Epigenetic small molecule screening identifies a new HDACi compound for ameliorating Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common inherited muscle disease. There are currently few effective therapies to treat the disease, although many approaches are being pursued. Certain histone deacetylase inhibitors (HDACi) have been shown to ameliorate DMD phenotypes in mouse and zebrafish models, and the HDACi givinostat has recently gained FDA approval for DMD.

Fully biocompatible, thermally drawn fiber supercapacitors for long-term bio-implantation.

Recent advancements in implantable bioelectronic devices have increased the demand for biocompatible energy sources with long-term electrochemical and mechanical stability. Here, we present a tough hydrogel-based supercapacitor (THBS) fiber, fabricated via a thermal drawing process (TDP), that enables the integration of all components-electrodes, electrolyte, current collectors, and encapsulation-into a single, unified, and mechanically robust fiber-shaped architecture. Through thermal/mechanical optimization and the incorporation of self-healing properties, THBS fibers exhibit durable, high electrochemical performance under dynamic, high-curvature deformations mimicking in vivo physiological motions.

Scanned particle-beam tracking with beam correction based on predictive volumetric imaging: A simulation study.

Background: Tracking irradiation to moving targets in spot-scanning particle therapy, which corrects the spot position and energy in real-time, may decrease treatment time and increase accuracy. However, because of the temporal performance of the system, clinical translation remains challenging. Processing time, including image acquisition, volumetric image synthesis, correction assessment, and system response, is required to control the actual treatment system.

Human myocardial-derived highly proliferative cells improve cardiac remodeling after myocardial infarction in mice.

Human highly proliferative cells (hHiPCs) isolated from the adult heart have progenitor and angiogenic properties. However, the mechanisms underlying hHiPCs in myocardial repair in vivo have yet to be investigated. We characterized the hHiPC proteome and secretome and found that hHiPCs express and secrete proangiogenic and proreparative proteins, including CXCL6, CTHRC1, and CD73, and are ontologically enriched in pathways related to cytokine signaling and glucose metabolism.

Septin Organization is Regulated by the Gpa1 Ubiquitination Domain and Endocytic Machinery During the Yeast Pheromone Response.

detect and respond to mating pheromone using a G-Protein Coupled Receptor signaling pathway to initiate polarized growth toward mating partners. Septins form structures at the base of the mating projection to control morphogenesis in a manner that is dependent upon desensitization of the large G-protein Gpa1. We sought to identify the pathway through which Gpa1 regulates septin organization using gene deletions in the presence of a hyperactive Gpa1 mutant, live cell imaging, and computational approaches.

Evaluation of intra-fractional target displacement by patient motion during a single-isocenter multi-target stereotactic radiation therapy for brain metastases.

Background: Single-isocenter multi-target volumetric modulated arc therapy (SIMT-VMAT) has been implemented widely in fractionated stereotactic radiosurgery (fSRS) to treat brain metastases. The impact of rotational intra-fractional patient motion (IFPM) is influenced by the distance between the geometric target's center and the isocenter (DTI).

Purpose: We hypothesized that IFPM's impact on each target would increase with greater DTI during fSRS.

MUTE-Seq: An Ultrasensitive Method for Detecting Low-Frequency Mutations in cfDNA With Engineered Advanced-Fidelity FnCas9.

In this study, we present the development of the Mutation tagging by CRISPR-based Ultra-precise Targeted Elimination in Sequencing (MUTE-Seq) method. We engineered a highly precise advanced-fidelity FnCas9 variant, named FnCas9-AF2, to effectively discriminate single-base mismatches at all positions of the single guide RNA (sgRNA) target sequences. FnCas9-AF2 exhibited significantly lower off-target effects compared to existing high-fidelity CRISPR-Cas9 variants.

Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.

CRISPR-Cas systems have been explored for targeted genome editing of several organisms. It is rapid, cost-effective, specific, and versatile technology. It requires expression of multidomain single Cas9 protein and single guide RNA (sgRNA) that targets desired nucleic acids in the presence of a protospacer adjacent motif (PAM).

In silico chemical fingerprint screening identifies fisetin as a novel stemotoxic flavonoid.

Despite recent advances in stem cell therapy using human pluripotent stem cells (hPSCs), the risk of teratoma formation due to residual undifferentiated cells remains a significant safety concern. Numerous small molecules, termed stemotoxic agents, have been developed to eliminate these residual cells, such as the promising natural flavonoid quercetin (QC). Application of QC in clinical settings during the differentiation of dopaminergic neurons from hPSCs has demonstrated its safety and efficacy in selectively targeting residual hPSCs without affecting neural stem cells (NSCs).

Synthesis and preclinical evaluation of a Ga-labeled peptide for PET imaging of transferrin receptor 1 in tumor.

Purpose: Transferrin receptor 1 (TfR1) is a transmembrane glycoprotein that mediates cellular iron uptake. Despite its potential as a target for tumor diagnosis, the lack of suitable TfR1 ligands has hindered the development of effective TfR1 imaging agents. We labeled a recently discovered TfR1 ligand, TfRB1G3, with Ga-68 and evaluated its potential for TfR1 imaging through preclinical experiments.

Exosome Trafficking Is a Key Regulator of Adipocyte Thermogenesis.

Activation of beige adipocytes enhances energy expenditure and promotes metabolic health, presenting a promising approach for combating obesity and diabetes. As part of this process, thermogenesis, fueled in part by uncoupled mitochondrial respiration, plays a central role in converting calories into thermal energy, thereby preventing their storage as fat. Here, we identify a role for exosome trafficking as an intrinsic regulator of beige adipocyte thermogenesis.

Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis.

Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer.

Revolutionizing CRISPR technology with artificial intelligence.

Genome engineering has made remarkable strides, evolving from DNA-binding proteins such as zinc fingers and transcription activator-like effectors to CRISPR-Cas systems. CRISPR technology has revolutionized the field through its simplicity and ability to target specific genome regions via guide RNA and Cas proteins. Progress in CRISPR tools-CRISPR nucleases, base editors and prime editors-has expanded the toolkit to induce targeted insertions or deletions, nucleotide conversions and a wider array of genetic alterations.

Tracking clonal dynamics of CD8 T cells and immune dysregulation in progression of systemic lupus erythematosus with nephritis.

The fluctuating nature of disease activity in systemic lupus erythematosus (SLE), alternating between flares and remissions, poses substantial challenges for its effective management. The use of current biomarkers for monitoring SLE is limited in clinical settings owing to insufficient comprehension of the complex immune involvement underlying the disease course. Here, therefore, we profiled peripheral blood mononuclear cells at both stable and exacerbation states (total of n = 19) from six patients with SLE and 32 healthy donors using integrated single-cell RNA and T cell receptor (TCR) sequencing.

Creating interpretable deep learning models to identify species using environmental DNA sequences.

Monitoring species' presence in an ecosystem is crucial for conservation and understanding habitat diversity, but can be expensive and time consuming. As a result, ecologists have begun using the DNA that animals naturally leave behind in water or soil (called environmental DNA, or eDNA) to identify the species present in an environment. Recent work has shown that when used to identify species, convolutional neural networks (CNNs) can be as much as 150 times faster than ObiTools, a traditional method that does not use deep learning.

Blocking YAP1-Liprin-β2 interaction impedes metastasis and promotes tumor suppression in head and neck squamous carcinoma.

Our research investigates the role of the YAP1-PPFIBP2 axis in the epithelial-mesenchymal transition (EMT) and its subsequent impact on invasion and migration in head and neck squamous cell carcinoma (HNSCC). Utilizing both in vitro assays and genomic analyses, we demonstrate that YAP1 upregulates EMT by suppressing PPFIBP2/liprin-β2 expression. This regulatory pathway contributes to enhanced invasiveness and correlates with poorer prognostic outcomes in HNSCC.

Computational biology meets oncology: designing custom protein and peptide binders to outsmart cancer.

Cancer remains one of the most formidable global health challenges, with conventional therapies often limited by off-target toxicity, drug resistance, and the inability to target key oncogenic drivers. In recent years, de novo protein and peptide binder engineering has emerged as an approach to overcome these barriers, offering precise and customizable solutions for cancer diagnosis and treatment. By leveraging computational design, directed evolution, and artificial intelligence, researchers can now engineer binding molecules with high specificity, stability, and therapeutic potential, unconstrained by the limitations of natural protein scaffolds.

Alpha-particle-induced reactions on natural tin for production of Te.

The excitation function of the Sn(α,x)Te reaction was measured up to 50 MeV using the stacked-foil activation technique and high-resolution γ-ray spectrometry. The cross sections of the co-products, In, Sn,Sb, and Te, were also determined. Based on the measured cross section, the physical thick target yields of Te, Te, Te, and Te were deduced.

Increased rate of single nucleotide mutation in house mice born through assisted reproduction.

Approximately 2.6% of live births in the United States are conceived using assisted reproductive technologies (ARTs). While some ART procedures, including in vitro fertilization (IVF) and intracytoplasmic sperm injection, are known to alter the epigenetic landscape of early embryonic development, their impact on DNA sequence stability is unclear.

Altered metabolomics and inflammatory transcriptomics in human bone marrow adipocytes after acute high calorie diet and acute fasting.

Expansion of bone marrow (BM) adipocytes has been linked to nutritional pressures, suggesting that BM is a dynamic compartment that responds to fluctuations in systemic nutritional availability to regulate osteogenesis and hematopoiesis. Here, we investigated BM metabolism in response to acute overnutrition (high calorie diet; HCD) and calorie deprivation (fasting). Participants underwent a 10-day HCD followed by a two-week interval of an ad libitum diet and then underwent 10 days of fasting.

Patient-Derived Cortical Organoids Reveal Senescence of Neural Progenitor Cells in Hutchinson-Gilford Progeria Syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature aging and primarily caused by the accumulation of progerin, a mutant form of lamin A. Although the effects of progerin on multiple tissues have been previously studied, its impact on brain development is not completely understood. We established cortical organoids derived from HGPS patient-induced pluripotent stem cells (iPSCs) from patients with HGPS to investigate the role of progerin in the brain.

EGFR inhibitor suppresses tumor growth by blocking lipid uptake and cholesterol synthesis in non-small cell lung cancer.

Accelerated cholesterol and lipid metabolism are hallmarks of non-small cell lung cancer (NSCLC). Recently, epidermal growth factor receptor (EGFR) signaling has been shown to regulate de novo cholesterol synthesis and low-density lipoprotein receptor (LDLR) expression through SREBP-1-dependent pathways. This suggests that targeting EGFR signaling in cholesterol metabolism might provide a new therapeutic strategy for NSCLC.

Tunable Drug Release through Varying Drug Affinities for Ocular Chronic Disease.

Effective drug delivery is critical for the management of chronic diseases such as glaucoma, where sustained therapeutic levels can significantly enhance treatment outcomes. In this study, we present a Particles-on-a-Gel (PoG) system that leverages differential nanocarrier affinities to modulate drug release kinetics. By integrating poly(N-isopropylacrylamide) nanogels (pNIPAM) and silver nanoparticles (AgNPs), the PoG platform enables both controlled initial release and prolonged drug delivery.

Proteomic Profiling of Exosomes Derived from Endometrial Stem Cells and Adipose-Derived Stem Cells.

Endometrial stem cells (EnSCs) are mesenchymal stem cells (MSCs) derived from endometrial tissue and serve as a valuable MSC source, as they are naturally replenished during menstruation. Exosomes, vesicles secreted by cells, contain various biomolecules such as proteins and nucleic acids and play crucial roles in intracellular communication, protein and nucleic acid metabolism, immune response regulation, and antigen presentation. This study investigated the protein profiles of EnSC-derived exosomes isolated from the endometrium of menstruating women and compared them with those of adipose-derived stem cell (ASC)-derived exosomes.