CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.

Background: Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated.

Methods: We identified circUCK2(2,3) through circRNA sequencing, RT-PCR, and Sanger sequencing.

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.

Design, modeling, and control of coaxial integrated macro-micro composite actuator with high-precision and long-stroke.

This paper presents a coaxial integrated macro-micro composite actuator. The macro-actuator of the macro-micro composite actuator is similar to a moving coil type voice coil motor, and a giant magnetostrictive actuator is installed coaxially inside it as a micro-actuator. In this work, kinetic models are established for both the macro-actuator and micro-actuator, and based on the models, an automatic disturbance rejection controller is adopted to control the macro-actuator, and a fuzzy sliding mode controller is adopted for the micro-actuator.

The neutrophil-lymphocyte ratio as a risk factor for all-cause mortality among individuals with resolved HBV infection: evidence from the NHANES 1999-2018.

Background: Inflammation is a critical component in the process of resolved hepatitis B virus (HBV) infection. The neutrophil-to-lymphocyte ratio (NLR) serves as a sensitive indicator of systemic inflammation and immune activation. Our study aimed to investigate the correlation between elevated NLR levels and the risk of all-cause mortality in patients with resolved HBV infection.