Systemic sclerosis (SSc) is characterised by progressive multiple organ fibrosis leading to morbidity and mortality. Lysyl oxidases play a vital role in the cross-linking of collagens and subsequent build-up of fibrosis in the extracellular matrix. As such, their inhibition provides a novel treatment paradigm for SSc. A novel small molecule pan-lysyl oxidase inhibitor, PXS-5505, currently in clinical development for myelofibrosis treatment was evaluated using in vivo rodent models resembling the fibrotic conditions in SSc. Both lysyl oxidase and lysyl oxidase-like 2 (LOXL2) expression were elevated in the skin and lung of SSc patients. The oral application of PXS-5505 inhibited lysyl oxidase activity in the skin and LOXL2 activity in the lung. PXS-5505 exhibited anti-fibrotic effects in the SSc skin mouse model, reducing dermal thickness and α-smooth muscle actin. Similarly, in the bleomycin-induced mouse lung model, PXS-5505 reduced pulmonary fibrosis toward normal levels, mediated by its ability to normalise collagen/elastin crosslink formation. PXS-5505 also reduced fibrotic extent in models of the ischaemia-reperfusion heart, the unilateral ureteral obstruction kidney, and the CCl4-induced fibrotic liver. PXS-5505 consistently demonstrates potent anti-fibrotic efficacy in multiple models of organ fibrosis relevant to the pathogenesis of SSc, suggesting that it may be efficacious as a novel approach for treating SSc. 相似文献
Dps (DNA-binding protein from starved cells) is well known for the structural protection of bacterial DNA by the formation of highly ordered intracellular assemblies under stress conditions. Moreover, this ferritin-like protein can perform fast oxidation of ferrous ions and subsequently accumulate clusters of ferric ions in its nanocages, thus providing the bacterium with physical and chemical protection. Here, cryo-electron microscopy was used to study the accumulation of iron ions in the nanocage of a Dps protein from Escherichia coli. We demonstrate that Fe2+ concentration in the solution and incubation time have an insignificant effect on the volume and the morphology of iron minerals formed in Dps nanocages. However, an increase in the Fe2+ level leads to an increase in the proportion of larger clusters and the clusters themselves are composed of discrete ~1–1.5 nm subunits. 相似文献
The single crystalline nanostructure of organic semiconductors provides a very promising class of materials for applications in modern optoelectronic devices. However, morphology control and optoelectronic property modulation of high quality single crystalline samples remain a challenge. Here, we report the morphology-controlled growth of single crystalline nanorod arrays of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). We demonstrate that, unlike PTCDA film, PTCDA nanorods exhibits optical waveguide features, enhanced absorption, and Frenkel excitation emission in the visible region. Additionally, we measured the electrical properties of PTCDA nanorods, including the conductivity along the growth direction of the nanorod, which is roughly 0.61 S·m–1 (much higher than that of pure crystalline PTCDA films).
Ultrasensitive and rapid detection of nano‐objects is crucial in both fundamental studies and practical applications. Optical sensors using evanescent fields in microcavities, plasmonic resonators, and nanofibers allow label‐free detection down to single molecules, but practical applications are severely hindered by long response time and device reproducibility. Here, an on‐chip dense waveguide sensor to monitor single unlabeled nanoparticles in a strong optical evanescent field is demonstrated. The spiral nanowaveguide design enables two orders of magnitude enhancement in sensing area compared to a straight waveguide, significantly improving the particle capture ability and shortening the target analysis time. In addition, the measurement noise is suppressed to a level of 10?4 in the transmitted power, pushing the detection limit of single particles down to the size of 100 nm. The waveguide sensor on the silicon‐on‐isolator platform can be fabricated reproducibly by the conventional semiconductor processing and compatible with surface functionalization chemistries and microfluidics, which could lead to widespread use for sensing in environmental monitoring and human health. 相似文献
