In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV. Coronaviruses are animal viruses containing an enveloped, positive-sense, single-stranded RNA genome; and include the common cold human coronavirus (CoV)-229E & CoV-OC43, severe acute respiratory syndrome (SARS) CoV, Middle East respiratory syndrome (MERS) CoV, porcine transmissible gastroenteritis virus (TGEV), and murine hepatitis virus (MHV) etc 1-3 . Since the 2003 SARS outbreak (which had a mortality rate of ~10%), novel anti-SARS-CoV treatments have been vigorously pursued. No new cases of SARS have been reported since the 2003 outbreak, but another novel coronavirus (MERS-CoV), this time with a mortality rate of ~35%, came to light in 2012 4 . To date, neither a commercially available vaccine for human coronaviruses nor a specific treatment for SARS-CoV or MERS-CoV is available. Coronaviruses primarily infect the upper respiratory and gastrointestinal tract and induce host inflammation 5 . Nuclear factor κB (NF-κB) activation by coronaviruses is usually responsible for mediating the production of pro-inflammatory cytokines and chemokines and thus plays an important role in the pathogenesis of disease caused by coronaviruses 6, 7 . Inhibition of NF-κB-mediated inflammation induced by coronavirus in mice was reported to increase the survival rate 6 . Thus, NF-κB inhibitors constitute a promising class of antivirals in infections caused by pathogenic coronaviruses. However, targeting NF-κB is limited by intrinsic pathway complexity, cross talk with other pathways, and drug resistance 8 . In addition, many small chemical molecules targeting either viral entry or the intracellular viral life cycle were reported to impart anti-coronavirus activity 2, 9, 10 . Despite these advances, however, SARS-CoV and MERS-CoV remain untreatable diseases for which novel therapies are sought. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 4105 | Tylophorine based compounds, whether isolated from plants, e.g. Asclepiadaceae and Moraceae or chemically synthesized, exert potent anti-coronaviral activities against a variety of coronaviruses including SARS-CoV, MHV, and TGEV 11, 12 , but both the underlying mechanism(s) of this inhibitory effect and the target are unknown. NF-κB is significantly activated after infection by coronaviruses, e.g. TGEV, and MHV etc 6, 7, [13] [14] [15] . Otherwise, coronaviral nucleocapsid (N) protein plays a vital role in the regulation of viral genome replication and host gene transcription 16 . Therefore, the combination treatment for the inhibition of coronavirus per se, e.g. viral genome replication, and blocking cellular NF-κB activation by coronaviruses, is a promising approach for the development of anti-coronavirals. TGEV infected swine testicular (ST) cells constitute a surrogate system for the search and study of potential anti-coronavirus agents 11, 12, 17 . Herein, we report: (1) tylophorine-based compounds exert potent anti-TGEV replication by directly targeting the viral RNA/ribonucleoprotein (RNP) complex for viral replication/synthesis; (2) NF-κB inhibition also leads to anti-TGEV replication; (3) A combination treatment consisting of both a tylophorine compound and an NF-κB inhibitor acts additively or synergically to more effectively and comprehensively inhibit TGEV replication than either (1) or (2) alone.
Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity OPEN

Electron microscopy (EM) allows fast visualization of viruses in a wide range of clinical specimens. Viruses are grouped into families based on their morphology. Viruses from various families look distinctly and these morphological variances are the basis for identification of viruses by EM. The identification to the family level is often sufficient for the clinician or recognition of an unknown infectious agent. Diagnostic EM has two advantages over enzyme-linked immunosorbent assay and nucleic acid amplification tests. After a simple and fast negative staining, EM allows fast morphological identification and differential diagnosis of infectious agents contained in the specimen without the need for special considerations and/or reagents. Nevertheless, EM has the disadvantage of being unsuitable as a screening method. Abbreviations CSF cerebrospinal fluid PBS phosphate-buffered saline ELISA enzyme-linked immunosorbent assay PCR polymerase chain reaction EM electron microscopy PTA phosphotungstic acid IEM immune electron microscopy SARS severe acute respiratory syndrome NAT nucleic acid amplification (techniques) SPIEM solid phase immune electron microscopy NRL/ELM
The Role of Electron Microscopy in the Rapid Diagnosis of Viral Infections -review and Foreign Cell in Clinical Specimens CONTENTS

Part of the dorsal funiculus of the adult male rat (Wistar) spinal cord was treated for I h at the thoracolumbar level by running hot water, at approximately 48-50 ~ C, through a polyethylene tube 2 mm in diameter in contact with the dura. Animals were fixed 1 day to 4 weeks later and the spinal cords were examined by light and electron microscopy. The affected area in the dorsal funiculus was approximately i mm long and less than 1 mm wide at the dorsal surface, and varied from 0.4 to 0.7 mm in depth. Within 3 days after treatment, almost all the myelin sheaths in the affected area were degraded, leaving the axons denuded, and at the same time astrocyte endfeet at the glial limiting membrane were swollen and partly destroyed. Almost all the denuded axons remained intact, exhibiting no noticeable morphological changes. There was evidence of a moderate vasogenic oedema, but minimal signs of haemorrhage in the lesion. Seven days after treatment, many immature Schwann cells but no oligodendrocytes were found between the denuded axons. By 2 weeks many of the denuded axons were remyelinated, and by 4 weeks almost all of those axons located near the pial and per;vascular surfaces had been remyelinated by Schwann cells, while most of those located in the deep and marginal zones bordering the adjoining intact areas were remyelinated by oligodendrocytes. Longitudinal sections revealed that at nodes of Ranvier PNS-type myelin sheaths were apposed by either intact or newly formed CNS-type myelin sheaths. A typical glial limiting rnembrane was not reformed beneath the pial surface, but an inconspicuous one was found between the PNS-and CNS-type fibre areas.

Demyelination and remyelination in the dorsal funiculus of the rat spinal cord after heat injury