Recombinant linear multiple epitopes of σB protein protect Muscovy ducks against novel duck reovirus infection.

Infection by the novel duck reovirus (NDRV) in ducklings causes high mortality, which leads to substantial economic losses in the duck industry in China. To date, no commercial vaccine is available for this disease. In this study, linear B cell epitopes of the σB protein of the NDRV were predicted and recombinant multiple linear B cell epitopes (MLBEs) were constructed through linkers. The recombinant MLBEs were then expressed and purified. One-day-old Muscovy ducklings were immunized with different doses of MLBEs and challenged with 5 × 104 ELD50 of the virulent CHY strain of NDRV 14 days after immunization. The ducklings vaccinated with 20 and 40 µg of MLBE performed no clinical signs or gross or histopathological lesions, indicating 100% protection against infection. The viral load in the liver and spleens of these birds was significantly lower than that in the control group. Additionally, these ducklings exhibited positive seroconversion at 7 days after vaccination on enzyme-linked immunosorbent assay. These results indicate that MLBE of σB could be used as a candidate for developing vaccines against NDRV infection.

Development of a rapid quantitative method to differentiate MS1 vaccine strain from wild-type Mycoplasma synoviae.

Mycoplasma synoviae (MS) is an economically important pathogen in the poultry industry. Vaccination is an effective method to prevent and control MS infections. Currently two live attenuated MS vaccines are commercially available, the temperature-sensitive MS-H vaccine strain and the NAD-independent MS1 vaccine strain. Differentiation of vaccine strains from wild-type (WT) strains is crucial for monitoring MS infection, especially after vaccination. In this study, we developed a Taqman duplex real-time polymerase chain reaction (PCR) method to identify MS1 vaccine strains from WT strains. The method was specific and did not cross-react with other avian pathogens. The sensitivity assay indicated that no inhibition occurred between probes or between mixed and pure templates in duplex real-time PCR. Compared with the melt-based mismatch amplification mutation assay (MAMA), our method was more sensitive and rapid. In conclusion, the Taqman duplex real-time PCR method is a useful method for the diagnosis and differentiation of WT-MS and MS1 vaccine strains in a single reaction.

Hippocampal ferroptosis is involved in learning and memory impairment in rats induced by microwave and electromagnetic pulse combined exposure.

Microwave (MW) and electromagnetic pulse (EMP) are considered environmental pollutants, both of which can induce learning and memory impairments. However, the bioeffects of combined exposure to MW and EMP have never been explored. This paper aimed to investigate the effects of combined exposure to MW and EMP on the learning and memory of rats as well as its association with ferroptosis in the hippocampus. In this study, rats were exposed to EMP, MW, or EMP and MW combined radiation. After exposure, impairment of learning and memory, alterations in brain electrophysiological activity, and damage to hippocampal neurons were observed in rats. Moreover, we also found alterations in ferroptosis hallmarks, including increased levels of iron, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, as well as downregulation of glutathione peroxidase 4 (GPX4) protein in the rat hippocampus after exposure. Our results suggested that either single or combined exposure to MW and EMP radiation could impair learning and memory and damage hippocampal neurons in rats. Moreover, the adverse effects caused by the combined exposure were more severe than the single exposures, which might be due to cumulative effects rather than synergistic effects. Furthermore, ferroptosis in the hippocampus might be a common underlying mechanism of learning and memory impairment induced by both single and combined MW and EMP exposure.

Construction of a scalable DNA computing nano-system for large-scale and complex logical operations.

The predictability of Watson-Crick base pairing provides unique structural programmability to DNA, facilitating the development and application of biomolecules in biocomputing. However, in DNA-based biocomputing, the scale of operation that can be achieved by an existing reaction system is very limited. How to expand the operation range of a logic circuit and realize the integration and extensibility of circuits is always the key problem to be solved in this field. In this work, by designing a multifunctional DNA-nanostructure-based reaction platform, which can realize an output of up to 2n scalable fluorescence signals, combined with the construction of an input "library" and a modular distribution strategy of output signals, for the first time, we successfully performed the calculation of both square roots and cube roots of consecutive integers within a decimal number of "10" and in each result of the operation, two digits after the decimal point are preserved (). We believe that the design concept presented in this work can help effectively solve the urgent problems of biological computing in terms of computational scaling, integration and scalability, and can open up new horizons for the design of new functional devices and complex computing circuits.

Effect of Volume Fraction of Reinforcement on Microstructure and Mechanical Properties of In Situ (Ti, Nb)B/Ti2AlNb Composites with Tailored Three-Dimensional Network Architecture.

The mechanical properties of (Ti, Nb)B/Ti2AlNb composites were expected to improve further by utilizing spark plasma sintering (SPS) and inducing the novel three-dimensional network architecture. In this study, (Ti, Nb)B/Ti2AlNb composites with the novel architecture were successfully fabricated by ball milling the LaB6 and Ti2AlNb mixed powders and subsequent SPS consolidation. The influence of the (Ti, Nb)B content on the microstructure and mechanical properties of the composites was revealed by using the scanning electron microscope (SEM), transmission electron microscopy (TEM) and electronic universal testing machine. The microstructural characterization demonstrated that the boride crystallized into a B27 structure and the α2-precipitated amount increased with the (Ti, Nb)B increasing. When the (Ti, Nb)B content reached 4.9 vol%, both the α2 and reinforcement exhibited a continuous distribution along the prior particle boundaries (PPBs). The tensile test displayed that the tensile strength of the composites presented an increasing trend with the increasing (Ti, Nb)B content followed by a decreasing trend. The composite with a 3.2 vol% reinforcement had the optimal mechanical properties; the yield strengths of the composite at 25 and 650 °C were 998.3 and 774.9 MPa, showing an 11.8% and 9.2% improvement when compared with the Ti2AlNb-based alloy. Overall, (Ti, Nb)B possessed an excellent strengthening effect and inhibited the strength weakening of the PPBs area at high temperatures; the reinforcement content mainly affected the mechanical properties of the (Ti, Nb)B/Ti2AlNb composites by altering the α2-precipitated amount and the morphology of (Ti, Nb)B in the PPBs area. Both the continuous precipitation of the brittle α2 phase and the agglomeration of the (Ti, Nb)B reinforcement dramatically deteriorated the mechanical properties.

Lipid Peroxides Mediated Ferroptosis in Electromagnetic Pulse-Induced Hippocampal Neuronal Damage via Inhibition of GSH/GPX4 Axis.

Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.

Gut microbiome is associated with the clinical response to anti-PD-1 based immunotherapy in hepatobiliary cancers.

BACKGROUND: The gut microbiome is associated with the response to immunotherapy for different cancers. However, the impact of the gut microbiome on hepatobiliary cancers receiving immunotherapy remains unknown. This study aims to investigate the relationship between the gut microbiome and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced hepatobiliary cancers. METHODS: Patients with unresectable hepatocellular carcinoma or advanced biliary tract cancers who have progressed from first-line chemotherapy (gemcitabine plus cisplatin) were enrolled. Fresh stool samples were collected before and during anti-PD-1 treatment and analyzed with metagenomic sequencing. Significantly differentially enriched taxa and prognosis associated taxa were identified. The Kyoto Encyclopedia of Genes and Genomes database and MetaCyc database were further applied to annotate the differentially enriched taxa to explore the potential mechanism of the gut microbiome influencing cancer immunotherapy. RESULTS: In total, 65 patients with advanced hepatobiliary cancers receiving anti-PD-1 treatment were included in this study. Seventy-four taxa were significantly enriched in the clinical benefit response (CBR) group and 40 taxa were significantly enriched in the non-clinical benefit (NCB) group. Among these taxa, patients with higher abundance of Lachnospiraceae bacterium-GAM79 and Alistipes sp Marseille-P5997, which were significantly enriched in the CBR group, achieved longer progression-free survival (PFS) and overall survival (OS) than patients with lower abundance. Higher abundance of Ruminococcus calidus and Erysipelotichaceae bacterium-GAM147 enriched in the CBR group was also observed in patients with better PFS. In contrast, worse PFS and OS were found in patients with higher abundance of Veillonellaceae, which was significantly enriched in the NCB group. Functional annotation indicated that the taxa enriched in the CBR group were associated with energy metabolism while the taxa enriched in the NCB group were associated with amino acid metabolism, which may modulate the clinical response to immunotherapy in hepatobiliary cancers. In addition, immunotherapy-related adverse events were affected by the gut microbiome diversity and relative abundance. CONCLUSIONS: We demonstrate that the gut microbiome is associated with the clinical response to anti-PD-1 immunotherapy in patients with hepatobiliary cancers. Taxonomic signatures enriched in responders are effective biomarkers to predict the clinical response and survival benefit of immunotherapy, which might provide a new therapeutic target to modulate the response to cancer immunotherapy.

Spark Plasma Sintering of AlN/Al Functionally Graded Materials.

In this paper, six-layer AlN/Al gradient composites were prepared by a spark plasma sintering process to study the influences of sintering temperature and holding time on the microstructure and mechanical properties. The well-bonded interface enables the composite to exhibit excellent thermal and mechanical properties. The hardness and thermal expansion properties of the composite exhibit a gradient property. The hardness increased with the volume fraction of AlN while the CTE decreased as the volume fraction of AlN. The thermal expansion reaches the lowest value of 13-14 ppm/K, and the hardness reaches the maximum value of 1.25 GPa, when the target volume fraction of AlN is 45%. The simulation results show that this gradient material can effectively reduce the thermal stress caused by the mismatch of the thermal expansion coefficient as a transmitter and receiver (T/R) module. This paper attempts to provide experimental support for the preparation of gradient Al matrix composites.

Role of oncogene PIM-1 in the development and progression of papillary thyroid carcinoma: Involvement of oxidative stress.

In this study, we aimed to clarify the role of PIM-1 in papillary thyroid carcinoma (PTC) in vitro and investigate the relationship between PIM-1 and redox proteins (NOX4, SOD2, and GPX2) at the tissue and cellular levels. As a PIM-1 inhibitor, SGI-1776 inhibited cell proliferation, colony formation, migration and induced an increase in apoptosis and reactive oxygen species in two PTC cell lines (BCPAP and TPC-1). The expressions of PIM-1, SOD2 and GPX2 were downregulated after siNOX4 exposure. Immunohistochemistry in 120 PTC patients showed that all four proteins exhibited higher expression levels in PTC tissues than in adjacent normal tissues. PIM-1 expression was related to NOX4, SOD2, and GPX2 expressions. The Cancer Genome Atlas database analysis showed the significant correlation between the expression of NOX4 and PIM-1. Our results demonstrated that PIM-1 played an important oncogenic role in PTC carcinogenesis that may be related to oxidative stress.

Self-assembly of a layered two-dimensional molecularly woven fabric.

Fabrics-materials consisting of layers of woven fibres-are some of the most important materials in everyday life1. Previous nanoscale weaves2-16 include isotropic crystalline covalent organic frameworks12-14 that feature rigid helical strands interlaced in all three dimensions, rather than the two-dimensional17,18 layers of flexible woven strands that give conventional textiles their characteristic flexibility, thinness, anisotropic strength and porosity. A supramolecular two-dimensional kagome weave15 and a single-layer, surface-supported, interwoven two-dimensional polymer16 have also been reported. The direct, bottom-up assembly of molecular building blocks into linear organic polymer chains woven in two dimensions has been proposed on a number of occasions19-23, but has not previously been achieved. Here we demonstrate that by using an anion and metal ion template, woven molecular 'tiles' can be tessellated into a material consisting of alternating aliphatic and aromatic segmented polymer strands, interwoven within discrete layers. Connections between slowly precipitating pre-woven grids, followed by the removal of the ion template, result in a wholly organic molecular material that forms as stacks and clusters of thin sheets-each sheet up to hundreds of micrometres long and wide but only about four nanometres thick-in which warp and weft single-chain polymer strands remain associated through periodic mechanical entanglements within each sheet. Atomic force microscopy and scanning electron microscopy show clusters and, occasionally, isolated individual sheets that, following demetallation, have slid apart from others with which they were stacked during the tessellation and polymerization process. The layered two-dimensional molecularly woven material has long-range order, is birefringent, is twice as stiff as the constituent linear polymer, and delaminates and tears along well-defined lines in the manner of a macroscopic textile. When incorporated into a polymer-supported membrane, it acts as a net, slowing the passage of large ions while letting smaller ions through.

Effects of turn-structure on folding and entanglement in artificial molecular overhand knots.

The length and constitution of spacers linking three 2,6-pyridinedicarboxamide units in a molecular strand influence the tightness of the resulting overhand (open-trefoil) knot that the strand folds into in the presence of lanthanide(iii) ions. The use of ß-hairpin forming motifs as linkers enables a metal-coordinated pseudopeptide with a knotted tertiary structure to be generated. The resulting pseudopeptide knot has one of the highest backbone-to-crossing ratios (BCR)-a measure of knot tightness (a high value corresponding to looseness)-for a synthetic molecular knot to date. Preorganization in the crossing-free turn section of the knot affects aromatic stacking interactions close to the crossing region. The metal-coordinated pseudopeptide knot is compared to overhand knots with other linkers of varying tightness and turn preorganization, and the entangled architectures characterized by NMR spectroscopy, ESI-MS, CD spectroscopy and, in one case, X-ray crystallography. The results show how it is possible to program specific conformational properties into different key regions of synthetic molecular knots, opening the way to systems where knotting can be systematically incorporated into peptide-like chains through design.

ENdb: a manually curated database of experimentally supported enhancers for human and mouse.

Enhancers are a class of cis-regulatory elements that can increase gene transcription by forming loops in intergenic regions, introns and exons. Enhancers, as well as their associated target genes, and transcription factors (TFs) that bind to them, are highly associated with human disease and biological processes. Although some enhancer databases have been published, most only focus on enhancers identified by high-throughput experimental techniques. Therefore, it is highly desirable to construct a comprehensive resource of manually curated enhancers and their related information based on low-throughput experimental evidences. Here, we established a comprehensive manually-curated enhancer database for human and mouse, which provides a resource for experimentally supported enhancers, and to annotate the detailed information of enhancers. The current release of ENdb documents 737 experimentally validated enhancers and their related information, including 384 target genes, 263 TFs, 110 diseases and 153 functions in human and mouse. Moreover, the enhancer-related information was supported by experimental evidences, such as RNAi, in vitro knockdown, western blotting, qRT-PCR, luciferase reporter assay, chromatin conformation capture (3C) and chromosome conformation capture-on-chip (4C) assays. ENdb provides a user-friendly interface to query, browse and visualize the detailed information of enhancers. The database is available at http://www.licpathway.net/ENdb.

Packet error rate analysis of OOK, DPIM, and PPM modulation schemes for ground-to-satellite laser uplink communications.

Performance of on-off keying (OOK), digital pulse interval modulation (DPIM), and pulse position modulation (PPM) schemes are researched for ground-to-satellite laser uplink communications. Packet error rates of these modulation systems are compared, with consideration of the combined effect of intensity fluctuation and beam wander. Based on the numerical results, performances of different modulation systems are discussed. Optimum divergence angle and transmitted beam radius of different modulation systems are indicated and the relations of the transmitted laser power to them are analyzed. This work can be helpful for modulation scheme selection and system design in ground-to-satellite laser uplink communications.

Pointing error due to temperature distribution of SiC reflectors in intersatellite laser communications.

Wave-front aberrations due to thermal deformation of elliptical reflectors in periscopic laser communication terminals are studied, and are fitted by Zernike elliptical polynomials. The relationship between pointing error and temperature distribution of elliptical reflectors in intersatellite laser communication systems is researched. The back-fixing method is introduced for fixing the elliptical reflectors, and is proven to reduce pointing error compared to the traditional around-fixing method using a press board. It is shown that the difference between uniform temperature and reference temperature has a much stronger influence than the temperature gradient. For the back-fixing method, the pointing error changes periodically as the uniform temperature changes with a period value of 1.6 degrees C, and the maximum pointing error value is 16.7murad. The result also tells us that, if the difference between uniform temperature and reference temperature is within 1.0 degrees C, there is no pointing error caused by back-fixed reflectors. We hope this work can contribute to the thermal control of elliptical reflectors in intersatellite laser communication terminals.