Valence Fluctuation of Uranium Ions in Uranium Sesquinitride Revealed by Dynamical Mean-field Theory Merged with Density Functional Theory.

The electronic properties, in particular, the occupation number of 5f electrons and the valence state of U ions in uranium sesquinitride (U2 N3 ) are studied by using density functional theory (DFT) calculations merged with dynamical mean-field theory (DMFT). The results demonstrate that j=5/2 and j=7/2 manifolds are in the weakly correlated metallic and weakly correlated insulating regimes, respectively. The quasi-particle weights indicate that LS coupling scheme is more feasible for 5f electrons, which are not in the orbital-selective localized state. The weighted summation of the occupation probabilities of 5fn (n=0,1,2,3,4) atomic configurations suggests that 5f electrons have the inter-configuration fluctuation, or the mixed-valence state for U ions, together with an average occupation number of 5f electrons n5f ∼2.234, which is in good agreement with the electron localization function (ELF) and occupation analysis based on other DFT-based calculations. The 5fn -mixing-driven inter-configuration fluctuation might originate from the dual nature of 5f electrons, and the flexible electronic configuration of U ions. Finally, the so-called quasiparticle band structure is also discussed.

Attenuation of renal injury by depleting cDC1 and by repurposing Flt3 inhibitor in anti-GBM disease.

Previous studies found cDC1s to be protective in early stage anti-GBM disease through Tregs, but pathogenic in late stage Adriamycin nephropathy through CD8+ T cells. Flt3 ligand is a growth factor essential for cDC1 development and Flt3 inhibitors are currently used for cancer treatment. We conducted this study to clarify the role and mechanisms of effects of cDC1s at different time points in anti-GBM disease. In addition, we aimed to utilize drug repurposing of Flt3 inhibitors to target cDC1s as a treatment of anti-GBM disease. We found that in human anti-GBM disease, the number of cDC1s increased significantly, proportionally more than cDC2s. The number of CD8+ T cells also increased significantly and their number correlated with cDC1 number. In XCR1-DTR mice, late (day 12-21) but not early (day 3-12) depletion of cDC1s attenuated kidney injury in mice with anti-GBM disease. cDC1s separated from kidneys of anti-GBM disease mice were found to have a pro-inflammatory phenotype (i.e. express high level of IL-6, IL-12 and IL-23) in late but not early stage. In the late depletion model, the number of CD8+ T cells was also reduced, but not Tregs. CD8+ T cells separated from kidneys of anti-GBM disease mice expressed high levels of cytotoxic molecules (granzyme B and perforin) and inflammatory cytokines (TNF-α and IFN-γ), and their expression reduced significantly after cDC1 depletion with diphtheria toxin. These findings were reproduced using a Flt3 inhibitor in wild type mice. Therefore, cDC1s are pathogenic in anti-GBM disease through activation of CD8+ T cells. Flt3 inhibition successfully attenuated kidney injury through depletion of cDC1s. Repurposing Flt3 inhibitors has potential as a novel therapeutic strategy for anti-GBM disease.

[MicroRNA-125b regulates osteogenic differentiation of human periodontal ligament stem cells].

PURPOSE: To investigate the effect of microRNA-125b (miR-125b) on osteogenic differentiation of periodontal ligament stem cell (PDLSCs). METHODS: The surface factor of isolated PDLSCs was detected by flow cytometry. After transfected with miR-125b or anti-miR125b in PDLSCs, MTT and LDH were used to detect cell viability and cytotoxicity; ALP activity and calcium level were detected by ALP assay kit and calcium colorimetric assay kit. Western blot and RT-qPCR were used to determine the expression of osteogenesis-related genes. The interaction between miR-125b and connexin 43 (Cx43) was detected by dual luciferase gene reporter assay. The data were analyzed with SPSS 17.0 software. RESULTS: The cultured PDLSCs showed the characteristics of mesenchymal stem cells. After transfected with miR-125b in PDLSCs, the cell viability was decreased, cytotoxicity was increased; ALP activity, calcium level and the expression of osteogenesis-related genes were significantly decreased. On the contrary, cell viability, ALP activity, calcium level and the expression of osteogenesis-related genes in PDLSCs were increased after anti-miR-125b transfection. Dual luciferase gene reporter assay showed that miR-125b could target Cx43. In addition, the effect of miR-125b on osteogenic differentiation of PDLSCs was reversed after Cx43 overexpression. CONCLUSIONS: miR-125b may inhibit osteogenic differentiation of PDLSCs by targeting Cx43.

[SiRNA silencing Rsk2 gene expression inhibits proliferation and osteogenic differentiation of human periodontal ligament cells].

PURPOSE: To study the effect of ribosomal S6 kinase (Rsk2) gene on proliferation and osteogenic differentiation of human periodontal ligament cells (hPDLCs) and underlying mechanism. METHODS: Premolar surgically extracted were collected, the periodontal ligament was separated and hPDLCs were primarily cultured. Cells of 4 to 6 passage were used in the experiment. The silencing efficiency of small interfering RNA (siRNA) on Rsk2 in hPDLCs was detected by RT-PCR and Western blot. MTT assay was used to detect the effect of Rsk2 siRNA on cell proliferation. Alkaline phosphatase (ALP) kit was used to detect ALP activity. P38MAPK signal pathway inhibitor SB203580 was used to detect hPDLCs after transfection. Western blot was used to detect the effect of Rsk2 siRNA on MAPK signaling pathway p38 protein phosphorylation. The expressions of Runt-related transcription factor-2 (Runx2), osteocalcin (OCN) and osteogenic protein BMP2 were detected by RT-PCR and Western blot. The data were analyzed using SPSS18.0 software package. RESULTS: The expression of Rsk2 was down-regulated by hPDLCs transfected with Rsk2 siRNA, the difference was statistically significant (P<0.05). Rsk2 siRNA significantly reduced phosphorylation of p38 protein (P<0.05), inhibition of hPDLCs proliferation (P<0.05), decreased ALP activity (P<0.01); the expression of Runx2, OCN and BMP2 was different, and the difference was statistically significant (P<0.05). After SB203580 treatment, hPDLCs transfected with Rsk2 siRNA showed increased cell proliferation, ALP activity, Runx2, OCN and BMP2 expression; compared with Rsk2 siRNA transfected hPDLCs, the difference was statistically significant. CONCLUSIONS: Rsk2 siRNA inhibits hPDLCs proliferation and osteogenic differentiation through p38MAPK signaling pathway.

A first principles study of the thermal stability of A(m)(MH(4))(n) light complex hydrides.

From the physical point of view, the cohesive energy of a reactant is preferable to its formation energy for characterizing its influence on the reaction processes from the reactants to the products. In fact it has been found that there is a certain correlation between the experimental hydrogen desorption temperature and the cohesive energy calculated by a first principles method for a series of A(m)(MH(4))(n) (A = Li, Na, Mg; M = Be, B, Al) light complex hydrides (including Na(2)BeH(4), Li(2)BeH(4), NaAlH(4), LiAlH(4), Mg(AlH(4))(2), LiBH(4) and NaBH(4)), which suggests that cohesive energy may be a useful physical quantity for evaluating the hydrogen desorption ability of complex hydrides, especially in cases when dehydrogenation products have unknown crystal structures, or may even be unknown. To understand this correlation more deeply, the ionic interaction between A and the MH(4) complex and the covalent interaction between M and H were calculated and their contributions to the cohesive energy evaluated quantitatively. The calculated results show that the covalent M-H interaction in the MH(4) complex is the dominant part of the cohesive energy E(coh) (up to more than 75%) and hardly changes during high-pressure structural transitions of A(m)(MH(4))(n). It was also found that low electronegativity of M or high electronegativity of A is responsible for the weak covalent M-H interaction and finally leads to the low thermodynamic stability of A(m)(MH(4))(n), suggesting that complex hydrides A(m)(MH(4))(n) can be destabilized by partial substitution of M (A) with an element with electronegativity lower (higher) than Ms (As). This conclusion has been confirmed by lots of experimental results and may be a useful guideline for the future design of new complex hydrides of the type A(m)(MH(4))(n).

A clinical evaluation of serological diagnosis for pancreatic cancer.

AIM:To assess the diagnostic values of tumor markers for pancreatic cancer.METHODS:Pancreatic cancer-associated antigen from colonic mucosa (PCAAc), pancreas-specific antigen (PaA), pancreatic oncofetal antigen (POA) and minimolecular pancreatic antigen (mPOA) were detected by double antibodies Sandwich ELISA; CA19-9,elastase 1 (E1), human pancreatic elastase 1 (HPE1) and carcinoembryonic antigen (CEA) by radioimmunoassay (RIA); general activities of ribo-nuclease (RNase) and its isoenzymes (RNase I and RNase I) by biochemistry and PAEG;glycylproline dipeptidyl aminopeptidase (GPDA) by biochemistry andalpha 1-antitrypsin (alpha1AT) by rocket immunoelectrophoresis (rocket-IE).RESULTS:The detection of serum POA,mPOA,PaA,PCAAc,CA19-9,RNase and RNase I was able to differentiate pancreatic cancer from the benign disorders and non-pancreatic malignancies with a sensitivity from 66.75% to 80.0% and a specificity from 88.5% to 96.69%. POA, mPOA, PCAAc, HPE1, E1 and GPDA were related to the pancreatic cancer at the head which demonstrated higher sensitivity from 63.64% to 85.71%. The detection of serum HPE1 was especially helpful for the diagnosis of pancreatic cancer with smaller diameters. The determination of 3 or 4 kinds of tumor markers simultaneously would increase the detection rate of pancreatic cancer, which will be an important procedure for the diagnosis of this malignancy.CONCLUSION:A single test of tumor markers is helpful to detect pancreatic cancer clinically,but the determination of 3 or 4 kinds of tumor markers simultaneously would significantly increase the detection rate of pancreatic cancer, which will be an important procedure for the diagnosis of this malignancy.