Aims/hypothesis We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome. Methods A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome. Results Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements; no side effects from the intervention were identified. HOMA-IR came down from 3.1±1.8 to 1.9±1.3 (p<0.001) in the L-AGE group, while it increased from 2.9±1.2 to 3.6±1.7 (p<0.002) in the Reg-AGE group. Conclusions/interpretation L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat ‘at-risk’ obesity. Trial registration ClinicalTrials.gov NCT01363141 Funding The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231)

An aged liver has decreased reparative capacity during ischemia-reperfusion (IR) injury. A recent study showed that plasma irisin levels predict telomere length in healthy adults. The aim of the present study is to clarify the role of irisin, telomerase activity, and autophagy during hepatic IR in the elderly. To study this, hepatic IR was established in 22-month- and 3-month-old rats and primary hepatocytes were isolated. The results showed that the old rats exhibited more serious liver injury and lower levels of irisin expression, telomerase activity, autophagy ability, and mitochondrial function than young rats during hepatic IR. Irisin activated autophagy and improved mitochondrial function via increasing telomerase activity in aged hepatocytes. Inhibition of telomerase activity by BIBP1532 abolished the protective role of irisin in hepatocytes during hypoxia and reoxygenation. Additionally, this study proved irisin increased the telomerase activity via inhibition of the phosphorylation of JNK during hepatic IR. Administration of exogenous irisin significantly mitigated the inflammation, oxidative stress, apoptosis, and liver injury in an old rat model of hepatic IR. In conclusion, irisin improves autophagy of aged hepatocytes via increasing telomerase activity in hepatic IR. Irisin exhibits conspicuous benefits in increasing reparative capacity of an aged liver during hepatic IR.

CYP2A6 is associated with human obesity; CYP2A5 protects against obesity and NAFLD in mice. PPARα contributes to the CYP2A5 protective effects on fatty liver but it opposes to the protective effects on obesity.

This paper describes a simple and environmentally friendly method for the preparation of highly stable dispersions of Fe3O4 nanoparticles with controlled morphologies, in the same synthesis system for the first time. During the process, the Fe3O4 nanoparticles are formed using urease as a multifunctional reagent, including catalyst, template and dispersant, due to its enzymatic activity and special enzymatic steric structure. A possible formation mechanism for these Fe3O4 nanoparticles, which have various morphologies including nanospheres, nanosheets and nanorods, is proposed. The as-prepared nanoparticles show a larger specific surface area and a stronger magnetism, which enhances their dye adsorption capacity and increases their potential for application in wastewater treatment.

In order to investigate the role of TNF-and ICAM-1 in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of TNF-and ICAM-1 in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rates of TNF-alpha and ICAM-1 expressions in lichen planus were significantly higher than those in normal skins (both P<0.05). Meanwhile, there was a obvious correlation between the increase of TNF-alpha and that of ICAM-1 in lichen planus. The expression of TNF-alpha and ICAM-1 might play an important role in the development of lichen planus.

As radio telescopes become more sensitive, radio frequency interference (RFI) is becoming more important for interesting signals of radio astronomy. There is a demand for developing an automatic, accurate and efficient RFI mitigation method. Therefore, we have investigated an RFI detection algorithm. First, we introduce an asymmetrically reweighted penalized least squares (ArPLS) method to estimate the baseline more accurately. After removing the estimated baseline, several novel strategies were proposed based on the SumThreshold algorithm for detecting different types of RFI. The threshold parameter in SumThreshold can be determined automatically and adaptively. The adaptiveness is essential for reducing human intervention and for the online RFI processing pipeline. Applications to data from the Five-hundred-meter Aperture Spherical Telescope (FAST) show that the proposed scheme based on ArPLS and SumThreshold is superior to some typically available methods for RFI detection with respect to efficiency and performance.

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K + current (I K1 ), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD 90 ) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased I K1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

Induction of long-term potentiation (LTP) in excitatory neurons triggers a large transient increase in the volume of dendritic spines followed by decays to sustained size expansion, a process termed structural LTP (sLTP) that contributes to the cellular basis of learning and memory. Although mechanisms regulating the early and sustained phases of sLTP have been studied intensively, how the acute spine enlargement immediately after LTP stimulation is achieved remains elusive. Here, we report that endophilin A1 orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in NMDAR-mediated LTP. Upon LTP induction, Ca2+/calmodulin enhances binding of endophilin A1 to both membrane and p140Cap, a cytoskeletal regulator. Consequently, endophilin A1 rapidly localizes to the plasma membrane and recruits p140Cap to promote local actin polymerization, leading to spine head expansion. Moreover, its molecular functions in activity-induced rapid spine growth are required for LTP and long-term memory. Thus, endophilin A1 serves as a calmodulin effector to drive acute structural plasticity necessary for learning and memory.