ADP-Hep-Induced Liquid Phase Condensation of TIFA-TRAF6 Activates ALPK1/TIFA-Dependent Innate Immune Responses.

The ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with fork head-associated domain)-TRAF6 signaling pathway plays a pivotal role in regulating inflammatory processes, with TIFA and TRAF6 serving as key molecules in this cascade. Despite its significance, the functional mechanism of TIFA-TRAF6 remains incompletely understood. In this study, we unveil that TIFA undergoes liquid-liquid phase separation (LLPS) induced by ALPK1 in response to adenosine diphosphate (ADP)-β-D-manno-heptose (ADP-Hep) recognition.

USP15 promotes cGAS activation through deubiquitylation and liquid condensation.

Double-stranded DNA (dsDNA) is recognized as a danger signal by cyclic GMP-AMP synthase (cGAS), which triggers innate immune responses. cGAS activity must be properly regulated to maintain immune homeostasis. However, the mechanism by which cGAS activation is controlled remains to be better understood.

MARCH8 attenuates cGAS-mediated innate immune responses through ubiquitylation.

Cyclic GMP-AMP synthase (cGAS) binds to microbial and self-DNA in the cytosol and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING) and downstream mediators to elicit an innate immune response. Regulation of cGAS activity is essential for immune homeostasis. Here, we identified the E3 ubiquitin ligase MARCH8 (also known as MARCHF8, c-MIR, and RNF178) as a negative regulator of cGAS-mediated signaling.

ZDHHC18 negatively regulates cGAS-mediated innate immunity through palmitoylation.

Double-stranded DNA is recognized as a danger signal by cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS), triggering innate immune responses. Palmitoylation is an important post-translational modification (PTM) catalyzed by DHHC-palmitoyl transferases, which participate in the regulation of diverse biological processes. However, whether palmitoylation regulates cGAS function has not yet been explored.

Orthosteric-allosteric dual inhibitors of PfHT1 as selective antimalarial agents.

Artemisinin-resistant malaria parasites have emerged and have been spreading, posing a significant public health challenge. Antimalarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a "selective starvation" strategy by inhibiting hexose transporter 1 (PfHT1), the sole hexose transporter in , over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites.

Structural Basis for Blocking Sugar Uptake into the Malaria Parasite Plasmodium falciparum.

Plasmodium species, the causative agent of malaria, rely on glucose for energy supply during blood stage. Inhibition of glucose uptake thus represents a potential strategy for the development of antimalarial drugs. Here, we present the crystal structures of PfHT1, the sole hexose transporter in the genome of Plasmodium species, at resolutions of 2.

A comparative study of three nutritional risk screening tools in surgical inpatients with laryngeal cancer.

Background And Objectives: Nutritional screening has been recommended for hospitalized patients. The goal of this study was to compare the screening value of Nutritional Risk Screening 2002 (NRS-2002), Malnutrition Universal Screening Tool (MUST), and Malnutrition Screening Tool (MST) in inpatients with laryngeal cancer, and to identify which is the most accurate.

Methods And Study Design: An observational cross-sectional study of 197 laryngeal cancer patients admitted for surgery was conducted using continuous sampling.

Discovery of Small-Molecule Cyclic GMP-AMP Synthase Inhibitors.

Cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) (cGAS), a cytosolic DNA sensor, plays an important role in the type I interferon response. DNA from either invading microbes or self-origin triggers the enzymatic activity of cGAS. Aberrant activation of cGAS is associated with various autoimmune disorders.