A fluorescent nanoprobe and paper-based nanofiber platform for detection and imaging of Fe3+ in actual samples and living cells.

In this study, a novel fluorescent nanoprobe (ZIF-90@FSS) was constructed using a zeolite imidazolium ester skeleton (ZIF-90) incorporating sodium fluorescein within its porous structure. Notably, this nanoprobe exhibited regular fluorescence "off" detection performance of Fe3+ in actual samples and living cells. The concentration range of 0-150 ng/mL exhibited a lowest detection limit of 0.26 ng/mL. A nanofiber paper-based platform (VL78/ZIF-90@FSS) was further developed by coupling the prepared nanoprobe to a multi-dimensional fiber paper via CN bonds, enabling rapid visual white light colorimetric and fluorescence imaging of Fe3+ within 2 min. The constructed nanoprobe and its paper-based detection platforms demonstrated a stable recovery range in tap water, beer, and soy sauce samples during spiking-recovery assessments. The recovery rates ranged from 98.46 % to 108.24 % for the nanoprobe and from 91.75 % to 108.71 % for the nanofiber paper-based platform. Therefore, the developed nano-fluorescent sensor and paper-based nanofiber sensing platform offer a promising strategy for the visual detection of Fe3+, while also presenting novel and valuable methods to investigate the regulatory mechanisms of Fe3+ in living cells.

MSCohi-O lenses for long-term retention of mesenchymal stem cells on ocular surface as a therapeutic approach for chronic ocular graft-versus-host disease.

Chronic ocular graft-versus-host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can lead to vision loss if not diagnosed and treated promptly. Currently, no approved drugs exist for oGVHD treatment. However, umbilical cord-derived mesenchymal stem cells (UCMSCs) have known immunoregulatory properties and have been employed in clinical trials for immune-mediated diseases. To address oGVHD, the application of UCMSCs to the ocular surface is a logical approach. Intravenous administration of UCMSCs poses risks, necessitating topical and local delivery. Retaining UCMSCs on the ocular surface remains a challenge. To overcome this, we invented mesenchymal stem cell-coating high oxygen-permeable hydrogel lenses combining UCMSCs and machinery to enable the long-term retention of UCMSCs on the ocular surface. Animal model experiments demonstrated that these lenses effectively retained UCMSCs, providing therapeutic benefits by decreasing corneal inflammation and damage, and inhibiting immune rejection and response, all crucial aspects in oGVHD treatment.

Design, synthesis and biological evaluation of novel osimertinib derivatives as reversible EGFR kinase inhibitors.

A series of osimertinib derivatives without acrylamide groups were synthesized and their inhibitory rates against L858R/T790M/C797S mutated EGFR kinase and antiproliferation activities against non-small cell lung cancer cell lines (A549, H1975) were evaluated. The preferred compounds were selected and their in vitro inhibitory activities against various EGFR kinases (wild-type, L858R/T790M, L858R/T790M/C797S) and c-Met kinase were tested. Compound 9h showed remarkable inhibitory activity against the wild type (IC50 = 29 nM), L858R/T790M mutant type (IC50 = 10 nM) and L858R/T790M/C797S mutant type (IC50 = 242 nM) as reversible EGFR kinase inhibitor, which was selected to further perform the AO/EB staining assays, cell cycle distribution assays and wound-healing assays on A549 and/or H1975 cell lines. The results showed dose-dependent activities of the induction of cell apoptosis, G1/G0-phase arrestation and inhibition of migration. Compound 22a showed remarkable inhibitory activity against the L858R/T790M/C797S mutant EGFR kinase (IC50 = 137 nM), which was nearly three times compared to osimertinib (IC50 = 410 nM). It's worth noting that 22a exhibited excellent kinase selectivity against the L858R/T790M/C797S mutant EGFR kinase rather than the wild-type, which reached 5.4 times and far more than the 0.012 times of osimertinib. Additionally, molecular docking analyses were performed to explain the action modes between the compounds and the corresponding EGFR kinases. In conclusion, compounds 9h and 22a have been demonstrated as promising candidates and worth further study.