Gallic acid [3,4,5-trihydroxybenzoic acid (GA)], a natural phytochemical, is known to have a variety of cellular functions including beneficial effects on metabolic syndromes. However, the molecular mechanism by which GA exerts its beneficial effects is not known. Here we report that GA plays its role through the activation of AMP-activated protein kinase (AMPK) and by regulating mitochondrial function via the activation of peroxisome proliferator-activated receptor-γ coactivator1α (PGC1α). Sirtuin 1 (Sirt1) knockdown significantly blunted GA's effect on PGC1α activation and downstream genes, suggesting a critical role of the AMPK/Sirt1/PGC1α pathway in GA's action. Moreover, diet-induced obese mice treated with GA showed significantly improved glucose and insulin homeostasis. In addition, the administration of GA protected diet-induced body weight gain without a change in food intake. Biochemical analyses revealed a marked activation of AMPK in the liver, muscle, and interscapular brown adipose tissue of the GA-treated mice. Moreover, uncoupling protein 1 together with other genes related to energy expenditure was significantly elevated in the interscapular brown adipose tissue. Taken together, these results indicate that GA plays its beneficial metabolic roles by activating the AMPK/Sirt1/PGC1α pathway and by changing the interscapular brown adipose tissue genes related to thermogenesis. Our study points out that targeting the activation of the AMPK/Sirt1/PGC1α pathway by GA or its derivatives might be a potential therapeutic intervention for insulin resistance in metabolic diseases.
Sepsis is the most common cause of in-hospital deaths, especially from low-income and lower-middle-income countries (LMICs). This study aimed to investigate the mortality rate and associated factors from sepsis in intensive care units (ICUs) in an LMIC. We did a multicenter cross-sectional study of septic patients presenting to 15 adult ICUs throughout Vietnam on the 4 days representing the different seasons of 2019. Of 252 patients, 40.1% died in hospital and 33.3% died in ICU. ICUs with accredited training programs (odds ratio, OR: 0.309; 95% confidence interval, CI 0.122–0.783) and completion of the 3-h sepsis bundle (OR: 0.294; 95% CI 0.083–1.048) were associated with decreased hospital mortality. ICUs with intensivist-to-patient ratio of 1:6 to 8 (OR: 4.533; 95% CI 1.621–12.677), mechanical ventilation (OR: 3.890; 95% CI 1.445–10.474) and renal replacement therapy (OR: 2.816; 95% CI 1.318–6.016) were associated with increased ICU mortality, in contrast to non-surgical source control (OR: 0.292; 95% CI 0.126–0.678) which was associated with decreased ICU mortality. Improvements are needed in the management of sepsis in Vietnam such as increasing resources in critical care settings, making accredited training programs more available, improving compliance with sepsis bundles of care, and treating underlying illness and shock optimally in septic patients.
Multilayer graphene with rhombohedral and Bernal stacking is supposed to be metallic, as predicted by density functional theory calculations using semilocal functionals. However, recent angular resolved photoemission and transport data have questioned this point of view. In particular, rhombohedral flakes are suggested to be magnetic insulators, a view supported also by hybrid-functional calculations. Bernal flakes composed of an even number of layers are insulating (for N 6), while those composed of an odd number of layers are pseudogapped (for N 7). Here, by systematically benchmarking with plane-waves codes, we develop very accurate all-electron Gaussian basis sets for graphene multilayers, allowing a precise description of the electronic structure in the 100 meV energy range from the Fermi energy at the hybrid-functional level. We find, in agreement with our previous calculations, that rhombohedral stacked multilayers are gapped and magnetic. However, the valence band curvature and the details of the electronic structure at the ∼10 meV scale show a dependence on the basis set. A substantially extended basis set is needed to describe the long-range interlayer interactions and, consequently, to correctly reproduce the effective mass of the valence band top at the K point. In the case of Bernal stacking, we show that exact exchange gaps the flakes composed by four layers and opens pseudogaps for N = 3, 6, 7, 8. However, the gap or pseudogap size and its behavior as a function of thickness are not compatible with experimental data. Moreover, hybrid functionals lead to a metallic solution for five layers and a magnetic ground state for five, six, and eight layers. Magnetism is very weak with practically no effect on the electronic structure and the magnetic moments are mostly concentrated in the central layers. Our hybridfunctional calculations on trilayer Bernal graphene are in excellent agreement with GW results. For thicker multilayers, our calculations are a benchmark for many-body theoretical modeling of the low energy electronic structure.
SnTe materials are one of the most flexible material platforms for exploring the interplay of topology and different types of symmetry breaking. We study symmetry-protected topological states in SnTe nanowires in the presence of various combinations of Zeeman field, s-wave superconductivity and inversion-symmetry-breaking field. We uncover the origin of robust corner states and hinge states in the normal state. In the presence of superconductivity, we find inversion-symmetry-protected gapless bulk Majorana modes, which give rise to quantized thermal conductance in ballistic wires. By introducing an inversion-symmetry-breaking field, the bulk Majorana modes become gapped and topologically protected localized Majorana zero modes appear at the ends of the wire.
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