Virus-free CRISPR knock-in of a chimeric antigen receptor into KLRC1 generates potent GD2-specific natural killer cells.

Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood.

Real-World Evidence of the Impact of CanAssist Breast on Physician's Decision About the Use of Adjuvant Chemotherapy in Early Breast Cancer.

Background Clinicians use prognostic biomarker/multi-gene-based tests for predicting recurrence in hormone receptor-positive/HER2-negative (HR+/HER2-) early-stage breast cancer (EBC). CanAssist Beast (CAB) uses the expression of five protein biomarkers in combination with tumor-specific parameters such as tumor size, histopathological grade, and lymph node status to predict the risk of distant recurrence within five years of diagnosis for patients with HR+/HER2-, EBC. The current study aimed to evaluate the impact of prognostic tests on adjuvant chemotherapy decisions by assessing the agreement between clinical and CAB risk stratification as low-risk (LR) or high-risk (HR) for distant recurrence.

Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation.

Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited.

Structural and optical studies of fluoride ion binding using N-heteroaromatic ligands.

8-Hydroxyquinoline and imidazole, two important N-heteroaromatic systems, have a strong affinity towards various anions their acidic OH or NH protons. Three receptor ligands, 5-(1-benzo[]imidazol-2-yl)quinolin-8-ol (1), 5-(benzo[]thiazol-2-yl)quinolin-8-ol (2), and 4-(1-benzo[]imidazol-2-yl)benzene-1,3-diol (3), were synthesized, and their fluoride (F) ion binding properties were investigated. These ligands could selectively bind F ions, and their respective F complexes, namely, 1-TBAF, 2-TBAF, and 3-TBAF (TBAF = tetrabutylammonium fluoride), were characterized using single crystal X-ray analysis, NMR, UV-vis, Hirshfeld surface (HS) analysis and computational studies.

Tetramerization of deoxyadenosine kinase meets the demands of a DNA replication substrate challenge in Giardia intestinalis.

The protozoan parasite Giardia intestinalis is one of only a few organisms lacking de novo synthesis of DNA building blocks (deoxyribonucleotides). Instead, the parasite relies exclusively on salvaging deoxyadenosine and other deoxyribonucleosides from its host environment. Here, we report that G.