Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target.

A diamidobenzimidazole STING agonist protects against SARS-CoV-2 infection.

Coronaviruses are a family of RNA viruses that cause acute and chronic diseases of the upper and lower respiratory tract in humans and other animals. SARS-CoV-2 is a recently emerged coronavirus that has led to a global pandemic causing a severe respiratory disease known as COVID-19 with significant morbidity and mortality worldwide. The development of antiviral therapeutics are urgently needed while vaccine programs roll out worldwide.

Think Health Literacy to Improve the Patient Experience.

Nurses directly influence the experience that patients and their families have in their interactions with the health care system. This article addresses how nurses holistically influence the patient experience through the lens of health literacy, as nurses guide their patients and families through a confusing and complex system of care, replete with jargon and labyrinthine paths.

Holistic in the Hectic: Family Presence During Resuscitation in the Emergency Department.

Despite public knowledge of advanced directives and end-of-life wishes, desire for control over destiny often conflicts with the reality of end-of-life presentation. Recognized as best practice by both the Emergency Nurses Association and the American College of Emergency Physicians, family presence during resuscitation can actually prevent unintended harm to patients and their families.

Design, synthesis and structure-activity relationship of N-substituted tropane muscarinic acetylcholine receptor antagonists.

A novel series of N-substituted tropane derivatives was characterized as potent muscarinic acetylcholine receptor antagonists (mAChRs). Kinetic washout studies showed that the N-endosubstituted analog 24 displayed much slower reversibility at mAChRs than the methyl-substituted parent molecule darotropium. In addition, it was shown that this characteristic appeared to translate into enhanced which duration of action in a mouse model of bronchonstriction.