Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after surgery, especially amongst elderly patients. Neuroinflammation and iron homeostasis are key hallmarks of several neurological disorders. In this study, we investigated the role of deferoxamine (DFO), a clinically used iron chelator, in a mouse model of surgery-induced cognitive dysfunction and assessed its neuroprotective effects on neuroinflammation, oxidative stress, and memory function. METHODS: A model of laparotomy under general anesthesia and analgesia was used to study POCD. Twelve to 14 months C57BL/6J male mice were treated with DFO, and changes in iron signaling, microglia activity, oxidative stress, inflammatory cytokines, and neurotrophic factors were assessed in the hippocampus on postoperative days 3, 7, and 14. Memory function was evaluated using fear conditioning and Morris water maze tests. BV2 microglia cells were used to test the anti-inflammatory and neuroprotective effects of DFO. RESULTS: Peripheral surgical trauma triggered changes in hippocampal iron homeostasis including ferric iron deposition, increase in hepcidin and divalent metal transporter-1, reduction in ferroportin and ferritin, and oxidative stress. Microglia activation, inflammatory cytokines, brain-derived neurotropic factor impairments, and cognitive dysfunction were found up to day 14 after surgery. Treatment with DFO significantly reduced neuroinflammation and improved cognitive decline by modulating p38 MAPK signaling, reactive oxygen species, and pro-inflammatory cytokines release. CONCLUSIONS: Iron imbalance represents a novel mechanism underlying surgery-induced neuroinflammation and cognitive decline. DFO treatment regulates neuroinflammation and microglia activity after surgery

Investigation into the Diversity of the Asia-Pacific Region and Scope for Collaboration Report on Research Project

千葉大学人文社会科学研究科研究プロジェクト報告書第200

Clinical and Biological Implications of Mutational Spectrum in Acute Myeloid Leukemia of FAB Subtypes M0 and M1

Background/Aims: Acute myeloid leukemia (AML) of French-American-British (FAB) subtypes M0 and M1 are both poorly differentiated AML, but their mutational spectrum and molecular characteristics remain unknown. This study aimed to explore the mutational spectrum and prognostic factors of AML-M0 and M1. Methods: Sixty-five AML patients derived from The Cancer Genome Atlas (TCGA) database were enrolled in this study. Whole-genome sequencing was performed to depict the mutational spectrum of each patient. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), FAB subtypes and the frequencies of known recurrent genetic mutations were described. Survival was estimated using the Kaplan-Meier methods and log-rank test. Univariate and multivariate Cox proportional hazard models were constructed procedure. Results: Forty-six patients had more than five recurrent genetic mutations. FLT3 had the highest mutation frequency (n=20, 31%), followed by NPM1 (n=18, 28%), DNMT3A (n=16, 25%), IDH1 (n=14, 22%), IDH2 (n=12, 18%), RUNX1 (n=11, 17%) and TET2 (n=7, 11%). Univariate analysis showed that age >= 60 years and TP53 mutations had adverse effect on EFS (P=0.015, P=0.036, respectively) and OS (P=0.003, P=0.004, respectively), WBC count >= 50x10(9)/L and FLT3-ITD negatively affected EFS (P=0.003, P=0.034, respectively), whereas NPM1 mutations had favorable effect on OS (P=0.035) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) on EFS and OS (all P= 50x10(9)/L was an independent risk factor for EFS (P=0.002) and TP53 mutations for OS (P=0.043). Conclusions: Our study provided new insights into the mutational spectrum and molecular signatures of AML-M0 and M1. We proposed that FLT3-ITD, NPM1 and TP53 be identified as markers for risk stratification of AML-M0 and M1. Patients with AML-M0 and M1 would likely benefit from allo-HSCT. (C) 2018 The Author(s) Published by S. Karger AG, Base

Momentum matching and band-alignment type in van der Waals heterostructures: Interfacial effects and materials screening

Momentum-matched type II van der Waals heterostructures (vdWHs) have been designed by assembling layered two-dimensional semiconductors (2DSs) with special band-structure combinations - that is, the valence band edge at the Gamma point (the Brillouin-zone center) for one 2DS and the conduction band edge at the Gamma point for the other [Ubrig et al., Nat. Mater. 19, 299 (2020)]. However, the band offset sizes, band-alignment types, and whether momentum matched or not, all are affected by the interfacial effects between the component 2DSs, such as the quasichemical-bonding (QB) interaction between layers and the electrical dipole moment formed around the vdW interface. Here, based on density-functional theory calculations, first we probe the interfacial effects (including different QBs for valence and conduction bands, interface dipole, and, the synergistic effects of these two aspects) on band-edge evolution in energy and valley (location in the Brillouin zone) and the resulting changes in band alignment and momentum matching for a typical vdWH of monolayer InSe and bilayer WS2, in which the band edges of subsystems satisfy the special band-structure combination for a momentum-matched type II vdWH. Then, based on the conclusions of the studied interfacial effects, we propose a practical screening method for robust momentum-matched type II vdWHs. This practical screening method can also be applied to other band alignment types. Our current study opens a way for practical screening and designing of vdWHs with robust momentum-matching and band alignment type

Higher Serum Uric Acid Is Associated with Higher Bone Mineral Density in Chinese Men with Type 2 Diabetes Mellitus

Accumulating evidence suggests that oxidative stress is associated with osteoporosis. Serum uric acid (UA) is a strong endogenous antioxidant. Therefore, we investigated the relationship between the serum UA and BMD in Chinese men with T2DM. In this cross-sectional study of 621 men with T2DM, BMDs at lumbar spine (L2–4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of UA, calcium (Ca), 25-OH vitamin D3 (vitD3), parathyroid hormone (PTH), and creatinine (Cr) were also tested. Data analyses revealed that serum UA levels were positively associated with BMD at all sites (p<0.05) in men with T2DM after adjusting for multiple confounders. The serum UA levels were positively correlated with body weight (r=0.322), body mass index (BMI) (r=0.331), Ca (r=0.179), and Cr (r=0.239) (p<0.001) and were also positively associated with the concentrations of PTH (r=0.10, p<0.05). When compared with those in the lowest tertile of UA levels, men with T2DM in the highest tertile had a lower prevalence of osteoporosis or osteopenia (adjusted odds ratio 0.54, 95% confidence interval [CI] 0.31–0.95). These data suggest that higher serum levels of UA are associated with higher BMDs and lower risks of osteoporosis in Chinese men with T2DM

Design & Optimization of the HV divider for JUNO 20-inch PMT

The Jiangmen Underground Observatory (JUNO) is a 20-kton liquid scintillator detector that employs 20,000 20-inch photomultiplier tubes (PMTs) as photon sensors, with 5,000 dynode-PMTs from HAMAMATSU Photonics K.K. (HPK), and 15,000 MCP-PMTs from North Night Vision Technology (NNVT) installed in pure water. JUNO aims to provide long-lasting and the best performance operation by utilizing a high-transparency liquid scintillator, high detection efficiency PMTs, and specially designed electronics including water-proof potting for the high voltage (HV) dividers of PMTs. In this paper, we present a summary of the design and optimization of HV dividers for both types of 20-inch PMTs, which includes collection efficiency, charge resolution, HV divider current, pulse shape, and maximum amplitude restriction. We have developed and finalized four schemes of the HV divider for different scenarios, including the final version selected by JUNO. All 20,000 20-inch PMTs have successfully undergone production and burning tests.Comment: 14pages,28figure

Molecular Design Principle of All‐organic Dyes for Dye‐Sensitized Solar Cells

All‐organic dyes have shown promising potential as an effective sensitizer in dye‐sensitized solar cells (DSSCs). The design concept of all‐organic dyes to improve light‐to‐electric‐energy conversion is discussed based on the absorption, electron injection, dye regeneration, and recombination. How the electron‐donor–acceptor‐type framework can provide better light harvesting through bandgap‐tuning and why proper arrangement of acceptor/anchoring groups within a conjugated dye frame is important in suppressing improper charge recombination in DSSCs are discussed. Separating the electron acceptor from the anchoring unit in the donor–acceptor‐type organic dye would be a promising strategy to reduce recombination and improve photocurrent generation. A guiding light : All‐organic dyes have shown promising potential as an effective sensitizer in DSSCs. Their chemical nature decisively affects the current generation and open‐circuit voltage. Several molecular design strategies of all‐organic dyes to improve DSSC performance as well as factors for the improvement of photocurrent generation and reduction of improper recombination are discussed (see figure).Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97444/1/5220_ftp.pd