SG-SP1, a newly synthesised gallic acid derivative, blocks histamine release by reducing calcium influx in mast cells and inhibits inflammatory cytokine expression. This derivative has promising anti-allergic potential. Our research was designed to establish a quantitative determination method for SG-SP1 in rat plasma using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), to validate the analytical method including stability and to characterise its pharmacokinetic behaviour in rats. After simple protein precipitation with acetonitrile including an internal standard, SG-SP1 was eluted on a reversed-phase column using a mobile phase of water and acetonitrile (28 v/v, including 0.1 % formic acid). The protonated precursor ion [M+H]+ and major fragment ion were confirmed at m/z 588.2 and 180.1, respectively. The substance was stable under bench and storage conditions. The analytical method met the criteria of FDA-validated bioanalytical methods and was successfully applied to a pharmacokinetic study for the first time. SG-SP1 decayed in a biphasic pattern with terminal half-life of 5.1 h and clearance of about 3.2 L/h/kg. Double peaks were observed following oral administration, and the absolute oral bioavailability was ∼1 %.Approximately 5% of cancers are caused by high-risk human papillomaviruses. Although very effective preventive vaccines will reduce this cancer burden significantly over the next several decades, they have no therapeutic effect for those already infected and remaining at risk for malignant progression of hrHPV lesions. HPV-associated cancers are dependent upon the expression of the viral E6 and E7 oncogenes. The oncogenic function of hrHPV E6 relies partially on its ability to induce p53 degradation. Since p53 is generally wildtype in hrHPV-associated cancers, p53 stabilization arrests proliferation, induces apoptosis and/or results in senescence. Here we describe a live cell, image-based high-throughput screen to identify compounds that stabilize p53 and/or affect viability in HPV-positive cancer HeLa cells. We validate the robustness and potential of this screening assay by assessing the activities of approximately 6,500 known bioactive compounds, illustrating its capability to function as a platform to identify novel therapeutics for hrHPV.Zika virus (ZIKV) is a mosquito-borne neurotropic flavivirus. this website ZIKV infection may lead to microcephaly in developing fetus and Guillain-Barré Syndrome (GBS) like symptoms in adults. ZIKV was first reported in humans in 1952 from Uganda and the United Republic of Tanzania. Later, ZIKV outbreak was reported in 2007 from the Yap Island. ZIKV re-emerged as major outbreak in the year 2013 from French Polynesia followed by second outbreak in the year 2015 from Brazil. ZIKV crosses the blood-tissue barriers to enter immune-privileged organs. Clinical manifestations in ZIKV disease includes rash, fever, conjunctivitis, muscle and joint pain, headache, transverse myelitis, meningoencephalitis, Acute Disseminated Encephalomyelitis (ADEM). The understanding of the molecular mechanism of ZIKV pathogenesis is very important to develop potential diagnostic and therapeutic interventions for ZIKV infected patients.Chronically SHIVSF162P3N-infected cynomolgus monkeys were used to determine the effects of the antibody-mediated acute CD4+ T cell depletion on viral load as well as on the immunological factors associated with disease progression. Compared with the control animals, CD4+ T cell-depleted animals with SHIV infection showed (i) little alteration in plasma viral load over the period of 22 weeks after the depletion; (ii) increased CD4+ T cell proliferation and turnover of macrophages at the early phase of the depletion, but subsequent decline to the basal levels; and (iii) little impact on the expression of the inflammatory cytokines and CC chemokines associated with disease progression. These findings indicate that the antibody-mediated acute CD4+ T cell depletion had minimal impact on plasma viral load and disease progression in chronically SHIVSF162P3N-infected cynomolgus monkeys. Future investigations are necessary to identify the key factor(s) related to the immune activation and macrophage infection during the CD4 deletion in chronic viral infection.Current treatment methods for hepatitis B are mainly antiviral drug therapy and immunotherapy, in which antiviral drugs are mainly nucleoside analogue and interferon. They can significantly reduce the viral load but rarely achieve hepatitis B surface antigen (HBsAg) loss. link2 3,5,6,7,3′,4′-Hexamethoxyflavone was screened out from a small molecule compound library for its lower cytotoxic effect and greater HBsAg inhibition activity. Meanwhile, we further performed experiments in HepG2.2.15, HepG2-NTCP cells, PHHs and HBV transgenic mouse model to evaluate the anti-HBV effects of 3,5,6,7,3′,4′-Hexamethoxyflavone. Our study found that 3,5,6,7,3′,4′-Hexamethoxyflavone can significantly reduce the level of HBV RNAs, HBV DNA and HBsAg, in addition, the activity of four HBV promoters and the ratio of total RNAs/cccDNA and 3.5 kb RNA/cccDNA were decreased by 3,5,6,7,3′,4′-Hexamethoxyflavone. Mechanistically, we found HNF3α plays important roles in Hex mediated HBV transcription inhibition. Our study indicated Hex was a potential anti-HBV therapeutic drug.Water is fundamental for life and hence, ensuring its sustainability is essential. Indices can be useful tools to monitor sustainability, understand trends and take necessary actions. China is one of the world’s most water-strained countries, and herein, a spatially and temporally-replicable index is developed to measure the sustainability of water resources in its provinces (from 2004-17). link3 Unlike previous indices that aggregate contributing indicators by taking their mean (weighted, unweighted, arithmetic, geometric, etc.), the present study proposes a distance-approach to measure sustainability – enabling it to circumvent concerns on choice of weights and aggregation method. This method of quantification is in conjunction with the ‘tripartite’ conceptualization of sustainability – which says that it is the equilibrium among the economy, society and environment. It is assumed that provinces can be plotted in a 3-dimensional plane using numeric values denoting their economic, social and environmental development. Thereafter, the measure of sustainability would be the distance of the province to the ideal point of development in these three dimensions. The economic, social and environmental dimensions of water resources are computed by choosing appropriate indicators and applying TOPSIS (Technique -for Order Preference by Similarity to Ideal Solution). The trends in indices over the years are analyzed using a modified Mann-Kendall test. Further, the indices are checked for any spatial correlation (among the provinces) using Moran’s I. Lastly, factors (such as forest cover, fertilizer use and illiteracy) that may act as determinants of the indices are examined through panel regression. The results of the study provide an extensive view of water resources sustainability in China since the past decade, and can be useful for steering the direction of water policy actions in the future.Human attitudes and behaviours have been linked to the degradation of global biodiversity, particularly forest ecosystems. Indeed, effective conservation actions require that the attitudes and behaviours of affected individuals and communities are taken into account. While several studies have examined how human attitudes and behaviours affect conservation, it is still unclear which, and how, human value orientations influence conservation attitudes and behaviour. This is critical because attitudes and behaviours are underpinned by the complex concept of human values. Thus, effective management and conservation of environmental resources requires an in-depth knowledge and understanding of these values, and how they affect attitudinal and behavioural preferences towards the natural environment and their protection. Here we review the human value orientations influencing people’s attitudes and behaviours towards forest conservation, and discuss how conservation projects can be more successful by aligning their s and behaviours. To effectively achieve forest conservation goals, environmental managers, conservationists, and decision-makers should understand the extent and directional influence of value orientations on conservation attitudes and behaviours.Climate change is affecting water quantity and quality, with severe impacts on agricultural production. The use of nature-based solutions to address these challenges is increasing. Natural water retention ponds have been identified as viable solutions for water management in agriculture. This paper aims to characterize water retention ponds, and to quantify their effectiveness, direct and indirect benefits, and costs. The paper analyses the case of the Lamone river catchment in Emilia-Romagna Region (Italy), characterized by large seasonal variability of water flow and availability. This is an important agricultural area that relies heavily on irrigation. Here water retention ponds are systematically applied to store water in winter, for use during the dry season. They can play a strategic role in ensuring irrigation water availability, while preserving minimum environmental flow. The paper analyses both the benefits of ponds for the water balance at sub-catchment scale, and the environmental effects producedo widely support NBS implementation.The recent years have been marked by the role of green tech innovation in decreasing carbon emissions worldwide to attain the carbon neutrality target. Despite many studies examining the nexus between the former and energy consumption, tech innovation’s effects on CO2 releases have not been extensively researched, and the extant empirical findings are often contradictory. Also, a major concern regarding the available literature is the scarcity of papers that scan the impact of tourism on carbon emissions, even though the industry has a high potential to affect ambient air pollution. In this case, the evidence is mixed, and no consensus among academics on the relationships between the two. Therefore, this study seeks to investigate the relevance of green innovation and tourism in decreasing environmental damage in Thailand based on the bootstrapping ARDL causality model suggested by (McNown et al., 2018). This specification includes a new cointegration feature and conventional ARDL bounds tests, which increases the power of the t- and of the f-test and has several advantages, being more adequate for dynamic models with more than one explanatory variable. Our findings reveal that green innovation and tourism lead to lower environmental damage by reducing CO2 emissions, similar to foreign investments and that green tech innovation improves the environmental quality via lower carbon emissions.Even though a great number of researches have explored the determinants of carbon emissions, the impact of economic policy uncertainty (EPU) on the environment has not been fully investigated in the energy-environment literature. Since recent studies show a strong relationship between the external environment and uncertainty, the present study for the first time in the literature aims to explore the function of EPU in the energy-environment nexus for China by using the novel bounds testing with dynamic simulations. The empirical results indicate that increases in the real income and energy intensity contribute to environmental pollution while increases in renewable energy lower the level of emissions. Besides, an increase in EPU causes an increase in the volume of carbon emissions. As EPU increases, the government’s attention to implement environmental protection policies decreases, and the execution of the environment-related strategies is likely directed in an expected way. The empirical findings suggest that the government should establish consistency in economic and environmental policies to mitigate environmental pollution and thus to reach environmental sustainability.