Orf virus DNA vaccines expressing ORFV 011 and ORFV 059 chimeric protein enhances immunogenicity

Background: ORFV attenuated live vaccines have been the main prophylactic measure against contagious ecthyma in sheep and goats in the last decades, which play an important role in preventing the outbreak of the disease. However, the available vaccines do not induce lasting immunity in sheep and goats. On the other hand, variation in the terminal genome of Orf virus vaccine strains during cell culture adaptation may affect the efficacy of a vaccine. Currently, there are no more effective antiviral treatments available for contagious ecthyma. Results: We constructed three eukaryotic expression vectors pcDNA3.1-ORFV011, pcDNA3.1-ORFV059 and pcDNA3.1-ORFV011/ORFV059 and tested their immunogenicity in mouse model. High level expression of the recombinant proteins ORFV011, ORFV059 and ORFV011/ORFV059 was confirmed by western blotting analysis and indirect fluorescence antibody (IFA) tests. The ORFV-specific antibody titers and serum IgG1/IgG2a titers, the proliferation of lymphocytes and ORFV-specific cytokines (IL-2, IL-4, IL-6, IFN-gamma, and TNF-alpha) were examined to evaluate the immune responses of the vaccinated mice. We found that mice inoculated with pcDNA3.1-ORFV 011/ORFV059 had significantly stronger immunological responses than those inoculated with pcDNA3.1-ORFV011, pcDNA3.1-ORFV059, or pcDNA3.1-ORFV011 plus pcDNA3.1-ORFV059. Compared to other vaccine plasmids immunized groups, pcDNA3.1-ORFV011/ORFV059 immunized group enhances immunogenicity. Conclusions: We concluded that DNA vaccine pcDNA3.1-ORFV011/ORFV059 expressing ORFV011 and ORFV059 chemeric-proteins can significantly improve the potency of DNA vaccination and could be served as more effective and safe approach for new vaccines against ORFV.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000304650500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701VirologySCI(E)3ARTICLEnull

Unveiling the spatial-temporal variation of urban land use efficiency of Yangtze River Economic Belt in China under carbon emission constraints

Under the constraint of carbon emission, measuring and analyzing the spatial-temporal evolution characteristics of urban land use efficiency in the Yangtze River Economic Belt is the inherent requirement of its ecological protection and sustainable development. In this paper, we calculated the urban land use efficiency of 107 cities in the Yangtze River Economic Belt from 2006 to 2020 by using the SBM-Undesirable model with unexpected output, and analyzed its temporal evolution trend and spatial correlation relationship by using kernel density and spatial autocorrelation method. The results showed that: except in 2020, the urban land use efficiency was generally low due to the COVID-19 epidemic, and the urban land use efficiency in other years was mostly concentrated in the middle levels, and showed a trend of slow fluctuation and rise year by year. The difference of urban land use efficiency level between regions increased, and the dispersion degree in upstream, midstream and downstream increased with each passing year. Urban land use efficiency spatial imbalance was significant, and the urban land use efficiency level of large and medium-sized cities was generally lower than that of cities with low economic development level. The spatial correlation was weak, and the global spatial autocorrelation was basically insignificant, while the local spatial agglomeration areas were mainly distributed in the upstream and downstream regions, with a small distribution range and weak spatial interaction. The distribution areas of the standard deviation ellipse were gradually flattened, and the center of gravity as a whole shift significantly to the southwest. The research results are helpful to understand the development history and future trend of urban land use efficiency in various regions, and propose that cities should consider the impact of public crisis events in advance, reasonably control the scale of land expansion, and lead coordinated development and other reasonable suggestions when formulating land use policies

Evaluation and Correction of Quantitative Precipitation Forecast by Storm-Scale NWP Model in Jiangsu, China

With the development of high-performance computer systems and data assimilation techniques, storm-scale numerical weather prediction (NWP) models are gradually used for short-term deterministic forecasts. The primary objective of this study is to evaluate and correct precipitation forecasts of a storm-scale NWP model called the advanced regional prediction system (ARPS). The evaluation and correction consider five heavy precipitation events that occurred in the summer of 2015 in Jiangsu, China. The performances of the original and corrected ARPS precipitation forecasts are evaluated as a function of lead time using standard measurements and a spatial verification method called Structure-Amplitude-Location (SAL). In general, the ARPS could not produce optimal forecasts for very short lead times, and the forecast accuracy improves with increasing lead time. The ARPS overestimates precipitation for all lead times, which is confirmed by large bias in many forecasts in the first and second quadrant of the diagram of SAL, especially at the 1 h lead time. The amplitude correction is performed by matching percentile values of the ARPS precipitation forecasts and observations for each lead time. Amplitude correction significantly improved the ARPS precipitation forecasts in terms of the considered performance indices of standard measures and A-component and S-component of SAL

Seasonal Variation in Microphysical Characteristics of Precipitation at the Entrance of Water Vapor Channel in Yarlung Zangbo Grand Canyon

Mêdog is located at the entrance of the water vapor channel in the Yarlung Zangbo Grand Canyon (YGC). This area has the largest annual accumulated rainfall totals and precipitation frequency on the Tibetan Plateau (TP). This paper investigates the seasonal variation in raindrop size distribution (DSD) characteristics in Mêdog based on disdrometer observations from 1 July 2019 to 30 June 2020. The DSD characteristics are examined under six rain rate classes and two rainfall types (stratiform and convective) in the winter, premonsoon, monsoon and postmonsoon periods. The highest (lowest) concentration of small raindrops is observed in monsoon (winter) precipitation, whereas large raindrops predominate in premonsoon precipitation. For stratiform rainfall, the mean mass-weighted mean diameter (Dm) exhibits overlooked differences in the four periods, while the mean normalized intercept parameter (Nw) is significantly higher in the monsoon period than in the other three periods. The convective rainfall in the monsoon and postmonsoon periods is characterized by a high concentration of limited-size drops and can be classified as maritime-like. This is probably attributed to abundant warm and humid airflow transported by the Indian Ocean monsoon into Mêdog. The westerly winds prevail over the TP during the premonsoon period, and thereby the premonsoon convective rainfall in Mêdog has a larger mean Dm and a lower mean Nw. In addition, the relationships of radar reflectivity Z and rain rate R for different precipitation types in different periods are also derived. A better understanding of the seasonal variation in the microphysical characteristics of precipitation in Mêdog is important for improving the microphysical parameterization scheme and the precipitation forecast of models on the TP

Potential Antiviral Strategy Exploiting Dependence of SARS-CoV-2 Replication on Lysosome-Based Pathway

The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as “garbage disposals” for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents

Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As2O3) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As2O3, and 300 µg/mL TMP combined with 0.5 µM As2O3, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright’s staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As2O3 alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As2O3 treatment versus almost a 13-fold increase in the TMP + As2O3 group. Cells treated with both TMP and As2O3 expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As2O3-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As2O3 has significant synergistic effects on the proliferative inhibition of HL-60 cells

Lung regeneration: diverse cell types and the therapeutic potential

Abstract Lung tissue has a certain regenerative ability and triggers repair procedures after injury. Under controllable conditions, lung tissue can restore normal structure and function. Disruptions in this process can lead to respiratory system failure and even death, causing substantial medical burden. The main types of respiratory diseases are chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute respiratory distress syndrome (ARDS). Multiple cells, such as lung epithelial cells, endothelial cells, fibroblasts, and immune cells, are involved in regulating the repair process after lung injury. Although the mechanism that regulates the process of lung repair has not been fully elucidated, clinical trials targeting different cells and signaling pathways have achieved some therapeutic effects in different respiratory diseases. In this review, we provide an overview of the cell type involved in the process of lung regeneration and repair, research models, and summarize molecular mechanisms involved in the regulation of lung regeneration and fibrosis. Moreover, we discuss the current clinical trials of stem cell therapy and pharmacological strategies for COPD, IPF, and ARDS treatment. This review provides a reference for further research on the molecular and cellular mechanisms of lung regeneration, drug development, and clinical trials