Explore the vast range of titles available.

In recent years, there has been significant interest in quantum technology, characterized by the emergence of quantum computers boasting immense processing power, ultra-sensitive quantum sensors, and ultra-precise atomic clocks. Miniaturization of quantum devices using cold atoms necessitates the employment of an ultra-high vacuum miniature cell with a pressure of approximately 10−6 Pa or even lower. In this study, we developed an ultra-high vacuum cell realized by a miniature ion pump using a high-efficiency plasma source. Initially, an unsealed miniature ion pump was introduced into a vacuum chamber, after which the ion pump’s discharge current, depending on vacuum pressures, was evaluated. Subsequently, a miniature vacuum cell was fabricated by hermetically sealing the miniature vacuum pump. The cell was successfully evacuated by a miniature ion pump down to an ultra-high vacuum region, which was derived by the measured discharge current. Our findings demonstrate the feasibility of achieving an ultra-high vacuum cell necessary for the operation of miniature quantum devices.

Purpose The breast shape differs between the prone position in breast magnetic resonance imaging (MRI) and the supine position on an operating table. We sought to determine the relationship between patient position-induced changes on prone and supine MRI in breast shape and mammographic breast density or thickness. Materials and methods We evaluated data from 68 women with 69 breast cancers in this retrospective observational study. The difference in the minimal distance from the nipple to the pectoralis major (DNPp-s) or the internal thoracic artery between the prone and supine MRI (DNIs-p) was defined as the breast shape changes. Mammographic breast density was assessed by conventional 4-level classification and automated and manual quantification using a dedicated mammography viewer. The compressed breast thickness was recorded during mammography (MMG). We determined the association between patient position-induced breast shape changes on MRI and mammographic breast density or compressed breast thickness on MMG. Results On the conventional 4-level qualification, one breast appeared fatty, 39 appeared with scattered density, 23 appeared heterogeneously dense, and 6 breasts appeared extremely dense. Both automated and manual quantification of mammographic breast density differed between the 4 levels ( p  < 0.01 for both) and correlated with the 4 levels ( p  < 0.001 for both, r  = 0.654 and 0.693, respectively). The manual quantification inversely correlated with DNPp-s and DNIs-p ( p  < 0.01 and < 0.05, r  =  − 0.330 and − 0.273, respectively). The compressed breast thickness significantly correlated with DNPp-s and DNIs-p ( p  < 0.01 for both, r  = 0.648 and 0.467, respectively). Conclusion Compressed breast thickness during MMG can predict the degree of patient position-induced changes in breast shape on MRI. The manual quantification of the mammographic breast density, which may reflect the biomechanical properties of the breast tissues, also correlates to the breast shape changes.

In this study, we design a highly efficient plasma source using a magnetic mirror trap with two opposing permanent magnets for a miniature high-efficiency ion pump. First, we simulated the distribution of the magnetic field line formed by the proposed magnetic mirror configuration. By optimizing the distance between two opposing permanent magnets and size of these magnets, a magnetic mirror ratio value of 27 could be obtained, which is an electron confinement efficiency of over 90%. We also conducted an experiment on a high-efficiency discharge plasma source for a miniature ion pump using an optimized magnetic circuit. As a result, we revealed that the proposed magnetic circuit has a pronounced effect on plasma generation, particularly in the high-vacuum region.

Key Points Adipose tissue is a target tissue for vitamin D, as 1,25-dihydroxyvitamin D 3 stimulates the expression of typical adipocyte genes, such as leptin, and inhibits the expression of uncoupling proteins in vitro Vdr −/− and Cyp27b1 −/− mice display increased energy expenditure and lower fat mass accumulation with ageing, whereas mice overexpressing Vdr in adipocytes become obese Two mechanisms might explain the increased energy expenditure of Vdr −/− and Cyp27b1 −/− mice: increased adipocyte expression of uncoupling proteins, such as UCP1 and UCP2, or an increased bile acid pool Bile acids are known stimulators of nuclear receptors, for example, BAR (also known as FXR), CAR, PXR and VDR, and G-protein-coupled receptors, such as GPBAR1 (also known as TGR5), which can act as potent regulators of energy expenditure Cross-sectional and long-term observational studies in different populations worldwide show that human obesity and the metabolic syndrome and its components are associated with poor vitamin D status Vitamin D deficiency generates resistance to diet-induced obesity in mice, whereas in humans poor vitamin D status is strongly associated with obesity: no satisfactory explanation for this discrepancy exists Enormous differences exist between human studies, which show a strong association of low vitamin D status with obesity, and mouse data, where low vitamin D signalling causes resistance to obesity. Understanding these discrepancies may provide better insight into the spectrum of activities of vitamin D and should be of interest considering the world epidemic of obesity and the metabolic syndrome. The vitamin D endocrine system has many extraskeletal targets, including adipose tissue. 1,25-Dihydroxyvitamin D 3 , the active form of vitamin D, not only increases adipogenesis and the expression of typical adipocyte genes but also decreases the expression of uncoupling proteins. Mice with disrupted vitamin D action—owing to gene deletion of the nuclear receptor vitamin D receptor ( Vdr ) or the gene encoding 1α-hydroxylase ( Cyp27b1 )—lose fat mass over time owing to an increase in energy expenditure, whereas mice with increased Vdr -mediated signalling in adipose tissue become obese. The resistance to diet-induced obesity in mice with disrupted Vdr signalling is caused at least partially by increased expression of uncoupling proteins in white adipose tissue. However, the bile acid pool is also increased in these animals, and bile acids are known to be potent inducers of energy expenditure through activation of several nuclear receptors, including Vdr , and G-protein-coupled receptors, such as GPBAR1 (also known as TGR5). By contrast, in humans, obesity is strongly associated with poor vitamin D status. A causal link has not been firmly proven, but most intervention studies have failed to demonstrate a beneficial effect of vitamin D supplementation on body weight. The reasons for the major discrepancy between mouse and human data are unclear, but understanding the link between vitamin D status and energy homeostasis could potentially be very important for the human epidemic of obesity and the metabolic syndrome.

Disruption of iron metabolism is closely related to metabolic diseases. Iron deficiency is frequently associated with obesity and hepatic steatosis. However, the effects of iron supplementation on obesity and energy metabolism remain unclear. Here we show that a high-fat diet supplemented with iron reduces body weight gain and hepatic lipid accumulation in mice. Iron supplementation was found to reduce mitochondrial morphological abnormalities and upregulate gene transcription involved in mitochondrial function and beta oxidation in the liver and skeletal muscle. In both these tissues, iron supplementation increased the expression of genes involved in heme or iron–sulfur (Fe–S) cluster synthesis. Heme and Fe–S cluster, which are iron prosthetic groups contained in electron transport chain complex subunits, are essential for mitochondrial respiration. The findings of this study demonstrated that iron regulates mitochondrial signaling pathways—gene transcription of mitochondrial component molecules synthesis and their energy metabolism. Overall, the study elucidates the molecular basis underlying the relationship between iron supplementation and obesity and hepatic steatosis progression, and the role of iron as a signaling molecule.

Anionic exchange resins are bona fide cholesterol-lowering agents with glycemia lowering actions in diabetic patients. Potentiation of intestinal GLP-1 secretion has been proposed to contribute to the glycemia lowering effect of these non-systemic drugs. Here, we show that resin exposure enhances GLP-1 secretion and improves glycemic control in diet-induced animal models of “diabesity”, effects which are critically dependent on TGR5, a G protein-coupled receptor that is activated by bile acids. We identified the colon as a major source of GLP-1 secretion after resin treatment. Furthermore, we demonstrate that the boost in GLP-1 release by resins is due to both enhanced TGR5-dependent production of the precursor transcript of GLP-1 as well as to the local enrichment of TGR5 agonists in the colon. Thus, TGR5 represents an essential component in the pathway mediating the enhanced GLP-1 release in response to anionic exchange resins.

Turn up the heat Bile acids are known to mediate dietary lipid absorption and cholesterol catabolism, and recently an important signalling role emerged. Now they have been found to increase energy expenditure in brown adipose tissue and human skeletal muscle. As bile acid signalling may drive diet-induced heat production, it is a possible therapeutic target for the control of energy homeostasis. While bile acids (BAs) have long been known to be essential in dietary lipid absorption and cholesterol catabolism, in recent years an important role for BAs as signalling molecules has emerged. BAs activate mitogen-activated protein kinase pathways 1 , 2 , are ligands for the G-protein-coupled receptor (GPCR) TGR5 3 , 4 and activate nuclear hormone receptors such as farnesoid X receptor α (FXR-α; NR1H4) 5 , 6 , 7 . FXR-α regulates the enterohepatic recycling and biosynthesis of BAs by controlling the expression of genes such as the short heterodimer partner (SHP; NR0B2) 8 , 9 that inhibits the activity of other nuclear receptors. The FXR-α-mediated SHP induction also underlies the downregulation of the hepatic fatty acid and triglyceride biosynthesis and very-low-density lipoprotein production mediated by sterol-regulatory-element-binding protein 1c 10 . This indicates that BAs might be able to function beyond the control of BA homeostasis as general metabolic integrators. Here we show that the administration of BAs to mice increases energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This novel metabolic effect of BAs is critically dependent on induction of the cyclic-AMP-dependent thyroid hormone activating enzyme type 2 iodothyronine deiodinase (D2) because it is lost in D2 -/- mice. Treatment of brown adipocytes and human skeletal myocytes with BA increases D2 activity and oxygen consumption. These effects are independent of FXR-α, and instead are mediated by increased cAMP production that stems from the binding of BAs with the G-protein-coupled receptor TGR5. In both rodents and humans, the most thermogenically important tissues are specifically targeted by this mechanism because they coexpress D2 and TGR5. The BA–TGR5–cAMP–D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control.

Salt is an essential nutrient; however, excessive salt intake is a prominent public health concern worldwide. Various physiological functions are associated with circadian rhythms, and disruption of circadian rhythms is a prominent risk factor for cardiovascular diseases, cancer, and immune disease. Certain nutrients are vital regulators of peripheral circadian clocks. However, the role of a high-fat and high-salt (HFS) diet in the regulation of circadian gene expression is unclear. This study aimed to investigate the effect of an HFS diet on rhythms of locomotor activity, caecum glucocorticoid secretion, and clock gene expression in mice. Mice administered an HFS diet displayed reduced locomotor activity under normal light/dark and constant dark conditions in comparison with those administered a normal diet. The diurnal rhythm of caecum glucocorticoid secretion and the expression levels of glucocorticoid-related genes and clock genes in the adrenal gland were disrupted with an HFS diet. These results suggest that an HFS diet alters locomotor activity, disrupts circadian rhythms of glucocorticoid secretion, and downregulates peripheral adrenal gland circadian clock genes.

Elucidating the signalling mechanisms by which obesity leads to impaired insulin action is critical in the development of therapeutic strategies for the treatment of diabetes. Recently, mice deficient for S6 Kinase 1 (S6K1), an effector of the mammalian target of rapamycin (mTOR) that acts to integrate nutrient and insulin signals, were shown to be hypoinsulinaemic, glucose intolerant and have reduced β-cell mass. However, S6K1-deficient mice maintain normal glucose levels during fasting, suggesting hypersensitivity to insulin, raising the question of their metabolic fate as a function of age and diet. Here, we report that S6K1-deficient mice are protected against obesity owing to enhanced β-oxidation. However on a high fat diet, levels of glucose and free fatty acids still rise in S6K1-deficient mice, resulting in insulin receptor desensitization. Nevertheless, S6K1-deficient mice remain sensitive to insulin owing to the apparent loss of a negative feedback loop from S6K1 to insulin receptor substrate 1 (IRS1), which blunts S307 and S636/S639 phosphorylation; sites involved in insulin resistance. Moreover, wild-type mice on a high fat diet as well as K/K Ay and ob/ob (also known as Lep/Lep) micetwo genetic models of obesityhave markedly elevated S6K1 activity and, unlike S6K1-deficient mice, increased phosphorylation of IRS1 S307 and S636/S639. Thus under conditions of nutrient satiation S6K1 negatively regulates insulin signalling.

Besides well-established roles of bile acids (BA) in dietary lipid absorption and cholesterol homeostasis, it has recently become clear that BA is also a biological signaling molecule. We have shown that strategies aimed at activating TGR5 by increasing the BA pool size with BA administration may constitute a significant therapeutic advance to combat the metabolic syndrome and suggest that such strategies are worth testing in a clinical setting. Bile acid binding resin (BABR) is known not only to reduce serum cholesterol levels but also to improve glucose tolerance and insulin resistance in animal models and humans. However, the mechanisms by which BABR affects glucose homeostasis have not been established. We investigated how BABR affects glycemic control in diet-induced obesity models. We evaluated the metabolic effect of BABR by administrating colestimide to animal models for the metabolic syndrome. Administration of BABR increased energy expenditure, translating into significant weight reduction and insulin sensitization. The metabolic effects of BABR coincide with activation of cholesterol and BA synthesis in liver and thermogenesis in brown adipose tissue. Interestingly, these effects of BABR occur despite normal food intake and triglyceride absorption. Administration of BABR and BA had similar effects on BA composition and thermogenesis, suggesting that they both are mediated via TGR5 activation. Our data hence suggest that BABR could be useful for the management of the impaired glucose tolerance of the metabolic syndrome, since they not only lower cholesterol levels, but also reduce obesity and improve insulin resistance.