The Mainz University of Applied Sciences (German: Hochschule Mainz), is a 1971-founded university located in Mainz, Germany. The University of Applied Sciences Mainz consists of three faculties: School of Technology, School of Design and School of Business. The common feature of all fields of study is the practical orientation of the university, the short periods of study and the internationally orientated courses.In 2009 the School of Business, the School of Engineering with the departments Geoinformatics and Surveying and the administration of the university moved to the new location "Campus". All other departments will move as well in the near future to the new location "Campus"..
Background:Macrolide antibiotics have immunomodulatory activity and when taken chronically reduce exacerbations of COPD. However, chronic use can cause bacterial resistance. EP395 (glasmacinal), a novel macrolide, is being developed as a treatment to reduce exacerbations of COPD without inducing antimicrobial resistance. Methods:In this double-blind, placebo-controlled, phase 2a trial (NCT05572333), patients (≥45 years old, diagnosed with COPD for ≥2 years and stable on at least one maintenance inhaled therapy) were randomised (2:1) to EP395 or placebo daily for 12 weeks. The primary objective was safety, with key secondary objectives assessing pharmacodynamic effects of EP395. Results:A total of 61 patients were randomised (42 EP395, 19 placebo). A 12-week course of EP395 was well tolerated: no serious adverse events were considered related to EP395, and adverse events occurred in similar proportions in both groups (64.3% EP395, 63.2% placebo). Four patients were withdrawn due to adverse events (three EP395, one placebo). Sputum neutrophil elastase and myeloperoxidase, mediators of neutrophil activation, were reduced with EP395 (treatment difference (log scale): neutrophil elastase -0.415 ng·mL-1, 95% CI -0.787 to -0.043 ng·mL-1, p=0.030; myeloperoxidase -0.282 ng·mL-1, 95% CI -0.640 to 0.076 ng·mL-1, p=0.119). Relative changes in neutrophil elastase and myeloperoxidase from baseline with EP395 were 66% and 75%, respectively, of those observed with placebo. Exploratory 16S rRNA sequencing of sputum showed EP395 had no detectable effect on the lung microbiome, including the proportion of pathogenic Proteobacteria species. Conclusion:In patients with stable COPD, EP395 for 12 weeks was well tolerated, demonstrated selective anti-inflammatory activity and had no detectable effect on the lung microbiome.
Molecular photoswitches capable of controlling membrane properties under light stimulation represent promising tools for manipulating biomimetic and biological interfaces. We report the synthesis and photophysical characterization of amphiphilic P-type photoswitches exhibiting efficient and reversible E↔Z photoisomerization under both one-photon (1PA: 375/300 nm) and two-photon (2PA: 750/630 nm) excitation. Their incorporation into DPPC monolayers and bilayers enables light-driven modulation of membrane structure. Short-chain analogues (C4 derivatives) remain well-mixed with DPPC and promote curvature upon E↔Z photoisomerization, regardless of the polarity of their headgroup (hydroxyl, OH, or hexaethylenglycol, HEG). In contrast, long-chain derivatives (C12) behave either as light-activated compressants or expanders depending on the strength of their headgroup interactions. The HEG-terminated C12 photoswitch (Sw-HEG-C12) favors anchoring at the interface and induces lateral demixing (microsegregation) and domain stiffening, leading to a decrease in surface pressure in DPPC monolayers and an increase in vesicle size upon E→Z isomerization. Conversely, the hydroxylated analogue (Sw-OH-C12) mixes nearly ideally with DPPC but occupies different depths within the bilayer depending on isomerization state (E near the interface, Z internalized), resulting in an increase in surface pressure and a decrease in vesicle size upon E→Z isomerization. The two-photon-responsive photoswitches reported herein appear thus as versatile tools for the optical control of membrane architecture in biological environments where NIR light is required.
