Design, Structure Optimization, and Preclinical Characterization of JAB-21822, a Covalent Inhibitor of KRAS.

KRAS is the most frequently mutated driver oncogene in human cancer, and KRAS mutation is commonly found in non-small-cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC). Inhibitors that covalently modify the mutated codon 12 cysteine have completed proof-of-concept studies in the clinic. Here, we describe structure-based design and cocrystal-aided drug optimization of a series of compounds with the 1,8-naphthyridine-3-carbonitrile scaffold.

Unveiling the intricate interplay: Exploring biological bridges between renal ischemia-reperfusion injury and T cell-mediated immune rejection in kidney transplantation.

Unlabelled: Although the link between ischemia-reperfusion injury (IRI) and T cell-mediated rejection (TCMR) in kidney transplantation (KT) is well known, the mechanism remains unclear. We investigated essential genes and biological processes involved in interactions between IRI and TCMR.

Methods: Renal IRI and TCMR datasets were obtained from the Gene Expression Omnibus database.

Statins Combined with AAV8-TBG-LOX-1 Reduce the Vascular Lipid-driven Inflammatory Response and Inhibit Atherosclerosis.

Objective: Imbalances in liver lipid metabolism and inflammatory reactions driven by oxidized lipid deposition in blood vessels constitute the core of atherosclerosis. Insufficient degradation of cholesterol in the liver promotes oxidative modification of lipid particles and their deposition on the blood vessel wall in the peripheral circulation. The blood vessel wall engulfs and processes oxidized low-density lipoprotein (Ox-LDL) as foreign matter through pattern recognition receptors, ultimately forming lipid-encapsulated plaques.

A resting-state EEG dataset for sleep deprivation.

To investigate the impact of sleep deprivation (SD) on mood, alertness, and resting-state electroencephalogram (EEG), we present an eyes-open resting-state EEG dataset. The dataset comprises EEG recordings and cognitive data from 71 participants undergoing two testing sessions: one involving SD and the other normal sleep. In each session, participants engaged in eyes-open resting-state EEG.

Aspherical interferometric probe with wave-plate-array detection: system design and nonlinearity analysis.

Optical probes are the preferred choice for high-precision surface metrology, necessitating improved flexibility and a broader range of motion to adapt to the increasing complexity of surfaces. This study introduces an interferometric probe designed for measuring aspheric surfaces, utilizing a wave-plate-array detection component. By integrating splitter elements into the detector, the probe improves integration and dynamic scanning performance, while maintaining high-precision measurement capability.

NLRC4 inflammasome-dependent cell death occurs by a complementary series of three death pathways and determines lethality in mice.

Inflammasome is an innate immune defense mechanism, but its overactivation can lead to host death. Here, we show that cell death dictates mouse death caused by NLRC4 inflammasome overactivation. To execute NLRC4-dependent cell death, three death pathways complement each other in a specific order: Pyroptosis pathway requiring caspase-1 and GSDMD is the default path; impairment of it initiates ASC-mediated caspase-8–dependent apoptosis; when these two pathways are blocked, caspase-1 triggers intrinsic apoptotic pathway.

Mechanical insight into the formation of HS from thiophene pyrolysis: The influence of HO.

The thermal utilization of waste rubber is accompanied by the release of sulfur, and the release of HS to the gas phase is one of the crucial issues. In this work, density functional theory (DFT) calculations and wave function analysis were employed to explore the possible formation pathways of HS and its precursor (·SH radical) during the pyrolysis of thiophene in the presence of HO. It indicates that HO affects the decomposition of thiophene and the formation of HS in two patterns.

SAMD4 family members suppress human hepatitis B virus by directly binding to the Smaug recognition region of viral RNA.

HBV infection initiates hepatitis B and promotes liver cirrhosis and hepatocellular carcinoma. IFN-α is commonly used in hepatitis B therapy, but how it inhibits HBV is not fully understood. We screened 285 human interferon-stimulated genes (ISGs) for anti-HBV activity using a cell-based assay, which revealed several anti-HBV ISGs.