94 research outputs found
P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity
Inhibition of arachidonic acid metabolism and its implication on cell proliferation and tumour-angiogenesis
Arachidonic acid (AA) and its metabolites have recently generated a heightened interest due to growing evidence of their significant role in cancer biology. Thus, inhibitors of the AA cascade, first and foremost COX inhibitors, which have originally been of interest in the treatment of inflammatory conditions and certain types of cardiovascular disease, are now attracting attention as an arsenal against cancer. An increasing number of investigations support their role in cancer chemoprevention, although the precise molecular mechanisms that link levels of AA, and its metabolites, with cancer progression have still to be elucidated.
This article provides an overview of the AA cascade and focuses on the roles of its inhibitors and their implication in cancer treatment. In particular, emphasis is placed on the inhibition of cell proliferation and neo-angiogenesis through inhibition of the enzymes COX-2, 5-LOX and CYP450. Downstream effects of inhibition of AA metabolites are analysed and the molecular mechanisms of action of a selected number of inhibitors of catalytic pathways reviewed. Lastly, the benefits of dietary omega-3 fatty acids and their mechanisms of action leading to reduced cancer risk and impeded cancer cell growth are mentioned. Finally, a proposal is put forward, suggesting a novel and integrated approach in viewing the molecular mechanisms and complex interactions responsible for the involvement of AA metabolites in carcinogenesis and the protective effects of omega-3 fatty acids in inflammation and tumour prevention
Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world
Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic.
Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality.
Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States.
Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis.
Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection
Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease
BACKGROUND:
Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes.
METHODS:
We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization.
RESULTS:
During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events.
CONCLUSIONS:
Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)
The effect of sediment content to fluid - solid interface time-domain waveform
A model was established for the fluid - solid interface of semi-infinite medium, and the characteristic equation was established using the potential function. Applying line source at the fluid-solid interface, transform solution of displacement could be obtained, and time-domain solution could be evaluated through the inverse Fourier transform. Two kinds of ultrasound suspension model, UA and HT, were used to study and discuss the effect of sediment content to fluid-solid interface time-domain waveform. The results of two models have a good consistency. The sediment content have a great impact on the Scholte wave. With the increase of the sediment content, for Scholte wave, the velocity increases and the attenuation decreases
The effect of sediment content to fluid - solid interface time-domain waveform
A model was established for the fluid - solid interface of semi-infinite medium, and the characteristic equation was established using the potential function. Applying line source at the fluid-solid interface, transform solution of displacement could be obtained, and time-domain solution could be evaluated through the inverse Fourier transform. Two kinds of ultrasound suspension model, UA and HT, were used to study and discuss the effect of sediment content to fluid-solid interface time-domain waveform. The results of two models have a good consistency. The sediment content have a great impact on the Scholte wave. With the increase of the sediment content, for Scholte wave, the velocity increases and the attenuation decreases
Electrical Conduction Characteristic of a 2D MXene Device with Cu/Cr2C/TiN Structure Based on Density Functional Theory
The electronic structure and the corresponding electrical conductive behavior of the Cu/Cr2C/TiN stack were assessed according to a newly developed first-principle model based on density functional theory. Using an additional Cr2C layer provides the metal-like characteristic of the Cu/Cr2C/TiN stack with much larger electrical conduction coefficients (i.e., mobility, diffusivity, and electrical conductivity) than the conventional Ag/Ti3C2/Pt stack due to the lower activation energy. This device is therefore capable of offering faster switching speeds, lower programming voltage, and better stability and durability than the memristor device with conventional Ti3C2 MXene
Facilitation Drives the Positive Effects of Plant Richness on Trace Metal Removal in a Biodiversity Experiment
<div><p>Background</p><p>Phytoextraction is an environmentally acceptable and inexpensive technique for mine tailing rehabilitation that uses metallophyte plants. These plants reduce the soil trace metal contents to environmentally acceptable levels by accumulating trace metals. Recently, whether more trace metals can be removed by species-rich communities of these plants received great attention, as species richness has been reported having positive effects on ecosystem functions. However, how the species richness affects trace metals removal of plant communities of mine tailing is rarely known.</p><p>Methodology/Principal Findings</p><p>We examined the effects of species richness on soil trace metal removal in both natural and experimental plant communities. The root lengths and stem heights of each plant species were measured in order to calculate the functional diversity indices. Our results showed that trace metal (Cu, Cd, Pb and Zn) concentrations in mine tailing soil declined as species richness increased in both the natural and experimental plant communities. Species richness, rather than functional diversity, positively affected the mineralomass of the experimental plant communities. The intensity of plant-plant facilitation increased with the species richness of experimental communities. Due to the incremental role of plant-plant facilitation, most of the species had higher biomasses, higher trace metal concentrations in their plant tissues and lower malondialdehyde concentrations in their leaves. Consequently, the positive effects of species richness on mineralomass were mostly attributable to facilitation among plants.</p><p>Conclusions/Significance</p><p>Our results provide clear evidence that, due to plant-plant facilitation, species richness positively affects the removal of trace metals from mine tailing soil through phytoextraction and provides further information on diversity conservation and environmental remediation in a mine tailing environment.</p></div
Hybrid algorithm optimization for coverage problem in wireless sensor networks
With the continuous development of evolutionary computing, many excellent algorithms have emerged, which are applied in all walks of life to solve various practical problems. In this paper, two hybrid fish, bird and insect algorithms based on different architectures are proposed to solve the optimal coverage problem in wireless sensor networks. The algorithm combines the characteristics of three algorithms, namely, particle swarm optimization algorithm, Phasmatodea population evolution algorithm and fish migration optimization algorithm. The new algorithm has the advantages of the three algorithms. In order to prove the effectiveness of the algorithm, we first test it on 28 benchmark functions. The results show that the two hybrid fish, bird and insect algorithms with different architectures have significant advantages. Then we apply the proposed algorithm to solve the coverage problem of wireless sensor networks through experimental simulation. The experimental results show the advantages of our proposed algorithm and prove that our proposed hybrid fish, bird and insect algorithm is suitable for solving the coverage problem of wireless sensor networks.Web of Science80112110
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