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Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.

Dopaminergic (DA) neurons are involved in the integration of neuronal and hormonal signals to regulate food consumption and energy balance. Forkhead transcriptional factor O1 (FoxO1) in the hypothalamus plays a crucial role in mediation of leptin and insulin function. However, the homoeostatic role of FoxO1 in DA system has not been investigated. Here we report that FoxO1 is highly expressed in DA neurons and mice lacking FoxO1 specifically in the DA neurons (FoxO1 KO DAT ) show markedly increased energy expenditure and interscapular brown adipose tissue (iBAT) thermogenesis accompanied by reduced fat mass and improved glucose/insulin homoeostasis. Moreover, FoxO1 KO DAT mice exhibit an increased sucrose preference in concomitance with higher dopamine and norepinephrine levels. Finally, we found that FoxO1 directly targets and negatively regulates tyrosine hydroxylase (TH) expression, the rate-limiting enzyme of the catecholamine synthesis, delineating a mechanism for the KO phenotypes. Collectively, these results suggest that FoxO1 in DA neurons is an important transcriptional factor that directs the coordinated control of energy balance, thermogenesis and glucose homoeostasis. Dopaminergic neurons are important for regulating energy homeostasis. Here, the authors show the transcription factor FoxO1 negatively regulates tyrosine hydroxylase expression in midbrain dopaminergic neurons, and plays an important role in regulation of glucose homeostasis, energy expenditure, and resistance to diet-induced obesity.

Development of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1. Specifically, insulin increased the protein and RNA levels of SF-1 and steroidogenic target genes. Further, adrenal SF-1 expression was significantly increased by hyperactivation of insulin signaling in mice. Together with the elevated SF-1 expression in adrenal glands, hyperactivation of insulin signaling led to increased aldosterone and corticosterone levels. On the other hand, suppressing the insulin signaling using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In addition, overexpression of FoxO1 significantly suppressed SF-1 and its steroidogenic target genes implying that the positive effect of insulin on SF-1 activity might be through suppression of FoxO1 in the adrenal gland. Taken together, these results indicate that insulin regulates adrenal steroidogenesis through coordinated control of SF-1 and FoxO1.

AMP-activated protein kinase (AMPK) plays a crucial role in the regulation of energy homeostasis in both peripheral metabolic organs and the central nervous system. Recent studies indicated that p-Coumaric acid (CA), a hydroxycinnamic phenolic acid, potentially activated the peripheral AMPK pathway to exert beneficial effects on glucose metabolism in vitro. However, CA’s actions on central AMPK activity and whole-body glucose homeostasis have not yet been investigated. Here, we reported that CA exhibited different effects on peripheral and central AMPK activation both in vitro and in vivo. Specifically, while CA treatment promoted hepatic AMPK activation, it showed an inhibitory effect on hypothalamic AMPK activity possibly by activating the S6 kinase. Furthermore, CA treatment enhanced hypothalamic leptin sensitivity, resulting in increased proopiomelanocortin (POMC) expression, decreased agouti-related peptide (AgRP) expression, and reduced daily food intake. Overall, CA treatment improved blood glucose control, glucose tolerance, and insulin sensitivity. Together, these results suggested that CA treatment enhanced hypothalamic leptin signaling and whole-body glucose homeostasis, possibly via its differential effects on AMPK activation.

4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus. Obesity: Balancing the energy budget Ferulic acid (FA), which is found in grains, fruits and some algae, may help to protect against obesity by regulating eating behavior. An imbalance between food intake and energy expenditure can lead to obesity and related diseases such as type II diabetes. FA had previously been shown to aid in regulating metabolism, but the molecular pathway remained obscure. Ki Woo Kim at the Wonju College of Medicine in South Korea and co-workers used a mouse model to investigate the underlying mechanisms. They found that when mice were fed a high-fat diet, those treated with FA ate less food to compensate for the food's higher fat content. Further investigation revealed that FA may act on a genetic switch involved in feelings of hunger. The researchers conclude that FA shows potential for use as a food-derived supplement to prevent obesity.

Nicotinamide adenine dinucleotide (NAD + ) is an essential co-factor in metabolic reactions and co-substrate for signaling enzymes. Failing human hearts display decreased expression of the major NAD + biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) and lower NAD + levels, and supplementation with NAD + precursors is protective in preclinical models. Here we show that Nampt loss in adult cardiomyocytes caused depletion of NAD + along with marked metabolic derangements, hypertrophic remodeling and sudden cardiac deaths, despite unchanged ejection fraction, endurance and mitochondrial respiratory capacity. These effects were directly attributable to NAD + loss as all were ameliorated by restoring cardiac NAD + levels with the NAD + precursor nicotinamide riboside (NR). Electrocardiograms revealed that loss of myocardial Nampt caused a shortening of QT intervals with spontaneous lethal arrhythmias causing sudden cardiac death. Thus, changes in NAD + concentration can have a profound influence on cardiac physiology even at levels sufficient to maintain energetics. Doan et al. show that loss of cardiac NAD + is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Thermo-electric Coolers (TECs) nowadays are applied in a wide range of thermal energy systems. This is due to their superior features where no refrigerant and dynamic parts are needed. TECs generate no electrical or acoustical noise and are environmentally friendly. Over the past decades, many researches were employed to improve the efficiency of TECs by enhancing the material parameters and design parameters. The material parameters are restricted by currently available materials and module fabricating technologies. Therefore, the main objective of TECs design is to determine a set of design parameters such as leg area, leg length and the number of legs. Two elements that play an important role when considering the suitability of TECs in applications are rated of refrigeration (ROR) and coefficient of performance (COP). In this paper, the review of some previous researches will be conducted to see the diversity of optimization in the design of TECs in enhancing the performance and efficiency. After that, single-objective optimization problems (SOP) will be tested first by using Genetic Algorithm (GA) and Simulated Annealing (SA) to optimize geometry properties so that TECs will operate at near optimal conditions. Equality constraint and inequality constraint were taken into consideration.

4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides proopiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus. KCI Citation Count: 2

Most of the existing chest X-ray datasets include labels from a list of findings without specifying their locations on the radiographs. This limits the development of machine learning algorithms for the detection and localization of chest abnormalities. In this work, we describe a dataset of more than 100,000 chest X-ray scans that were retrospectively collected from two major hospitals in Vietnam. Out of this raw data, we release 18,000 images that were manually annotated by a total of 17 experienced radiologists with 22 local labels of rectangles surrounding abnormalities and 6 global labels of suspected diseases. The released dataset is divided into a training set of 15,000 and a test set of 3,000. Each scan in the training set was independently labeled by 3 radiologists, while each scan in the test set was labeled by the consensus of 5 radiologists. We designed and built a labeling platform for DICOM images to facilitate these annotation procedures. All images are made publicly available in DICOM format along with the labels of both the training set and the test set. Measurement(s) diseases and abnormal findings from chest X-ray scans Technology Type(s) AI is used to detect diseases and abnormal findings Sample Characteristic - Location Vietnam

Antibiotic resistance is a growing global health crisis. This study introduces a novel nanocomposite material incorporating superparamagnetic iron oxide nanoparticles (SPION), citric acid (CA), selenium (Se), silver (Ag), and a polymer matrix (M8) consisting of polyethylene glycol, polyvinylpyrrolidone, chitosan, and polyvinyl alcohol. The novel materials were used to inhibit Pseudomonas aeruginosa (PA), Staphylococcus aureus (SA), and Salmonella enterica (SE). The optimal molar ratio of SPION:CA: CSPION:Se: CSPION/Se/Ag was 1:2:0.5, yielding nanoparticles with an average size of 15.09 ± 2.95 nm (FE-SEM) and a saturation magnetization of 21.51 emu/g (VSM). XRD confirmed the coexistence of Fe₃O₄, Se, and Ag crystalline phases, while FTIR revealed ionic and hydrogen bonding interactions between the polymers, citric acid, and metal nanoparticles. EDS analysis validated the successful incorporation of Se (7.06 wt%) and Ag (22.00 wt%). At this ratio, the inhibition percentage against PA, SA, and SE (using the minimum inhibitory concentration method) at 50% dilution is 99.99 ± 0.52%, 99.31 ± 2.74%, and 47.41 ± 3.69%, respectively. The superior performance is attributed to synergistic effects between SPION, Se, Ag, and the polymer blend, offering a promising approach for combating antibiotic-resistant bacteria.