Oncogenic mutant KRAS inhibition through oxidation at cysteine 118.

Specific reactive oxygen species activate the GTPase Kirsten rat sarcoma virus (KRAS) by reacting with cysteine 118 (C118), leading to an electron transfer between C118 and nucleoside guanosine diphosphate (GDP), which causes the release of GDP. Here, we have mimicked permanent oxidation of human KRAS at C118 by replacing C118 with aspartic acid (C118D) in KRAS to show that oncogenic mutant KRAS is selectively inhibited via oxidation at C118, both in vitro and in vivo. Moreover, the combined treatment of hydrogen-peroxide-producing pro-oxidant paraquat and nitric-oxide-producing inhibitor N(ω)-nitro-l-arginine methyl ester selectively inhibits human mutant KRAS activity by inducing oxidization at C118.

Obsessive-Compulsive Symptoms in the General Population Under Stressful Conditions: Lessons Learned from the COVID-19 Pandemic.

: The COVID-19 pandemic had a negative impact on mental health in the general population. The fear, stress, and uncertainty surrounding that traumatic period could have contributed to the aggravation or possible new onset of obsessive-compulsive symptoms. The COvid Mental hEalth Trial (COMET) is a nationwide project organized by the University of Campania "Luigi Vanvitelli", designed as an observational investigation that aimed to gather data from a representative sample of the Italian general population.

Systemic metabolic crosstalk as driver of cancer cachexia.

Cachexia is a complex metabolic disorder characterized by negative energy balance due to increased consumption and lowered intake, leading to progressive tissue wasting and inefficient energy distribution. Once considered as passive bystander, metabolism is now acknowledged as a regulator of biological functions and disease progression. This shift in perspective mirrors the evolving understanding of cachexia itself, no longer viewed merely as a secondary consequence of cancer but as an active process.

Early detection of neonatal sepsis and reduction of overall antibiotic exposure: Towards precision medicine.

Infections claim the lives of over half a million newborns annually and expose survivors to the risk of lifelong disability. The challenge to clinicians is to identify newborns with invasive infections rapidly, promptly initiate antimicrobial treatment, and take measures to prevent and treat organ dysfunction. Moreover, excessive antibiotic use is a global public health problem.