Modulation of turbulent Rayleigh-Bénard convection under spatially harmonic heating.

We numerically study turbulent Rayleigh-Bénard (RB) convection under spatial temperature modulation, where the bottom temperature varies sinusoidally around a mean value in space. Both two- and three-dimensional simulations are performed over the Rayleigh number range 10^{7}≤Ra≤10^{10} and the wave number range 1≤k≤120 at fixed Prandtl number Pr=0.7. It is demonstrated that spatial temperature modulation with small wave numbers can enhance the global heat transfer (characterized by the Nusselt number Nu) in the turbulent regime, while Nu is close to that in standard RB convection in the case of large wave numbers. Further, we propose two characteristic modulation length scales: one is the penetration depth δ_{k} above which spatial modulation is negligible, the other is the inversion depth δ_{k2} below which there exists a stable inverse temperature gradient. Based on the relative thickness of the thermal boundary layer (BL) δ_{th} compared with these two length scales, the underlying modulation mechanism is physically explained and three regimes are identified: (1) an unperturbed BL regime (δ_{k}<δ_{th}), in which the modulation effect does not penetrate through the thermal BL and Nu is nearly unchanged; (2) a partially modulated BL regime (δ_{k2}<δ_{th}<δ_{k}), in which hot spots trigger more plume emissions from the thermal BL, resulting in Nu enhancement; and (3) a fully modulated BL regime (δ_{th}<δ_{k2}), in which the stable temperature inversion over the cold phases begins to affect convective flows, which alters the trend of Nu enhancement.

Pentamethylquercetin protects against cardiac remodeling via activation of Sestrin2.

Oxidative stress is widely involved in pathophysiological processes of cardiac remodeling. Molecules associated with antioxidant functions may be ideal targets for reversing cardiac remodeling. Sestrin2 is the important component of endogenous antioxidant defense, while there is little information on the pathophysiological roles of it in cardiac remodeling. The aim of this study was to investigate whether Sestrin2 is closely involved in cardiac remodeling, and whether the protective effect of pentamethylquercetin (PMQ) on cardiac remodeling is related to upregulation of the Sestrin2 endogenous antioxidant system. We generated a transverse aorta constriction (TAC)-induced pressure-overload cardiac-remodeling model in mice, and also established an isoproterenol (ISO)-induced neonatal rat cardiomyocyte (NRCM) hypertrophy model. The data showed Sestrin2 expression was downregulated significantly, and Nrf2 and HO-1 expression was also reduced in myocardial tissue or NRCM of model group, whereas keap1 expression was upregulated. PMQ significantly ameliorated cardiac remodeling and rectified the abnormal expression of Sestrin2/Nrf2/keap1. Sestrin2 small interfering RNA (SiRNA) reduced the protective effect of PMQ on NRCMs, as well as abolished its regulating effect on the Nrf2/keap1 pathway. In conclusion, Sestrin2 may be an important target in the anti-myocardial remodeling of PMQ.

Pentamethylquercetin induces adipose browning and exerts beneficial effects in 3T3-L1 adipocytes and high-fat diet-fed mice.

Browning white adipocytes may be a new target in anti-obesity therapy. Pentamethylquercetin (PMQ) has been shown to have anti-obesity effects in monosodium glutamate-induced obese mice. Here, we aimed to study the anti-obesity effects of PMQ in vitro and in vivo and to determine if adipose browning is involved in the mechanism underlying the anti-obesity effects of PMQ. We evaluated the effects of PMQ on cell proliferation, cell differentiation, glucose consumption, cellular lipid metabolism, and related brown gene expression in 3T3-L1 adipocytes. We also investigated the effects of PMQ in a mouse model of high-fat diet (HFD)-induced obesity. Our results demonstrated that PMQ increased the consumption of glucose, inhibited the accumulation of cellular triglycerides (TGs), and induced the expression of brown adipocyte-specific genes, such as uncoupling protein 1 (UCP-1), during the early stage of differentiation in 3T3-L1 adipocytes. In HFD mice, PMQ treatment reduced waist circumference, LEE index, white adipose tissue (WAT) weight and white adipocyte size and increased brown adipose tissue (BAT) weight. Moreover, PMQ treatment induced mitochondrial biogenesis and upregulated UCP-1 expression in WAT. These findings suggest that PMQ may induce browning of adipose tissue, a phenomenon that is at least partly related to its anti-obesity effects.

Pentamethylquercetin ameliorates fibrosis in diabetic Goto-Kakizaki rat kidneys and mesangial cells with suppression of TGF-ß/Smads signaling.

Pentamethylquercetin (PMQ) has been shown to possess glucose-lowering properties, but its effect on renal fibrosis in diabetes is still unclear. This study was designed to investigate the effect of PMQ on renal fibrosis and the underlying mechanisms in spontaneous type II diabetic Goto-Kakizaki rats and mesangial cells in high glucose. We found that in Goto-Kakizaki rats, PMQ treatment attenuated glomerular volume, glycogen deposition, renal collagen and fibronectin accumulation, in addition to amelioration of diabetic symptoms, including reduction of urine volume and urine glucose levels. In mesangial cells, PMQ remarkably inhibited the cell proliferation and total collagen accumulation, and suppressed cell hypertrophy. Further experiments showed that PMQ treatment down-regulated the expression of TGF-ß1, up-regulated Smad7 and inhibited Smad2/3 activation in vivo and vitro. Our results demonstrated that PMQ ameliorated renal fibrosis in diabetes, which may be associated with suppressed TGF-ß/Smads signaling.

Pentamethylquercetin protects against diabetes-related cognitive deficits in diabetic Goto-Kakizaki rats.

Diabetic patients have a signifiantly higher risk of developing all forms of dementia. Pentamethylquercetin (PMQ) has been proven to have potential as an anti-diabetic agent. Nevertheless, whether PMQ can improve diabetes-induced cognitive dysfunction has not been investigated. To address this, we evaluated the effectiveness and underlying mechanisms of PMQ for ameliorating diabetes-related cognitive dysfunction in vivo and in vitro. Our results showed that Goto-Kakizaki (GK) rats displayed impairment in their learning abilities and memory capabilities. Furthermore, GK rats reflected cognitive dysfunction in proportion to the intensity of insulin resistance index. In addition, dendritic spine density and the % cell viability significantly decreased in hippocampus neurons. High glucose conditions induced hippocampal neurons damage, inflicted dendritic spine dysontogenesis, and reduced Akt/cAMP response element-binding protein activation. Treatment with PMQ in GK rats significantly ameliorated cognitive deficits and neuronal damage and increased dendritic spine density, at least in part, by improving insulin resistance and metabolic disorders. Furthermore, PMQ significantly activated the Akt/cAMP response element-binding protein pathway and increased the expression of memory-related proteins in the downstream part of the Akt/cAMP response element-binding protein pathway, such as synaptophysin and glutamate receptor 1. In addition, PMQ inhibited high glucose-induced cellular toxicity. LY294002 appeared to partly inhibit PMQ-mediated protective effects in hippocampal neurons. The results suggest that insulin resistance could predominantly reduce Akt/cAMP response element-binding protein activation in the brain, which is associated with a higher risk of cognitive dysfunction. PMQ could provide a new potential option for the prevention of cognitive dysfunction in diabetes.