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Formation of Pdots and Pdot-siRNA and delivery mechanism to the cell. (A) Synthesis of Pdots and binding with siRNA around the Pdots. (B) Pdot-siRNA nanoplatform undergoes cellular uptake and siRNA delivery to target transcripts.more » « lessFree, publicly-accessible full text available February 5, 2026
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AbstractLeukopoiesis is lethally arrested in mice lacking the master transcriptional regulator PU.1. Depending on the animal model, subtotal PU.1 loss either induces acute myeloid leukemia or arrests early B-cell and dendritic-cell development. Although humans with absolute PU.1 deficiency have not been reported, a small cadre of congenital agammaglobulinemia patients with sporadic, inborn PU.1 haploinsufficiency was recently described. To better estimate the penetrance, clinical complications, immunophenotypic features, and malignancy risks of PU.1-mutated agammaglobulinemia (PU.MA), a collection of 134 novel or rare PU.1 variants from publicly available databases, institutional cohorts, previously published reports, and unsolved agammaglobulinemia cases were functionally analyzed. In total, 25 loss-of-function (LOF) variants were identified in 33 heterozygous carriers from 21 kindreds across 13 nations. Of individuals harboring LOF PU.1 variants, 22 were agammaglobulinemic, 5 displayed antibody deficiencies, and 6 were unaffected, indicating an estimated disease penetrance of 81.8% with variable expressivity. In a cluster of patients, disease onset was delayed, sometimes into adulthood. All LOF variants conveyed effects via haploinsufficiency, either by destabilizing PU.1, impeding nuclear localization, or directly interfering with transcription. PU.MA patient immunophenotypes consistently demonstrated B-cell, conventional dendritic-cell, and plasmacytoid dendritic-cell deficiencies. Associated infectious and noninfectious symptoms hewed closely to X-linked agammaglobulinemia and not monogenic dendritic-cell deficiencies. No carriers of LOF PU.1 variants experienced hematologic malignancies. Collectively, in vitro and clinical data indicate heterozygous LOF PU.1 variants undermine humoral immunity but do not convey strong leukemic risks.more » « lessFree, publicly-accessible full text available May 29, 2026
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Recently, nano-based cancer therapeutics have been researched and developed, with some nanomaterials showing anticancer properties. When it comes to cancer treatment, graphene quantum dots (GQDs) contain the ability to generate 1O2, a reactive oxidative species (ROS), allowing for the synergistic imaging and photodynamic therapy (PDT) of cancer. However, due to their small particle size, GQDs struggle to remain in the target area for long periods of time in addition to being poor drug carriers. To address this limitation of GQDs, hollow mesoporous silica nanoparticles (hMSNs) have been extensively researched for drug delivery applications. This project investigates the utilization and combination of biomass-derived GQDs and Stöber silica hMSNs to make graphene quantum dots-hollow mesoporous silica nanoparticles (GQDs-hMSNs) for fluorescent imaging and dual treatment of cancer via drug delivery and photodynamic therapy (PDT). Although the addition of hMSNs made the newly synthesized nanoparticles slightly more toxic at higher concentrations, the GQDs-hMSNs displayed excellent drug delivery using fluorescein (FITC) as a mock drug, and PDT treatment by using the GQDs as a photosensitizer (PS). Additionally, the GQDs retained their fluorescence through the surface binding to hMSNs, allowing them to still be used for cell-labeling applications.more » « less
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Abstract The purpose of this work is to develop an active self-cleaning system that removes contaminants from a solar module surface by means of an automatic, water-saving, and labor-free process. The output efficiency of a solar module can be degraded over time by dust accumulation on top of the cover glass, which is often referred to as “soiling”. This paper focuses on creating an active self-cleaning surface system using a combination of microsized features and mechanical vibration. The features, which are termed anisotropic ratchet conveyors (ARCs), consist of hydrophilic curved rungs on a hydrophobic background. Two different ARC systems have been designed and fabricated with self-assembled monolayer (SAM) silane and fluoropolymer thin film (Cytop). Fabrication processes were established to fabricate these two systems, including patterning Cytop without degrading the original Cytop hydrophobicity. Water droplet transport characteristics, including anisotropic driving force, droplet resonance mode, cleaning mechanisms, and system power consumption, were studied with the help of a high-speed camera and custom-made test benches. The droplet can be transported on the ARC surface at a speed of 27 mm/s and can clean a variety of dust particles, either water-soluble or insoluble. Optical transmission was measured to show that Cytop can improve transmittance by 2.5~3.5% across the entire visible wavelength range. Real-time demonstrations of droplet transport and surface cleaning were performed, in which the solar modules achieved a 23 percentage-point gain after cleaning.more » « less
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