In the absence of consistent clinical evidence, there are concerns that fructose contributes to non-alcoholic fatty liver disease (NAFLD). To determine the effect of fructose on markers of NAFLD, we ...conducted a systematic review and meta-analysis of controlled feeding trials.
We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library (through 3 September 2013). We included relevant trials that involved a follow-up of ≥ 7 days. Two reviewers independently extracted relevant data. Data were pooled by the generic inverse variance method using random effects models and expressed as standardized mean difference (SMD) for intrahepatocellular lipids (IHCL) and mean difference (MD) for alanine aminotransferase (ALT). Inter-study heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic).
Eligibility criteria were met by eight reports containing 13 trials in 260 healthy participants: seven isocaloric trials, in which fructose was exchanged isocalorically for other carbohydrates, and six hypercaloric trials, in which the diet was supplemented with excess energy (+21-35% energy) from high-dose fructose (+104-220 g/day). Although there was no effect of fructose in isocaloric trials, fructose in hypercaloric trials increased both IHCL (SMD=0.45 (95% confidence interval (CI): 0.18, 0.72)) and ALT (MD=4.94 U/l (95% CI: 0.03, 9.85)).
Few trials were available for inclusion, most of which were small, short (≤ 4 weeks), and of poor quality.
Isocaloric exchange of fructose for other carbohydrates does not induce NAFLD changes in healthy participants. Fructose providing excess energy at extreme doses, however, does raise IHCL and ALT, an effect that may be more attributable to excess energy than fructose. Larger, longer and higher-quality trials of the effect of fructose on histopathological NAFLD changes are required.
•Compound target ID technologies have unique strengths that can be used strategically.•Target ID approaches are trending toward unbiased, genome-wide methods.•Compound mechanisms involve efficacy ...targets as well as epistatic protein effectors.•Integration of chemical biology data facilitates systematic chemical biology.
The identification of the efficacy target(s) for hits from phenotypic compound screens remains a key step to progress compounds into drug development. In addition to efficacy targets, the characterization of epistatic proteins influencing compound activity often facilitates the elucidation of the underlying mechanism of action; and, further, early determination of off-targets that cause potentially unwanted secondary phenotypes helps in assessing potential liabilities. This short review discusses the most important technologies currently available for characterizing the direct and indirect target space of bioactive compounds following phenotypic screening. We present a comprehensive strategy employing complementary approaches to balance individual technology strengths and weaknesses.
Elemental sulfur (S8) is produced in abundance during petroleum refinement, generating millions of tons of waste. Inverse vulcanization utilizes this waste as a feedstock to create new materials. ...Heating S8 above 159 °C initiates ring-opening, forming radicals that react with difunctional monomers to create polysulfides. High temperature requirements limit the types of monomers that can be incorporated by inverse vulcanization. However, cleaving the linear sulfur chains present in the polysulfides requires less energy. Here, poly(S–divinylbenzene) with varied sulfur contents has been synthesized to act as a prepolymer capable of radical formation at much lower temperatures (90 °C). Dynamic sulfur bonds initiate polymerization with a family of vinylic and allylic ethers. Terpolymers were characterized by NMR spectroscopy, gel permeation chromatography, and differential scanning calorimetry to examine the impact on structure and physical properties. This method expands on inverse vulcanized polymers to create a mild, solvent-free route to polysulfide synthesis.
The role of dietary fiber in obesity management remains debatable. Evidence suggests that intake of viscous fiber may have the potential to facilitate weight loss.
We aimed to summarize and quantify ...the effects of viscous fiber on body weight, BMI, waist circumference, and body fat, independent of calorie restriction, through a systematic review and meta-analysis of randomized controlled trials.
Trials ≥4 wk in duration that assessed the effect of viscous fiber supplemented to an ad libitum diet along with comparator diets were included. MEDLINE, EMBASE, and the Cochrane library were searched through 24 July, 2019. Two independent reviewers extracted relevant data. Data were pooled using the generic inverse variance method and random-effects models and expressed as mean differences with 95% CIs. Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The overall certainty of evidence was explored using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
Findings from 62 trials (n = 3877) showed that viscous fiber reduced mean body weight (−0.33 kg; 95% CI: −0.51, −0.14 kg; P = 0.004), BMI (in kg/m2) (−0.28; 95% CI: −0.42, −0.14; P = 0.0001), and waist circumference (−0.63 cm; 95% CI: −1.11, −0.16 cm; P = 0.008), with no change in body fat (−0.78%; 95% CI: −1.56%, 0.00%; P = 0.05) when consumed with an ad libitum diet. Greater reductions in body weight were observed in overweight individuals and those with diabetes and metabolic syndrome. The certainty of evidence was graded moderate for body weight, high for waist circumference and body fat, and low for BMI.
Dietary viscous fiber modestly yet significantly improved body weight and other parameters of adiposity independently of calorie restriction. Future trials are warranted to address the inconsistency and imprecision identified through GRADE and to determine long-term weight-loss sustainability. This systematic review and meta-analysis was registered at clinicaltrials.gov as NCT03257449.
Natural materials have been used as glues throughout human history. Over the last century, society has come to rely heavily on synthetic, petroleum-based adhesives instead, consuming ∼14 million tons ...per year. In recent years, however, there has been a resurgence of glues formed with renewable materials. This work seeks to integrate the two to form strong adhesives. Here, elemental sulfur was combined with diallyl sulfide (DAS), diallyl disulfide (DADS), and garlic essential oil (GEO) to form adhesive polymers from recycled petroleum waste and renewable monomers. The labile sulfur bonds in DADS and GEO allowed these monomers to be homopolymerized, forming polysulfides entirely from renewable monomers. Heating these materials causes them to transition from viscous liquids to hardened solids. A family of copolymers containing different garlic components and varying sulfur-to-monomer ratios were synthesized, characterized, and tested for this study. Polymer structures were confirmed by 1H NMR. Changes to the polysulfide material properties upon curing were examined by gel permeation chromatography and differential scanning calorimetry. Characterization data of cured polymers were used to choose the optimal cure temperature for adhesion studies. The adhesion strength of polysulfides with varying compositions was determined by single-lap shear testing. Strong bonding was obtained for all garlic-based polysulfides with strengths 3 times higher than commercial hide glue.
Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and ...transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment. Mechanistically, we show that TOP1MT associates with mitoribosomal subunits, ensuring optimal mitochondrial translation and assembly of oxidative phosphorylation complexes that are critical for sustaining tumor growth. The TOP1MT genomic signature profile, based on Top1mt-KO liver cancers, is correlated with enhanced survival of hepatocellular carcinoma patients. Our results highlight the importance of TOP1MT for tumor development, providing a potential rationale to develop TOP1MT-targeted drugs as anticancer therapies.
The absolute-magnitude distributions of seven supernova (SN) types are presented. The data used here were primarily taken from the Asiago Supernova Catalogue, but were supplemented with additional ...data. We accounted for both foreground and host-galaxy extinction. A bootstrap method is used to correct the samples for Malmquist bias. Separately, we generate volume-limited samples, restricted to events within 100 Mpc. We find that the superluminous events (M sub(B) < -21) make up only about 0.1% of all SNe in the bias-corrected sample. The subluminous events (M sub(B) > -15) make up about 3%. The normal la distribution was the brightest with a mean absolute blue magnitude of -19.25. The HP distribution was the dimmest at -16.75.
The role of sugar-sweetened beverages (SSBs) that contain free or bound fructose in the pathogenesis of hypertension remains unclear.
We conducted a systematic review and meta-analysis of prospective ...cohort studies to quantify the association between fructose-containing SSBs and risk of hypertension.
MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane registry were searched from conception through 11 November 2014. Two independent reviewers extracted data and assessed the quality of studies (with the use of the Newcastle-Ottawa Scale). Risk estimates of extreme quantiles of SSB intake (lowest compared with highest) for hypertension incidence were generated with the use of generic inverse-variance methods with random-effects models and expressed as risk ratios with 95% CIs. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I(2) statistic.
Six prospective cohort studies (n = 240,508) with 79,251 cases of hypertension observed over ≥3,197,528 person-years of follow-up were included. SSB consumption significantly increased the risk of developing hypertension by 12% (risk ratio: 1.12; 95% CI: 1.06, 1.17) with evidence of significant heterogeneity (I(2) = 62%, P = 0.02) when highest ≥1 serving (6.7, 8, or 12 oz)/d and lowest (none) quantiles of intake were compared. With the use of a dose-response analysis, a significant 8.2% increase in risk of every additional SSB per day from none to ≥1 SSB/d (β = 0.0027, P < 0.001) was identified. Limitations include unexplained heterogeneity and residual confounding. The results may also have been subject to collinearity effects from aspects of a Western dietary pattern.
SSBs were associated with a modest risk of developing hypertension in 6 cohorts. There is a need for high-quality randomized trials to assess the role of SSBs in the development of hypertension and its complications. This study was registered at clinicaltrials.gov as NCT01608620.
Aquaculture is the fastest-growing farmed food sector and will soon become the primary source of fish and shellfish for human diets. In contrast to crop and livestock production, aquaculture ...production is derived from numerous, exceptionally diverse species that are typically in the early stages of domestication. Genetic improvement of production traits via well-designed, managed breeding programmes has great potential to help meet the rising seafood demand driven by human population growth. Supported by continuous advances in sequencing and bioinformatics, genomics is increasingly being applied across the broad range of aquaculture species and at all stages of the domestication process to optimize selective breeding. In the future, combining genomic selection with biotechnological innovations, such as genome editing and surrogate broodstock technologies, may further expedite genetic improvement in aquaculture.
In-situ irradiations with 150 keV W+ ions have been performed on W and W-5wt.% (Re; Ta; V) alloys in a comprehensive study of the influences of irradiation temperature Tirr, dose, alloying elements ...and grain orientations on radiation damage production and microstructural evolution. For Tirr between 30 K and 1073 K, the first observable defects in pure W appeared at doses ≤0.01 dpa, and were most likely vacancy loops, with Burgers vectors predominantly of type b = ½ . With increasing Tirr, the retained defect concentration decreased strongly and the maximum cluster size increased from ∼1300 point defects at 30 K to ∼2300 point defects at 1073 K. At all irradiation temperatures, the evolution of damage microstructures with dose from 0.1 to 1.0 dpa involved defect cluster migration, with mutual elastic interactions often leading to spatial inhomogeneities and loop reactions. In pure W, spatial ordering of loops was observed at doses >0.4 dpa and Tirr≥773 K in grains close to z = . No such ordering was found in similar grain orientations for the W-(Re; Ta) alloys, but it was found in the non-z = grains. Post-irradiation analysis on W and W-5 wt% (Re; Ta) at 1.0 dpa showed that ½ and loops of both vacancy and interstitial type were present, at number densities ∼ 1015 loops m−2. In all cases ½ loops were dominant, the fraction of these with interstitial nature increased with Tirr, and the proportion of loops decreased with increasing Tirr. Compared with pure W, microstructures in the W-(Re; Ta) alloys exhibited higher loop number densities and evolved more quickly with increasing dose towards damage saturation.
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