances the severity of diseases caused by mosquito-borne viruses; however, the underlying mechanisms are unknown. Here, we demonstrate that mosquito salivary gland extracts (SGEs) enhance flaviviral pathogenicity in vivo by activating innate immune responses following the accumulation of immune cells at the infection site. Among the innate immune signaling pathways, the TLR2 pathway enhances flaviviral pathogenicity in a manner similar to that of SGEs.

A Novel PROTAC G9a/GLP Degrader that Inhibits, Similar to G9a siRNA, the Migration of MCF-7 Breast-Cancer Cells without Affecting Proliferation.

G9a and G9a-like protein (GLP) are histone methyltransferases that regulate epigenetics by adding methyl groups to histone H3, thereby controlling gene expression. G9a/GLP dysregulation and overexpression have been reported to cause cancer proliferation, progression, and metastasis. So far, quinazoline-based inhibitors and degraders have been frequently used as chemical tools to elucidate the role of G9a/GLP.

Characterization of remdesivir resistance mutations in COVID-19 patients with various immunosuppressive diseases.

Immunocompromised patients (ICPs), such as those who receive certain immunosuppressive therapies, occasionally experience prolonged viral infections even after antiviral treatment. In some cases, antiviral-resistant viruses may eventually emerge. Remdesivir (RDV) is an adenosine nucleoside analog that inhibits the activity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA polymerase, which is composed of a catalytic subunit known as nsp12.

The impact of sleep quality on resting-state functional connectivity.

Objective: This study investigates the impact of natural sleep quality on the subsequent day's resting-state functional MRI (rsfMRI) connectivity patterns.

Methods: Fourteen healthy female subjects participated in two sets of tests that included sleep assessments and MRI scans across two consecutive days. Sleep quality was objectively measured using a portable EEG monitor in the participant's home environment.

Multi-omics analysis identifies an M-MDSC-like immunosuppressive phenotype in lineage-switched AML with KMT2A rearrangement.

Lineage switching (LS) is the conversion of cancer cell lineage during the course of a disease. LS in leukemia cell lineage facilitates cancer cells escaping targeting strategy like CD19 targeted immunotherapy. However, the genetic and biological mechanisms underlying immune evasion by LS leukemia cells are not well understood.

Source position evaluation using X-ray fluoroscopy of the Geneva and Venezia applicators for brachytherapy: An assessment of inter-applicator differences.

Purpose: This study aimed to evaluate the inter-applicator differences in source positions of the Geneva and Venezia applicators by using X-ray fluoroscopy to perform direct measurements of iridium-192 (Ir) source positions.

Materials And Methods: Offset measurements of two to six sets of Geneva tandem and ovoid applicators and Venezia tandem applicators were performed. Each applicator was irradiated with Ir at the most distal position and X-ray fluoroscopy images were acquired.

Function Provision to Fe-Porphyrin Complexes for CO Reduction.

CO reduction has recently attracted attention to address environmental and energy issues owing to its ability to convert greenhouse gases into valuable chemical fuels. Fe-porphyrin complexes ([Fe-(P)]-s) have been widely studied as catalysts for CO reduction owing to their high activity, selectivity, and robustness. In this perspective, [Fe-(P)]-s are classified in terms of our original concept, function provision, which serves to provide the function to approach key elements of the reaction.

ATG conjugation-dependent/independent mechanisms underlie lysosomal stress-induced TFEB regulation.

TFEB, a master regulator of autophagy and lysosomal biogenesis, is activated by several cellular stresses including lysosomal damage, but its underlying mechanism is unclear. TFEB activation during lysosomal damage depends on the ATG conjugation system, which mediates lipidation of ATG8 proteins. Here, we newly identify ATG conjugation-independent TFEB regulation that precedes ATG conjugation-dependent regulation, designated Modes I and II, respectively.

Dual-purpose dynamics emerge from a heterogeneous cell population in Drosophila metamorphosis.

Collective cell behavior is fundamental to structure multicellular organisms. There, constituting cells always have heterogeneous properties across cell types (macro-heterogeneity) and within a cell type (micro-heterogeneity). Many studies have described the existence of heterogeneity in various systems at the cellular level, whereas little has investigated its effect on the systems.

Effects of a Novel Mammalian-Derived Collagen Matrix on Human Articular Cartilage-Derived Chondrocytes from Osteoarthritis Patients.

Osteoarthritis (OA) is the most common joint disorder worldwide. Autologous chondrocyte implantation (ACI) is an established treatment for articular cartilage defects of the knee, but its effectiveness in OA is still under investigation. In this study, we investigated the effects of a newly developed mammalian-derived collagen matrix, NC-Col, on the proliferation, migration, adhesion, and gene expression of human articular cartilage-derived chondrocytes from OA patients in vitro, using proliferation assays, wound healing assays, adhesion assays, RT-qPCR, and RNA sequencing, respectively.

Associations Among Developmental Coordination Disorder Traits, Neurodevelopmental Difficulties and University Personality Inventory Scores in Undergraduate Students at a Japanese National University: A Cross-Sectional Correlational Study.

Background/objectives: Developmental coordination disorder (DCD) commonly co-occurs with attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and specific learning disorder (SLD), affecting academics, mental health, and lifestyle. Although screeners such as the Adolescents and Adults Coordination Questionnaire (AAC-Q) are widely used elsewhere, recognition and support for DCD in Japan remain limited. This study examined associations among DCD traits, ADHD/ASD-related difficulties, learning difficulties, mental health difficulties, and lifestyle factors in university students.

From cells to pixels: A decision tree for designing bioimage analysis pipelines.

Bioimaging has transformed our understanding of biological processes, yet extracting meaningful information from complex datasets remains a challenge, particularly for biologists without computational expertise. This paper proposes a simple general approach, to help identify which image analysis methods could be relevant for a given image dataset. We first categorise structures commonly observed in bioimage data into different types related to image analysis domains.