Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.

FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.

Highly sensitive, responsive, and selective iodine gas sensor fabricated using AgI-functionalized graphene.

Radioactive molecular iodine (I) is a critical volatile pollutant generated in nuclear energy applications, necessitating sensors that rapidly and selectively detect low concentrations of I vapor to protect human health and the environment. In this study, we design and prepare a three-component sensing material comprising reduced graphene oxide (rGO) as the substrate, silver iodide (AgI) particles as active sites, and polystyrene sulfonate as an additive. The AgI particles enable reversible adsorption and conversion of I molecules into polyiodides, inducing substantial charge density variation in rGO.

Fluconazole-induced changes in azole resistance and biofilm production in Candida glabrata in vitro.

Currently, the molecular mechanisms of azole resistance in C. glabrata are unresolved. This study aims to detect azole resistance of C.

Subattojoule Electrical Switching in a Two-Dimensional TaSe Oxide Device with High Endurance.

Recent developments in artificial intelligence and the internet-of-things have created great demand for low-power microelectronic devices. Two-dimensional (2D) electrical switching materials are extensively used in neuromorphic computing technology, yet their high leakage current and low endurance impede their further application. This study presents a vertical crossbar-structured conductive-bridge threshold switching device based on 2D TaSe oxide.

KaMLs for Predicting Protein p Values and Ionization States: Are Trees All You Need?

Despite its importance in understanding biology and computer-aided drug discovery, the accurate prediction of protein ionization states remains a formidable challenge. Physics-based approaches struggle to capture the small, competing contributions in the complex protein environment, while machine learning (ML) is hampered by the scarcity of experimental data. Here, we report the development of p ML (KaML) models based on decision trees and graph attention networks (GAT), exploiting physicochemical understanding and a new experiment p database (PKAD-3) enriched with highly shifted p's.