Structural and Mechanistic Bases for Resistance of the M66I Capsid Variant to Lenacapavir.

Unlabelled: Lenacapavir (LEN) is the first in class viral capsid protein (CA) targeting antiretroviral for treating multi-drug-resistant HIV-1 infection. Clinical trials and cell culture experiments have identified resistance associated mutations (RAMs) in the vicinity of the hydrophobic CA pocket targeted by LEN. The M66I substitution conferred by far the highest level of resistance to the inhibitor compared to other RAMs.

Design and Fabrication of a C-Band Patch Antenna with Low Loss BaMSiO Microwave Dielectric Ceramics.

Single-phase BaMSiO (M = Yb, Er, Y, Ho) ceramics have been investigated for their crystal structures, microwave dielectric properties, flexural strength, and potential applications in dielectric antennas. Rietveld refinement and TEM analysis revealed that the BaMSiO ceramics exhibit a monoclinic structure (space groups: 2/). The ε of the BaMSiO ceramics was dominated by ionic polarizability and ρ.

AUF1-mediated inhibition of autophagic lysosomal degradation contributes to CagA stability and -induced inflammation.

CagA, a virulence factor of (), is known to drive inflammation in gastric epithelial cells and is typically degraded through autophagy. However, the molecular mechanism by which CagA evades autophagy-mediated degradation remains elusive. This study found that inhibits autophagic flux by upregulating the expression of AU-rich element RNA-binding factor 1 (AUF1).

Ultralow-Permittivity and Temperature-Stable BaCaMgAlSiO Dielectric Ceramics for C-Band Patch Antenna Applications.

Ca-substituted BaCaMgAlSiO ceramics were prepared to explore the relationships among their crystal structural parameters, phase compositions, dielectric properties, and coefficients of thermal expansion and applications in C-band antenna. The maximum solubility of BaCaMgAlSiO was located at = 0.25, and BaCaMgAlSiO ceramics (0 ≤ ≤ 0.

Association of HBV serological markers with host antiviral immune response relevant hepatic inflammatory damage in chronic HBV infection.

The natural progression of chronic hepatitis B virus (HBV) infection is dynamic, but the longitudinal landscape of HBV serological markers with host antiviral immune response relevant hepatic inflammatory damage remains undetermined. To this issue, we studied the association of HBV serological markers with the severity of hepatic inflammatory damage and enumerated HBV-specific T cells using the cultured enzyme-linked immune absorbent spot (ELISpot). Five hundred and twenty-four treatment-naïve chronic HBV infection patients were enrolled.

Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B.

Background & Aims: HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy.

Methods: We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't.

A novel hepatitis B virus capsid assembly modulator QL-007 inhibits HBV replication and infection through altering capsid assembly.

The core protein allosteric modulators (CpAMs) have shown great potential as highly effective antiviral drugs against hepatitis B virus (HBV) in preclinical studies and clinical trials. In this study, we evaluated a small molecule compound called QL-007, which could potentially influence capsid assembly, using HBV replicated and susceptible cell models as well as mice infected with rAAV-HBV. QL-007 significantly inhibited HBV replication in a dose-dependent manner both in vitro and in vivo, resulting in significant decreases in HBV DNA, 3.

Möbius edge band and Weyl-like semimetal flat-band in topological photonic waveguide array by synthetic gauge flux.

The presence of gauge flux enabled by positive and negative hopping amplitude can lead to Möbius bands, which was recently demonstrated in both realistic acoustic and photonic lattices, twisted at = . Here, we show that the artificial gauge flux configuration can be achieved by exploiting the interactions between photonic and orbital-like fundamental modes in circular and peanut-shaped waveguides, respectively. By manipulating the interplay between the gauge fields and the crystal symmetry, we show that breaking the primitive translation symmetry through lattice site dimerization and deformation can cause the original Dirac semimetal phase, characterized by a four-fold Dirac point at the Brillouin zone center, to transform into various topological phases.

Structural and Mechanistic Bases of Viral Resistance to HIV-1 Capsid Inhibitor Lenacapavir.

Lenacapavir (LEN) is a long-acting, highly potent HIV-1 capsid (CA) inhibitor. The evolution of viral variants under the genetic pressure of LEN identified Q67H, N74D, and Q67H/N74D CA substitutions as the main resistance associated mutations (RAMs). Here, we determined high-resolution structures of CA hexamers containing these RAMs in the absence and presence of LEN.

Boundary configured chiral edge states in valley topological photonic crystal.

Chiral edge states (CESs) have been demonstrated at the external boundary of a valley photonic crystal (VPC), with flexibly tunable group velocity and frequency range by adjusting the boundary structure. In this work, we show parallel and antiparallel CESs located at two opposite VPC-air boundaries, which contain wave components belonging to opposite valleys or the same valley. In addition, we design a meta-structure with four types of air-contacted boundary that support CESs in different frequency ranges.

Four dimensional second-order topological insulator based on a synthetic plasmonic metasurface.

It is possible to explore higher dimensional topological properties in lower dimensional structures by introducing additional synthetic dimensions. In this Letter, we construct a four-dimensional (4D) second-order topological insulator using gradient nanoparticle arrays arranged in a periodic lattice. The nanoparticle array has spatially varying inter-particle distance along and directions, which can be regarded as two synthetic dimensions.

Square-root topological state of coupled plasmonic nanoparticles in a decorated Su-Schrieffer-Heeger lattice.

The square-root operation can generate systems with new (to the best of our knowledge) topological phases whose topological properties are inherited from the parent Hamiltonian. In this Letter, we introduce the concept of square-root topology in the two-dimensional (2D) Su-Schrieffer-Heeger (SSH) model and construct a square-root topological square nanoparticle lattice (SRTL) by inserting additional sites into the original 2D SSH model. We find that the topological states in the SRTL are intriguingly different from those in the corresponding SSH model (with on-site potential) due to the change in symmetrical characteristics.

Personalized neoantigen pulsed dendritic cell vaccine for advanced lung cancer.

Neoantigens are considered to be ultimate target of tumor immunotherapy due to their high tumor specificity and immunogenicity. Dendritic cell (DCs) vaccines based on neoantigens have exciting effects in treatment of some malignant tumors and are a promising therapeutic modality. Lung cancer is a lethal disease with the highest morbidity and mortality rate in the world.

The Unique, the Known, and the Unknown of Spumaretrovirus Assembly.

Within the family of , foamy viruses (FVs) are unique and unconventional with respect to many aspects in their molecular biology, including assembly and release of enveloped viral particles. Both components of the minimal assembly and release machinery, Gag and Env, display significant differences in their molecular structures and functions compared to the other retroviruses. This led to the placement of FVs into a separate subfamily, the .

Multiple Dirac points by high-order photonic bands in plasmonic-dielectric superlattices.

The emergence of Dirac points (DPs) characterizes the topological phase transition and the gapless interface states in composite metal-dielectric metamaterials. In this work, we study a kind of compound plasmonic-dielectric periodic structure (PDPS) which sustains both plasmonic modes and multiple photonic modes. The structure has primitive cell consisting of four layers made from triple constituent components.

TruNeo: an integrated pipeline improves personalized true tumor neoantigen identification.

Background: Neoantigen-based personal vaccines and adoptive T cell immunotherapy have shown high efficacy as a cancer treatment in clinical trials. Algorithms for the accurate prediction of neoantigens have played a pivotal role in such studies. Some existing bioinformatics methods, such as MHCflurry and NetMHCpan, identify neoantigens mainly through the prediction of peptide-MHC binding affinity.

Structural and mechanistic bases for a potent HIV-1 capsid inhibitor.

The potent HIV-1 capsid inhibitor GS-6207 is an investigational principal component of long-acting antiretroviral therapy. We found that GS-6207 inhibits HIV-1 by stabilizing and thereby preventing functional disassembly of the capsid shell in infected cells. X-ray crystallography, cryo-electron microscopy, and hydrogen-deuterium exchange experiments revealed that GS-6207 tightly binds two adjoining capsid subunits and promotes distal intra- and inter-hexamer interactions that stabilize the curved capsid lattice.

Frequency selective topological edge wave routing in meta-structures made of cylinders.

The propagation direction of edge states is essentially related to the band topology invariant of the constituent structures and the momentum of the excitation source. However, it is difficult to control the propagation path when the chirality of the excitation source and the boundary structures are determined. Here, we study a frequency selective waveguide structure based on photonic crystals with different topological invariant characterized by bulk polarization.

The chromatin binding domain, including the QPQRYG motif, of feline foamy virus Gag is required for viral DNA integration and nuclear accumulation of Gag and the viral genome.

The retroviral Gag protein, the major component of released particles, plays different roles in particle assembly, maturation or infection of new host cells. Here, we characterize the Gag chromatin binding site including the highly conserved QPQRYG motif of feline foamy virus, a member of the Spumaretrovirinae. Mutagenesis of critical residues in the chromatin binding site/QPQRYG motif almost completely abrogates viral DNA integration and reduces nuclear accumulation of Gag and viral DNA.

Replacement of feline foamy virus bet by feline immunodeficiency virus vif yields replicative virus with novel vaccine candidate potential.

Background: Hosts are able to restrict viral replication to contain virus spread before adaptive immunity is fully initiated. Many viruses have acquired genes directly counteracting intrinsic restriction mechanisms. This phenomenon has led to a co-evolutionary signature for both the virus and host which often provides a barrier against interspecies transmission events.

Mutagenesis of N-terminal residues of feline foamy virus Gag reveals entirely distinct functions during capsid formation, particle assembly, Gag processing and budding.

Background: Foamy viruses (FVs) of the Spumaretrovirinae subfamily are distinct retroviruses, with many features of their molecular biology and replication strategy clearly different from those of the Orthoretroviruses, such as human immunodeficiency, murine leukemia, and human T cell lymphotropic viruses. The FV Gag N-terminal region is responsible for capsid formation and particle budding via interaction with Env. However, the critical residues or motifs in this region and their functional interaction are currently ill-defined, especially in non-primate FVs.

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy.

The use of whole viruses as antigen scaffolds is a recent development in vaccination that improves immunogenicity without the need for additional adjuvants. Previous studies highlighted the potential of foamy viruses (FVs) in prophylactic vaccination and gene therapy. Replication-competent FVs can trigger immune signaling and integrate into the host genome, resulting in persistent antigen expression and a robust immune response.