TASK DEFINITION: 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.
PROBLEM: Several kinds of pressure can lead to the emergence of infectious diseases. In the case of zoonoses emerging from livestock, one of the most significant changes that has taken place since the mid twentieth century is what has been termed the "livestock revolution", whereby the stock of food animals, their productivity and their trade has increased rapidly to feed rising and increasingly wealthy and urbanized populations. Further increases are projected in the future in low and middle-income countries. Using avian influenza as an example, we discuss how the emergence of avian influenza H5N1 and H7N9 in China was linked to rapid intensification of the poultry sector taking place in landscapes rich in wetland agriculture and wild waterfowls habitats, providing an extensive interface with the wild reservoir of avian influenza viruses. Trade networks and live-poultry markets further exacerbated the spread and persistence of avian influenza as well as human exposure. However, as the history of emergence of highly pathogenic avian influenza (HPAI) demonstrates in high-income countries such as the USA, Canada, Australia, the United Kingdom or the Netherlands, this is by no way specific to low and middle-income countries. Many HPAI emergence events took place in countries with generally good biosecurity standards, and the majority of these in regions hosting intensive poultry production systems. Emerging zoonoses are only one of a number of externalities of intensive livestock production systems, alongside antimicrobial consumption, disruption of nutrient cycles and greenhouse gases emissions, with direct or indirect impacts on human health. In parallel, livestock production is essential to nutrition and livelihoods in many low-income countries. Deindustrialization of the most intensive production systems in high-income countries and sustainable intensifications in low-income countries may converge to a situation where the nutritional and livelihood benefits of livestock production would be less overshadowed by its negative impacts on human an ecosystem health.

SOLUTION: Intensifying poultry production systems and the emergence of avian influenza in China: a 'One Health/Ecohealth' epitome

PROBLEM: Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (,2-3-fold) of anti-SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (,10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.

SOLUTION: A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination

PROBLEM: Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CL pro ) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CL pro of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CL pro and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CL pro in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CL pro and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CL pro . Finally, we explored the substrate specificity of PEDV 3CL pro at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CL pro substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.

SOLUTION:
Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376