A sensitive and rapid HPLC-DAD method for the determination of 3-hydroxy-1,2-dimethyl-4-pyridone and its distribution in rats

Purpose: To establish a sensitive and rapid method for the determination of the tissue distribution of 3-hydroxy-1,2-dimethyl-4-pyridone (L1) in vivo, and its plasma protein binding capacity.Methods: This study optimized a reverse-phase HPLC method for specific and sensitive determination of L1 as well as its plasma and tissue  distributions. The optimized method was used to determine the plasma protein-binding capacity of L1 in Wistar rats.Results: A rapid, sensitive and simple HPLC-DAD method was established for studying the plasma and tissue distribution of L1. Following TI  administration, its liver concentrations peaked at 60 min and 360min, followed 360 min later with peak level in the kidney (second highest). The L1 concentration was significantly lower after 360 min than after 60 min, and values of its mean binding to plasma proteins was 5.2 % at different L1 concentrations.Conclusion: These results indicate that L1 is a drug with rapid-absorption and rapid-elimination thath is distributed widely in vivo in rats. Moreover, the drug has a weak plasma protein-binding capacity. Keywords: 3-Hydroxy-1,2-dimethyl-4-pyridone, Distribution, Alzheimer’s disease, Therap

Effect of dried distillers grains with solubles (DDGS) on cholesterol metabolism and xanthophylls bioavailability in rats

University of Minnesota M.S. thesis. November 2014. Major: Nutrition. Advisor: Daniel D. Gallaher, Ph.D. 1 computer file (PDF); ix, 112 pages, appendices 1-7.Dried distillers grain with solubles (DDGS), a co-product generated from the fuel ethanol industry, contain the same nutrients found in corn, except for starch, which has been fermented to ethanol and carbon dioxide. The U.S. Fuel ethanol industry has experienced a rapid increase in production in the past decades with 5 million metric tons produced in 2000 to 42.5 million metric tons produced in 2013 [1]. Currently, DDGS is primarily used as a feed ingredient for livestock and poultry [2], and it has been recognized as an excellent source of energy, amino acids, water-soluble vitamins and minerals for poultry, swine . Considering its high concentration of nutrients, it may have a great potential value as an ingredient in human foods. Therefore we examined several potential human health benefits of DDGS. Specifically, the effect of feeding DDGS, as well as a corn bran fraction and DDGS soluble fraction, on liver cholesterol, total fat, oxidative stress and xanthophyll bioavailability in rats was examined. The results showed that diets containing DDGS and DDGS co-products decreased liver cholesterol, increased bile acids and total neutral sterol excretion, and promoted intestinal fermentation. However, there was no evidence that these products decreased oxidative stress. Due to lack of sensitivity in the methods used, we were unable to assess xanthophylls bioavailability

Micro- and nanogels with labile crosslinks – from synthesis to biomedical applications

Micro- or nanosized three-dimensional crosslinked polymeric networks have been designed and described for various biomedical applications, including living cell encapsulation, tissue engineering, and stimuli responsive controlled delivery of bioactive molecules. For most of these applications, it is necessary to disintegrate the artificial scaffold into nontoxic residues with smaller dimensions to ensure renal clearance for better biocompatibility of the functional materials. This can be achieved by introducing stimuli- cleavable linkages into the scaffold structures. pH, enzyme, and redox potential are the most frequently used biological stimuli. Moreover, some external stimuli, for example light and additives, are also used to trigger the disintegration of the carriers or their assembly. In this review, we highlight the recent progress in various chemical and physical methods for synthesizing and crosslinking micro- and nanogels, as well as their development for incorporation of cleavable linkages into the network of micro- and nanogels

Human Ecology, Process Philosophy and the Global Ecological Crisis

This paper argues that human ecology, based on process philosophy and challenging scientific materialism, is required to effectively confront the global ecological crisis now facing us

Out of the Box Thinking: Improving Customer Lifetime Value Modelling via Expert Routing and Game Whale Detection

Customer lifetime value (LTV) prediction is essential for mobile game publishers trying to optimize the advertising investment for each user acquisition based on the estimated worth. In mobile games, deploying microtransactions is a simple yet effective monetization strategy, which attracts a tiny group of game whales who splurge on in-game purchases. The presence of such game whales may impede the practicality of existing LTV prediction models, since game whales' purchase behaviours always exhibit varied distribution from general users. Consequently, identifying game whales can open up new opportunities to improve the accuracy of LTV prediction models. However, little attention has been paid to applying game whale detection in LTV prediction, and existing works are mainly specialized for the long-term LTV prediction with the assumption that the high-quality user features are available, which is not applicable in the UA stage. In this paper, we propose ExpLTV, a novel multi-task framework to perform LTV prediction and game whale detection in a unified way. In ExpLTV, we first innovatively design a deep neural network-based game whale detector that can not only infer the intrinsic order in accordance with monetary value, but also precisely identify high spenders (i.e., game whales) and low spenders. Then, by treating the game whale detector as a gating network to decide the different mixture patterns of LTV experts assembling, we can thoroughly leverage the shared information and scenario-specific information (i.e., game whales modelling and low spenders modelling). Finally, instead of separately designing a purchase rate estimator for two tasks, we design a shared estimator that can preserve the inner task relationships. The superiority of ExpLTV is further validated via extensive experiments on three industrial datasets

Effect of sevoflurane post-conditioning on apoptosis and the expressions of Bcl-2 and Bax in lung tissue of cardiopulmonary bypass dogs

Purpose: To investigate the effects of sevoflurane post-conditioning on the expressions of Bcl-2 and Bax in lung tissues of cardiopulmonary bypass (CPB) dogs. Methods: Twelve healthy hybrid mongrels were divided into control (C) and sevoflurane postconditioning (S) groups. All dogs were subjected to thoracotomy in order to establish CPB. Ischemiareperfusion was conducted in the left lung of both groups. Thereafter, sevoflurane post-conditioning was given to group S. Femoral artery blood specimens were obtained prior to CPB (T1), as the left pulmonary artery was opened (T2), and 2 h after CPB (T3), for blood gas analysis. Respiration index (RI), oxygenation index (OI), and dynamic lung compliance (Cd) were calculated. Results: When T1 was compared with T2 and T3, their OI and Cd were significantly decreased in both groups, while RI showed the opposite trend (p < 0.05). Values of OI and Cd at T3 in group S were increased significantly, relative to group C, while RI decreased (p < 0.05). There were less lung tissue inflammation and structural disorder at T3 in Group S than in group C. Protein expressions and positive integral of Bcl-2 and Bax, and apoptosis at T2 and T3 in dog lung tissues of both groups were higher than those at T1 (p < 0.05). Conclusion: Post-conditioning with sevoflurane is lung-protective in CPB dogs. The underlying mechanism may be based on the promotion of Bcl-2 expression and inhibition of Bax expression, thereby reducing apoptosis in dog lung tissue. Further investigations to determine its suitability for clinical applications in humans are, however, required. Keywords: Sevoflurane; Cardiopulmonary bypass; Bcl-2, Bax; Apoptosis; Pulmonary ischemiareperfusion injur

Phosphorylation of TGB1 by protein kinase CK2 promotes barley stripe mosaic virus movement in monocots and dicots.

The barley stripe mosaic virus (BSMV) triple gene block 1 (TGB1) protein is required for virus cell-to-cell movement. However, little information is available about how these activities are regulated by post-translational modifications. In this study, we showed that the BSMV Xinjiang strain TGB1 (XJTGB1) is phosphorylated in vivo and in vitro by protein kinase CK2 from barley and Nicotiana benthamiana. Liquid chromatography tandem mass spectrometry analysis and in vitro phosphorylation assays demonstrated that Thr-401 is the major phosphorylation site of the XJTGB1 protein, and suggested that a Thr-395 kinase docking site supports Thr-401 phosphorylation. Substitution of Thr-395 with alanine (T395A) only moderately impaired virus cell-to-cell movement and systemic infection. In contrast, the Thr-401 alanine (T401A) virus mutant was unable to systemically infect N. benthamiana but had only minor effects in monocot hosts. Substitution of Thr-395 or Thr-401 with aspartic acid interfered with monocot and dicot cell-to-cell movement and the plants failed to develop systemic infections. However, virus derivatives with single glutamic acid substitutions at Thr-395 and Thr-401 developed nearly normal systemic infections in the monocot hosts but were unable to infect N. benthamiana systemically, and none of the double mutants was able to infect dicot and monocot hosts. The mutant XJTGB1T395A/T401A weakened in vitro interactions between XJTGB1 and XJTGB3 proteins but had little effect on XJTGB1 RNA-binding ability. Taken together, our results support a critical role of CK2 phosphorylation in the movement of BSMV in monocots and dicots, and provide new insights into the roles of phosphorylation in TGB protein functions

Efficacy of roxithromycin with gamma globulin in children with mycoplasma pneumonia and its effect on immunity

Purpose: To determine the efficacy of roxithromycin plus gamma globulin in the treatment of children with mycoplasma pneumonia (MPP) and its effect on immune function.Methods: From January 2019 to January 2021, 100 children with MPP assessed for eligibility in Qingdao Women and Children's Hospital, Shandong Province, China, were recruited and randomized (1:1) to receive either gamma globulin (control group) or roxithromycin plus gamma globulin (study group). Levels of tumor necrosis factor (TNF)-α, immunoglobulin (Ig)A, IgM, and IgG were evaluated. Clinical indices, including fever reduction, cough disappearance, duration of hospital stay, etc were also assessed.Results: The study group had a significantly higher clinical efficacy (88 %) than the control group (68 %) (p < 0.05). After treatment, patients in the study group showed lower levels of tumor necrosis factor (TNF)-α than those in the control group (p < 0.05). The eligible patients given roxithromycin plus gamma globulin showed significantly higher levels of immunoglobulin (Ig)A, IgM, and IgG versus those given gamma globulin alone (p < 0.05). Patients in the study group had a shorter time lapse before fever reduction, cough disappearance, lung sign disappearance, and duration of hospital stay than those in the control group (p < 0.05).Conclusion: Roxithromycin plus gamma globulin demonstrate significant benefits in the treatment of children with MPP by mitigating inflammatory response, enhancing immune function, and also significantly alleviating clinical symptoms. Thus, the combination treatment shows good potentials for use in clinical practice