Oriented Attachment of ZnO Nanocrystals

Self-organization of nanoparticles is a major issue to synthesize mesoscopic structures. Among the possible mechanisms leading to self-organization, the oriented attachment is efficient yet not completely understood. We investigate here the oriented attachment process of ZnO nanocrystals preformed in the gas phase. During the deposition in high vacuum, about 60% of the particles, which are uncapped, form larger crystals through oriented attachment. In the present conditions of deposition, no selective direction for the oriented attachment is noticed. To probe the driving force of the oriented attachment, and more specifically the possible influence of the dipolar interaction between particles, we have deposited the same nanocrystals in the presence of a constant electric field. The expected effect was to enhance the fraction of domains resulting from the oriented attachment due to the increased interaction of the particle dipoles with the electric field. The multiscale analytical and statistical analysis (TEM coupled to XRD) shows no significant influence of the electric field on the organization of the particles. We therefore conclude that the dipolar interaction between nanocrystals is not the prominent driving force in the process. Consequently, we argue, in accordance with recent theoretical and experimental investigations, that the surface reduction, possibly driven by Coulombic interaction, may be the major mechanism for the oriented attachment process

Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

Analysis of the transcriptomic signature of white adipose tissue in obese human subjects revealed increased interstitial fibrosis and an infiltration of inflammatory cells into the tissue

Flow photochemistry: a meso-scale reactor for industrial applications

Developing flow photochemistry, especially at meso-scale where significant productivity is required, remains challenging. There is a need for innovative equipments generating highly controlled flow under light irradiation. In this work, a commercial solution, developed by Corning, is presented and studied by LGC and MEPI on an intramolecular (2+2) photo-cycloaddition. Detailed experimental and modelling analysis has been performed to emphasize the flow reactor behaviour and performances, and demonstrate its capability in producing up to 30g.h-1 of the desired molecule. Through this simple model reaction, the G1 photo-reactor is shown to be an efficient meso-scale reactor for industrial photo-applications development and production

Deficiency of FcεR1 increases body weight gain but improves glucose tolerance in diet-induced obese mice

Prior studies demonstrated increased plasma immunoglobulin E (IgE) in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcεR1-deficient (Fcer1a–/–) mice and diet-induced obesity (DIO) mice demonstrated that FcεR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain, but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue (WAT) from Fcer1a–/– mice showed increased expression of phospho-AKT, C/EBPα, PPARγ, Glut4, and Bcl-2, but reduced UCP1 and phospho-JNK expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake, but induces energy expenditure, adipocyte apoptosis, and WAT inflammation. In 3T3-L1 cells, IgE inhibited the expression of C/EBPα and PPARγ, and preadipocyte adipogenesis, and induced adipocyte apoptosis. IgE reduced 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a–/– mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis, while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion

Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars

OBJECTIVE Nonalcoholic fatty liver disease (i.e., increased intrahepatic triglyceride [IHTG] content), predisposes to type 2 diabetes and cardiovascular disease. Adipose tissue lipolysis and hepatic de novo lipogenesis (DNL) are the main pathways contributing to IHTG. We hypothesized that dietary macronutrient composition influences the pathways, mediators, and magnitude of weight gain-induced changes in IHTG. RESEARCH DESIGN AND METHODS We overfed 38 overweight subjects (age 48 ± 2, BMI 31 ± 1 kg/m2, liver fat 4.7 ± 0.9%) 1,000 extra kcal/day of saturated (SAT) or unsaturated (UNSAT) fat or simple sugars (CARB) for 3 weeks. We measured IHTG (1H-MRS), pathways contributing to IHTG (lipolysis ([2H5]glycerol) and DNL (2H2O) basally and during euglycemic hyperinsulinemia, insulin resistance, endotoxemia, plasma ceramides, and adipose tissue gene expression at 0 and 3 weeks. RESULTS Overfeeding SAT increased IHTG more (+55%) than UNSAT (+15%, P < 0.05). CARB increased IHTG (+33%) by stimulating DNL (+98%). SAT significantly increased while UNSAT decreased lipolysis. SAT induced insulin resistance and endotoxemia and significantly increased multiple plasma ceramides. The diets had distinct effects on adipose tissue gene expression. CONCLUSIONS Macronutrient composition of excess energy influences pathways of IHTG: CARB increases DNL, while SAT increases and UNSAT decreases lipolysis. SAT induced greatest increase in IHTG, insulin resistance, and harmful ceramides. Decreased intakes of SAT could be beneficial in reducing IHTG and the associated risk of diabetes

Dietary factors and low-grade inflammation in relation to overweight and obesity

Low-grade inflammation is a characteristic of the obese state, and adipose tissue releases many inflammatory mediators. The source of these mediators within adipose tissue is not clear, but infiltrating macrophages seem to be especially important, although adipocytes themselves play a role. Obese people have higher circulating concentrations of many inflammatory markers than lean people do, and these are believed to play a role in causing insulin resistance and other metabolic disturbances. Blood concentrations of inflammatory markers are lowered following weight loss. In the hours following the consumption of a meal, there is an elevation in the concentrations of inflammatory mediators in the bloodstream, which is exaggerated in obese subjects and in type 2 diabetics. Both high-glucose and high-fat meals may induce postprandial inflammation, and this is exaggerated by a high meal content of advanced glycation end products (AGE) and partly ablated by inclusion of certain antioxidants or antioxidant-containing foods within the meal. Healthy eating patterns are associated with lower circulating concentrations of inflammatory markers. Among the components of a healthy diet, whole grains, vegetables and fruits, and fish are all associated with lower inflammation. AGE are associated with enhanced oxidative stress and inflammation. SFA and trans-MUFA are pro-inflammatory, while PUFA, especially long-chain n-3 PUFA, are anti-inflammatory. Hyperglycaemia induces both postprandial and chronic low-grade inflammation. Vitamin C, vitamin E and carotenoids decrease the circulating concentrations of inflammatory markers. Potential mechanisms are described and research gaps, which limit our understanding of the interaction between diet and postprandial and chronic low-grade inflammation, are identifie

Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically-characterised cohort

Correction: Volume: 74 Issue: 5 Pages: 1274-1275 DOI: 10.1016/j.jhep.2021.02.003 Correction: Volume78, Issue5 Page: 1085-1086 DOI: 10.1016/j.jhep.2023.02.028 Published MAY 2023Background and Aims Genetic factors associated with non-alcoholic fatty liver disease (NAFLD) remain incompletely understood. To date, most GWAS studies have adopted radiologically assessed hepatic triglyceride content as reference phenotype and so cannot address steatohepatitis or fibrosis. We describe a genome-wide association study (GWAS) encompassing the full spectrum of histologically characterized NAFLD. Methods The GWAS involved 1483 European NAFLD cases and 17781 genetically-matched population controls. A replication cohort of 559 NAFLD cases and 945 controls was genotyped to confirm signals showing genome-wide or close to genome-wide significance. Results Case-control analysis identified signals showing p-values ≤ 5 x 10-8 at four locations (chromosome (chr) 2 GCKR/C2ORF16; chr4 HSD17B13; chr19 TM6SF2; chr22 PNPLA3) together with two other signals with pPeer reviewe

GAD2 on chromosome 10p12 is a candidate gene for human obesity

The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11&ndash;12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of &gamma;-aminobutyric acid (GABA), which interacts with neuropeptide Y in the paraventricular nucleus to contribute to stimulate food intake. A case-control study (575 morbidly obese and 646 control subjects) analyzing GAD2 variants identified both a protective haplotype, including the most frequent alleles of single nucleotide polymorphisms (SNPs) +61450 C&gt;A and +83897 T&gt;A (OR = 0.81, 95% CI [0.681&ndash;0.972], p = 0.0049) and an at-risk SNP (&minus;243 A&gt;G) for morbid obesity (OR = 1.3, 95% CI [1.053&ndash;1.585], p = 0.014). Furthermore, familial-based analyses confirmed the association with the obesity of SNP +61450 C&gt;A and +83897 T&gt;A haplotype (&chi;2 = 7.637, p = 0.02). In the murine insulinoma cell line &beta;TC3, the G at-risk allele of SNP &minus;243 A&gt;G increased six times GAD2 promoter activity (p &lt; 0.0001) and induced a 6-fold higher affinity for nuclear extracts. The &minus;243 A&gt;G SNP was associated with higher hunger scores (p = 0.007) and disinhibition scores (p = 0.028), as assessed by the Stunkard Three-Factor Eating Questionnaire. As GAD2 is highly expressed in pancreatic &beta; cells, we analyzed GAD65 antibody level as a marker of &beta;-cell activity and of insulin secretion. In the control group, &minus;243 A&gt;G, +61450 C&gt;A, and +83897 T&gt;A SNPs were associated with lower GAD65 autoantibody levels (p values of 0.003, 0.047, and 0.006, respectively). SNP +83897 T&gt;A was associated with lower fasting insulin and insulin secretion, as assessed by the HOMA-B% homeostasis model of &beta;-cell function (p = 0.009 and 0.01, respectively). These data support the hypothesis of the orexigenic effect of GABA in humans and of a contribution of genes involved in GABA metabolism in the modulation of food intake and in the development of morbid obesity.<br /

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology