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Human soluble guanylate cyclase (sGC) is a heme-containing metalloprotein in NO-sGC-cGMP signaling. In this work, fluorescent proteins were employed to study the NO-induced sGC molecular mechanism via mutagenesis at the catalytic domain. The conformational change of sGC by mutant α 1 C595 was investigated in living cells through fluorescence lifetime imaging microscopy (FLIM). The results indicated that the NO-induced conformational change of the catalytic domain of sGC from "open to "closed" upon GTP-binding was regulated by the hydrogen (H)-bonding network of the catalytic domain. The mutation of C595 caused a big conformational change of catalytic domain with H-bond variation, which not only demonstrates the key role of the C595 site in the process of conformational change of the catalytic domain, but also reveals the regulatory mechanism of sGC at the catalytic domain. This finding would guide the design of small-molecule drugs targeting the catalytic domain to modulate sGC activity. • Mutagenesis of sGC at catalytic domain investigated in living cells through FLIM. • sGC conformational change regulated by H-bonding network of the catalytic domain. • The key site mutation at C595 revealed the regulatory mechanism of sGC. [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng C.A. Mey) has become widely recognized as a medicinal and food plant. Nevertheless, there has been minimal research on the impact of ginseng extract (GE) on the development of hazardous chemicals during meat preparation. In the present study, red GE (RGE) and white GE (WGE) were prepared and their active components were identified. The effects of RGE and WGE on heterocyclic aromatic amines (HAAs), precursors and physicochemical properties in roasted chicken were investigated, as well as the interaction among them. In chicken meat, 1% RGE effectively inhibited IQ and PhIP production by 100%, and 1% WGE inhibited harman and norharman by 0.73% and 24.83%, respectively. In chicken skin, 0.5% RGE effectively inhibited PhIP production by 94.52%, and 1% RGE inhibited IQ, harman and norharman by 78.43%, 68.15% and 83.15%, respectively. Therefore, GE can inhibit HAAs in roasted chicken. This could be because GE contains active compounds that scavenge intermediates/free radicals in the synthesis of HAAs or increase the creatine and glucose levels. PCA revealed that GE suppressed HAAs better in roasted chicken. Therefore, GE could be used in the roasted chicken manufacturing process to reduce HAA output while increasing its nutritional characteristics. • A novel route was developed to inhibit HAAs in roasted chicken by adding ginseng extract. • Ginseng extract may improve the nutritional characteristics of roasted chicken. • Variation of precursors revealed the involved HAA inhibition mechanism. [ABSTRACT FROM AUTHOR]

Under the influence of climate change and human activities, the problem of grassland degradation is becoming increasingly severe. Detection of changes in vegetation cover is crucial for a better understanding of the interaction between humans and ecosystems. This study maps changes in vegetation cover using the Google Earth Engine (GEE). We used 36 years of Landsat satellite imagery (1985–2020) in the Xilin River Basin, China, to classify grassland conditions and validated the results with field observation data. The overall classification of the model accuracy assessment was 83.3%. The Dynamic Reference Vegetation Cover Method (DRCM) was adopted to remove the effect of interannual variation of rainfall, allowing to focus on the impact of human activities on vegetation cover changes. The results identify five categories of vegetation cover changes: significantly increased , potentially increased , stable , potentially decreased , and significantly decreased. The reference level is derived from the most persistent land surface coverage across different grassland types and all years. Overall, 9.3% of the study area had a significant increase in vegetation cover, 14.2% a potential increase , 48.6% of the area showed a stable vegetation condition, 9.8% showed a potential decrease , and 18.1% a significant decrease in vegetation cover. The largest proportion of combined potential and significant reduction was 35.2% for desert grassland, where the vegetation faced the most severe reduction. This study will provide a basis for identifying grassland degradation and developing scientific management policies. • Dynamic Reference Vegetation Cover Method (DRCM) is applied for monitoring grasslands. • The impact of interannual changes in rainfall was eliminated. • The model simulation accuracy after improving the reference pixels is 83.3%. • 18.1% of grasslands show a significant decrease in vegetation cover. • The maximum reduction of vegetation cover of 35.2% is in desert grasslands. [ABSTRACT FROM AUTHOR]

[Display omitted] • The main HAAs found in spiced pork shoulder was β-carboline. • HAAs increased with the increase of temperature, time and number of soup cycles. • Recycling soup may contribute greatly to the contents of HAAs in spiced pork shoulders. • HAAs in products were mainly from the adsorption and penetration of HAAs from soup. Spiced pork shoulder is a traditional Chinese meat product that is produced by long-term stewing in recycled soup. This study investigated the effects of cooking temperature, cooking time and number of soup cycles on the formation of heterocyclic aromatic amines (HAAs) in spiced pork shoulder. The main HAAs found in spiced pork shoulder was β-carboline. When the cooking temperature rose from 70 °C to 100 °C, the total HAAs increased from 27.17 ± 1.76 ng/g to 42.37 ± 0.91 ng/g. When the cooking time was extended from 1 h to 4 h, the total HAAs increased by 50.23 %. When the number of soup cycles was 15, the total HAAs in the meat and soup were 40.69 ± 0.28 ng/g and 55.84 ± 1.51 ng/g, respectively. Recycling soup may contribute greatly to the contents of HAAs in spiced pork shoulders. The high levels of HAAs in spiced pork shoulders were mainly from the adsorption of the HAAs in the soup onto the surface of the meat and their penetration into the meat. We recommend lowering the cooking temperature and shortening the cooking time to reduce the formation of HAAs in spiced pork shoulder. In addition, it is necessary to study effective methods to inhibit the formation of HAAs in soup. [ABSTRACT FROM AUTHOR]

Obese patients, often accompanied by hyperleptinemia, are prone to liver fibrogenesis. Leptin is an adipocyte-derived hormone and plays a promotion role in liver fibrosis. Sterol regulatory element binding protein-1c (SREBP1c) exerts a crucial role in inhibiting hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Our previous studies indicated that leptin inhibited SREBP1c expression, contributing to leptin-induced HSC activation and liver fibrosis. microRNAs (miR) have emerged as important layers of regulatory control and regulate gene expression, and are implicated in numerous diseases. The present study revealed leptin up-regulation of miR-27a/b-3p levels in HSCs in vitro and in vivo. Three signaling pathways were required for leptin regulation of miR-27a/b-3p levels. miR-27a/b-3p could reduce SREBP1c and liver x receptor α (LXRα) levels, increased α-smooth muscle actin (α-SMA, a marker for HSC activation) and α1(I)collagen levels in cultured HSCs. miR-27a/b-3p regulation of SREBP1c and LXRα were independent of 3′-untranslated region of SREBP1c and LXRα mRNA. In vivo experiments further demonstrated the miR-27a/b-3p involved in leptin-associated decrease in SREBP1 level in HSCs, HSC activation, and liver fibrosis. These data might have potential implications for our understanding of molecular mechanisms underlying leptin roles in liver fibrogenesis of obese patients with hyperleptinaemia. [ABSTRACT FROM AUTHOR]

Adipocytokine leptin promotes hepatic stellate cell (HSC) activation (a key step in liver fibrogenesis) and liver fibrosis. microRNA-122 (miR-122) is the most abundant liver-specific miRNA and was demonstrated to inhibit liver fibrosis and reduced HSC proliferation. Our previous study revealed that leptin reduced miR-122 level in HSCs. This study was aimed to investigate whether leptin affected miR-122 promoter and the underlying mechanisms in HSCs. Results showed that leptin inhibited miR-122 promoter activity. Forkhead box protein O1(FoxO1) bound to miR-122 promoter at a site around – 56 and thus promoted miR-122 promoter activity, which could be suppressed by leptin-induced phosphorylation of FoxO1 at serine 256. The PI3K/Akt signaling pathway was involved in leptin-induced phosphorylation of FoxO1 and the effect of leptin on miR-122 expression. Furthermore, FoxO1 increased miR-122 and pri-miR-122 (primary miR-122) levels in HSCs in vivo, and reduced leptin-induced HSC activation and liver fibrosis in ob/ob mouse (leptin deficient) model. In conclusion, leptin suppressed microRNA-122 expression by PI3K/Akt/foxO1 axis in HSCs. These results have potential implications for clarifying the mechanisms for liver fibrogenesis in obese patients with hyperleptinaemia. [ABSTRACT FROM AUTHOR]

The responses of soil moisture to rainfall are of great significance for watershed hydrological modeling. However, few studies have been done to investigate these responds on hillslope in a typical semi-arid grassland region. This study used high temporal resolution soil moisture data to explore the soil moisture dynamics, response conditions and its controls of 0–40 cm soil profile in the upslope (14°), midslope (9°), and downslope (4°) of a typical grassland inland river basin under bare ground (BG), stubble (SG), and natural grassland (CK) treatments. The results showed that soil water content and water storage increased in the downslope direction, and all showed as BG > SG > CK. The dry and wet changes in fast-changing layer (5 cm) and active layer (10 cm) were rapid, while soil moisture below 20 cm was relatively stable and fluctuated only in heavy or continuous rainfalls. The soil moisture response process varied greatly under different rainfall, rainfall intensity and antecedent soil moisture conditions, which explained 41.1% of the total difference. The rainfall replenishment threshold and the required initial soil profile water content of soil moisture response in 5 cm, 10 cm and 20 cm soil layers were 5.8 mm, 8.0 mm, 11.4 mm and 8.7 vol%, 9.4 vol%, 10.8 vol%, respectively. Soil properties, vegetation characteristics and topography could explain 38.8%, 14.5% and 5.6% of the soil moisture variation on the hillslope. In addition, under the comprehensive influence of environmental factors, changes in soil moisture of the upslope were significantly affected by soil sand content, the differences in the midslope were mainly due to soil clay content and belowground biomass, whereas the vegetation characteristics were the main factors in the downslope. This study can contribute to the further understanding of slope-scale ecohydrological processes and hydrological simulation of semi-arid grassland watersheds. • The response of soil moisture to rainfall under different vegetation treatments at different hillslope positions was investigated. • Rainfall recharge thresholds and initial soil profile water content for soil moisture responses at different soil depths were determined. • The effects of water condition, vegetation characteristics and soil properties on soil water responses at different hillslope locations were quantified. [ABSTRACT FROM AUTHOR]

Abstract: Hepatic stellate cell (HSC) activation is a key step in process of liver fibrosis. Transforming growth factor-β1 (TGF-β1) is the most powerful mediator of HSC activation and plays a central role in liver fibrosis. Peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of adipocyte differentiation and has been proposed as a crucial factor for inhibition of HSC activation. The effect of TGF-β1 on PPARγ in HSCs is largely unknown. This study is aimed to examine whether TGF-β1 can influence PPARγ expression, focusing on the role of β-catenin pathway, a key pathway linked to adipogenesis, in TGF-β1 regulation of PPARγ in cultured HSCs. Our results demonstrated that TGF-β1 evidently inhibited PPARγ expression and activity in cultured HSCs, which were mediated through β-catenin pathway. TGF-β1 promoted β-catenin expression and also increased the stability of β-catenin protein through ERK1/2/glycogen synthase kinase-3β (GSK-3β) axis in cultured HSCs. Moreover, TGF-β1 inhibition of PPARγ expression by β-catenin pathway caused the increase in alpha1(1) collagen and tissue inhibitor of matrix metalloproteinase expression. These results indicated for the first time that TGF-β1 could down-regulate PPARγ expression through β-catenin pathway and subsequently contributed to the increase in alpha1(1) collagen level in cultured HSCs. [Copyright &y& Elsevier]