Brain-derived neurotrophic factor (BDNF) provides neuroprotective effects towards therapeutic cerebral ischemia-reperfusion (I/R) injury. This view has been proposed by more and more evidence. However, due to the lack of permeability of the blood-brain barrier (BBB) as well as the brief half-life in serum, clinical application is not widespread. To study the participation of exosomes containing BDNF in I/R, we isolated exosomes from BDNF-overexpressing HEK293. The protective outcomes of exosomes in hypoxia/reoxygenation (H/R) experiments were determined by the use of SY-5Y cells. Exosome-BDNF therapy restrained H/R-induced apoptosis by inhibition of the reducing levels of oxidative stress and calcium ions in the cells while maintaining stable levels of mitochondrial membrane potential in brain cells damaged by I/R. We then constructed a cerebral I/R injury model using SD rats to find the function of BDNF in exosome-mediated neuroprotection. The in vivo experiments conducted established that exosomes from BDNF-overexpressing HEK293 cells improved cerebral I/R injury by concealing neuronal apoptosis. Findings gained demonstrated that BDNF is a part of preventing cerebral I/R injury due to exosome mediation by regulating the cellular internal environment and inhibiting apoptosis.
Background Cuproptosis induced by FDX1 is a newly discovered mechanism regulating cell death. However, the role of FDX1 in the pathogenesis of colon adenocarcinoma (COAD) remains to be studied. Methods FDX1 expression was analyzed with The Cancer Genome Atlas (TCGA) database and Human Protein Atlas (HPA) database. Association between FDX1 expression and COAD prognosis was investigated via the Kaplan–Meier (KM) survival curve. The differentially expressed genes (DEGs) of FDX1 were screened with R packages and the PPI were constructed via STRING database. Cytoscape software was used to detect the most profound modules in the PPIs network. CancerSEA database was used to analyze the effect of FDX1 expression levels on different functional status of COAD cells. The relationship between FDX1 expression and immune infiltration of COAD was analyzed by TIMER2.0 database. The COAD patients with high expression of FDX1 by Western blot, and the levels of immune infiltration were measured by flow cytometry. Results FDX1 was low expressed in most cancers, such as BRCA, KICH, and COAD. The overall survival (OS) and disease-specific survival (DSS) of COAD with high FDX1 expression were better than that of the low expression group. GO-KEGG enrichment analysis revealed that FDX1 and its co-expressed genes played an important role in the pathogenesis of COAD. Moreover, FDX1 expression in COAD were positively associated with “quiescence” and “inflammation” but negatively correlated with “invasion”. FDX1 expression was positively correlated with infiltration levels of CD8+ T cells, NK cells, and neutrophils. Oppositely, FDX1 expression was negatively correlated with that of CD4+ T cells and cancer-associated fibroblasts (CAFs). Finally, 6 COAD patients with high expression of FDX1 were screened, and the proportion of CD8+ T cells in cancer tissues of these patients was significantly higher than that in paracancerous, while the CD4+ T cells presented the opposite pattern. Conclusion FDX1 plays a role in inducing cuproptosis and modulating tumor immunity, which could be considered as potential therapeutic targets in COAD.
Low-energy recoil events in yttrium aluminum garnet (YAG) were investigated by using ab initio molecular dynamics simulations. This work provided insights into understanding the defect formation processes and the resulting defect configurations. The threshold displacement energies (TDEs) of the lattice atoms and related defect structures were determined along specific directions. Both the TDEs and the production of defect structures showed great dependence on the orientation and atom type. The minimum TDEs are 42, 38, 41, and 19 eV for Aloct along [111], Altetra along [1¯11], Y along [001], and O along [111] directions, respectively. The O atoms exhibited smaller TDEs than the Al and Y atoms, indicating that the O-related defects are the main ones in YAG used under irradiation circumstances. These results are helpful for electronic and photoelectronic devices based on YAG under a radiation environment.
A thin film plastic scintillator detector has been developed for the measurement of radiation power and yield of soft x rays produced from Z-pinch implosion. To enable soft x-ray measurements using plastic scintillators, the detector geometry has been specially designed to minimize visible light and alleviate nonlinear behavior. Energy response has been calibrated, and saturation effects have been explored and described in details. The possibility and limitation of its application to such high-density radiation bursts are analyzed. The detector has been fielded on several meters away in vacuum pipes for hundreds of shots at different Z-pinch facilities, and the measured data in these experiments agreed well with the results from other diagnostics, demonstrating the feasibility and reliability of the detector.
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