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To examine the differences between HbA 1c and glucose related variables in predicting weight loss and glycaemic changes following 8 weeks of low energy diet (LED) in individuals with overweight and hyperglycaemia. 2178 individuals with ADA-defined pre-diabetes - impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) - who started an 8 week LED weight loss diet, were included in this analysis. Participants were enrolled in the PREVIEW (PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World) clinical trial. Multivariable linear mixed effects regression models and generalised additive mixed effect logistic models were used. Only 1 in 3 participants (33%) had HbA 1c levels defined as pre-diabetes. Neither baseline HbA 1c , IFG or IGT were associated with body weight change at 8 weeks. Higher baseline body weight, baseline fasting insulin and weight loss predicted normalisation of fasting plasma glucose (FPG), whilst higher baseline fasting insulin, C-reactive protein (hsCRP) and older age predicted normalisation of HbA 1c. Additionally, male sex and higher baseline BMI, body fat and energy intake were positively associated with weight loss, whereas greater age and higher HDL-cholesterol predicted less weight loss. Whilst neither HbA 1c nor fasting glucose predicts short-term weight loss success, both may impact the metabolic response to rapid weight loss. We propose a role of inflammation versus total body adiposity since these variables are independent predictors of the normalisation of HbA 1c and fasting glucose, respectively. [ABSTRACT FROM AUTHOR]

Low-energy diet replacement is an effective tool to induce large and rapid weight loss and improve metabolic health, but in the long-term individuals often experience significant weight regain. Little is known about the role of animal-based foods in weight maintenance and metabolic health. We aimed to examine longitudinal associations of animal-based foods with weight maintenance and glycaemic and cardiometabolic risk factors. We also modelled replacement of processed meat with other high-protein foods. In this secondary analysis, longitudinal data were analysed from 688 adults (26–70 years) with overweight and prediabetes after 8-week low-energy diet-induced weight loss (≥8% of initial body weight) in a 3-year, multi-centre, diabetes prevention study (PREVIEW). Animal-based food consumption, including unprocessed red meat, processed red meat, poultry, dairy products, fish and seafood, and eggs, was repeatedly assessed using 4-day food records. Multi-adjusted linear mixed models and isoenergetic substitution models were used to examine the potential associations. The available-case analysis showed that each 10-g increment in processed meat, but not total meat, unprocessed red meat, poultry, dairy products, or eggs, was positively associated with weight regain (0.17 kg⋅year−1, 95% CI 0.10, 0.25, P < 0.001) and increments in waist circumference, HbA 1c , and triacylglycerols. The associations of processed meat with HbA 1c or triacylglycerols disappeared when adjusted for weight change. Fish and seafood consumption was inversely associated with triacylglycerols and triacylglycerol-glucose index, independent of weight change. Modelled replacement of processed meat with isoenergetic (250–300 kJ·day−1 or 60–72 kcal·day−1) dairy, poultry, fish and seafood, grains, or nuts was associated with −0.59 (95% CI -0.77, −0.41), −0.66 (95% CI -0.93, −0.40), −0.58 (95% CI -0.88, −0.27), and −0.69 (95% CI -0.96, −0.41) kg·year−1 of weight regain, respectively (all P < 0.001) and significant improvements in HbA 1c , and triacylglycerols. Higher intake of processed meat, but not total or unprocessed red meat, poultry, dairy products, or eggs may be associated with greater weight regain and more adverse glycaemic and cardiometabolic risk factors. Replacing processed meat with a wide variety of high-protein foods, including unprocessed red meat, poultry, dairy products, fish, eggs, grains, and nuts, could improve weight maintenance and metabolic health after rapid weight loss. This study was registered as ClinicalTrials.gov , NCT01777893. [ABSTRACT FROM AUTHOR]

The association of quantity and quality of carbohydrate sources with appetite during long-term weight-loss maintenance (WLM) after intentional weight loss (WL) is unclear. We aimed to investigate longitudinal associations of quantity and quality of carbohydrate sources with changes in subjective appetite sensations during WLM. This secondary analysis evaluated longitudinal data from the 3-year WLM phase of the PREVIEW study, a 2 × 2 factorial (diet–physical activity arms), multi-center, randomized trial. 1279 individuals with overweight or obesity and prediabetes (25–70 years; BMI≥25 kg m−2) were included. Individuals were merged into 1 group to assess longitudinal associations of yearly changes in appetite sensations. Quantity and quality of carbohydrate sources including total carbohydrate, glycemic index (GI), glycemic load (GL), and total dietary fiber were assessed via 4-day food diaries at 4 timepoints (26, 52, 104, and 156 weeks) during WLM. Visual analog scales were used to assess appetite sensations in the previous week. During WLM, participants consumed on average 160.6 (25th, 75th percentiles 131.1, 195.8) g·day−1 of total carbohydrate, with GI 53.8 (48.7, 58.8) and GL 85.3 (67.2, 108.9) g day−1, and 22.3 (17.6, 27.3) g·day−1 of dietary fiber. In the available-case analysis, multivariable-adjusted linear mixed models with repeated measures showed that each 30-g increment in total carbohydrate was associated with increases in hunger (1.36 mm year−1, 95% CI 0.77, 1.95, P < 0.001), desire to eat (1.10 mm year−1, 0.59, 1.60, P < 0.001), desire to eat something sweet (0.99 mm year−1, 0.30, 1.68, P = 0.005), and weight regain (0.20%·year−1, 0.03, 0.36, P = 0.022). Increasing GI was associated with weight regain, but not associated with increases in appetite sensations. Each 20-unit increment in GL was associated with increases in hunger (0.92 mm year−1, 0.33, 1.51, P = 0.002), desire to eat (1.12 mm year−1, 0.62, 1.62, P < 0.001), desire to eat something sweet (1.13 mm year−1, 0.44, 1.81, P < 0.001), and weight regain (0.35%·year−1, 0.18, 0.52, P < 0.001). Surprisingly, dietary fiber was also associated with increases in desire to eat, after adjustment for carbohydrate or GL. In participants with moderate carbohydrate and dietary fiber intake, and low to moderate GI, we found that higher total carbohydrate, GL, and total fiber, but not GI, were associated with increases in subjective desire to eat or hunger over 3 years. This study was registered as ClinicalTrials.gov , NCT01777893. [ABSTRACT FROM AUTHOR]

Currently, chromium-containing wastewater from tanning process has seriously restricted the sustainable development of the leather industry. This problem can be solved by high-exhaustion chrome tanning technology and chrome-less tanning technology. However, these techniques not only fail to achieve a uniform tanning effect but also reduce the performance of the leather. In this work, pH-sensitive and chromium (III)-loaded nanoparticles were fabricated by self-assembly of poly [poly (ethylene glycol) methyl ether acrylate-co-acrylic acid-co-glycidyl methacrylate (PEGMA-co-AA-co-GMA)] terpolymers templated Cr(OH) 3 mineralization, which were defined as Cr-PPAG NPs and utilized as smart high chrome exhaustion and chrome-less tanning agents. Due to the core-shell structure, these Cr-PPAG NPs exhibit a 'Trojan horses' behavior which can protect Cr3+ from reacting with skin collagen during the penetration process, leading to effective and uniform delivery of Cr3+ to the rawhide's interior. Then, the released Cr3+ from Cr-PPAG NPs could cross-link the carboxyl groups both on the skin collagen and poly (PEGMA- co -AA- co -GMA), thereby producing the high-exhaustion chrome tanning effect. Furthermore, the GMA moieties of poly (PEGMA- co -AA- co -GMA) could further react with amino groups of collagen fiber. The synergy between chrome tanning and the organic tanning effects provided by Cr-PPAG NPs resulted in a chrome-less tanning technology. Finally, the final leather tanned with Cr-PPAG NPs exhibiting improved hygienic characteristics with excellent antiadhesive properties against E. coli and S. aureus bacterial strains. Image 1 • pH-sensitive and chromium (III)-loaded nanoparticles (Cr-PPAG NPs) were fabricated as a smart tanning system. • Cr-PPAG NPs tanning system is the unity of chrome-less tanning technology and high-exhaustion chrome tanning technology. • Cr-PPAG NPs adopt a transmission strategy similar to 'Trojan horses', leading to uniform chrome tanning effect. • The final leather tanned by Cr-PPAG NPs exhibiting improved hygienic characteristics. [ABSTRACT FROM AUTHOR]

• Flame temperature and soot characteristics are measured via optical diagnostics. • Adding propylene causes the transition from a non-smoking flame to a smoking flame. • The synergistic effect on soot particle diameter is found when blending propane. • Earlier inception time and longer growth time account for the synergistic effect. Soot evolution of the ethylene-based laminar coflow diffusion flame doping with methane, propane, and propylene with the blending ratio ranging from 0 to 50% has been investigated experimentally. These fuels were selected for their different fuel structure. Spatially resolved distribution maps of the flame temperature, soot volume fraction, the fluorescence signals of polycyclic aromatic hydrocarbons (PAHs), and primary soot particle diameter and number density were determined utilizing laser-induced incandescence (LII), laser-induced fluorescence (LIF), and ratio pyrometry (RP). It was found that the flame height surged and the flame temperature dropped dramatically when the propylene blending ratio was 20% while they were almost constant with the increasing addition of methane or propane. The soot/PAHs loading decreased monotonically with the addition of methane and the opposite was true in the cases of blending propylene. The synergistic effect of mixing propane into ethylene was found on both the soot/PAHs loading. The same trends were observed in the percentage of carbon conversion to soot and the primary soot particle diameter. It can be seen from the soot evolution analysis that methane addition suppressed the soot nucleation and surface growth simultaneously. The enhanced soot surface growth for the flames doping with propane at a low addition level and for the whole flame sets doping with propylene were attributed to the earlier inception time and the longer mass growth time. The preferential diffusion and weakened oxidation of soot particles because of the decreased flame temperature perhaps accounted for the transition from a non-smoking flame to a smoking flame when the propylene blending ratio was greater than 40%. [ABSTRACT FROM AUTHOR]

Abstract: G protein-coupled receptors (GPCRs) are the most frequently addressed drug targets in the pharmaceutical industry. However, achieving highly safety and efficacy in designing of GPCR drugs is quite challenging since their primary amino acid sequences show fairly high homology. Systematic study on the interaction spectra of inhibitors with multiple human GPCRs will shed light on how to design the inhibitors for different diseases which are related to GPCRs. To reach this goal, several proteochemometric models were constructed based on different combinations of two protein descriptors, two ligand descriptors and one ligand–receptor cross-term by two kinds of statistical learning techniques. Our results show that support vector regression (SVR) performs better than Gaussian processes (GP) for most combinations of descriptors. The transmembrane (TM) identity descriptors have more powerful ability than the z-scale descriptors in the characterization of GPCRs. Furthermore, the performance of our PCM models was not improved by introducing the cross-terms. Finally, based on the TM Identity descriptors and 28-dimensional drug-like index, two best PCM models with GP and SVR (GP-S-DLI: R 2 =0.9345, Q 2 test =0.7441; SVR-S-DLI: R 2 =1.0000, Q 2 test =0.7423) were derived respectively. The area of ROC curve was 0.8940 when an external test set was used, which indicates that our PCM model obtained a powerful capability for predicting new interactions between GPCRs and ligands. Our results indicate that the derived best model has a high predictive ability for human GPCR–inhibitor interactions. It can be potentially used to discover novel multi-target or specific inhibitors of GPCRs with higher efficacy and fewer side effects. [Copyright &y& Elsevier]

Abstract: Uricase was lost in hominoids during primate evolution, but the inactivation mechanism remains controversial. To investigate the inactivation process of hominoid uricase, chimeric constructions between canine and human uricase were employed to screen the target regions that may contain labile or inactivated mutations in deduced human uricase. Four chimeric uricases were constructed and showed different enzymatic characteristics. Homology modeling, rational site-directed mutagenesis and DNA alignment were used to analyze the changes. Arg119 is conserved in functional mammalian uricases and its side-chains are crucial in maintaining the stability of the β-barrel core. A single CGT (Arg) to CAT (His) mutation at codon 119 that is shared by the human and great ape clade greatly reduces this stability and could cause the loss of uricase activity. We speculate that this missense mutation occurred first and inactivated the uricase protein in humans and great apes and that later the known nonsense mutation at codon 33 occurred and silenced the uricase gene. A single GTC (Val) to GCC (Ala) mutation at codon 296 in canine uricase is regarded as deleterious structural mutation, but such kinds of deleterious mutations have been widely accumulated in extant mammalian uricases. We speculate that a reduction in uricase activity has been an evolutionary tendency in mammals. Moreover, from structure–activity analysis of helix 2 in ancestral primate uricase, we suggest that before the inactivation of hominoid uricase, deleterious structural evolutionary changes had occurred in ancestral primates. The loss of hominoid uricase should be caused by progressive multistep mutations rather than a single mutation event. [Copyright &y& Elsevier]

Abstract: The toxicity of melamine has attracted much attention since the outbreak of nephrolithiasis among children ingesting melamine-contaminated infant formula in China. However, there is little knowledge about the molecular mechanisms underlying the melamine-induced toxicity. In this paper, a ligand–protein docking method (INVDOCK) was applied to predict the toxicity-related target proteins for melamine and its metabolite, cyanuric acid. As a result, 23 and 35 proteins were finally identified as the potential target proteins for melamine and cyanuric acid, respectively. Through an enrichment analysis, it was found that nephrotoxicity and lung toxicity might be the most significant toxicities induced by melamine and cyanuric acid. Four target proteins (glutathione peroxidase 1, beta-hexosaminidase subunit beta, l-lactate dehydrogenase and lysozyme C) may be related to the molecular basis of the nephrotoxicity induced by melamine except for known kidney crystals formation. After mapping all these toxicity-related target proteins onto cellular pathways, it was indicated that the toxicities of melamine and cyanuric acid might also be caused by breaking down redox balance, perturbing the arginine and proline metabolism and damaging the homeostasis of energy production system. To further explore the mechanisms underlying the toxicities of melamine and cyanuric acid, a biological signal cascades network constructed by some of the toxicity-related target proteins was discussed. [Copyright &y& Elsevier]