Highly Thermally Sensitive Cascaded Wannier-Mott Exciton Ionization/Carrier Localization in Manganese-Doped Perovskite Nanocrystals.

Transition-metal doping in perovskite nanocrystals strongly alters the photophysical properties of these nanocrystals. However, the details of the underlying thermal and optical processes within such an intriguing symmetry-breaking nanosystem are far from clear. Herein, we study the sensitively temperature-dependent and highly competent delocalized exciton and transition-metal ion-captured carrier recombination processes in manganese-doped CsPbBr0.6Cl2.4 nanocrystals. The combined experimental and theoretical studies reveal that both the exciton ionization and capture of the band-edge carriers by the manganese ions play the dominant roles in determining the proportion of the manganese ions-dominated recombination process. A density functional theory calculation of the temporal fluctuation of the manganese ions-accommodated localized orbitals further confirms that the thermally enhanced nonadiabatic electron-phonon coupling promotes the probability of the carrier localization. These findings reveal the respective crucial roles of the exciton ionization and carrier capture in the localized recombination process in the transition-metal-doped semiconductor nanocrystals.

Mechanism of Gentisic Acid on Rheumatoid Arthritis Based on miR-19b-3p/RAF1 Axis.

OBJECTIVE: To investigate the therapeutic effect of gentisic acid (GA) on rheumatoid arthritis (RA) based on the miR-19b-3p/RAF1 axis. METHODS: The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells, and the drug concentration of GA was determined in the experiment. The quantificational real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-19b-3p and RAF1. RAF1, extracellular regulated protein kinases1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) were examined by Western blotting. Three methods (dual-luciferase assay, qRT-PCR and Western blot analysis) were used to verify miR-19b-3p targeting RAF1. Flow cytometry was performed to detect MH7A cell apoptosis. Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells. RESULTS: The growth of MH7A cells was gradually inhibited with increasing GA concentration. When the GA concentration exceeded 80 mmol/L, GA was significantly cytotoxic to MH7A cells, so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L. GA upregulated miR-19b-3p expression, downregulated RAF1 expression, inhibited ERK1/2 phosphorylation, induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration (P<0.05 or P<0.01). RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression (P<0.05 or P<0.01). The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation, suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration (P<0.01). CONCLUSION: GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.

The protective effect of gentisic acid on rheumatoid arthritis via the RAF/ERK signaling pathway.

BACKGROUND: RAF and ERK pathways are known to be activated in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS), which play an important role in the pathogenesis and destruction of RA. Gentisic acid (GA) was a natural product derived from plants, which has been reported can attenuate pressure overload-induced cardiac hypertrophy and fibrosis in mice through inhibition of the ERK1/2 pathway. Whether GA can inhibit the occurrence and development of RA through RAF/ERK signaling pathway has not been reported. The purpose of this study is to determine whether GA may have a certain therapeutic effect on RA-FLS. METHOD: Bovine type II collagen was used to establish a rat model of rheumatism. Enzyme-linked immunosorbent assay was used to detect inflammatory factors, anti-inflammatory mediators, and rheumatoid factor. Hematoxylin and eosin and TUNEL staining were used to detect the effect of GA on histochemical with rheumatoid arthritis. RAF, ERK, and p-ERK expressions in synovial tissue were measured by western blot and immunohistochemical. Besides, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was used to investigate the biological behavior influenced by GA. Apoptosis assay was performed to detect apoptosis of GA on MH7A cells. Transwell invasion assay was performed to detect the ability of cell migration. RESULT: The result showed that GA could reduce joint swelling and inflammation. At the same time, it can also promote the apoptosis of synovial cells and down-regulate the RAF/ERK pathway. CONCLUSION: GA may ameliorate inflammatory factors' abnormality, synovial hyperplasia, and apoptosis of synovium via inhibiting the RAF/ERK signaling pathway.

Effect of Jiawei Fengshining on Synovial Cell Apoptosis and TGF-ß1/Smad Signaling Pathway in Rats with Rheumatoid Arthritis.

BACKGROUND/AIMS: Jiawei Fengshining (JWFSN) is a new formula originated from Fengshining, a classic formula for the treatment of rheumatoid arthritis (RA). The mechanism of JWFSN in the treatment of RA is still unclear. The aim of this study was to evaluate the effect of JWFSN formula on the inflammatory mediator levels in the serum and the TGF-ß1/Smad pathway in the synovium and to explore the underlying mechanisms of JWFSN formula to ameliorate synovial hyperplasia and apoptosis inhibition of synovium in rats with RA. METHOD: SPF female Wistar rats were randomly divided into 6 groups: the blank control group, the model control group, the positive drug group, and the low-, medium-, and high- dose JWFSN groups, with 8 rats in each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory mediators, anti-inflammatory mediators, and rheumatoid factor (RF). The pathological condition and apoptosis of the synovial tissue were detected by hematoxylin and eosin (HE) and TUNEL staining, respectively. TGF-ß1, p-Smad2, p-Smad3, and Smad7 protein expressions in synovial tissue were measured by western blot assay. In addition, human rheumatoid arthritis fibroblast-like synoviocytes cell line MH7A was treated with 20% JWFSN-containing serum to obtain in vitro data. RESULT: The administration of JWFSN was found to ameliorate synovial hyperplasia and promote apoptosis; increase the serum contents of anti-inflammatory mediators; reduce inflammatory mediators and RF contents; and inhibit the TGF-ß1/Smad signaling pathway in CIA rats. In vitro JWFSN treatment increased the apoptosis of MH7A cells and decreased cell viability. Additionally, JWFSN treatment inhibited the TGF-ß1/Smad signaling pathway in MH7A cells. Interestingly, kartogenin (TGF-ß1/Smad pathway activator) treament reversed the effects of JWFSN treatment. CONCLUSION: JWFSN may ameliorate inflammatory factors' abnormality, synovial hyperplasia, and apoptosis inhibition of synovium via the TGF-ß1/Smad signaling pathway.