The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis and dysregulated B cell receptor signaling. CBL deficiency impairs humoral immunity by limiting memory B cell formation and reducing class switching and somatic hypermutation. Consequently, antigen-specific B cell generation and adaptive immune memory are disrupted, predisposing individuals to infection. Human CBL is critical for B cell development and function but redundant for T cell biology.
This work reports, for the first time, the fabrication of poly(vinyl alcohol)-methylcellulose (PVA-MC)/BaTiO3-SiO2 nanocomposite films via a simple casting method. This innovative approach enables the synergistic integration of the flexibility and film-forming ability of PVA-MC with the high dielectric and optical properties of BaTiO3-SiO2 nanoparticles. As a result, the hybrid films exhibit enhanced structural integrity and superior optical performance compared to conventional nanocomposite membranes. The microstructural, morphological, and optical characteristics of the PVA-MC/BaTiO3-SiO2 films were systematically investigated. Results show that absorbance increased by 88.7% in the UV region (lambda = 320 nm) and by 92% in the near-infrared region (lambda = 760 nm) at a BaTiO3-SiO2 content of 6.7 wt%. Moreover, the allowed indirect band gap decreased from 4.1 to 1.6 eV with increasing nanoparticle loading, confirming the improved optical performance. These findings highlight the novelty and potential of PVA-MC/BaTiO3-SiO2 hybrid films as cost-effective, high-performance nanomaterials for nano-optical and optoelectronic applications. The (PVA-MC)/BaTiO3-SiO2 nanocomposite films were tested for gamma radiation shielding application. The results showed these nanocomposite films included high attenuation coefficients, good flexibility, and low cost.
Existing treatments for lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) focus on symptom relief. Until recently, altering the disease course was rarely considered a therapeutic objective. The first-in-class, direct, competitive telomerase inhibitor, imetelstat, demonstrated significantly higher rates of red blood cell (RBC) transfusion independence (TI) versus placebo in patients with non-del(5q), RBC transfusion-dependent LR-MDS who were relapsed/refractory to or ineligible for erythropoiesis-stimulating agents in the Phase 3 IMerge study (NCT02598661). In this exploratory analysis of IMerge, patients treated with imetelstat had greater sustained reductions in variant allele frequency of multiple mutations versus placebo recipients, which was positively associated with RBC-TI duration. Subsequent analyses showed that 70% of patients with a cytogenetic response with imetelstat achieved ≥1-year RBC-TI. Additionally, higher rates of ≥1-year RBC-TI were observed in patients with maximum variant allele frequency reduction of ≥50% in SF3B1 (58% vs. 7%), TET2 (90% vs. 9%), DNMT3A (100% vs. 13%), or ASXL1 (50% vs. 0%) and patients with ≥50% bone marrow ring sideroblast reduction (46% vs. 0%) versus patients who did not. Lastly, 60% of patients with ≥1-year RBC-TI had ≥50% reduction in telomerase activity/human telomerase reverse transcriptase RNA. These results suggest that imetelstat targets clonal progenitor cells and may modify LR-MDS biology.
This experimental study aimed to improve the output of the Conical Distiller (CD) using low-cost natural bio-materials. Three CDs (simple CD (SCD), a CD with Natural Peanut Shells (CD-NPS) and a CD with Black-Painted Peanut Shells (CD-BPS)) were fabricated for comparative analysis under identical climatic conditions. Experimental results revealed that the daily yields, energy, and exergy efficiencies for SCD, CD-NPS, and CD-BPS are 4.69 kg, 6.49%, 45.30%, and 7.43%, 31.23%, 52.06%, and 1.15%, 1.78%, 2.38%, respectively. The results showed that the daily yields of CD-NPS and CD-BPS increased by 38.4% and 58.4%, respectively, and the daily energy efficiency of CD-NPS and CD-BPS increased by 45.06% and 66.69%, respectively, compared with the SCD. The daily exergy efficiency of CD-NPS and CD-BPS increased by 54.20% and 106.64%, respectively, compared with the SCD. The economic analysis confirmed that integrating BPS is an effective and cost-effective way to improve the CD yield.
Pesticides tend to cause serious reproductive defects, disturbing endocrine functions and reducing fertility, especially in females. The objective of this work was to identify the reprotoxic effects of Ampligo® 150 ZC (AP), a mixture formulation of lambda cyhalothrin and chlorantraniliprole, on the ovary of female rabbits (Oryctolagus cuniculus) and the possible protective effect of co-treatment with thyme essential oil (TEO), extracted from (Thymus vulgaris) species, and vitamin C (vit C). Twenty female rabbits were divided into four equal groups (n = 5): Control (distilled water), AP (20 mg/ kg bw of the insecticide mixture every other day, by gavage for 28 days), AP+TEO (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO every other day), and AP+TEO+Vit C (20 mg/ kg bw of AP + 0.5 mg/ kg bw of TEO + 200 mg/ kg bw of vitamin C every other day). The effects were tested on body weight, ovary histomorphometry, and immunohistochemical expression of AFP, estrogen receptor (ER), and progesterone receptor (PR). The results revealed that AP decreased body and ovarian weights, caused ovarian histological damages, and increased collagen fiber deposition. The immunostaining of the ovary showed a significant (p < .001) increase in AFP and decrease in both ER and PR expressions. In the opposite, co-administration of TEO and vitamin C was effective in improving all caused alterations. In conclusion, combined use of TEO and vitamin C ameliorated the toxic effects of Ampligo® on the ovary in female rabbits.
