23 research outputs found

    Genetic Variation of SARS Coronavirus in Beijing Hospital

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    To characterize genetic variation of severe acute respiratory syndrome–associated coronavirus (SARS-CoV) transmitted in the Beijing area during the epidemic outbreak of 2003, we sequenced 29 full-length S genes of SARS-CoV from 20 hospitalized SARS patients on our unit, the Beijing 302 Hospital. Viral RNA templates for the S-gene amplification were directly extracted from raw clinical samples, including plasma, throat swab, sputum, and stool, during the course of the epidemic in the Beijing area. We used a TA-cloning assay with direct analysis of nested reverse transcription–polymerase chain reaction products in sequence. One hundred thirteen sequence variations with nine recurrent variant sites were identified in analyzed S-gene sequences compared with the BJ01 strain of SARS-CoV. Among them, eight variant sites were, we think, the first documented. Our findings demonstrate the coexistence of S-gene sequences with and without substitutions (referred to BJ01) in samples analyzed from some patients

    Mechanism and Treatment Related to Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy

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    Hypoxic ischemic encephalopathy (HIE) is a type of neonatal brain injury, which occurs due to lack of supply and oxygen deprivation to the brain. It is associated with a high morbidity and mortality rate. There are several therapeutic strategies that can be used to improve outcomes in patients with HIE. These include cell therapies such as marrow mesenchymal stem cells (MSCs) and umbilical cord blood stem cells (UCBCs), which are being incorporated into the new protocols for the prevention of ischemic brain damage. The focus of this review is to discuss the mechanism of oxidative stress in HIE and summarize the current available treatments for HIE. We hope that a better understanding of the relationship between oxidative stress and HIE will provide new insights on the potential therapy of this devastating condition

    The Enhancing Effects of the Light Chain on Heavy Chain Secretion in Split Delivery of Factor VIII Gene

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    Coagulation factor VIII (FVIII) is secreted as a heterodimer consisting of a heavy chain (HC) and a light chain (LC), which can be expressed independently and reassociate with recovery of biological activity. Because of the size limitation of adeno-associated virus (AAV) vectors, a strategy for delivering the HC and LC separately has been developed. However, the FVIII HC is secreted 10–100-fold less efficiently than the LC. In this study, we demonstrated that the F309S mutation and enhanced B-domain glycosylations alone are not sufficient to improve FVIII HC secretion, which suggested a role of the FVIII LC in regulating HC secretion. To characterize this role of the FVIII LC, we compared FVIII HC secretion with and without the LC via post-translational protein trans-splicing. As demonstrated in vitro, ligation of the LC to the HC significantly increased HC secretion. Such HC secretion increases were also confirmed in vivo by hydrodynamic injection of FVIII intein plasmids into hemophilia A mice. Moreover, similar enhancement of HC secretion can also be observed when the LC is supplied in trans, which is probably due to the spontaneous association of the HC and the LC in the secretion pathway. In sum, enhancing the secretion of the FVIII HC polypeptide may require the proper association of the FVIII LC polypeptide in cis or in trans. These results may be helpful in designing new strategies to improve FVIII gene delivery

    In-plane-gate flexible single-crystalline silicon thin-film transistors with high-k gate dielectrics on plastic substrates

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    Flexible single-crystalline silicon in-plane-gate thin-film transistors (TFTs) with high-k gate dielectrics on plastic substrates have been demonstrated in this letter. The high-k Nb2O5-Bi2O3-MgO (BMN) ceramic has been deposited as gate dielectric layer by magnetron sputtering at room temperature. ∼200 nm Si nanomembrane as the device active layer has been transferred onto the flexible substrates. An in-plane-gate structure has been employed for the flexible TFTs, to achieve high control ability and low leakage current. The flexible TFT demonstrates ∼106 on/off ratio, ∼230 cm2v-1s-1 electron field effect mobility, and only ∼nA leakage current. The capacitances of the in-plane-gate structure are measured and analyzed to better understand the channel control mechanism of the flexible TFTs with high-k gate dielectrics. Mechanical bending tests have been conducted and the underlying mechanism for the device performance variations has been discussed. The flexible TFTs show great potential for the applications in high performance, large area and high integrated flexible circuits

    High-Performance Flexible Single-Crystalline Silicon Nanomembrane Thin-Film Transistors with High‑<i>k</i> Nb<sub>2</sub>O<sub>5</sub>–Bi<sub>2</sub>O<sub>3</sub>–MgO Ceramics as Gate Dielectric on a Plastic Substrate

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    A novel method of fabricating flexible thin-film transistor based on single-crystalline Si nanomembrane (SiNM) with high-<i>k</i> Nb<sub>2</sub>O<sub>5</sub>–Bi<sub>2</sub>O<sub>3</sub>–MgO (BMN) ceramic gate dielectric on a plastic substrate is demonstrated in this paper. SiNMs are successfully transferred to a flexible polyethylene terephthalate substrate, which has been plated with indium-tin-oxide (ITO) conductive layer and high-<i>k</i> BMN ceramic gate dielectric layer by room-temperature magnetron sputtering. The BMN ceramic gate dielectric layer demonstrates as high as ∼109 dielectric constant, with only dozens of pA current leakage. The Si–BMN–ITO heterostructure has only ∼nA leakage current at the applied voltage of 3 V. The transistor is shown to work at a high current on/off ratio of above 10<sup>4</sup>, and the threshold voltage is ∼1.3 V, with over 200 cm<sup>2</sup>/(V s) effective channel electron mobility. Bending tests have been conducted and show that the flexible transistors have good tolerance on mechanical bending strains. These characteristics indicate that the flexible single-crystalline SiNM transistors with BMN ceramics as gate dielectric have great potential for applications in high-performance integrated flexible circuit

    Circulating DNA methylation level of CXCR5 correlates with inflammation in patients with rheumatoid arthritis

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    Abstract Objectives To assess the differences in circulating DNA methylation levels of CXCR5 between rheumatoid arthritis (RA) and osteoarthritis (OA) and healthy controls (HC), and the correlation of methylation changes with clinical characteristics of RA patients. Methods Peripheral blood samples were collected from 239 RA patients, 30 patients with OA, and 29 HC. Target region methylation sequencing to the promoter region of CXCR5 was achieved using MethylTarget. The methylation level of cg04537602 and methylation haplotype were compared among the three groups, and the correlation between methylation levels and clinical characteristics of RA patients was performed by Spearman's rank correlation analysis. Results The methylation level of cg04537602 was significantly higher in the peripheral blood of RA patients compared with OA patients (p = 1.3 × 10−3) and in the HC group (p = 5.5 × 10−4). The sensitivity was enhanced when CXCR5 methylation level combined with rheumatoid factor and anti–cyclic citrullinated peptide with area under curve (AUC) of 0.982 (95% confidence interval 0.970–0.995). The methylation level of cg04537602 in RA was positively correlated with C‐reactive protein (CRP) (r = .16, p = .01), and in RA patients aged 60 years and above, cg04537602 methylation levels were positively correlated with CRP (r = .31, p = 4.7 × 10−4), tender joint count (r = .21, p = .02), visual analog scales score (r = .21, p = .02), Disease Activity Score in 28 joints (DAS28) using the CRP level DAS28‐CRP (r = .27, p = 2.1 × 10−3), and DAS28‐ESR (r = .22, p = .01). We also observed significant differences of DNA methylation haplotypes in RA patients compared with OA patients and HC, which was consistent with single‐loci‐based CpG methylation measurement. Conclusion The methylation level of CXCR5 was significantly higher in RA patients than in OA and HC, and correlated with the level of inflammation in RA patients, our study establishes a link between CXCR5 DNA methylation and clinical features that may help in the diagnosis and disease management of RA patients

    Behaviors of the Interfacial Consecutive Multistep Electron Transfer Controlled by Varied Transition Metal Ions in Porphyrin Cores

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    Almost all life activities involve the process of multistep electron transfer (ET) which occurs on biomembrane. Metalloporphyrins (MTPPs) are a class of molecules which are closely related to life course. Here, the <i>n</i>-step (<i>n</i> = 1, 2) ET behaviors controlled by different metal ions in porphyrin cores were investigated by thin-layer cyclic voltammetry (TLCV). The bimolecular ET was reacted between the MTPP (M = Fe, Zn, Co, Cu, Ni) and Fe­(CN)<sub>6</sub><sup>4–</sup> in nitrobenzene and aqueous phase, respectively, and the interface between nitrobenzene and aqueous phase was considered as a bionic membrane. The thin-layer theory, which has been revised, was used to calculate the kinetic constants for each step electron transfer reactions. It was shown that the kinetic data were affected dramatically by the different coordinated ions in porphyrin complexes
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