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.
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Question: Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3-5 days post inoculation (dpi) and in the kidney at 8 dpi, with heavy viral loads at 1-11 and 1-28 dpi, respectively. The expression of mRNAs encoding Toll-like receptor (TLR) 3 and TLR7 were upregulated at 3-8 dpi, and that of TIR-domain-containing adapter-inducing interferon (IFN) β (TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88 (MyD88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor (TRAF) 3 and TRAF6 were upregulated expression in both tissues. Moreover, melanoma differentiation-associated protein 5 (MDA5), laboratory of genetics and physiology 2 (LGP2), stimulator of IFN genes (STING), and mitochondrial antiviral signaling protein (MAVS), as well as TANK binding kinase 1 (TBK1), inhibitor of kappaB kinase (IKK) ԑ, IKKα, IKKβ, IFN regulatory factor (IRF) 7, nuclear factor of kappaB (NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β (MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally, consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.

Answer: Responses of the Toll-like receptor and melanoma differentiation- associated protein 5 signaling pathways to avian infectious bronchitis virus infection in chicks


Question: Thread-based microfluidics Point-of-care Cotton Colorimetric Electrochemical A B S T R A C T Over the past decades, researchers have been seeking attractive substrate materials to keep microfluidics improving to outbalance the drawbacks and issues. Cellulose substrates, including thread, paper and hydrogels are alternatives due to their distinct structural and mechanical properties for a number of applications. Thread have gained considerable attention and become promising powerful tool due to its advantages over paper-based systems thus finds numerous applications in the development of diagnostic systems, smart bandages and tissue engineering. To the best of our knowledge, no comprehensive review articles on the topic of thread-based microfluidics have been published and it is of significance for many scientific communities working on Microfluidics, Biosensors and Lab-on-Chip. This review gives an overview of the advances of thread-based microfluidic diagnostic devices in a variety of applications. It begins with an overall introduction of the fabrication followed by an in-depth review on the detection techniques in such devices and various applications with respect to effort and performance to date. A few perspective directions of thread-based microfluidics in its development are also discussed. Thread-based microfluidics are still at an early development stage and further improvements in terms of fabrication, analytical strategies, and function to become low-cost, low-volume and easy-to-use pointof-care (POC) diagnostic devices that can be adapted or commercialized for real world applications.

Answer: Recent advances in thread-based microfluidics for diagnostic applications


Question: and subtropical countries and is a significant public health concern and socioeconomic burden. There is an urgent need to develop antivirals that can effectively reduce dengue virus (DENV) replication and decrease viral load. Niclosamide, an antiparasitic drug approved for human use, has been recently identified as an effective antiviral agent against a number of pH-dependent viruses, including flaviviruses. Here, we reveal that neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Specifically, niclosamide-induced endosomal neutralization not only prevents viral RNA replication but also affects the maturation of DENV particles, rendering them non-infectious. We found that niclosamide-induced endosomal neutralization prevented E glycoprotein conformational changes on the virion surface of flaviviruses, resulting in the release of non-infectious immature virus particles with uncleaved pr peptide from host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug. Dengue virus (DENV) represents a major mosquito-borne pathogen responsible for significant public health and socioeconomic burden in large regions of tropical and subtropical countries 1,2 . There are four distinct serotypes, DENV-1 to DENV-4, that are transmitted mainly by mosquitoes of Aedes species, which continuously spread to new geographical areas around the world 3 . The World Health Organization estimates a prevalence of 50-100 million cases of DENV infection per year; however, a recent global estimate study suggested that 390 million DENV infections occur annually, of which 96 million cases have clear symptoms 2 . DENV infection causes a wide range of clinical symptoms, from acute febrile illness (dengue fever) to life-threatening haemorrhagic fever/dengue shock syndrome 1 . To date, clinically approved therapeutic options for treating DENV-infected patients are still lacking. DENV is an enveloped, single-stranded, positive-sense RNA virus that belongs to Flavivirus genus in the family Flaviviridae 4 . The genus Flavivirus comprises many important emerging arboviruses including Japanese encephalitis virus, West Nile virus and Zika virus (ZIKV). Recently, ZIKV infection has emerged as a global public health concern due to its association with newborn microcephaly 5,6 and neurological sequelae such as Guillain-Barré syndrome, meningoencephalitis, and myelitis in infected adults 6-10 . The flavivirus genome is approximately 11 kb in length and encodes a polyprotein that is processed into three structural (capsid [C], premembrane [prM], and envelope [E]) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, www.nature.com/scientificreports www.nature.com/scientificreports/ and NS5) by cellular and viral proteases 11,12 . Flavivirus infection is initiated by attachment of the virus to a cellular receptor on the plasma membrane followed by receptor-mediated endocytosis and transportation of viral particles to endosomes 13, 14 . Viral membrane fusion with the endosomal membrane is triggered upon exposure of the virus to the low-pH environment of endosomes, through which the viral genome is released into the cytoplasm 15-19 . Following RNA replication and protein translation, immature virions containing prM proteins are assembled within the endoplasmic reticulum (ER) and mature through passaging the acidic environment of the trans-Golgi network (TGN), wherein E proteins undergo conformational changes and the pr peptides are cleaved by furin endoproteases, after which progeny virions are released from the host cell 20-24 . It is well established that neutralization of the acidic TGN environment prevents furin cleavage, resulting in immature particles containing uncleaved prM proteins [25] [26] [27] . These immature particles are non-infectious since the uncleaved prM peptides block the low-pH-induced conformational changes of the viral E proteins essential for binding to the cell surface as well as membrane fusion of the virus during entry 23, 26, 28, 29 . Thus, several studies have shown that lysosomotropic agents, such as chloroquine, exert modest antiviral effects against pH-dependent viruses, including flaviviruses, by interfering with endosomal fusion and furin-dependent maturation in vivo and in vitro 23,30-32 . Recently, niclosamide, a U.S. Food and Drug Administration (FDA)-approved antiparasitic drug used in humans 33-35 , has been identified as an effective antiviral agent against a number of pH-dependent viruses, such as human rhinoviruses and influenza virus 36 , severe acute respiratory syndrome-coronavirus 37 , Chikungunya virus 38 , and flaviviruses [39] [40] [41] . These studies suggested that the broad antiviral activity of niclosamide is associated with neutralization of endo-lysosomal pH that interferes with pH-dependent membrane fusion which is a critical step for virus entry 36 . In a recent study, Kao et al. 41 , determined the inhibitory role of endosomal deacidification in DENV viral genome replication and uncoating but not in later steps of the viral life cycle. Therefore, the possible effect of niclosamide-induced neutralization of endosomal compartments on later stages of the DENV infectious cycle remains to be elucidated. In this study, we investigated and confirmed that the neutralization of low-pH intracellular compartments by niclosamide affects multiple steps of the DENV infectious cycle. Our data indicate that niclosamide-induced endosomal neutralization prevents viral genome release and replication as well as maturation of DENV particles rendering it non-infectious. Specifically, we found that niclosamide-induced endosomal neutralization blocks conformational changes of E glycoproteins on the virion surface of both DENV and ZIKV, resulting in the release of immature virus particles with uncleaved pr peptide and preventing them from infecting new host cells. Collectively, our findings support the potential application of niclosamide as an antiviral agent against flavivirus infection and highlight a previously uncharacterized mechanism of action of the drug. Scientific RepoRts | (2019) 9:8682 | https://doi.

Answer:
2 convergent Research center for emerging Virus infection