A virus-like particle of the hepatitis B virus preS antigen elicits robust neutralizing antibodies and T cell responses in mice

The preS antigen of hepatitis B virus (HBV) corresponds to the N-terminal polypeptide in the large (L) antigen in addition to the small (S) antigen. The virus-like particle (VLP) of the S antigen is widely used as a vaccine to protect the population from HBV infection. The presence of the S antigen and its antibodies in patient blood has been used as markers to monitor hepatitis B. However, there is very limited knowledge about the preS antigen. We generated a preS VLP that is formed by a chimeric protein between preS and hemagglutinin (HA), and the matrix protein M1 of influenza virus. The HBV preS antigen is displayed on the surface of preS VLP. Asn112 and Ser98 of preS in VLP were found to be glycosylated and O-glycosylation of Ser98 has not been reported previously. The preS VLP shows a significantly higher immunogenicity than recombinant preS, eliciting robust anti-preS neutralizing antibodies. In addition, preS VLP is also capable of stimulating preS-specific CD8+ and CD4+ T cell responses in Balb/c mice and HBV transgenic mice. Furthermore, preS VLP immunization provided protection against hydrodynamic transfection of HBV DNA in mice. The data clearly suggest that this novel preS VLP could elicit robust immune responses to the HBV antigen, and can be potentially developed into prophylactic and therapeutic vaccines

Corrigendum: A Novel Phage PD-6A3, and Its Endolysin Ply6A3, With Extended Lytic Activity Against Acinetobacter baumannii

With widespread abuse of antibiotics, bacterial resistance has increasingly become a serious threat. Acinetobacter baumannii has emerged as one of the most important hospital-acquired pathogens worldwide. Bacteriophages (also called “phages”) could be used as a potential alternative therapy to meet the challenges posed by such pathogens. Endolysins from phages have also been attracting increasing interest as potential antimicrobial agents. Here, we isolated 14 phages against A. baumannii, determined the lytic spectrum of each phage, and selected one with a relatively broad host range, named vB_AbaP_PD-6A3 (PD-6A3 for short), for its biological characteristics. We over-expressed and purified the endolysin (Ply6A3) from this phage and tested its biological characteristics. The PD-6A3 is a novel phage, which can kill 32.4% (179/552) of clinical multidrug resistant A. baumannii (MDRAB) isolates. Interestingly, in vitro, this endolysin could not only inhibit A. baumannii, but also that of other strains, such as Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). We found that lethal A. baumannii sepsis mice could be effectively rescued in vivo by phage PD-6A3 and endolysin Ply6A3 intraperitoneal injection. These characteristics reveal the promising potential of phage PD-6A3 and endolysin Ply6A3 as attractive candidates for the control of A. baumannii-associated nosocomial infections.</p

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Engineering Hepadnaviruses as Reporter-Expressing Vectors: Recent Progress and Future Perspectives

The Hepadnaviridae family of small, enveloped DNA viruses are characterized by a strict host range and hepatocyte tropism. The prototype hepatitis B virus (HBV) is a major human pathogen and constitutes a public health problem, especially in high-incidence areas. Reporter-expressing recombinant viruses are powerful tools in both studies of basic virology and development of antiviral therapeutics. In addition, the highly restricted tropism of HBV for human hepatocytes makes it an ideal tool for hepatocyte-targeting in vivo applications such as liver-specific gene delivery. However, compact genome organization and complex replication mechanisms of hepadnaviruses have made it difficult to engineer replication-competent recombinant viruses that express biologically-relevant cargo genes. This review analyzes difficulties associated with recombinant hepadnavirus vector development, summarizes and compares the progress made in this field both historically and recently, and discusses future perspectives regarding both vector design and application

Analysis of the Electromechanical Characteristics of Power Transformer under Different Residual Fluxes

When the electromagnetic transients occur in a power transformer, an inrush current is generated in its winding. The inrush current not only affects the performance of the transformer windings, but also affects the lifetime of the transformer. Many factors affect the inrush current, the most influential ones among which are the closing phase angle and the residual flux. In this paper, a dry-type transformer simulation model is built to analyze the influence of the inrush current on the performance of transformer windings during no-load reclosing conditions. Firstly, the inrush current was generated in the transformer windings during the no-load reclosing operation under different residual fluxes. Secondly, the field-circuit coupling 3d finite element method is used to analyze the electromagnetic force at different locations of the transformer windings under the influence of different inrush currents. The results of winding structural parameter variations are obtained through electromagnetic-structural coupling simulation, and the electromagnetic forces are used as the input parameter for the structural analysis. Finally, the residual flux is generated by controlling the opening and closing angle of the transformer through the phase-controlled switch, and the winding electromechanical characteristics are tested under different residual fluxes. Finally, comparisons of the test and simulation results are drawn to verify the impact of the closing angle and residual flux on inrush current and the winding deformation during the no-load reclosing conditions

Analysis of the Electromechanical Characteristics of Power Transformer under Different Residual Fluxes

When the electromagnetic transients occur in a power transformer, an inrush current is generated in its winding. The inrush current not only affects the performance of the transformer windings, but also affects the lifetime of the transformer. Many factors affect the inrush current, the most influential ones among which are the closing phase angle and the residual flux. In this paper, a dry-type transformer simulation model is built to analyze the influence of the inrush current on the performance of transformer windings during no-load reclosing conditions. Firstly, the inrush current was generated in the transformer windings during the no-load reclosing operation under different residual fluxes. Secondly, the field-circuit coupling 3d finite element method is used to analyze the electromagnetic force at different locations of the transformer windings under the influence of different inrush currents. The results of winding structural parameter variations are obtained through electromagnetic-structural coupling simulation, and the electromagnetic forces are used as the input parameter for the structural analysis. Finally, the residual flux is generated by controlling the opening and closing angle of the transformer through the phase-controlled switch, and the winding electromechanical characteristics are tested under different residual fluxes. Finally, comparisons of the test and simulation results are drawn to verify the impact of the closing angle and residual flux on inrush current and the winding deformation during the no-load reclosing conditions

A potential biological signature of 7-methylguanosine-related lncRNA to predict the immunotherapy effects in bladder cancer

Background: Bladder urothelial carcinoma (BLCA) is the second prevalent genitourinary carcinoma globally. N7-methylguanosine (m7G) is important for tumorigenesis and progression. This study aimed to build a predictive model for m7G-related long non-coding RNAs (lncRNAs), elucidate their role in the tumor immune microenvironment (TIME), and predict immunotherapy response in BLCA. Methods: We first used univariate Cox regression and coexpression analyses to identify m7G-related lncRNAs. Next, the prognostic model was built by utilizing LASSO regression analysis. Then, the prognostic significance of the model was examined utilizing Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, nomogram, and univariate, multivariate Cox regression. We also analyzed Gene set enrichment analyses (GSEA), immune analysis and principal component analysis (PCA) in risk groups. To further predict immunotherapy effectiveness, we evaluated the predictive ability for immunotherapy in 2 risk groups and clusters using tumor immune dysfunction and exclusion (TIDE) score and Immunophenoscore (IPS). Results: Seven lncRNAs related to m7G were used to create a model. The calibration plots for the model suggested a strong fit with the prediction of overall survival (OS). The area under the curve (AUC) for first, second, and third years was respectively, 0.722, 0.711, and 0.686. In addition, the risk score had strong correlation with TIME features and genes linked to immune checkpoint blockade (ICB). TIDE scores were dramatically different between two risk groups (p < 0.05), and IPS scores were markedly different between two clusters (p < 0.05). Conclusion: Our research constructed a novel m7G-related lncRNAs that could be used to predict patient outcomes and the effectiveness of immunotherapy in BLCA. Immunotherapy may be more effective for the low-risk group and cluster 2