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Current therapies for hepatitis B virus (HBV) infection can slow disease progression but cannot cure the infection, as it is difficult to eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The interaction between host factors and cccDNA is essential for their formation, stability, and transcriptional activity. Here, we focused on the regulatory role of the host factor ENPP1 and its interacting transcription factor LMNB1 in HBV replication and transcription to better understand the network of host factors that regulate HBV, which may facilitate the development of new antiviral drugs. Overexpression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) in Huh7 cells decreased HBV pregenomic RNA (pgRNA) and hepatitis B core antigen (HBcAg) expression levels, whereas knockdown of ENPP1 increased them. A series of HBV promoter and mutant plasmids were constructed, and a luciferase reporter assay showed that overexpression of ENPP1 caused inhibition of the HBV promoter and its mutants. A DNA pull-down assay showed that lamin B1 (LMNB1), but not ENPP1, interacts directly with the HBV enhancer II/ basic core promoter (EnhII/BCP). ZDOCK and PyMOL software were used to predict the interaction of ENPP1 with LMNB1. Overexpression of LMNB1 inhibited the activity of the HBV promoter and its mutant. The acetylation levels at the amino acids 111K, 261K, and 483K of LMNB1 were reduced compared to the control, and an LMNB1 acetylation mutant containing 111R, 261Q, 261R, 483Q, and 483R showed increased promoter activity. In summary, ENPP1 together with LMNB1 increased the acetylation level at 111K and 261K, and LMNB1 inhibited the activity of HBV promoter and downregulated the expression of pregenomic RNA and HBcAg. Our follow-up studies will investigate the expression, clinical significance, and relevance of ENPP1 and LMNB1 in HBV patient tissues, explore the effect of LMNB1 on post-transcriptional progression, and examine whether ENPP1 can reduce cccDNA levels in the nucleus. [ABSTRACT FROM AUTHOR]

Based on daily mean temperature data from 32 meteorological stations in the Qinling Mountains (QMs) of China, we analyzed the characteristics and differences of the spatiotemporal changes in the climatic growing season (CGS) in the QMs from 1964 to 2015. Our results are as follows. First, over the past 52 years, the temperature of the QMs significantly increased at a mean rate of 0.22 °C/decade (P < 0.01) in over 98.04% of the area. Significant north–south spatial differences were observed in temperature changes; also, significant differences in the temperature changing trends were observed before and after the abrupt change in temperature. Second, the spatial distributions of the mean growing season start (GSS), end (GSE), and length (GSL) in the QMs varied based on regional differences in latitude and topography. Notably, the GSS, GSE, and GSL were gradually delayed, advanced, and shortened, respectively, as latitude and elevation increased. After the abrupt change in temperature, whether it is in the NSQM (northern slopes of the QMs) or the SSQM (southern slopes of the QMs), the GSS, GSE, and GSL expanded into high-elevation areas. Third, over the past 52 years, the GSS in the QMs exhibited a significant advancing trend of 2.7 days/decade, the GSE was delayed at a rate of 0.66 days/decade, and the GSL displayed a significant extension of 3.36 days/decade. Before the abrupt change in temperature, the GSS, GSE, and GSL exhibited non-significant changing trends; however, the trends in the GSS, GSE, and GSL were more significant after the abrupt change than before. Fourth, the GSS, GSE, and GSL trends in the QMs were significantly different in the NSQM and SSQM regions. After the abrupt change, the GSS, GSE, and GSL trends along the NSQM were more significant than those along the SSQM. [ABSTRACT FROM AUTHOR]

It is of great significance to study on the shift of temperature zone boundaries for revealing the climate change pattern and its environmental effects. Based on daily average temperature data from 32 standard meteorological stations in the Qinling Mountains from 1964 to 2015, the growing season start and end (GSS and GSE) of the climatic growing season parameters were calculated based on a temperature threshold of 10 °C, and the growing season length (GSL) was obtained by subtracting GSE from GSS. We have analyzed the spatiotemporal variations of these parameters in the Qinling Mountains and the shift rules of the warm temperate zone and northern subtropics zone boundaries in China over the past 52 years. Our research generated three primary results. First, the spatial distribution and changing trends of the GSS, GSE, and GSL were significantly different before and after abrupt changes in temperature. After the abrupt change, the coverages of the three were all gradually expanding to the higher altitude areas. The change rates of the three were faster, the trends were more significant, and the differences between the north and the south were obvious, especially in the northern slope. Second, the boundaries of both the warm temperate zone and the northern subtropical zone in China showed upward position shifts, and the area coverage changed along the northern and southern slopes of the Qinling Mountains, and the change amplitudes were even greater after the abrupt change in temperature. Third, there was a significant north–south difference in the response of China's temperature zones to climate change. The temperature zone on the northern slope was more sensitive to climate warming. It is worth emphasizing that the shifts of the temperature zones did not change the fact that the Qinling Mountains are the boundary between China's subtropical and the warm temperate zones. The north subtropical zone is still located on the southern slope of the Qinling Mountains, and the northern slope is still in the warm temperate zone. [ABSTRACT FROM AUTHOR]

Based on daily mean temperature data from 32 meteorological stations in the study area, this paper discusses the relationship between the changes in the climatic growing season and altitude and the differences in the northern (NSQM) and southern (SSQM) slopes of the Qinling Mountains (QMs) from 1985 to 2015. Our analyses generated three primary results. First, the spatial distribution patterns of the growing season start (GSS), growing season end (GSE), and growing season length (GSL) exhibited an altitudinal gradient and differences between the NSQM and SSQM. The occurrence time of the GSS, GSE, and the GSL of the NSQM was approximately 15 days later, 10 days earlier, and 25 days shorter respectively than that of the SSQM. Second, the three factors exhibited regular changes with an increasing elevation gradient: the GSS, GSE, and GSL were gradually delayed, advanced, and shortened, respectively. In the area below 1800 m above sea level, the GSS, GSE, and GSL of the NSQM was later, earlier, and shorter, respectively, than that of the SSQM; while the changing trends in the three were opposite in the areas above 2700 m; and the three in the areas between 1800 and 2700 m varied little in the NSQM and SSQM. The sensitivities of the GSS, GSE, and GSL of the NSQM and SSQM to elevation also reflected in the trends of inter-annual variability. Third, among the different altitudinal vegetation belts from low-altitude to high-altitude areas, the occurrence time of the GSS and GSE and the duration of the GSL in the alpine meadow areas were all exchanged in the NSQM and SSQM. The GSS, GSE, and GSL of the NSQM were earlier, later, and longer respectively than that of the SSQM. [ABSTRACT FROM AUTHOR]

Fighting against multidrug-resistant bacteria requires reliable methods to evaluate the effect of antibacterial agents. As a universal, non-destructive, and highly sensitive tool, microcalorimetry has been used in many biological investigations to provide continuous real-time monitoring of the metabolic activity. This method, based on heat-flow output, was used to evaluate the influence of two flavonoid compounds (liquiritigenin and liquiritin) on Escherichia coli. Some crucial information, such as the thermogenic power-time curve and thermokinetic parameters of E. coli growth affected by the two compounds, was obtained and further studied by chemometric techniques including similarity analysis, multivariate analysis of variance, and principal component analysis. By comparing the values of two main parameters, k (growth rate constant of the second exponential phase) and Q (heat output of the first exponential growth phase) of E. coli based on the box and whisker plot, liquiritigenin and liquiritin could be differentiated according to their antibacterial effects; liquiritin with IC (half-inhibitory concentration) of 198.6 μg mL expressed a stronger antibacterial effect than liquiritigenin with IC of 337.8 μg mL. The glucoside group in liquiritin containing four additional free hydroxyls in the diphenylpropane skeleton was crucial for inducing the antibacterial effect. Liquiritin might be a promising candidate against E. coli. This study provides a valuable method for searching for novel antibacterial agents using microcalorimetry with chemometrics. [ABSTRACT FROM AUTHOR]