Inhibition of porcine deltacoronavirus entry and replication by Cepharanthine.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteropathogenic coronavirus (CoV) that mainly causes acute diarrhea/vomiting, dehydration, and mortality in piglets, possessing economic losses and public health concerns. However, there are currently no proven effective antiviral agents against PDCoV. Cepharanthine (CEP) is a naturally occurring alkaloid used as a traditional remedy for radiation-induced symptoms, but its underlying mechanism of CEP against PDCoV has remained elusive. The aim of this study was to investigate the anti-PDCoV effects and mechanisms of CEP in LLC-PK1 cells. The results showed that the antiviral activity of CEP was based on direct action on cells, preventing the virus from attaching to host cells and virus replication. Importantly, Surface Plasmon Resonance (SPR) results showed that CEP has a moderate affinity to PDCoV receptor, porcine aminopeptidase N (pAPN) protein. AutoDock predicted that CEP can form hydrogen bonds with amino acid residues (R740, N783, and R790) in the binding regions of PDCoV and pAPN. In addition, RT-PCR results showed that CEP treatment could significantly reduce the transcription of ZBP1, cytokine (IL-1ß and IFN-α) and chemokine genes (CCL-2, CCL-4, CCL-5, CXCL-2, CXCL-8, and CXCL-10) induced by PDCoV. Western blot analysis revealed that CEP could inhibit viral replication by inducing autophagy. In conclusion, our results suggest that the anti-PDCoV activity of CEP is not only relies on competing the virus binding with pAPN, but also affects the proliferation of the virus in vitro by downregulating the excessive immune response caused by the virus and inducing autophagy. CEP emerges as a promising candidate for potential anti-PDCoV therapeutic development.

Electrolysis Process-Facilitated Engineering of Primary Particles of Cobalt-Free LiNiO2 for Improved Electrochemical Performance.

The particle morphology of LiNiO2 (LNO), the final product of Co-free high-Ni layered oxide cathode materials, must be engineered to prevent the degradation of electrochemical performance caused by the H2-H3 phase transition. Introducing a small amount of dopant oxides (Nb2O5 as an example) during the electrolysis synthesis of the Ni(OH)2 precursor facilitates the engineering of the primary particles of LNO, which is quick, simple, and inexpensive. In addition to the low concentration of Nb that entered the lattice structure, a combination of advanced characterizations indicates that the obtained LNO cathode material contains a high concentration of Nb in the primary particle boundaries in the form of lithium niobium oxide. This electrolysis method facilitated LNO (EMF-LNO) engineering successfully, reducing primary particle size and increasing particle packing density. Therefore, the EMF-LNO cathode material with engineered morphology exhibited increased mechanical strength and electrical contact, blocked electrolyte penetration during cycling, and reduced the H2-H3 phase transition effects.

Sodium Niobate with a Large Interlayer Spacing: A Fast-Charging, Long-Life, and Low-Temperature Friendly Lithium-Storage Material.

Niobate Li+ -storage anode materials with shear ReO3 crystal structures have attracted intensive attention due to their inherent safety and large capacities. However, they generally suffer from limited rate performance, cyclic stability, and temperature adaptability, which are rooted in their insufficient interlayer spacings. Here, sodium niobate (NaNb13 O33 ) micron-sized particles are developed as a new anode material owning the largest interlayer spacing among the known shear ReO3 -type niobates. The large interlayer spacing of NaNb13 O33 enables very fast Li+ diffusivity, remarkably contributing to its superior rate performance with a 2500 to 125 mA g-1 capacity percentage of 63.2%. Moreover, its large interlayer spacing increases the volume-accommodation capability during lithiation, allowing small unit-cell-volume variations (maximum 6.02%), which leads to its outstanding cyclic stability with 87.9% capacity retention after as long as 5000 cycles at 2500 mA g-1 . Its cyclic stability is the best in the research field of niobate micron-sized particles, and comparable to that of "zero-strain" Li4 Ti5 O12 . At a low temperature of -10 °C, it also exhibits high rate performance with a 1250 to 125 mA g-1 capacity percentage of 65.6%, and even better cyclic stability with 105.4% capacity retention after 5000 cycles at 1250 mA g-1 . These comprehensively good electrochemical results pave the way for the practical application of NaNb13 O33 in high-performance Li+ storage.

Multi-party co-signature scheme based on SM2.

Two-party collaborative signature scheme is an important cryptographic technology for user authentication and data integrity protection when using mobile devices for financial and securities transactions. However, the two-party collaboration scheme has the following shortcomings: firstly, it is not flexible enough, and it requires the collaborating parties to be secure and trusted; secondly, the two-party collaboration security still needs to be improved. Once a hacker obtains the signature private key and collaborative identity of a mobile device, it can construct a legitimate two-party collaborative signature. Third, the application scenario of two-party co-signature is limited and cannot meet the application scenario of multi-device co-signature. For this reason, this paper designs a multi-party collaborative signature scheme based on SM2 digital signature algorithm in the standard "SM2 Elliptic Curve Public Key Cryptography" of GM/T003-2012. This scheme consists of multiple (more than 2) participants to jointly generate the signature group public key and valid signature in an interactive manner, while ensuring that each user cannot know the signature key other than their own during the signing process. We implement this scheme based on the GMP library. The experimental results show that this scheme is not only flexible but also more secure and trustworthy to meet the application scenario of multi-device collaborative signing. In addition, the time for multiple participants to construct signatures in this scheme is similar, and the time for signature verification is less different from that of the original SM2 signature.

Graphene Oxide Nanoparticles Combined with CRISPR/Cas9 System Enable Efficient Inhibition of Pseudorabies Virus.

We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.

Host-virus interactions in PK-15 cells infected with Pseudorabies virus Becker strain based on RNA-seq.

Pseudorabies is a highly contagious viral disease caused by the pseudorabies virus (PRV), and it is one of the most devastating diseases for the swine industry worldwide. However, the host-virus interaction and virus-related host factors at the mRNA level in virus natural host (pig) cells, are not fully understood. Here, we performed time-course RNA sequencing of the PK-15 cells infected with a recombinant strain PRV-Becker-GFP to study the dynamic competition between the host and the virus. At early stage of infection (3 hpi), our results suggested that the activation of cytosolic DNA-sensing pathway and NOD-like receptor signaling pathway might play a role in recognition of PRV, and the activation of NF-kappa B signaling pathway and TNF signaling pathway might be involved in immune response against the virus. However, all these pathways were subsequently inhibited by PRV. Additionally, our data indicated the fatty acid degradation pathway was significantly downregulated during late stage of infection (9 hpi), which was likely to accumulate fatty acids for viral envelope synthesis. Moreover, we verified the expression of 5 representative genes (ALDH1B1, ACAA2, ACSL3, ADH5, and EHHADH) related to fatty acid degradation pathway by RT-qPCR. Overall, our findings provide valuable information to better understand host-virus interactions and the immune escape mechanism of PRV-Becker as a virulent strain, offering novel targets for porcine anti-PRV breeding research and potential clinical treatment.

Fabrication of ß-Phase-Enriched PVDF Sheets for Self-Powered Piezoelectric Sensing.

The fabrication of self-powered pressure sensors based on piezoelectric materials requires flexible piezoelectric generators produced with a continuous, large-scale, and environmentally friendly approach. In this study, continuous poly(vinylidene fluoride) (PVDF) sheets with a higher ß-phase content were facilely fabricated by the melt-extrusion-calendering technique and a PVDF-based piezoelectric generator (PEG) was further assembled. Such a PEG exhibits a remarkable piezoelectric output performance. Moreover, it possesses prominent stability even after working for a long time, exhibiting potential applications for real-time monitoring of various human movements (i.e., hopping, running, and walking) and gait. This work not only provides the possibility of continuous and environmentally friendly fabrication of PVDF sheets with remarkable piezoelectric properties but also paves a new promising pathway for powering portable microelectronic applications without any external power supply.

Testing for mean and correlation changes in microarray experiments: an application for pathway analysis.

BACKGROUND: Microarray experiments examine the change in transcript levels of tens of thousands of genes simultaneously. To derive meaningful data, biologists investigate the response of genes within specific pathways. Pathways are comprised of genes that interact to carry out a particular biological function. Existing methods for analyzing pathways focus on detecting changes in the mean or over-representation of the number of differentially expressed genes relative to the total of genes within the pathway. The issue of how to incorporate the influence of correlation among the genes is not generally addressed. RESULTS: In this paper, we propose a non-parametric rank test for analyzing pathways that takes into account the correlation among the genes and compared two existing methods, Global and Gene Set Enrichment Analysis (GSEA), using two publicly available data sets. A simulation study was conducted to demonstrate the advantage of the rank test method. CONCLUSIONS: The data indicate the advantages of the rank test. The method can distinguish significant changes in pathways due to either correlations or changes in the mean or both. From the simulation study the rank test out performed Global and GSEA. The greatest gain in performance was for the sample size case which makes the application of the rank test ideal for microarray experiments.