Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenuated viruses are capable of infecting principle mosquito vectors, as demonstrated in the laboratory, which in combination with their intrinsic genetic instability could potentially lead to a vaccine virus reversion back to wild-type in nature, followed by introduction and dissemination of potentially dangerous viral strains into new geographic locations. To mitigate this risk we developed a microRNA-targeting approach that selectively restricts replication of flavivirus in the mosquito host. Introduction of sequences complementary to a mosquito-specific mir-184 and mir-275 miRNAs individually or in combination into the 3’NCR and/or ORF region resulted in selective restriction of dengue type 4 virus (DEN4) replication in mosquito cell lines and adult Aedes mosquitos. Moreover a combined targeting of DEN4 genome with mosquito-specific and vertebrate CNS-specific mir-124 miRNA can silence viral replication in two evolutionally distant biological systems: mosquitoes and mouse brains. Thus, this approach can reinforce the safety of newly developed or existing vaccines for use in humans and could provide an additional level of biosafety for laboratories using viruses with altered pathogenic or transmissibility characteristics. Despite advances in developing flavivirus live attenuated vaccine (LAV) candidates, a concern exists that they might not be safe in the environment due to their intrinsic genetic instability leading to potential reversion back to wild-type that could be associated with possible dissemination of these mutated viruses by mosquitoes. Here, we describe a miRNA targeting approach that can be adapted to support the design of environmentally-safe LAV restricted in their ability to infect and be transmitted by competent vectors, thereby limiting the possibility of subsequent viral evolution and unpredictable consequences. A combined co-targeting of flavivirus genome with mosquito- and vertebrate brain- specific miRNAs resulted in simultaneous restriction of dengue virus infection and replication in mosquitoes and in brains of newborn mice indicating that the miRNA-mediated approach for virus attenuation represents an alternative to non-specific strategies for the control of viral tissue tropism and pathogenesis in the vertebrate host and replicative efficacy in permissive vectors.

Tick-borne viruses include medically important zoonotic pathogens that can cause life-threatening diseases. Unlike mosquito-borne viruses, whose impact can be restrained via mosquito population control programs, for tick-borne viruses only vaccination remains the reliable means of disease prevention. For live vaccine viruses a concern exists, that spillovers from viremic vaccinees could result in introduction of genetically modified viruses into sustainable tick-vertebrate host transmission cycle in nature. To restrict tick-borne flavivirus (Langat virus, LGTV) vector tropism, we inserted target sequences for tick-specific microRNAs (mir-1, mir-275 and mir-279) individually or in combination into several distant regions of LGTV genome. This caused selective attenuation of viral replication in tick-derived cells. LGTV expressing combinations of target sequences for tick- and vertebrate CNS-specific miRNAs were developed. The resulting viruses replicated efficiently and remained stable in simian Vero cells, which do not express these miRNAs, however were severely restricted to replicate in tick-derived cells. In addition, simultaneous dual miRNA targeting led to silencing of virus replication in live Ixodes ricinus ticks and abolished virus neurotropism in highly permissive newborn mice. The concurrent restriction of adverse replication events in vertebrate and invertebrate hosts will, therefore, ensure the environmental safety of live tick-borne virus vaccine candidates.

Based on 465 panel data from 31 provinces, autonomous regions, and municipalities in China from 2001 to 2015 (data come from “China Statistical Yearbook”), static and dynamic panel models were established by Stata16.0 software to analyze the impact of housing rent on household consumption. In order to explore the specific impact of rising housing rents on residents’ consumption, and then adjust housing policies to stimulate consumer demand, this article analyses three research topics: (a) the impact of rising housing rent on the overall consumption level of residents and whether there are regional differences; (b) the internal mechanism underlying the effect of rising housing rent on residents’ consumption; and (c) the different impacts of rising housing rent on different types of residents’ consumption by establishing fixed-effects and random-effects models. The results show that a rise in housing rent causes a wealth effect on residents’ consumption at the national level in all regions. The upgrading of the industrial structure plays a positive role in the relationship between the fluctuation in housing rent and residents’ consumption, that is, the more rational the industrial structure, the stronger the wealth effect of rising housing rent on residents’ consumption. The rise in housing rent positively affects residents’ daily necessities and services consumption; transportation and telecommunication consumption; education, culture, and entertainment consumption; and habitation consumption; while negatively affects food, tobacco, and alcohol consumption; clothing consumption; and other supplies and services consumption. However, the impact on health care consumption is not significant. Accordingly, the government should start by improving the housing rental market and reasonably promote the further development of the housing rental market, thereby further stimulating Chinese consumption level.

By analyzing the principles of the project earned value management method, we find that the performance monitoring of project earned value encounters the problem of neglecting the impacts of the project’s scope and quality on the cost and schedule deviations, which will affect the project earned value performance monitoring. This paper designed a process and method of project earned value performance monitoring considering the scope and quality, and its application is analyzed using a specific case. The results show that the scientific project schedule and cost performance results can be obtained by integrating the scope and quality into the project earned value performance monitoring system while also considering the project’s baseline changes based on the activity and critical path perspectives. Finally, the conclusions of this research are summarized and future research directions are given.

Purpose: The aim of this study is to analyze the influence mechanism of real estate enterprises' status on debt default risk and explore the heterogeneity effect of the characteristics of enterprises.Design/methodology/approach: Against the background of the “three red lines” regulation of the financing of real estate enterprises and the COVID-19 pandemic, the authors select 123 real estate enterprises listed on China's Shanghai and Shenzhen A-shares markets from the first quarter of 2021 to the second quarter of 2022 as a research sample. The social network analysis method and Z-score financial risk early warning model are used to measure real estate enterprises' status and debt default risk. The authors construct a panel regression model to analyze how the status of real estate enterprises influences their debt default risk.Findings: The results show that the status of real estate enterprises negatively and significantly affects their debt default risk. Economic policy uncertainty and financing constraints play negative moderating and mediating roles, respectively. Further research has found that the effect of real estate enterprises' status on debt default risk is characterized by heterogeneity in equity characteristics, i.e. it is significant in the sample of nonstate-owned enterprises but not in the sample of state-owned enterprises.Practical implications: It is helpful for real estate enterprises to attach importance to the value of social networks, and the authors provide policy suggestions for real estate enterprises to constantly improve their risk management systems.Originality/value: Using economic policy uncertainty as the moderating variable and financing constraints as the mediating variable, the authors analyze how the status of real estate enterprises influences debt default risk, which contributes to a better understanding of the formation of the debt default risk of real estate enterprises.

Utilizing panel data from 30 large- and medium-sized cities in China from 2003 to 2018, this study employs the bootstrap method to investigate the heterogeneous impact of air pollution on housing prices and its underlying mechanisms. The research findings indicate that an increase in the concentration of various air pollutants has a restraining effect on housing prices, with the primary components of haze exerting a greater influence. Air pollution indirectly affects housing prices by influencing urban economic development and the development of the tertiary industry, with population density and the development of the secondary industry not serving as mediators in this relationship. Finally, policy recommendations are provided, including enhancing mandatory standards for energy consumption and waste gas emissions by enterprises, establishing a robust environmental monitoring system, and promoting industrial transformation and upgrading, aiming to provide insights for the stable development of the real estate industry.