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Ecosystem respiration (RE) plays a critical role in terrestrial carbon cycles, and quantification of RE is important for understanding the interaction between climate change and carbon dynamics. We used a multi-level attention network, Geoman, to identify the relative importance of environmental factors and to simulate spatiotemporal changes in RE in northern China's grasslands during 2001–2015, based on 18 flux sites and multi-source spatial data. Results indicate that Geoman performed well (R2 = 0.87, RMSE = 0.39 g C m−2 d−1, MAE = 0.28 g C m−2 d−1), and that grassland type and soil texture are the two most important environmental variables for RE estimation. RE in alpine grasslands showed a decreasing gradient from southeast to northwest, and that of temperate grasslands showed a decreasing gradient from northeast to southwest. This can be explained by the enhanced vegetation index (EVI), and soil factors including soil organic carbon density and soil texture. RE in northern China's grasslands showed a significant increase (1.81 g C m−2 yr−1) during 2001–2015. The increase rate of RE in alpine grassland (2.36 g C m−2 yr−1) was greater than that in temperate grassland (1.28 g C m−2 yr−1). Temperature and EVI contributed to the interannual change of RE in alpine grassland, and precipitation and EVI were the main contributors in temperate grassland. This study provides a key reference for the application of advanced deep learning models in carbon cycle simulation, to reduce uncertainties and improve understanding of the effects of biotic and climatic factors on spatiotemporal changes in RE. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effects of the dietary supplementation of chitosan oligosaccharides (COS) on intestinal integrity, oxidative status, and the inflammation response with hydrogen peroxide (H2O2) challenge. In total, 30 rats were randomly assigned to three groups with 10 replications: CON group, basal diet; AS group, basal diet + 0.1% H2O2 in drinking water; ASC group, basal diet + 200 mg/kg COS + 0.1% H2O2 in drinking water. The results indicated that COS upregulated (p < 0.05) villus height (VH) of the small intestine, duodenum, and ileum; mucosal glutathione peroxidase activity; jejunum and ileum mucosal total antioxidant capacity; duodenum and ileum mucosal interleukin (IL)-6 level; jejunum mucosal tumor necrosis factor (TNF)-α level; duodenum and ileum mucosal IL-10 level; the mRNA expression level of zonula occludens (ZO)-1 in the jejunum and ileum, claudin in the duodenum, nuclear factor-erythroid 2-like 2 in the jejunum, and heme oxygenase-1 in the duodenum and ileum; and the protein expression of ZO-1 and claudin in jejunum; however, it downregulated (p < 0.05) serum diamine oxidase activity and D-lactate level; small intestine mucosal malondialdehyde content; duodenum and ileum mucosal IL-6 level; jejunum mucosal TNF-α level; and the mRNA expression of IL-6 in the duodenum and jejunum, and TNF-α in the jejunum and ileum. These results suggested COS could maintain intestinal integrity under oxidative stress by modulating the intestinal oxidative status and release of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Simple Summary: Oxidative stress adversely affects animal health and performance. Feed additives with antioxidant abilities supplementation can alleviate oxidative stress. The aim of this study was to evaluate the hypothesis that dietary supplementation with COS alleviates the damage caused by oxidative stress in Sprague Dawley rats challenged with hydrogen peroxide (H2O2). The results shown that COS exhibited better radical scavenging capacity of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O2−), H2O2, and ferric ion reducing antioxidant power (FRAP) than butylated hydroxy anisole (BHA), increasing activity of SOD, CAT, GSH-Px, GSH, and T-AOC, as well as decreasing MDA level in serum, liver, spleen, and kidney. Our results indicated that COS can protect Sprague Dawley rats from H2O2 challenge by reducing lipid peroxidation and restoring antioxidant capacity. Oxidative stress is induced by excessive oxidative radicals, which directly react with biomolecules, and damage lipids, proteins and DNA, leading to cell or organ injury. Supplementation of antioxidants to animals can be an effective way to modulate the antioxidant system. Chitosan oligosaccharides (COS) are the degraded products of chitosan or chitin, which has strong antioxidant, anti-inflammatory, and immune-enhancing competency. Therefore, the current study was conducted to evaluate the hypothesis that dietary supplementation with COS alleviates the damage caused by oxidative stress in Sprague Dawley rats challenged with hydrogen peroxide (H2O2). The rats were randomly divided into three groups: CON, control group, in which rats were fed a basal diet with normal drinking water; AS, H2O2 group, in which rats were fed the basal diet and 0.1% H2O2 in the drinking water; ASC, AS + COS group, in which rats were fed the basal diet with 200 mg/kg COS, and with 0.1% H2O2 in the drinking water. In vitro, COS exhibited better radical scavenging capacity of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), superoxide anion (O2−), H2O2, and ferric ion reducing antioxidant power (FRAP) than butylated hydroxy anisole (BHA). In vivo, dietary supplementation with COS alleviated the H2O2-induced oxidative damage, evidenced by comparatively increasing activity of SOD, CAT, GSH-Px, GSH, and T-AOC, and comparatively decreasing level of MDA in serum, liver, spleen, and kidney. COS also comparatively alleviated the H2O2-induced inflammation. In conclusion, COS supplementation reduced lipid peroxidation and restored antioxidant capacity in Sprague Dawley rats, which were challenged with H2O2. [ABSTRACT FROM AUTHOR]

Simple Summary: Heat stress has negative effects on animal health and performance, and chitosan oligosaccharides (COS) exhibits antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the effects of COS alleviation of oxidative stress and inflammatory response in heat-stressed rats. The results indicated heat stress decreased (p < 0.05) growth performance; the relative weight of spleen and kidney; and the level of antioxidant enzymes and IL-10 in liver, spleen, and kidney, while it increased (p < 0.05) the MDA and inflammatory cytokines concentration. Dietary COS supplementation enhanced (p < 0.05) ADG, the relative weight of spleen and kidney, and the level of antioxidant enzymes and IL-10 in liver, spleen, and kidney. Collectively, COS was beneficial to heat-stressed rats by alleviating oxidative damage and inflammatory response. Chitosan oligosaccharides (COS) exhibits antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the effects of COS on antioxidant system and inflammatory response in heat-stressed rats. A total of 30 male rats were randomly divided to three groups and reared at either 24 °C or 35 °C for 4 h/d for this 7-day experiment: CON, control group with basal diet; HS, heat stress group with basal diet; HSC, heat stress with 200mg/kg COS supplementation. Compared with the CON group, HS significantly decreased (p < 0.05) average daily gain (ADG); average daily feed intake (ADFI); the relative weight of spleen and kidney; the level of liver CAT, GSH-Px, T-AOC, and IL-10; spleen SOD, GSH-Px, GSH, and IL-10; and kidney SOD, GSH-Px, T-AOC, and IL-10, while significantly increased the MDA concentration in liver, spleen, and kidney; the liver IL-1β concentration; and spleen and kidney IL-6 and TNF-α concentration. In addition, dietary COS supplementation significantly improved (p < 0.05) ADG; the relative weight of spleen and kidney; the level of liver GSH-Px, spleen GSH-Px, GSH, and IL-10; and kidney GSH-Px, while significantly decreased (p < 0.05) liver IL-1β concentration under heat stress condition. Collectively, COS was beneficial to heat-stressed rats by alleviating oxidative damage and inflammatory response. [ABSTRACT FROM AUTHOR]

GC20, a novel soluble bis-chelated gold(I)−diphosphine compound, has been reported as a promising anticancer candidate. Assessing the pharmacokinetic properties of GC20 is critical for its medicinal evaluation. First, a sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and well validated to determine GC20 in rat plasma and rat tissue homogenate after one step protein precipitation. Chromatographic separation was achieved on an Angilent ZORBAX-C18 column (3.5 μm, 2.1 × 50 mm) with gradient elution and mass spectrometry was performed on a triple quadrupole in positive ion mode using an electrospray ionization source. This method was then applied to investigate the pharmacokinetics and tissue distribution of GC20 in rats after intravenous administration. The results showed that the plasma exposure of GC20 in vivo increased with increasing doses after a single dose. However, after multiple doses, a significant accumulation and a saturation at elimination were observed for GC20 in rats. Moreover, after intravenous administration, GC20 was widely distributed in various tissues, with the highest levels in the lung, spleen, liver, and pancreas, followed by the kidney and heart, while the lowest level was found in the brain. This is the first report on the pharmacokinetic properties of GC20. [ABSTRACT FROM AUTHOR]

Ib is a new nonpeptide AT1 receptor antagonist, which plays an active role in cardiovascular protection. Ib monoglucuronide has been identified as its main metabolite. A detailed study of Ib glucuronidation is important for predicting potential DDI. Besides, the elucidation of the "BSA effect" in Ib glucuronidation would make obtained kinetic parameters more predictive in IVIVE. "BSA effect" means that there is a significant change in in vitro kinetic parameters when generated from incubations performed in the presence of bovine serum albumin (BSA). Five UGTs (UGT1A3, UGT2B4, UGT2B7, UGT1A9 and UGT1A8) were identified that produced abundant Ib monoglucuronide, especially UGT1A3. We investigated Ib glucuronidation in liver microsomes from different species (rat, dog, human) and in five identified major human UGTs. Ib glucuronidation in liver microsomes and recombinant human UGTs all showed substrate inhibition kinetics. DLM showed the strongest affinity and activity, HLM showed the lowest affinity, and RLM showed the weakest activity. The addition of BSA did not alter the enzyme kinetics, but significantly altered enzyme kinetic parameters resulting in a reduction in K m value and an increase in CL int value. However, high concentrations of BSA could significantly attenuate this positive effect on enzyme affinity and activity, and the effect of BSA on the V max of Ib glucuronidation was opposite in different enzyme sources. In conclusion, this study demonstrated the substrate inhibition kinetics of Ib glucuronidation in the liver metabolism and the effect of BSA on its kinetic parameters, in order to provide more accurate in vitro data for in vivo prediction., Competing Interests: The authors declare that they have no conflict of interest.