A clinically attenuated double-mutant of porcine reproductive and respiratory syndrome virus-2 that does not prompt overexpression of proinflammatory cytokines during co-infection with a secondary pathogen.

Porcine reproductive and respiratory syndrome virus (PRRSV) is known to suppress the type I interferon (IFNs-α/ß) response during infection. PRRSV also activates the NF-κB signaling pathway, leading to the production of proinflammatory cytokines during infection. In swine farms, co-infections of PRRSV and other secondary bacterial pathogens are common and exacerbate the production of proinflammatory cytokines, contributing to the porcine respiratory disease complex (PRDC) which is clinically a severe disease. Previous studies identified the non-structural protein 1ß (nsp1ß) of PRRSV-2 as an IFN antagonist and the nucleocapsid (N) protein as the NF-κB activator. Further studies showed the leucine at position 126 (L126) of nsp1ß as the essential residue for IFN suppression and the region spanning the nuclear localization signal (NLS) of N as the NF-κB activation domain. In the present study, we generated a double-mutant PRRSV-2 that contained the L126A mutation in the nsp1ß gene and the NLS mutation (ΔNLS) in the N gene using reverse genetics. The immunological phenotype of this mutant PRRSV-2 was examined in porcine alveolar macrophages (PAMs) in vitro and in young pigs in vivo. In PAMs, the double-mutant virus did not suppress IFN-ß expression but decreased the NF-κB-dependent inflammatory cytokine productions compared to those for wild-type PRRSV-2. Co-infection of PAMs with the mutant PRRSV-2 and Streptococcus suis (S. suis) also reduced the production of NF-κB-directed inflammatory cytokines. To further examine the cytokine profiles and the disease severity by the mutant virus in natural host animals, 6 groups of pigs, 7 animals per group, were used for co-infection with the mutant PRRSV-2 and S. suis. The double-mutant PRRSV-2 was clinically attenuated, and the expressions of proinflammatory cytokines and chemokines were significantly reduced in pigs after bacterial co-infection. Compared to the wild-type PRRSV-2 and S. suis co-infection control, pigs coinfected with the double-mutant PRRSV-2 exhibited milder clinical signs, lower titers and shorter duration of viremia, and lower expression of proinflammatory cytokines. In conclusion, our study demonstrates that genetic modification of the type I IFN suppression and NF-κB activation functions of PRRSV-2 may allow us to design a novel vaccine candidate to alleviate the clinical severity of PRRS-2 and PRDC during bacterial co-infection.

Lossless Spin-Orbit Torque in Antiferromagnetic Topological Insulator MnBi_{2}Te_{4}.

We formulate and quantify the spin-orbit torque (SOT) in intrinsic antiferromagnetic topological insulator MnBi_{2}Te_{4} of a few septuple-layer thick in charge-neutral condition, which exhibits pronounced layer-resolved characteristics and even-odd contrast. Contrary to traditional current-induced torques, our SOT is not accompanied by Ohm's currents, thus being devoid of Joule heating. We study the SOT-induced magnetic resonances, where in the tri-septuple-layer case we identify a peculiar exchange mode that is blind to microwaves but can be exclusively driven by the predicted SOT. As an inverse effect, the dynamical magnetic moments generate a pure adiabatic current, which occurs concomitantly with the SOT and gives rise to an overall reactance for the MnBi_{2}Te_{4}, enabling a lossless conversion of electric power into magnetic dynamics.

Unidirectional Spin Hall Magnetoresistance in Antiferromagnetic Heterostructures.

Unidirectional spin Hall magnetoresistance (USMR) has been widely reported in the heavy metal/ferromagnet bilayer systems. We observe the USMR in Pt/α-Fe_{2}O_{3} bilayers where the α-Fe_{2}O_{3} is an antiferromagnetic (AFM) insulator. Systematic field and temperature dependent measurements confirm the magnonic origin of the USMR. The appearance of AFM-USMR is driven by the imbalance of creation and annihilation of AFM magnons by spin orbit torque due to the thermal random field. However, unlike its ferromagnetic counterpart, theoretical modeling reveals that the USMR in Pt/α-Fe_{2}O_{3} is determined by the antiferromagtic magnon number with a non-monotonic field dependence. Our findings extend the generality of the USMR which pave the ways for the highly sensitive detection of AFM spin state.

Recent advances in two-dimensional ferromagnetism: strain-, doping-, structural- and electric field-engineering toward spintronic applications.

Since the first report on truly two-dimensional (2D) magnetic materials in 2017, a wide variety of merging 2D magnetic materials with unusual physical characteristics have been discovered and thus provide an effective platform for exploring the associated novel 2D spintronic devices, which have been made significant progress in both theoretical and experimental studies. Herein, we make a comprehensive review on the recent scientific endeavors and advances on the various engineering strategies on 2D ferromagnets, such as strain-, doping-, structural- and electric field-engineering, toward practical spintronic applications, including spin tunneling junctions, spin field-effect transistors and spin logic gate, etc. In the last, we discuss on current challenges and future opportunities in this field, which may provide useful guidelines for scientists who are exploring the fundamental physical properties and practical spintronic devices of low-dimensional magnets.

Suppression of TRIM19 by arterivirus nonstructural protein 1 promotes viral replication.

Tripartite motif (TRIM)-containing proteins are a family of regulatory proteins that can participate in the induction of antiviral cytokines and antagonize viral replication. Promyelocytic leukemia (PML) protein is known as TRIM19 and is a major scaffold protein organizing the PML nuclear bodies (NBs). PML NBs are membrane-less organelles in the nucleus and play a diverse role in maintaining cellular homeostasis including antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV), a member virus of the family Arteriviridae, inhibits type I interferon (IFN) response during infection, and nonstructural protein 1 (nsp1) of the virus has been identified as a potent IFN antagonist. We report that the numbers of PML NBs per nucleus were significantly downregulated during infection of PRRSV. The overexpression of all six isoforms of PML suppressed the PRRSV replication, and conversely, the silencing of PML gene expression enhanced the PRRSV replication. The suppression of PML NBs by the nsp1 protein was common in other member viruses of the family, represented by equine arteritis virus, lactate dehydrogenase elevating virus of mice, and simian hemorrhagic fever virus. Our study unveils a conserved viral strategy in arteriviruses for innate immune evasion.

Mechanical force-induced dispersion of starch nanoparticles and nanoemulsion: Size control, dispersion behaviour, and emulsified stability.

High amylose starch nanoparticles (HS-SNPs) were rapidly synthesised by high-speed circumferential force of homogenisation (3000 and 15,000 rpm) during nanoprecipitation. Morphology and dynamic light scattering analyses showed that HS-SNPs fabricated by stronger circumferential shearing were excellent stabilisers in smaller sizes (20-50 nm). Their aggregates were liable to separate in the aqueous phase with the nano effect under either homogenisation over 6 min or ultrasonication in 2 min. SNP-based nanoemulsion (<200 nm) of high-water fraction was achieved, though the high hydrophilicity of the SNPs were identified by the contact angle. For homogenisation (with 100-2000 nm emulsion size), only time prolongation led to a better dispersion of SNP aggregates. Ultrasonication with periodic cavitation could disintegrate SNP aggregates into micro-aggregates for a stable emulsion system in a short period. In contrast, long-term ultrasound caused simultaneous re-agglomeration and solubilisation of the SNPs, leading to weakened interface barriers and decreased storage stability.

Heat-induced conversion of multiscale molecular structure of natural food nutrients: A review.

Thermal process is the most important way of treating foods. Heat energy inputted into the natural food system induces the depolymerization of multi-scale structures of matrix, and causes the intramolecular and intermolecular interactions of different nutrients. It attacks and breaks the original polymeric molecule structures and the functional properties of macronutrients such as carbohydrates, proteins and lipids. Micronutrients such as vitamins and other novel functional ingredients are also thermally converted. The heat-induced conversions of nutrients are slightly or totally with discrepancy in simple-, simulated- and real-food systems, respectively. Thus, this review aims to extensively summarize the heat-induced structural characteristics, thermal conversion pathways and pyrolysis mechanism of nutrients both in simple and complex food matrices. The structural change of each nutrient and its thermal reaction kinetics depend on the molecule structure and polymeric characteristic of the unit substances in the system.

Arrest of Cell Cycle by Avian Reovirus p17 through Its Interaction with Bub3.

Avian reoviruses (ARV) are a group of poultry pathogens that cause runting and stunting syndrome (RSS), a condition otherwise known as "frozen chicken", which are characterized by dramatically delayed growth in broilers. It has been known that p17, a nonstructural protein encoded by ARV, prohibits cellular proliferation by halting the cell cycle at the G2/M phase, the result of which is directly associated with the typical clinical sign of RSS. Nevertheless, the mechanism by which p17 modulates cell-cycle progression remains largely unknown. Here, we screened the interactome of ectopically expressed p17 through a yeast two-hybrid assay and identified Bub3, a cellular mitotic checkpoint protein, as a binding partner of p17. The infection of the Vero cells by ARV downregulated the Bub3 expression, while the knockdown of Bub3 alleviated the p17-modulated cell-cycle arrest during ARV infection. Remarkably, the suppression of Bub3 by RNAi in the Vero cells significantly reduced the viral mRNA and protein abundance, which eventually led to diminished virus replication. Altogether, our findings reveal that ARV p17 impedes host cell proliferation through a Bub3-dependent cell-cycle arrest, which eventually contributes to efficient virus replication. These results also unveil a hitherto unknown therapeutic target for RSS.

A comprehensive review of cereal germ and its lipids: Chemical composition, multi-objective process and functional application.

Cereal germ (CG), a by-product of grain milling, has drawn much attention in the food industry because of its nutritional and functional advantages. Nowadays, the utilization of cereal germ from animal feeds to foodstuff is a popular trend. CGs have high content of polyunsaturated fatty acids in their lipids (43.9-64.9% of total fatty acids), but they are also induced to oxidative rancidity under the catalytic reaction of enzymes. Chemical and structural properties of lipids in CGs are affected by different treatments. Thermal and non-thermal effects prevent lipid oxidation or promote lipid combination with starch/protein in CG. Thus, the functional properties and final quality of CG are directly changed. In this review, the chemical composition and application of CGs especially the endogenous lipids are summarized and the effects of various processes on CG lipids/matrices are discussed for CG future development.