Advancing Luciferase Activity and Stability beyond Directed Evolution and Rational Design through Expert Guided Deep Learning.

Engineered luciferases have transformed biological imaging and sensing, yet optimizing NanoLuc luciferase (NLuc) remains challenging due to the inherent stability-activity trade-off and its limited sequence homology with characterized proteins. We report a hybrid approach that synergistically integrates computational deep learning with structure-guided rational design to develop enhanced NLuc variants that improve thermostability and thereby activity at elevated temperatures. By systematically analyzing libraries of engineered variants, we established that modifications to termini and loops distal from the catalytic center, combined with preservation of allosterically coupled networks, effectively enhance thermal resilience while maintaining enzymatic function.

Pumping and hygiene practices are associated with bacterial load and microbial composition in human milk expressed at home.

Background: Human milk (HM) harbors a unique microbiome that contributes to the development of the infant gastrointestinal microbiome and influences long-term health outcomes. While pumping and bottle-feeding HM are increasingly common, doing so may introduce exogenous bacteria, altering this microbial community. The extent to which real-world pumping and hygiene practices alter the HM microbial community remains inadequately characterized.

Per- and polyfluorinated substances (PFAS) promote osteoclastogenesis and bone loss through PPARα activation.

Per- and polyfluoroalkyl substances (PFAS) are emerging as significant environmental contaminants affecting bone health, with studies linking their exposure to decreased bone mineral density (BMD), enhanced osteoclastogenesis, and disruptions in the bone marrow microenvironment. While current research highlights the effects on bone and BMD, there is a critical gap in understanding the mechanisms behind these effects. Studies presented here investigate the effects of legacy and alternative PFAS, particularly hexafluoropropylene oxide dimer acid (GenX) and perfluorohexane sulfonic acid (PFHxS), on bone health using and models.

Bowel Preparation Quality in Patients Using Glucagon-Like Peptide-1 Agonists: A Systematic Review and Meta-Analysis.

Background And Aims: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now the mainstay treatment for many chronic conditions including diabetes mellitus, obesity, heart failure and chronic kidney disease. GLP-1 RAs may affect bowel preparation for a colonoscopy by modifying intestinal motility and gastric emptying. We conducted a systematic review and meta-analysis to investigate the impact of GLP-1 RA use on bowel preparation quality, measured by the Boston Bowel Preparation Scale (BBPS), and the frequency of inadequate preparation events.