Our previous studies found that mitochondrial uncouplers CCCP and niclosamide inhibited artery constriction and the mechanism involved AMPK activation in vascular smooth muscle cells. BAM15 is a novel type of mitochondrial uncoupler. The aim of the present study is to identify the vasoactivity of BAM15 and characterize the BAM15-induced AMPK activation in vascular smooth muscle cells (A10 cells). BAM15 relaxed phenylephrine (PE)-induced constricted rat mesenteric arteries with intact and denuded endothelium. Pretreatment with BAM15 inhibited PE-induced constriction of rat mesenteric arteries with intact and denuded endothelium. BAM15, CCCP, and niclosamide had the comparable IC50 value of vasorelaxation in PE-induced constriction of rat mesenteric arteries. BAM15 was less cytotoxic in A10 cells compared with CCCP and niclosamide. BAM15 depolarized mitochondrial membrane potential, induced mitochondrial fission, increased mitochondrial ROS production, and increased mitochondrial oxygen consumption rate in A10 cells. BAM15 potently activated AMPK in A10 cells and the efficacy of BAM15 was stronger than that of CCCP, niclosamide, and AMPK positive activators metformin and AICAR. In conclusion, BAM15 activates AMPK in vascular smooth muscle cells with higher potency than that of CCCP, niclosamide and the known AMPK activators metformin and AICAR. The present work indicates that BAM15 is a potent AMPK activator.
Rock fragment cover has long been an important agricultural crop production technique on the Loess Plateau, China. Although this approach plays an important role in controlling hydrological processes and preventing soil erosion, inconsistent results have been recovered in this field. In this study, we investigated the effects of rock fragment cover on infiltration, run‐off, soil erosion, and hydraulic parameters using rainfall simulation in the field in a semi‐arid region of China. Two field plots encompassing 6 rock fragment coverages (0%, 10%, 20%, 25%, 30%, and 40%), as well as 2 rock fragment positions and sizes were exposed to rainfall at a particular intensity (60 mm h−1). The results of this study showed that increasing the rock fragment coverage with rock fragments resting on the soil surface increased infiltration but decreased run‐off generation and sediment yield. A contrasting result was found, however, when rock fragments were partially embedded into the soil surface; in this case, a positive relationship between rock fragment coverage and run‐off rate as well as a nonmonotonic relationship with respect to soil loss rate was recovered. The size of rock fragments also exerted a positive effect on run‐off generation and sediment yield but had a negative effect on infiltration. At the same time, both mean flow velocity and Froude number decreased with increasing rock fragment coverage regardless of rock fragment position and size, whereas both Manning roughness and Darcy–Weisbach friction factor were positively correlated. Results show that stream power is the most sensitive hydraulic parameter affecting soil loss. Combined with variance analysis, we concluded that the order of significance of rock fragment cover variables was position followed by coverage and then size. We also quantitatively incorporated the effects of rock fragment cover on soil loss via the C and K factors in the Revised Universal Soil Loss Equation. Overall, this study will enable the development of more accurate modelling approaches and lead to a better understanding of hydrological processes under rock fragment cover conditions.
Objective Recent studies demonstrated cutaneous phosphorylated α synuclein (p‐syn) deposition in idiopathic and some monogenetic Parkinson disease (PD) patients, suggesting synucleinopathy identical to that in the brain. Although the LRRK2 Gly2385Arg (G2385R) variant is a common PD risk factor in the Chinese population, the pathogenesis of PD with G2385R variant has not been reported. We investigated whether synucleinopathy and small fiber neuropathy (SFN) are associated with the G2385R variant. Methods We performed genotyping in 59 PD patients and 30 healthy controls from the skin biopsy database. The scale of SFN was assessed, as well as bright‐field immunohistochemistry against antiprotein gene product 9.5 (PGP9.5) and double‐labeling immunofluorescence with anti‐PGP9.5 and anti‐p‐syn. Results (1) p‐syn deposited in the skin nerve fibers of G2385R carrier PD patients, which was a different pattern from noncarriers, without no difference observed between proximal and distal regions; (2) decreased distal intraepidermal nerve fiber density was found in both the G2385R carrier and the noncarrier PD group, and was negatively correlated with composite autonomic symptom score‐31 item (COMPASS‐31) scores; (3) PD patients with the G2385R variant showed a more peculiar clinical profile than noncarriers with a higher nonmotor symptoms scale, COMPASS‐31 score, and levodopa equivalent dose, in addition to an increased prevalence of certain autonomic symptoms or rapid eye movement sleep behavior disorders. Interpretation Synucleinopathy is related to the LRRK2 G2385R genotype and implies a different pathogenesis in G2385R variant carriers and noncarriers. This study also extended the clinical profiles of PD patients with the G2385R variant.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.