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The TNNT2 gene encodes cardiac troponin T (cTnT), a critical protein in cardiac muscle contraction. Mutations in TNNT2 are associated with various cardiomyopathies, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM), which contribute to significant morbidity and mortality. In this study, we established a novel TNNT2 knockout human embryonic stem cell (hESC) line, WAe009-A-3B, utilizing the CRISPR/Cas9 genome editing system. This novel hESC line provides an important tool for investigating the molecular mechanisms underlying TNNT2-related cardiomyopathies and may serve as a promising in vitro model for the development of therapeutic strategies targeting TNNT2 mutations in cardiac diseases.
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http://dx.doi.org/10.1016/j.scr.2025.103729 | DOI Listing |
Bioorg Chem
September 2025
Department of Medicinal Chemistry, Shandong Key Laboratory of Druggability Optimization and Evaluation for Lead Compounds, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, PR China. Electronic address:
A series of novel 3,3-dimethyl-2,3,4,9-tetrahydro-1H-carbazole derivatives were rationally designed, synthesized and evaluated for their biological activity as AcrB inhibitors. The compounds were assessed for their antibiotic potentiating effects, followed by evaluation of Nile Red efflux inhibition, and off-target effects including activity on the outer and inner bacterial membranes. Ten compounds potentiated antibiotic activity at sub-inhibitory concentrations, reducing the minimum inhibitory concentrations (MICs) of at least one of the tested antibiotics by at least 8-fold, with three derivatives (7c, 11g, and 11i) achieving 32-fold MIC reductions at 128 μg/mL.
View Article and Find Full Text PDFJ Obstet Gynaecol Res
September 2025
Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Aims: Preterm delivery (PTD) is a leading cause of neonatal morbidity and mortality. Accurate prediction is crucial for optimizing clinical outcomes, particularly in women with a short cervix. Although fetal fibronectin (FFN) is widely used to predict PTD, placental alpha-microglobulin-1 (PAMG-1) has gained attention for its potential to improve predictive accuracy.
View Article and Find Full Text PDFCell Stem Cell
September 2025
Friedrich Miescher Institute for Biomedical Research, Fabrikstrasse 24, Basel 4056, Switzerland. Electronic address:
Stem cells and organoids enable the modeling of various aspects of human development in vitro, yet integrating them to study maternal-fetal interactions remains challenging. In this review, we explore the current in vitro models of the endometrium, placenta, and embryo and identify key challenges associated with their integration, including the establishment of morpho-functional complexity, spatiotemporal coordination, and appropriate in vivo benchmarking. We propose an interdisciplinary perspective that emphasizes a shift from "building blocks" to "building interactions.
View Article and Find Full Text PDFStem Cell Rev Rep
September 2025
Department of Endodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, China.
Stem cells are undifferentiated cells with self-renewal and multidirectional differentiation potential. Embryonic and adult stem cells perform a variety of functions, including cell proliferation, quiescence, and multidirectional differentiation. Research into the physiological and pathological mechanisms of stem cells is important for elucidating the processes underlying the development, treatment, and progression of diseases, as well as the therapeutic and physiological functions of cells.
View Article and Find Full Text PDFHum Mol Genet
September 2025
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease (MIND), Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, United States.
A de novo mutation in the transcription factor Nucleus accumbens associated protein 1 (NACC1) gene (c.892C > T p.R298W) causes a rare, severe neurodevelopmental disorder which manifests postnatally.
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