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Hepatitis B virus (HBV) is an important human pathogen that chronically infects 254 million people in the world. This virus contains a core particle, which plays an important role in the transport and replication of the viral DNA genome. The major protein constituent of this particle is the viral core protein. In this report, we examined how the subcellular compartments and the related precore protein might affect the core particle structure and viral DNA replication. We found that the subcellular localizations could affect the core particle assembly, and membranes and the precore protein could regulate HBV DNA replication. We also found that the inhibition of autophagic degradation increased the precore protein level, suggesting a role of autophagy in the regulation of precore protein activities. These findings provided important information for further understanding the HBV life cycle, which will aid in the development of novel drugs for the treatment of HBV patients.

Carbon-encapsulated iron nanoparticles (Fe@C) with a mean diameter of 15 nm have been synthesized using evaporation–condensation flow–levitation method by the direct iron-carbon gas-phase reaction at high temperatures. Further, Fe@C were stabilized with bovine serum albumin (BSA) coating, and their electromagnetic properties were evaluated to test their performance in magnetic hyperthermia therapy (MHT) through a specific absorption rate (SAR). Heat generation was observed at different Fe@C concentrations (1, 2.5, and 5 mg/mL) when applied 331 kHz and 60 kA/m of an alternating magnetic field, resulting in SAR values of 437.64, 129.36, and 50.4 W/g for each concentration, respectively. Having such high SAR values at low concentrations, obtained material is ideal for use in MHT.

Carbon‐doped TiO2 nanoparticles were prepared by a facile carbothermal treatment at different temperatures. The synthesis was conducted in a rotary tube furnace under an acetylene/nitrogen gas flow. A detailed analysis of the morphology of the particles revealed a layered graphene structure surrounding the TiO2 core with a temperature‐dependent shell thickness of 1–1.5 nm. The material exhibits a significant shift in the Raman Eg(1) mode toward higher wavenumbers. High carbon contents were determined by X‐ray photoelectron spectroscopy. This led to the conclusion that in addition to the carbon in the shell, carbon is also incorporated into the TiO2 structure. Substitutional doping in favor of titanium or oxygen atoms could be excluded based on XPS measurements due to the absence of Ti–C bonds and the lack of changes in lattice parameters of the unit cell or microstrain. An interstitial incorporation of carbon is therefore most likely. Either the incorporation of carbon or the carbon shell suppressed the phase transition from anatase to the thermodynamically stable rutile which is expected above 600∘C $^{\\circ }{\\rm C}$ . Additionally, the process inhibits the crystallite growth at higher treatment temperatures. Carbon‐doped TiO2 ${\\rm TiO}_2$nanoparticles were produced by heating pristine TiO2 ${\\rm TiO}_2$in acetylene/nitrogen gas, forming a thin graphene‐like shell around each particle. The analysis of the particles indicate that some carbon enters the TiO2 ${\\rm TiO}_2$structure at interstitial sites. This carbon, whether inside the particles or in the shell, inhibits crystal growth and the anatase‐to‐rutile phase transition, which typically occurs at temperatures above 600 ∘C $^{\\circ }{\\rm C}$ .

We developed a procedure to prepare luminescent LiYF 4 :Yb/LiYF 4 and LiYF 4 :Yb,Er/LiYF 4 core/shell nanocrystals with a size of approximately 40 nm revealing luminescence decay times of the dopant ions that approach those of high-quality laser crystals of LiYF 4 :Yb (Yb:YLF) and LiYF 4 :Yb,Er (Yb,Er:YLF) with identical doping concentrations. As the luminescence decay times of Yb 3+ and Er 3+ are known to be very sensitive to the presence of quenchers, the long decay times of the core/shell nanocrystals indicate a very low number of defects in the core particles and at the core/shell interfaces. This improvement in the performance was achieved by introducing two important modifications in the commonly used oleic acid based synthesis. First, the shell was prepared via a newly developed method characterized by a very low nucleation rate for particles of pure LiYF 4 shell material. Second, anhydrous acetates were used as precursors and additional drying steps were applied to reduce the incorporation of OH − in the crystal lattice, known to quench the emission of Yb 3+ ions. Excitation power density ( P )-dependent absolute measurements of the upconversion luminescence quantum yield ( Φ UC ) of LiYF 4 :Yb,Er/LiYF 4 core/shell particles reveal a maximum value of 1.25% at P of 180 Wcm −2 . Although lower than the values reported for NaYF 4 :18%Yb,2%Er core/shell nanocrystals with comparable sizes, these Φ UC values are the highest reported so far for LiYF 4 :18%Yb,2%Er/LiYF 4 nanocrystals without additional dopants. Further improvements may nevertheless be possible by optimizing the dopant concentrations in the LiYF 4 nanocrystals.

Smart biocompatible materials that respond to a variety of external stimuli have a lot of potential in the creation of low-cost diagnostic biosensors. The present work describes the creation of core–shell nanoparticles as a biosensor for smart enzyme detection of salivary alpha-amylase (sAA). A chitosan-tripolyphosphate core was generated via ionic gelation and was coated with a starch–iodine shell to create biocompatible core–shell nanoparticles. The starch–iodine shell was ruptured in the presence of certain amounts of amylase, exposing the core. This application explains a noticeable color change from blue to white that can be used to identify sAA at the point of care. Synthesized nanoparticles were examined for scanning electron microscopy analysis and energy-dispersive X-ray (EDX). An EDX report reveals that the nanoparticles have higher carbon content at 55% followed by an oxygen atom of 35%. Fourier-transform infrared spectroscopic analysis revealed that the core–shell nanoparticles have carbonyl (C═O) functional groups present. A confirmatory test of amylase reaction on nanoparticle-impregnated paper turns blue to white indicating that the nanoparticle reacts with amylase as an indicator. This paper-based method can be used in future applications in forensic and medical applications.

Here, we demonstrate that the peptidyl-prolyl cis/trans isomerase Pin1 interacts noncovalently with the hepatitis B virus (HBV) core particle through phosphorylated serine/threonine-proline (pS/TP) motifs in the carboxyl-terminal domain (CTD) but not with particle-defective, dimer-positive mutants of HBc. This suggests that neither dimers nor monomers of HBc are Pin1-binding partners. The 162 TP, 164 SP, and 172 SP motifs within the HBc CTD are important for the Pin1/core particle interaction. Although Pin1 dissociated from core particle upon heat treatment, it was detected as an opened-up core particle, demonstrating that Pin1 binds both to the outside and the inside of the core particle. Although the amino-terminal domain S/TP motifs of HBc are not involved in the interaction, 49 SP contributes to core particle stability, and 128 TP might be involved in core particle assembly, as shown by the decreased core particle level of S49A mutant through repeated freeze and thaw and low-level assembly of the T128A mutant, respectively. Overexpression of Pin1 increased core particle stability through their interactions, HBV DNA synthesis, and virion secretion without concomitant increases in HBV RNA levels, indicating that Pin1 may be involved in core particle assembly and maturation, thereby promoting the later stages of the HBV life cycle. By contrast, parvulin inhibitors and PIN1 knockdown reduced HBV replication. Since more Pin1 proteins bound to immature core particles than to mature core particles, the interaction appears to depend on the stage of virus replication. Taken together, the data suggest that physical association between Pin1 and phosphorylated core particles may induce structural alterations through isomerization by Pin1, induce dephosphorylation by unidentified host phosphatases, and promote completion of virus life cycle.

Background Although accumulating evidence suggests that the crosstalk between malignant cells and cancer-associated fibroblasts (CAFs) actively contributes to tumour growth and metastatic dissemination, therapeutic strategies targeting tumour stroma are still not common in the clinical practice. Metal-based nanomaterials have been shown to exert excellent cytotoxic and anti-cancerous activities, however, their effects on the reactive stroma have never been investigated in details. Thus, using feasible in vitro and in vivo systems to model tumour microenvironment, we tested whether the presence of gold, silver or gold-core silver-shell nanoparticles exerts anti-tumour and metastasis suppressing activities by influencing the tumour-supporting activity of stromal fibroblasts. Results We found that the presence of gold-core silver-shell hybrid nanomaterials in the tumour microenvironment attenuated the tumour cell-promoting behaviour of CAFs, and this phenomenon led to a prominent attenuation of metastatic dissemination in vivo as well. Mechanistically, transcriptome analysis on tumour-promoting CAFs revealed that silver-based nanomaterials trigger expressional changes in genes related to cancer invasion and tumour metastasis. Conclusions Here we report that metal nanoparticles can influence the cancer-promoting activity of tumour stroma by affecting the gene expressional and secretory profiles of stromal fibroblasts and thereby altering their intrinsic crosstalk with malignant cells. This potential of metal nanomaterials should be exploited in multimodal treatment approaches and translated into improved therapeutic outcomes.

A complex composed of Pba3-Pba4 and subunits α5, α6, and α7 is identified as an early intermediate in proteasome core particle assembly in wild-type Saccharomyces cerevisiae cells. The same complex can be reconstituted from recombinantly produced components in vitro. Assembly of α6 and α7 with Pba3-Pba4 depends on the presence of the α5 subunit, the binding of which apparently initiates the formation of this intermediate. Our data suggest the following order of events: first, Pba3-Pba4 binds α5, then α6 is incorporated, and at the end α7. In the absence of the chaperones Pba1-Pba2 or Ump1, alternative Pba4-containing complexes are detected, the formation of which depends on the Blm10/PA200 protein. Overexpression of Pba1-Pba2 abolishes the formation of these complexes containing Pba4 and Blm10, suggesting that Blm10 may replace Pba1-Pba2 as an alternative assembly factor.

Human parvulin 14 (Par14) and parvulin 17 (Par17) are peptidyl-prolyl cis/trans isomerases that upregulate hepatitis B virus (HBV) replication by binding to the conserved 133Arg-Pro134 (RP) motif of HBc and core particles, and 19RP20-28RP29 motifs of HBx. In the absence of HBx, Par14/Par17 have no effect on HBV replication. Interaction with Par14/Par17 enhances the stability of HBx, core particles, and HBc. Par14/Par17 binds outside and inside core particles and is involved in HBc dimer–dimer interaction to facilitate core particle assembly. Although HBc RP motif is important for HBV replication, R133 residue is solely important for its interaction with Par14/Par17. Interaction of Par14 and Par17 with HBx involves two substrate-binding residues, Glu46/Asp74 (E46/D74) and E71/D99, respectively, and promotes HBx translocation to the nucleus and mitochondria. In the presence of HBx, Par14/Par17 are efficiently recruited to cccDNA and promote transcriptional activation via specific DNA-binding residues Ser19/44 (S19/44). S19 and E46/D74 of Par14, and S44 and E71/D99 of Par17, are also involved in the recruitment of HBc onto cccDNA. Par14/Par17 upregulate HBV replication via various effects that are mediated in part through the HBx–Par14/Par17–cccDNA complex and triple HBc, Par14/Par17, and cccDNA interactions in the nucleus, as well as via core particle-Par14/Par17 interactions in the cytoplasm.

High sensitizer and activator concentrations have been increasingly examined to improve the performance of multi-color emissive upconversion (UC) nanocrystals (UCNC) like NaYF 4 :Yb,Er and first strategies were reported to reduce concentration quenching in highly doped UCNC. UC luminescence (UCL) is, however, controlled not only by dopant concentration, yet by an interplay of different parameters including size, crystal and shell quality, and excitation power density ( P ). Thus, identifying optimum dopant concentrations requires systematic studies of UCNC designed to minimize additional quenching pathways and quantitative spectroscopy. Here, we quantify the dopant concentration dependence of the UCL quantum yield ( Φ UC ) of solid NaYF 4 :Yb,Er/NaYF 4 :Lu upconversion core/shell nanocrystals of varying Yb 3+ and Er 3+ concentrations (Yb 3+ series: 20%–98% Yb 3+ ; 2% Er 3+ ; Er 3+ series: 60% Yb 3+ ; 2%–40% Er 3+ ). To circumvent other luminescence quenching processes, an elaborate synthesis yielding OH-free UCNC with record Φ UC of ∼9% and ∼25 nm core particles with a thick surface shell were used. High Yb 3+ concentrations barely reduce Φ UC from ∼9% (20% Yb 3+ ) to ∼7% (98% Yb 3+ ) for an Er 3+ concentration of 2%, thereby allowing to strongly increase the particle absorption cross section and UCNC brightness. Although an increased Er 3+ concentration reduces Φ UC from ∼7% (2% Er 3+ ) to 1% (40%) for 60% Yb 3+ . Nevertheless, at very high P (> 1 MW/cm 2 ) used for microscopic studies, highly Er 3+ -doped UCNC display a high brightness because of reduced saturation. These findings underline the importance of synthesis control and will pave the road to many fundamental studies of UC materials.