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The samples of xLi3V2(PO4)3·yLiFe0.8Mn0.2PO4/C (x:y = 1:0, 3:1, 1:1, 1:2, 0:1) are facilely prepared via a ball milling-assisted two-step sintering route. According to the results of Rietveld refinement, the xLi3V2(PO4)3·yLiFe0.8Mn0.2PO4/C (x, y ≠ 0) composites are composed of orthorhombic LiFe0.8Mn0.2PO4 and monoclinic L3V2(PO4)3. Electrochemical tests show that the faster reaction kinetics improve the electrochemical properties of the xLi3V2(PO4)3·yLiFe0.8Mn0.2PO4/C (x, y ≠ 0) composites, in which all multiphase composites release more than capacity of 100 mAh g−1 at 2C at the potential range of 2.5–4.5 V. In particular, the diffusion coefficient of lithium ion is in the magnitude of 10−7 to 10−9 cm2 s−1; Li3V2(PO4)3·2LiFe0.8Mn0.2PO4/C shows the highest specific capacity at the rate range of 0.1–2C and exhibits excellent long-term rate performance with capacity retention of 93.4% (relative to the initial discharge capacity) after 280 cycles at the rate of 5C.

We report on the synthesis of novel boron nitride nanoarchitectures through in-situ conversion of porous boron nitride via a metal ion-assisted annealing method. Numerous highly crystallized nanoplates with thickness of ∼20 nm aggregate as building blocks to form the boron nitride nanoarchitecture. The adsorption of low concentration of metal ions, i.e. terbium ions, plays an important role for the in-situ conversion of porous boron nitride microfibers to nanoarchitectures. Owing to their unique microstructure with rough surfaces, the as-prepared boron nitride nanoarchitectures show superhydrophobicity with a high contact angle of 167.9°. Photoluminescence studies indicate that the nanoarchitectures exhibit intense ultraviolet emission from boron nitride nanostructures and green emission from terbium ions. The combination of unique microstructures and properties enables boron nitride nanoarchitectures to be attractive for applications in catalytic support and self-cleaning coatings.

One-dimensional (1D) boron nitride (BN) nanostructures with a high aspect ratio are of prime interest due to their importance in fundamental research and wide-range potential applications. Herein we developed a facile method for the first synthesis of ultrafine porous BN nanofibers in high purity and a high yield. The method included two-steps, freeze-drying of a hot melamine/boric acid solution and post pyrolysis of the as-obtained products. The extremely rapid cooling of the hot melamine/boric acid solution during the freeze-drying process resulted in the formation of ultrafine precursors, which was the key for the final synthesis of porous BN nanofibers with downsized diameters (20–60 nm) and high aspect ratios. The as-synthesized ultrafine BN nanofibers possessed a high specific surface area and a large pore volume, which could be tuned by the pyrolysis parameters. All of these characteristics make the porous BN nanofibers promising in the applications of water treatment, hydrogen storage, catalyst support, etc. Especially, ultrafast adsorption of methylene blue (MB) in water has been demonstrated using the present porous BN nanofibers as an adsorbent.

Although Treg-cell-mediated suppression during infection or autoimmunity has been described, functions of Treg cells during highly pathogenic avian influenza virus infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic mice, CD8+ Foxp3+ Treg cells, but not CD4+ Foxp3+ Treg cells, were remarkably induced during H5N1 infection. In addition to expressing CD25, the CD8+ Foxp3+ Treg cells showed a high level of GITR and produced IL-10. In an adoptive transfer model, CD8+ Treg cells suppressed CD8+ T-cell responses and promoted H5N1 virus infection, resulting in enhanced mortality and increased virus load in the lung. Furthermore, in vitro neutralization of IL-10 and studies with IL-10R-deficient mice in vitro and in vivo demonstrated an important role for IL-10 production in the capacity of CD8+ Treg cells to inhibit CD8+ T-cell responses. Our findings identify a previously unrecognized role of CD8+ Treg cells in the negative regulation of CD8+ T-cell responses and suggest that modulation of CD8+ Treg cells may be a therapeutic strategy to control H5N1 viral infection.

We report the design and synthesis of a novel kind of organic-inorganic hybrid material via the incorporation of europium (III) β-diketonate complexes (Eu(TTA)3, TTA = 2-thenoyltrifluoroacetone) into one-dimensional (1D) porous boron nitride (BN) microfibers. The developed Eu(TTA)3@BN hybrid composites with typical 1D fibrous morphology exhibit bright visible red-light emission on UV illumination. The confinement of Eu(TTA)3 within pores of BN microfibers not only decreases the aggregation-caused quenching in solid Eu(TTA)3, but also improves their thermal stabilities. Moreover, The strong interactions between Eu(TTA)3 and porous BN matrix result in an interesting energy transfer process from BN host to TTA ligand and TTA ligand to Eu3+ ions, leading to the remarkable increase of red emission. The synthetic approach should be a very promising strategy which can be easily expanded to other hybrid luminescent materials based on porous BN.

To explore the renoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) and its potential mechanism in type 2 diabetic db/db mice.8-week-old db/db mice (6 h fasting plasma glucose16.7 mmol/L) were allocated randomly into Control group (non-intervention group, n=8), EGCG A group (50 mg·kg(-1)·d(-1,)n=8), EGCG B group (100 mg·kg(-1)·d(-1,)n=8). Before the study and after the intervention (in the 4(th)and 8(th)week), the body weight, the level of fasting plasma glucose, oral glucose tolerance test (OGTT) were measured and 24 h urine samples were collected. 24 h proteinuria was measured by routine chemical method. The levels of angiotensin Ⅱ(AngⅡ), fasting plasma insulin and urinary 8-OHdG were measured with enzyme-linked immunosorbent assay (ELISA). The protein expression levels of angiotensin Ⅱ type 1 receptor (AT-1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit P22-phox, NADPH oxidase subunit P47-phox, phospho-extracellular regulated protein kinases (p-Erk1/2), phospho-P38 mitogen-activated protein kinase (p-P38MAPK), phospho -phosphatidylinositol 3-hydroxy kinase (p-PI3K) and phospho-protein kinase B (p-AKT) were determined by Western blot. The renal pathological changes were examined by the method of PAS (periodic acid-Schiff stain).After 8 weeks of treatment with EGCG, the level of fasting plasma glucose decreased[(14.4±1.0) mmol/L, (14.2±0.7) mmol/L vs. (17.2±0.8) mmol/L]; the level of fasting plasma insulin increased[(13.2±1.2)mU/L, (13.4±1.3) mU/L vs. (9.9±1.0) mU/L]; the area under the curve (AUC) of OGTT decreased[(49.3±1.8) mmol·L(-1)·h(-1,)(44.8±0.7) mmol·L(-1)·h(-1)vs. (60.0±0.8) mmol·L(-1)·h(-1)]; the level of 24 h proteinuria[(8.8±1.0) mg, (8.6±1.1) mg vs. (11.7±1.3) mg]and urinary 8-OHdG[(90±5) ng/d, (78±5) ng/d vs. (118±10) ng/d]decreased; the level of serum Ang-Ⅱ[(498±23) ng/L, (511±19) ng/L vs. (688±17) ng/L]and renal cortex AngⅡ[(367±5) ng/L, (384±10) ng/L vs. (406±7) ng/L]decreased; the expression levels of AT-1R, P22-phox, P47-phox, p-Erk1/2, p-P38MAPK downregulated obviously and the expression levels of p-PI3K, p-AKT increased significantly (P0.05), and renal pathology improved as compared with the control group. After 8 weeks of treatment with EGCG, the level of urinary 8-OHdG decreased (P=0.007) and the AUC of OGTT also decreased (P=0.01) in EGCG B group when compared with the EGCG A group.EGCG protects the kidney in diabetic db/db mice via anti-oxidative stress pathway, as well as inhibiting Erk1/2-P38MAPK pathway and improving PI3K-AKT signaling transduction pathway.

Interleukin-21 (IL-21) is a T-cell-derived cytokine that modulates T-cell, B-cell, and natural killer cell responses. It is not known if it could be used as an adjuvant for HIV DNA vaccination. In our study, we investigated if a DNA construct expressing IL-21 (designated as pVAX-IL-21) as a molecule adjuvant could enhance antigen-specific immune responses to an HIV DNA vaccine (pGX-EnvC). We found that a higher level of antigen-specific cytotoxic responses was induced in BALB/C mice immunized with pGX-EnvC with the pVAX-IL-21 via electroporation. The increased response was associated with higher expression of IFN-γ in CD8⁺ T cells. In contrast, the administration of pVAX-IL-21 inhibited the antibody responses to HIV induced by the pGX-EnvC. The plasma cell inhibitory transcription factors B-cell lymphoma 6 protein (Bcl-6) and Pax-5 were increased in B cells from mice that had been immunized by HIV DNA vaccine plus pVAX-IL-21, suggesting that the expressed IL-21 may inhibit the differentiation from B cells to plasma cells. These results indicate that IL-21 could enhance CD8⁺ T-cell immunity, but inhibit humoral responses during HIV DNA vaccination.

With computed tomography (CT) technology more and more widely used in clinical applications, low-dose CT arouses people's attention gradually. In this paper, we propose an adaptive low-dose CT reconstruction framework. This framework is based on the iterative algorithm, and tries to find the fewest projection angles adaptively insuring the image quality, achieves the goal of reducing the radiation dose at last. The simulation results show that this adaptive low-dose CT reconstruction framework can find the fewest projection angles adaptively according to the requirement of image quality.

In SPECT, in order to achieve a useful sensitivity, the aperture of collimator hole cannot be reduced to zero. This nonzero aperture results in distance-dependent resolution variation (DDRV) in the acquired projection data and in the reconstructed images. Based on the special characteristics of the Fourier coefficients of sinogram, Lewitt proposed a method that can correct the DDRV of the parallel-beam projection in frequency domain. For clinical applications, fan-beam collimators would be preferred for brain and chest imaging, which can improves count density and spatial resolution for imaging small objects. In this case, someone needs to rebin the fan-beam sinogram to the parallel-beam sinogram, and then use Lewitt's method to correct the DDRV in frequency domain. In this work, we propose a new method for the DDRV correction of fan-beam SPECT projection, which doesn't need rebinning, can obtain the Fourier coefficients of parallel-beam projection from the fan-beam projection data directly.

The p42.3 gene was recently identified and characterized as having tumor-specific and mitosis phase-dependent expression in many types of cancer. This suggested that p42.3 antigen could be used as a target for vaccines against cancers. In this study, we immunized C57BL/6 mice with a DNA vaccine encoding p42.3. We used intramuscular injection with electroporation, either before or after challenge with tumor B16F10 cells. Vaccination with pcDNA3-p42.3 induced some degree of antitumor effect both therapeutically and prophylactically, as evaluated by the inhibition of tumor growth and decrease in tumor weight. Immunized mice showed a high level of specific cytotoxic activity against the p42.3 protein in vivo and had activated CD8 T cells that secreted IFN-γ, perforin, and granzyme B in response to stimulation with the antigen in vitro. Thus, this study presents the DNA vaccination against novel tumor target p42.3 as a promising antitumor modality.

Although Treg-cell-mediated suppression during infection or autoimmunity has been described, functions of Treg cells during highly pathogenic avian influenza virus infection remain poorly characterized. Here we found that in Foxp3-GFP transgenic mice, CD8(+) Foxp3(+) Treg cells, but not CD4(+) Foxp3(+) Treg cells, were remarkably induced during H5N1 infection. In addition to expressing CD25, the CD8(+) Foxp3(+) Treg cells showed a high level of GITR and produced IL-10. In an adoptive transfer model, CD8(+) Treg cells suppressed CD8(+) T-cell responses and promoted H5N1 virus infection, resulting in enhanced mortality and increased virus load in the lung. Furthermore, in vitro neutralization of IL-10 and studies with IL-10R-deficient mice in vitro and in vivo demonstrated an important role for IL-10 production in the capacity of CD8(+) Treg cells to inhibit CD8(+) T-cell responses. Our findings identify a previously unrecognized role of CD8(+) Treg cells in the negative regulation of CD8(+) T-cell responses and suggest that modulation of CD8(+) Treg cells may be a therapeutic strategy to control H5N1 viral infection.

Incorporation of molecular adjuvants into DNA vaccines is often used to improve the induction of immune responses, but few approaches aim to specifically activate B cells for an enhanced humoral response only. Hemokinin-1 (HK-1) is a factor that activates B cells for proliferation, survival, differentiation into plasma cells, and Ab production. Therefore, we investigated if it may be used as a molecular adjuvant for DNA vaccines to elicit strong humoral and memory responses. The HK-1 coding sequence was sub-cloned as single or triple copies in-frame downstream of S2 HBsAg in the proVAX/S2 construct. Compared to mice immunized with proVAX/S2 or proVAX/S2-HK-1, proVAX/S2-3HK-1 induced a higher level of IgG production, a higher percentage of differentiated antibody-secreting plasma cells, and a higher level of T-cell proliferation. Furthermore, a higher proportion of B cells had the B220(+)CD27(+) phenotype in these groups, and specific antigen re-challenge induced a higher level of total IgG production 60 d after the last immunization, suggesting that the use of HK-1 as an adjuvant promoted immunological memory. Taken together, these results suggest that using HK-1 as an adjuvant molecule could enhance the immunogenicity of HBsAg DNA vaccines, and result in stronger humoral and memory responses. Therefore, HK-1 may lead to the development of a novel humoral-biased molecular adjuvant for an HBsAg DNA vaccine against hepatitis B infection.

Background H5N1 is a highly pathogenic influenza A virus, which can cause severe illness or even death in humans. Although the widely used killed vaccines are able to provide some protection against infection via neutralizing antibodies, cytotoxic T-lymphocyte responses that are thought to eradicate viral infections are lacking. Methodology/principal findings Aiming to promote cytotoxic responses against H5N1 infection, we extended our previous finding that praziquantel (PZQ) can act as an adjuvant to induce IL-17-producing CD8(+) T cells (Tc17). We found that a single immunization of 57BL/6 mice with killed viral vaccine plus PZQ induced antigen-specific Tc17 cells, some of which also secreted IFN-γ. The induced Tc17 had cytolytic activities. Induction of these cells was impaired in CD8 knockout (KO) or IFN-γ KO mice, and was even lower in IL-17 KO mice. Importantly, the inoculation of killed vaccine with PZQ significantly reduced virus loads in the lung tissues and prolonged survival. Protection against H5N1 virus infection was obtained by adoptively transferring PZQ-primed wild type CD8(+) T cells and this was more effective than transfer of activated IFN-γ KO or IL-17 KO CD8(+) T cells. Conclusions/significance Our results demonstrated that adding PZQ to killed H5N1 vaccine could promote broad Tc17-mediated cytotoxic T lymphocyte activity, resulting in improved control of highly pathogenic avian influenza virus infection.

Background: CD8(+) cytotoxic T lymphocytes (CTLs) are crucial for eliminating hepatitis B virus (HBV) infected cells. DNA vaccination, a novel therapeutic strategy for chronic virus infection, has been shown to induce CTL responses. However, accumulated data have shown that CTLs could not be effectively induced by HBV DNA vaccination. Methodology/principal Findings: Here, we report that praziquantel (PZQ), an anti-schistoma drug, could act as an adjuvant to overcome the lack of potent CTL responses by HBV DNA vaccination in mice. PZQ in combination with HBV DNA vaccination augmented the induction of CD8(+) T cell-dependent and HBV-specific delayed hypersensitivity responses (DTH) in C57BL/6 mice. Furthermore, the induced CD8(+) T cells consisted of both Tc1 and Tc17 subtypes. By using IFN-gamma knockout (KO) mice and IL-17 KO mice, both cytokines were found to be involved in the DTH. The relevance of these findings to HBV immunization was established in HBsAg transgenic mice, in which PZQ also augmented the induction of HBV-specific Tc1 and Tc17 cells and resulted in reduction of HBsAg positive hepatocytes. Adoptive transfer experiments further showed that PZQ-primed CD8(+) T cells from wild type mice, but not the counterpart from IFN-gamma KO or IL-17 KO mice, resulted in elimination of HBsAg positive hepatocytes. Conclusions/Significance: Our results suggest that PZQ is an effective adjuvant to facilitate Tc1 and Tc17 responses to HBV DNA vaccination, inducing broad CD8(+) T cell-based immunotherapy that breaks tolerance to HBsAg.