instruction:
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.
question:
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.
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Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity OPEN


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Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. β-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance β-glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of β-glucuronidase could be increased by 2.66-fold via the addition of ISL to a β-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the K m and E a of β-glucuronidase reacting with GL. This study sheds new light on the mechanism of βglucuronidase and helps to make industrial production of GAMG through fermentation feasible. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 12503 |
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Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide OPEN


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The enhancement of hybridization efficiency of deoxyribonucleic acid (DNA) targets using oligonucleotide pre-hybridization is studied on two sequence-inversed micro-arrayed probes. The sequences for pre-hybridizing both oligo and target DNA are designed to be fully complementary with their shared DNA probe in a coaxial stacking configuration; i.e. they hybridize immediately alongside each other along the continuous complement probe strand. The pre-hybridizing oligo and target DNA are differentiated by being labeled with two distinct fluorescent dyes, and the cooperative effect on hybridization efficiency is investigated through the comparison of the stacking and individual hybridization configurations based on the detection signals of the labeling dyes. The results show that the pre-hybridization of a DNA oligo enhances the subsequent hybridization efficiency of the target-DNA coupling onto the same probe. The efficiency is enhanced if the hybridization position occurs at a site close to the substrate surface. #
answer:

Enhancement of target-DNA hybridization efficiency by pre-hybridization on sequence-orientated micro-arrayed probes