Fluorogenic Platform for Real-Time Imaging of Subcellular Payload Release in Antibody-Drug Conjugates.

Antibody-drug conjugates (ADCs) represent promising therapeutic constructs to enhance the selective delivery of drugs to target cells; however, attaining precise control over the timing and location of payload release remains challenging due to the complex intracellular processes that define ADC internalization, trafficking, and linker cleavage. In this study, we present novel real-time fluorogenic probes to monitor both subcellular dynamics of ADC trafficking and payload release. We optimized a tandem molecular design of sequential pH- and enzyme-activatable naphthalimide fluorophores to (1) track their subcellular localization along the endolysosomal pathway and (2) monitor linker cleavage with OFF-to-ON fluorescence switches.

Description of an Enterococcus faecium genotype vanB outbreak in a hospitalization ward.

Background And Objectives: Vancomycin-resistant Enterococcus faecium (VRE) infections have increased in the last years. Hospital outbreaks have been described with a challenging microbiological diagnosis and control of the transmission.

Methods: This is a prospective study of a nosocomial outbreak of VRE in a conventional hospitalization ward.

Isolation and anti-Xanthomonas citri activity of unguinol produced by Aspergillus unguis CBMAI 2140.

This research investigated active biomolecules from the endophytic fungus Aspergillus unguis (CBMAI 2140), isolated from Passiflora incarnata leaves, as potential antibacterial agents against Xanthomonas citri subsp. citri, the causative agent of citrus canker. The fungal extract was obtained via liquid-liquid extraction with ethyl acetate.

Automated High-Throughput Affinity Capture-Mass Spectrometry Platform with Data-Independent Acquisition.

Affinity capture (AC) combined with mass spectrometry (MS)-based proteomics is highly utilized throughout the drug discovery pipeline to determine small-molecule target selectivity and engagement. However, the tedious sample preparation steps and time-consuming MS acquisition process have limited its use in a high-throughput format. Here, we report an automated workflow employing biotinylated probes and streptavidin magnetic beads for small-molecule target enrichment in the 96-well plate format, ending with direct sampling from EvoSep Solid Phase Extraction tips for liquid chromatography (LC)-tandem mass spectrometry (MS/MS) analysis.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.