The validation and clinical bioanalysis of the Bicycle® Toxin Conjugate zelenectide pevedotin in human plasma.

Background: The Bicycle® toxin conjugate (BTC) zelenectide pevedotin, formerly known as BT8009, is a novel bicyclic peptide targeting the Nectin-4 tumor antigen conjugated to the cytotoxin monomethyl auristatin E (MMAE) via a valine-citrulline cleavable linker. Zelenectide pevedotin is currently being investigated in a Phase 1/2 (Duravelo-1, NCT04561362) clinical trial to determine safety and efficacy in patients with tumors associated with Nectin-4 expression. A simple regulated bioanalytical assay was developed to quantify intact zelenectide pevedotin in patient plasma samples.

Assessing microbial growth in drinking water using nucleic acid content and flow cytometry fingerprinting.

This study utilizes flow cytometry (FCM) to evaluate the high nucleic acid (HNA) and low nucleic acid (LNA) content of intact cells for monitoring bacterial dynamics in drinking water treatment and supply systems. Our findings indicate that chlorine and nutrients differently impact components of bacterial populations. HNA bacteria, characterized by high metabolic rates, quickly react to nutrient alterations, making them suitable indicators of growth under varying water treatment and supply conditions.

Alpha-synuclein preformed fibril-induced aggregation and dopaminergic cell death in cathepsin D overexpression and ZKSCAN3 knockout mice.

α-synuclein accumulation is recognized as a prominent feature in the majority of Parkinson's disease cases and also occurs in a broad range of neurodegenerative disorders including Alzheimer's disease. It has been shown that α-synuclein can spread from a donor cell to neighboring cells and thus propagate cellular damage, antagonizing the effectiveness of therapies such as transplantation of fetal or iPSC derived dopaminergic cells. As we and others previously have shown, insufficient lysosomal function due to genetic mutations or targeted disruption of cathepsin D can cause α-synuclein accumulation.

Thyroid cancer incidence in cohorts exposed in childhood to I released during the Windscale nuclear reactor accident at Sellafield, England, in 1957.

A fire in one of the Windscale nuclear reactors at Sellafield (Cumbria, England) in October 1957 released 1,800 TBq of I (half-life, 8 days) to atmosphere. Measurements of I activity in thyroids of exposed children showed typical thyroid doses of tens of milligray, but with some exceeding 100 mGy. Radiation exposure in childhood is known to increase the risk of thyroid cancer.

Potent and specific antibiotic combination therapy against Clostridioides difficile.

Keratinicyclins and keratinimicins are recently discovered glycopeptide antibiotics. Keratinimicins show broad-spectrum activity against Gram-positive bacteria, while keratinicyclins form a new chemotype by virtue of an unusual oxazolidinone moiety and exhibit specific antibiosis against Clostridioides difficile. Here we report the mechanism of action of keratinicyclin B (KCB).