Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination

Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection (CHB) has been challenging due to HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface antigen in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg antibody in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist, resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral antigen with neutralizing antibodies followed by vaccination

Bimetal based inorganic-carbonic anhydrase hybrid hydrogel membrane for CO2 capture

In this study, we synthesized for the first time a bimetal-based inorganic-carbonic anhydrase (CA) hybrid nanoflower to immobilize CA using Cu2+ and Zn2+ instead of single metal ion. Subsequently, the synthesized bimetallic hybrid nanoflowers (CANF) were embedded into the poly(vinyl alcohol) (PVA)-chitosan (CS) hydrogel networks to obtain PVA/CS@CANF hydrogel membrane. The CANF exhibited a significantly higher activity recovery of 70 % compared with 35 % with CA/Zn3(PO4)2 hybrid nanoflowers and 10 % with CA/Cu3(PO4)2 hybrid nanoflowers. The PVA/CS@CANF hydrogel membrane possessed excellent mechanical strength, high catalytic activity, and were easy to flow out without centrifugation or filtration. At the same time, the PVA/CS@CANF displayed higher thermostability, storage stability, and pH stability than free CA and CANF, and superior reusability and CO2 capture capacity. The hydrogel membrane maintained more than 75 % of its original activity after 8 cycles. However, CANF only maintained 12 % of its original activity. Furthermore, the amount of CaCO3 produced by PVA/CS@CANF membrane was 9.0-fold and 2.0-fold compared with free CA and CANF, respectively. Therefore, This approach to synthesizing bimetallic-based protein hybrid hydrogel membrane could have a bright future in CO2 capture

Vaccines targeting preS1 domain overcome immune tolerance in hepatitis B virus carrier mice

Strong tolerance to hepatitis B virus (HBV) surface antigens limits the therapeutic effect of the conventional hepatitis B surface antigen (HBsAg) vaccination in both preclinical animal models and patients with chronic hepatitis B (CHB) infection. In contrast, we observed that clinical CHB patients presented less immune tolerance to the preS1 domain of HBV large surface antigen. To study whether targeting the weak tolerance of the preS1 region could improve therapy gain, we explored vaccination with the long peptide of preS1 domain for HBV virions clearance. Our study showed that this preS1-polypeptide rather than HBsAg vaccination induced robust immune responses in HBV carrier mice. The anti-preS1 rapidly cleared HBV virions in vivo and blocked HBV infection to hepatocytes in vitro. Intriguingly, vaccination of preS1-polypeptide even reduced the tolerized status of HBsAg, opening a therapeutic window for the host to respond to the HBsAg vaccine. A sequential administration of antigenically distinct preS1-polypeptide and HBsAg vaccines in HBV carrier mice could finally induce HBsAg/hepatitis B surface antibody serological conversion and clear chronic HBV infection in carrier mice. Conclusion: These results suggest that preS1 can function as a therapeutic vaccine for the control of CHB. (Hepatology 2017;66:1067-1082)

Distributions and Physical Properties of Molecular Clouds in the Third Galactic Quadrant: ll = [219.75, 229.75]∘^\circ and bb = [-5.25, 5.25]∘^\circ

We present the results of an unbiased $^{12}$CO/$^{13}$CO/C$^{18}$O ($J$ = 1-0) survey in a portion of the third Galactic quadrant (TGQ): $l$ = [219.75, 229.75]$^\circ$ and $b$ = [-5.25, 5.25]$^\circ$. The high-resolution and high-sensitivity data sets help to unravel the distributions and physical properties of the molecular clouds (MCs) in the mapped area. In the LSR velocity range from -1 to 85 km/s, the molecular material successfully traces the Local, Perseus, and Outer arms. In the TGQ, the Outer arm appears to be more prominent than that in the second Galactic quadrant (SGQ), but the Perseus arm is not as conspicuous as that in the SGQ. A total of 1,502 $^{12}$CO, 570 $^{13}$CO, and 53 C$^{18}$O molecular structures are identified, spanning over $\sim2$ and $\sim6$ orders of magnitude in size and mass, respectively. Tight mass-radius correlations and virial parameter-mass anticorrelations are observable. Yet, it seems that no clear correlations between velocity dispersion and effective radius can be found over the full dynamic range. The vertical distribution of the MCs renders evident pictures of the Galactic warp and flare.Comment: 22 pages, 13 figures, 7 tables (with machine-readable versions), published in ApJ

Systematic biases in determining dust attenuation curves through galaxy SED fitting

While the slope of the dust attenuation curve ($\delta$) is found to correlate with effective dust attenuation ($A_V$) as obtained through spectral energy distribution (SED) fitting, it remains unknown how the fitting degeneracies shape this relation. We examine the degeneracy effects by fitting SEDs of a sample of local star-forming galaxies (SFGs) selected from the Galaxy And Mass Assembly survey, in conjunction with mock galaxy SEDs of known attenuation parameters. A well-designed declining starburst star formation history is adopted to generate model SED templates with intrinsic UV slope ($\beta_0$) spanning over a reasonably wide range. The best-fitting $\beta_0$ for our sample SFGs shows a wide coverage, dramatically differing from the limited range of $\beta_0<-2.2$ for a starburst of constant star formation. Our results show that strong degeneracies between $\beta_0$, $\delta$, and $A_V$ in the SED fitting induce systematic biases leading to a false $A_V$--$\delta$ correlation. Our simulation tests reveal that this relationship can be well reproduced even when a flat $A_V$--$\delta$ relation is taken to build the input model galaxy SEDs. The variations in best-fitting $\delta$ are dominated by the fitting errors. We show that assuming a starburst with constant star formation in SED fitting will result in a steeper attenuation curve, smaller degeneracy errors, and a stronger $A_V$--$\delta$ relation. Our findings confirm that the $A_V$--$\delta$ relation obtained through SED fitting is likely driven by the systematic biases induced by the fitting degeneracies between $\beta_0$, $\delta$, and $A_V$.Comment: 21 pages, 13 figures, accepted for publication in the MNRAS, Comments welcome

An exploitation plan of tidal power in the Severn Estuary

The Severn Estuary has the second largest tidal range in the world and full of potential tidal power. The estuary area has great ecological value due to its nature conservation sites, biological habitats and unique coastal ecological system. Various kinds of plans and projects about exploiting the Severn Estuary have been proposed by many organizations for years. Giving the consideration of electricity generating efficiency, financial costs and especially environmental impacts, it is reasonable to believe that the application of a tidal lagoon system in the estuary area is the most suitable choice among all the options, which has the features of eco-friendly, effective, predictable and flood defending. The implementation of the Severn Estuary tidal lagoon system can be a long-term and stable renewable energy source for UK and will provide reference value for the development of other coastal area

An exploitation plan of tidal power in the Severn Estuary

The Severn Estuary has the second largest tidal range in the world and full of potential tidal power. The estuary area has great ecological value due to its nature conservation sites, biological habitats and unique coastal ecological system. Various kinds of plans and projects about exploiting the Severn Estuary have been proposed by many organizations for years. Giving the consideration of electricity generating efficiency, financial costs and especially environmental impacts, it is reasonable to believe that the application of a tidal lagoon system in the estuary area is the most suitable choice among all the options, which has the features of eco-friendly, effective, predictable and flood defending. The implementation of the Severn Estuary tidal lagoon system can be a long-term and stable renewable energy source for UK and will provide reference value for the development of other coastal area

Does financial leverage volatility induce systemic financial risk? Empirical insight based on the Chinese fintech sector

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Financial leverage volatility is a significant factor contributing to the formation of systemic financial risk, which is more apparent in China's fast-growing fintech (financial technology) field. Using the Conditional Value-at-risk approach (ΔCoVaR) risk metric, the generalized autoregressive conditional heteroskedasticity (Structural Vector Autoregression with Stochastic Volatility model [SV-TVP-SAVR]) model, and the generalized forecast error variance decomposition (Tvpdy) model, this paper discusses how financial leverage volatility shocks fintech sectoral risks and the evolution of the risk within fintech under the shocks on the basis of the classification criteria of the Chinese fintech enterprise database and daily trading data of A-share listed companies. The statistical results show that financial leverage volatility causes risk changes across fintech sectors, which is especially significant during economic downturns or government interventions. Also, under the shock of financial leverage volatility, the fintech sectors will absorb or diffuse risks outward through spillover channels, with significant differences in the risk spillover conditions of different types of sectors. Finally, the fintech sector can produce a contagion system with the Internet consumer finance, payment, and Internet microcommercial credit sectors as the core of risks, resulting in a systemic risk crisis. Our findings have major implications for Chinese regulators to balance financial leverage and prevent systemic risks in the fintech sector

Kinematics of the Local Spiral Structure Revealed by Young Stars in Gaia DR3

Using young open clusters and O–B2-type stars in Gaia Data Release 3, we investigate the kinematics of the local spiral structure. In general, the young sources in the outer spiral arms may present larger peculiar motions than those in the inner spiral arms. The young open clusters appear to have smaller peculiar motions than the O–B2-type stars, and the sources in both the Perseus and Local Arms may show an inward motion toward the Galactic center and rotate slower than Galactic rotation. Meanwhile, the sources in the Carina Arm may move in the opposite direction from the Sun to the Galactic center and rotate marginally faster than Galactic rotation. In addition, using young open clusters and O–B2-type stars, we have improved the distance estimations of kinematic methods for several regions near the Sun

Local Spiral Structure Traced by Red Clump Stars

Using the cross-matched data of Gaia EDR3 and the 2MASS Point Source Catalog, a sample of RC stars with parallax accuracies better than 20% is identified and used to reveal the nearby spiral pattern traced by old stars. As shown in the overdensity distribution of RC stars, there is an arc-like feature extended from $l~\sim$ 90$^\circ$ to $\sim$ 243$^\circ$, which passed close to the Sun. This feature is probably an arm segment traced by old stars, indicating the Galaxy potential in the vicinity of the Sun. By comparing to the spiral arms depicted by young objects, we found that there are considerable offsets between the two different components of Galactic spiral arms. The spiral arm traced by RC stars tends to have a larger pitch angle, hence a more loose wound pattern.Comment: 10 pages, 6 figures, accepted for publication in Ap