Expression of Raf kinase inhibitor protein is downregulated in response to Newcastle disease virus infection to promote viral replication.

Newcastle disease virus (NDV) causes a severe and economically significant disease affecting almost the entire poultry industry worldwide. However, factors that affect NDV replication in host cells are poorly understood. Raf kinase inhibitory protein (RKIP) is a physiological inhibitor of c-RAF kinase and NF-κB signalling, known for their functions in the control of immune response as well as tumour invasion and metastasis. In the present study, we investigated the consequences of overexpression of host RKIP during viral infection. We demonstrate that NDV infection represses RKIP expression thereby promoting virus replication. Experimental upregulation of RKIP in turn acts as a potential antiviral defence mechanism in host cells that restricts NDV replication by repressing the activation of Raf/MEK/ERK and IκBα/NF-κB signalling pathways. Our results not only extend the concept of linking NDV-host interactions, but also reveal RKIP as a new class of protein-kinase-inhibitor protein that affects NDV replication with therapeutic potential.

High Genetic Diversity of Newcastle Disease Virus in Wild and Domestic Birds in Northeastern China from 2013 to 2015 Reveals Potential Epidemic Trends.

Newcastle disease (ND), caused by the virulent Newcastle disease virus (NDV), is one of the most important viral diseases of birds globally, but little is currently known regarding enzootic trends of NDV in northeastern China, especially for class I viruses. Thus, we performed a surveillance study for NDV in northeastern China from 2013 to 2015. A total 755 samples from wild and domestic birds in wetlands and live bird markets (LBMs) were collected, and 10 isolates of NDV were identified. Genetic and phylogenetic analyses showed that five isolates from LBMs belong to class I subgenotype 1b, two (one from wild birds and one from LBMs) belong to the vaccine-like class II genotype II, and three (all from wild birds) belong to class II subgenotype Ib. Interestingly, the five class I isolates had epidemiological connections with viruses from southern, eastern, and southeastern China. Our findings, together with recent prevalence trends of class I and virulent class II NDV in China, suggest possible virus transmission between wild and domestic birds and the potential for an NDV epidemic in the future.

Research progress on post-stroke depression.

Stroke is a highly prevalent and widely detrimental cardiovascular disease, frequently resulting in impairments of both motor function and neural psychological capabilities, such as post-stroke depression (PSD). PSD is the most prevalent neuropsychological disorder among stroke patients, characterized by persistent emotional lowness and diminished interest as its primary features. This article summarizes the mechanism research, animal models and related treatments of PSD. Further improvements are needed in the screening of research subjects and the construction of animal models in the study of PSD. At the same time, in the study of the mechanism of PSD, we need to consider the interaction between multiple systems. The treatment of PSD requires more careful consideration. This can help us to find something new in the study of the mechanism of complex PSD, which provides a new direction for us to develop new treatment delivery.

Deep-Blue Perovskite Light-Emitting Diodes Realized by a Dynamic Interfacial Ion Exchange.

The external quantum efficiency (EQE) of the sky-blue perovskite light-emitting diodes (PeLEDs) has reached 18.65%. However, the EQE of the deep-blue PeLEDs is still inferior to that of sky-blue PeLEDs, which restricts the PeLED application in displays. Herein, a novel dynamic interfacial ion-exchange technique is developed to obtain deep-blue PeLEDs. By spin-coating quaternary ammonium chloride on top of a quasi-2D green perovskite film, a 68 nm spectral transition from green light emission at 513 nm to deep-blue light emission at 445 nm has been successfully realized. To the best of our knowledge, it is the largest spectrum transition ever achieved. By further introducing tricyclohexylphosphine oxide into the perovskite precursor solution to passivate defects, high-quality deep-blue PeLEDs have been fabricated with color coordinates at (0.13, 0.06). The maximum EQE reaches 1.8%, and the peak luminance reaches 847 cd/m2.

Aging-associated changes in CD47 arrangement and interaction with thrombospondin-1 on red blood cells visualized by super-resolution imaging.

CD47 serves as a ligand for signaling regulatory protein α (SIRPα) and as a receptor for thrombospondin-1 (TSP-1). Although CD47, TSP-1, and SIRPα are thought to be involved in the clearance of aged red blood cells (RBCs), aging-associated changes in the expression and interaction of these molecules on RBCs have been elusive. Using direct stochastic optical reconstruction microscopy (dSTORM)-based imaging and quantitative analysis, we can report that CD47 molecules on young RBCs reside as nanoclusters with little binding to TSP-1, suggesting a minimal role for TSP-1/CD47 signaling in normal RBCs. On aged RBCs, CD47 molecules decreased in number but formed bigger and denser clusters, with increased ability to bind TSP-1. Exposure of aged RBCs to TSP-1 resulted in a further increase in the size of CD47 clusters via a lipid raft-dependent mechanism. Furthermore, CD47 cluster formation was dramatically inhibited on thbs1-/- mouse RBCs and associated with a significantly prolonged RBC lifespan. These results indicate that the strength of CD47 binding to its ligand TSP-1 is predominantly determined by the distribution pattern and not the amount of CD47 molecules on RBCs, and offer direct evidence for the role of TSP-1 in phagocytosis of aged RBCs. This study provides clear nanoscale pictures of aging-associated changes in CD47 distribution and TSP-1/CD47 interaction on the cell surface, and insights into the molecular basis for how these molecules coordinate to remove aged RBCs.

A Raf kinase inhibitor demonstrates antiviral activities both in vitro and in vivo against different genotypes of virulent Newcastle disease virus.

Newcastle disease (ND) is still one of the major plagues of birds worldwide. Combat actions are limited to vaccines, highlighting the urgent need for new and amply available antiviral drugs. Previous results have shown that Newcastle disease virus (NDV) downregulates the intracellular Raf kinase inhibitor protein (RKIP) expression for efficient replication, suggesting that this molecular may be a suitable target for antiviral intervention. In the present work, we investigated whether or not the Raf kinase inhibitor V (RKIV), which functions in the same way as RKIP by targeting the intracellular Raf kinase, is able to suppress the propagation of enzootic virulent NDV in vitro and in vivo. In vitro antiviral activity of RKIV was assessed by cell-based assay, and in vivo activity was determined in the chicken model. Our results clearly showed that RKIV treatment protected the cells from NDV-induced CPE with the effective concentrations on nM level, and inhibited virus replication in the lungs of infected chickens in a dose-dependent manner and protected chickens from the lethal infection by NDV. Thus, we conclude that the Raf kinase inhibitor compound RKIV, by inhibiting the host cellular target Raf kinase, might be very promising as a new class of antivirals against the enzootic virulent NDV infection.