Ubiquitination on Lysine 247 of Newcastle Disease Virus Matrix Protein Enhances Viral Replication and Virulence by Driving Nuclear-Cytoplasmic Trafficking.

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding, and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M protein nuclear-cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were analyzed. Here, two types of combined NLSs and NESs were identified within the NDV-M protein. The Herts/33-type M protein was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M protein was retained mostly in the nuclei and showed retarded VLP production. Two critical residues, namely, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, of which its modification regulates the nuclear-cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued LaSota (rLaSota) strains rLaSota-R247K, -S263R, and -double mutation (DM) showed about 2-fold higher hemagglutination (HA) titers and 10-fold higher 50% egg infective dose (EID50) titers than wild-type (wt) rLaSota. Furthermore, the mean death time (MDT) and intracerebral pathogenicity index (ICPI) values of those recombinant viruses were slightly higher than those of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV and even those of all other paramyxoviruses. This information is beneficial for the development of vaccines and therapies for paramyxoviruses. IMPORTANCE Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked Newcastle disease (ND) as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and open up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach for improving paramyxovirus vaccines.

Structural diversity and biological role of the 5' untranslated regions of picornavirus.

The genomic arrangement of most picornavirus of the Picornaviridae family shares a similar monocistronic genomic pattern and a defining organizational feature. A defining feature of picornavirus is the presence of evolutionarily conserved and highly-structured RNA elements in untranslated regions (UTRs) at the genome' 5'and 3' ends, essential for viral replication and translation. Given the diversity and complexity of RNA structure and the limitations of molecular biology techniques, the functional characterization and biological significance of UTRs remain to be fully elucidated, especially for 5' UTR. Here, we summarize the current knowledge of the 5' UTR of picornavirus. This review focuses on the structural characterization and the biological function of the RNA secondary and tertiary structures in the 5' UTR of picornavirus. Understanding the role of the 5' UTR of picornavirus can provide a deep insight into the viral replication cycle and pathogenic mechanisms.

Cu2-x Sx Capped AuCu Nanostars for Efficient Plasmonic Photothermal Tumor Treatment in the Second Near-Infrared Window.

Plasmonic nanohybrids are promising photo energy conversion materials in photoelectronics and biomedicine, due to their unique surface plasmon resonance (SPR). Au and Cu2-x Sx nanostructures with strong SPR in the near-infrared (NIR) spectral region are classic plasmonic systems used to convert NIR photons into heat for photothermal therapy (PTT). The rational design of the Au/Cu2-x Sx nanohybrids is expected to induce better photothermal conversion; however, the construction of such hybrids via wet-chemistry methods with a well-controlled interfacial structure is still challenging. Here, the synthesis of an AuCu Star/Cu2-x Sx nanohybrid is reported, where the Cu2-x Sx components are selectively grown on the AuCu nanostar tips to form "caps". The spatial formation of the Cu2-x Sx caps on star tips is mainly governed by surfactant concentration, tip curvature, and experimental manipulation. The nanohybrids show low cytotoxicity and superior photothermal conversion efficiency, enabling robust PTT to kill cancer cells in the second NIR window. Numerical simulation reveals that the coupling of Cu2-x Sx on nanostar tips generates strong interfacial electric field, improving photothermal conversion. Moreover, the spatial separation structure favors the continuous flow of hot charge carriers to produce active radicals, further promoting the tumor treatment effect.

Bifunctional Single-Atom Cobalt Electrocatalysts with Dense Active Sites Prepared via a Silica Xerogel Strategy for Rechargeable Zinc-Air Batteries.

The N-doped cobalt-based (Co) bifunctional single atom catalyst (SAC) has emerged as one of the most promising candidates to substitute noble metal-based catalysts for highly efficient bifunctionality. Herein, a facile silica xerogel strategy is elaborately designed to synthesize uniformly dispersed and dense Co-Nx active sites on N-doped highly porous carbon networks (Co-N-C SAC) using economic biomass materials. This strategy promotes the generation of massive mesopores and micropores for substantially improving the formation of Co-Nx moieties and unique network architecture. The Co-N-C SAC electrocatalysts exhibit an excellent bifunctional activity with a potential gap (ΔE) of 0.81 V in alkaline medias, outperforming those of the most highly active bifunctional electrocatalysts. On top of that, Co-N-C SAC also possesses outstanding performance in ZABs with superior power density/specific capacity. This proposed synthetic method will provide a new inspiration for fabricating various high-content SACs for varied applications.

Establishment of a fetal cow (Bos Borus) skin fibroblasts cell line with immortalized characterization through human telomerase reverse transcriptase (hTERT) ectopic expression.

The ectopic introduction of the human telomerase reverse transcriptase (hTERT) is an effective way to establish an immortalized cell line. Here, hTERT was obtained by RT-PCR, and the eukaryotic expression plasmid and lentivirus shuttle plasmid of hTERT was successfully constructed by the homologous recombination method. The stable expression of hTERT in fetal cow skin fibroblasts (CSF) was established using the lentivirus package system. The hTERT-CSF proliferate and have immortalized characteristics. Meanwhile, the chromosome analysis identified that the number and structure of the hTERT-CSF genome maintain stable. The indirect immunofluorescence, western blot, and flow cytometry showed that the hTERT gene had been successfully integrated into the primary genome of bovine skin and stably expressed. The viral infection experiment first identifies the hTERT-CSF as a vulnerable cell model responding to the Lumpy skin disease virus (LSDV). Establishing hTERT-CSF provides an important cell model for basic and applied research, clinical application, and vaccine development. It provides an essential reference for the future's rapid establishment of other immortalized cell lines.

Enhancement of Scattering and Near Field of TiO2-Au Nanohybrids Using a Silver Resonator for Efficient Plasmonic Photocatalysis.

Recently, localized surface plasmon resonances (SPRs) of metallic nanoparticles (NPs) have been widely used to construct plasmonic nanohybrids for heterogeneous photocatalysis. For example, the combination of plasmonic Au NPs and TiO2 provides pure TiO2 visible-light activity. The SPR effect induces an electric field and consequently enhances light scattering and absorption, favoring the transfer of photon energy to hot carriers for catalytic reactions. Numerous approaches have been dedicated to the improvement of SPR absorption in photocatalysts. Here, we have designed a core@shell-satellite nanohybrid catalyst whereby an Ag NP core, as a plasmonic resonator featuring unique dual functions of strong scattering and near-field enhancement, is encapsulated by SiO2 and TiO2 layers in sequence, with Au NPs on the outer surface, Ag@SiO2@TiO2-Au, for efficient plasmonic photocatalysis. By varying the size and number of Ag NP cores, the Au SPR can be tailored over the visible and near-infrared spectral region to reabsorb the scattered photons. In the presence of the Ag core, the incident light is efficiently confined in the reaction suspension by undergoing multiple scattering, thus leading to an increase of the optical path to the photocatalysis. Moreover, using numerical analysis and experimental verifications, we demonstrate that the Ag core also induces a strong near-field enhancement at the Au-TiO2 interface via SPR coupling with Au. Consequently, the activity of the TiO2-Au plasmonic photocatalyst is significantly enhanced, resulting in a high H2 production rate under visible light. Thus, the design of a single structural unit with strong scattering and field enhancement, induced by a plasmonic resonator, is a highly effective strategy to boost photocatalytic activity.

Polymer Nanocomposite-based Coatings for Corrosion Protection.

Corrosion of metals induces enormous loss of material performance and increase of cost, which has been a common and intractable issue that needs to be addressed urgently. Coating technology has been acknowledged to be the most economic and efficient approach to retard the metal corrosion. For several decades, polymers have been recognized as an effective anticorrosion coating material in both industries and scientific communities, as they demonstrate good barrier properties, ease of altering properties and massive production. Nanomaterials show distinctively different physical and chemical properties compared with their bulk counterparts, which have been considered as highly promising functional materials in various applications, impacting virtually all the fields of science and technologies. Recently, the introduction of nanomaterials with various properties into polymer matrix to form a polymer nanocomposite has been devoted to improve anticorrosive ability of polymer coatings. In this review article, we highlight the recent advances and synopsis of these high-performance polymer nanocomposites as anticorrosive coating materials. We expect that this work could be helpful for the researchers who are interested in the development of functional nanomaterials and advanced corrosion protection technology.