Choroidal hemangioma in Sturge-Weber syndrome elucidated by ultra-widefield swept-source optical coherence tomography angiography.

Background: Sturge-Weber syndrome (SWS) is a rare congenital phacomatosis disorder. choroidal hemangioma (CH) is one of the most common ocular manifestations. The advancements in swept-source optical coherence tomography angiography (SS-OCTA) provide us a comprehensive view of the CH.

Lats1/2 Differentially Modulate the Proliferative State of Dental Epithelial Progenitors and Ameloblasts in the Murine Incisor.

Objective(s): Yes-Associated Protein (YAP) is a critical regulator of cell proliferation and differentiation, having the capacity to convert differentiated cells into somatic stem cells in several contexts. Here we investigate the plasticity of adult mouse dental epithelial cells by testing the effects of ectopic YAP activation in dental epithelial progenitors and differentiated ameloblasts during incisor renewal.

Materials And Methods: Using mice with dental epithelial deletion of Lats1 and Lats2, which encode negative regulators of YAP, we assessed how ectopic YAP activation altered tissue structure, cell proliferation, and differentiation via histological analysis, EdU/BrdU labeling, and immunostaining.

Safety Profiles of Trofinetide in Pediatric Rett Syndrome Population: A Real-World Postmarketing Pharmacovigilance Analysis.

Purpose: Trofinetide, a synthetic analog of glycine-proline-glutamate, is the only approved therapy for Rett syndrome. This study evaluated the safety profile of trofinetide in pediatric patients with Rett syndrome using real-world pharmacovigilance data.

Methods: Adverse event (AE) reports were extracted from the U.

Targeting ECM-producing cells with CAR-T therapy alleviates fibrosis in chronic kidney disease.

Kidney fibrosis is a hallmark of chronic kidney disease (CKD) and a potential therapeutic target. However, clinical interventions and therapies targeting kidney fibrosis remain conceptual and practical challenges due to the complex origin, functional heterogeneity, and regulation of scar-forming cells. Here, we define fibroblasts, pericytes, and myofibroblasts as the major extracellular matrix (ECM)-producing cells in the kidney, highlighting their primary contribution to kidney fibrosis.

Effect of active and heat-killed Clostridium butyricum on in vitro gas production, ruminal fermentation, and microbiota varying with pH levels.

Objective: : The objective of this study was to evaluate the effects of inactive (heat-killed) Clostridium butyricum (ICB) on gas production kinetics, fermentation parameters, and microbiota with varying media pH levels in batch culture.

Methods: : The in vitro experiment was designed as a completely randomized factorial arrangement, with 2 media pH levels (5.8 and 6.

Correlated protein-RNA associations reveal a requirement for HNRNPU in long-range Polycomb recruitment by the lncRNAs , , and .

The lncRNAs , , and recruit Polycomb Repressive Complexes (PRCs) and repress genes over multi-megabase genomic regions, but how they interact with proteins to carry out repression remains poorly understood. To investigate, we conducted RNA-immunoprecipitations from formaldehyde-crosslinked mouse trophoblast stem cells, using antibodies against 27 proteins known to associate with . Relative to other chromatin-bound transcripts, , , and exhibited enriched and highly correlated associations with several RNA-binding proteins.

Repeat A coordinates an assembly of SR proteins to recruit SPEN and induce gene silencing.

The lncRNA silences gene expression by recruiting the protein SPEN through its 5'-proximal Repeat A domain. How Repeat A recruits SPEN, how SPEN enacts silencing, and why Repeat A is required for biogenesis in addition to silencing remain unclear. We find that sequences in Repeat A critical for SPEN recruitment, silencing, and biogenesis directly bind SR-rich splicing factors and not SPEN.

A ROS-Responsive Dual-Targeting Drug Nanocarrier Serving as a GSI Synergist and Ferroptosis Sensitizer for T-Cell Acute Lymphoblastic Leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological malignancy for which targeted therapies remain underdeveloped. Oncogenic mutations in Notch1 occur in up to 75% of T-ALL patients. Although γ-secretase inhibitors (GSIs) can block Notch1 activation, their clinical application is limited by side effects and reduced sensitivity.

From Mechanism to Therapy: The Role of MSC-EVs in Alleviating Radiation-Induced Injuries.

Radiation injury is a severe issue in both nuclear accidents and cancer radiotherapy. Ionizing radiation impairs the regenerative and repair capabilities of tissues and organs, resulting in a scarcity of effective therapeutic approaches to prevent or mitigate such injuries. Mesenchymal stem cells (MSCs) possess favorable biological characteristics and have emerged as ideal candidates for the treatment of radiation injury.

Isogenic comparison of Airn and Xist reveals core principles of Polycomb recruitment by lncRNAs.

The mechanisms and biological roles of Polycomb repressive complex (PRC) recruitment by long noncoding RNAs (lncRNAs) remain unclear. To gain insight, we expressed two lncRNAs that recruit PRCs to multi-megabase domains, Airn and Xist, from an ectopic locus in mouse stem cells and compared effects. Unexpectedly, ectopic Airn recruited PRC1 and PRC2 to chromatin with a potency resembling Xist yet did not repress genes.

Relationship between personality traits and spontaneous coronary artery dissection risk: evidence from Mendelian randomization.

Background: Spontaneous coronary artery dissection (SCAD) significantly contributes to myocardial infarction among young individuals. Despite the elusive nature of its etiology, empirical evidence indicates a substantial correlation between sociopsychological factors and the disorder. This investigation endeavored to discern a genetic basis for personality traits influencing SCAD susceptibility.

Dual targeting PPARα and NPC1L1 metabolic vulnerabilities blocks tumorigenesis.

Dysregulated lipid metabolism is linked to tumor progression. In this study, we identified Niemann-Pick C1-like 1 (NPC1L1) as a downstream effector of PKM2. In breast cancer cells, PKM2 knockout (KO) enhanced NPC1L1 expression while downregulating peroxisome proliferator-activated receptor α (PPARα) signaling pathway.

Fine-tuned calcium homeostasis is crucial for murine erythropoiesis.

Intracellular calcium (Ca) is a crucial signaling molecule involved in multiple cellular processes. However, the functional role of Ca in terminal erythropoiesis remains unclear. Here, we uncovered the dynamics of intracellular Ca levels during mouse erythroid development.

Regulating tumor cells to awaken T cell antitumor function and enhance melanoma immunotherapy.

Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX).

Napabucasin-loaded PLGA nanoparticles trigger anti-HCC immune responses by metabolic reprogramming of tumor-associated macrophages.

Background: JAK/STAT3 is one of the critical signaling pathways involved in the occurrence and development of hepatocellular carcinoma (HCC). BBI608 (Napabucasin), as a novel small molecule inhibitor of STAT3, has shown previously excellent anti-HCC effects in vitro and in mouse models. However, low bioavailability, high cytotoxicity and other shortcomings limit its clinical application.

TransformerLSR: Attentive joint model of longitudinal data, survival, and recurrent events with concurrent latent structure.

In applications such as biomedical studies, epidemiology, and social sciences, recurrent events often co-occur with longitudinal measurements and a terminal event, such as death. Therefore, jointly modeling longitudinal measurements, recurrent events, and survival data while accounting for their dependencies is critical. While joint models for the three components exist in statistical literature, many of these approaches are limited by heavy parametric assumptions and scalability issues.

Influence of New Internet Usage on Depressive Symptoms Among Older Adults: Does the Effect Vary in People with Different Economic Status?

This study investigated the longitudinal effect of new internet usage on depressive symptoms and whether economic status modified this association. Data were from the China Health and Retirement Longitudinal Study, involving 5,259 participants who were 60 +, did not use the internet in 2015, and were followed up in 2018. Linear regression with standard errors clustered at the city level was employed.

Acid-responsive CST@NPs enhanced diabetic wound healing through rescuing mitochondrial dysfunction.

Diabetic ulcers (DUs) are persistent and challenging complications of diabetes. The consequences of DUs include a decline in functional status, increased risk of infection, hospitalization, and even death. Our study revealed a significant decrease in the levels of cortistatin (CST) in the skin tissue of patients with DUs and diabetic rats.

Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy.

Diabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages.

Tumor-Selective Nano-Dispatcher Enforced Cancer Immunotherapeutic Effects via Regulating Lactate Metabolism and Activating Toll-Like Receptors.

The development of tumors relies on lactate metabolic reprogramming to facilitate their unchecked growth and evade immune surveillance. This poses a significant challenge to the efficacy of antitumor immunity. To address this, a tumor-selective nano-dispatcher, PIMDQ/Syro-RNP, to enforce the immunotherapeutic effect through regulation of lactate metabolism and activation of toll-like receptors is developed.

Choroidal Optical Coherence Tomography Angiography: Noninvasive Choroidal Vessel Analysis via Deep Learning.

The choroid is the most vascularized structure in the human eye, associated with numerous retinal and choroidal diseases. However, the vessel distribution of choroidal sublayers has yet to be effectively explored due to the lack of suitable tools for visualization and analysis. In this paper, we present a novel choroidal angiography strategy to more effectively evaluate vessels within choroidal sublayers in the clinic.

Eicosapentaenoic acid activates the P62/KEAP1/NRF2 pathway for the prevention of diabetes-associated cognitive dysfunction.

Diabetes-associated cognitive dysfunction (DCD) is a severe complication of diabetes mellitus (DM), threatening the life quality of the diabetic population. However, there is still a lack of effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid that was not previously investigated for its effect on DCD.