Ultra-compact and fabrication-tolerant multimode photonic jumpers based on dual Bezier curves.

Compact routing of multimode bus waveguides is of great significance for on-chip mode-division multiplexing (MDM) systems to realize high integration density and flexible layout. In this Letter, we propose and experimentally demonstrate a novel, to the best of our knowledge, multimode photonic jumper (MPJ) on a standard silicon-on-insulator (SOI) platform. It enables an ultra-compact connection between two parallel multimode waveguides (MWGs) with an arbitrary displacement. As a proof of concept, we describe two MPJs with displacements of 5.9 µm and 0.6 µm, each supporting three modes and featuring a longitudinal distance of around 14 µm. For both MPJs, the experimental results show insertion losses (ILs) below 0.086 dB and inter-modal cross talk (CT) below -17.6 dB over the wide wavelength range of 1525-1600 nm for all three modes.

GmDFB1, an ARM-repeat superfamily protein, regulates floral organ identity through repressing siRNA- and miRNA-mediated gene silencing in soybean.

The development of flowers in soybean (Glycine max) is essential for determining the yield potential of the plant. Gene silencing pathways are involved in modulating flower development, but their full elucidation is still incomplete. Here, we conducted a forward genetic screen and identified an abnormal flower mutant, deformed floral bud1-1 (Gmdfb1-1), in soybean. We mapped and identified the causal gene, which encodes a member of the armadillo (ARM)-repeat superfamily. Using small RNA sequencing (sRNA-seq), we found an abnormal accumulation of small interfering RNAs (siRNAs) and microRNA (miRNAs) in the Gmdfb1 mutants. We further demonstrated that GmDFB1 interacts with the RNA exosome cofactor SUPER KILLER7 (GmSKI7). Additionally, GmDFB1 interacts with the PIWI domain of ARGONAUTE 1 (GmAGO1) to inhibit the cleavage efficiency on the target genes of sRNAs. The enhanced gene silencing mediated by siRNA and miRNA in the Gmdfb1 mutants leads to the downregulation of their target genes associated with flower development. This study revealed the crucial role of GmDFB1 in regulating floral organ identity in soybean probably by participating in two distinct gene silencing pathways.

Active polarization controller based on micro-ring resonators.

On-chip polarization handling is of great significance for optical interconnects to overcome polarization sensitivity. In this Letter, we propose and experimentally demonstrate a novel, to the best of our knowledge, on-chip polarization controller (PC) on a 220 nm silicon-on-insulator (SOI) platform. It is the first demonstration of a PC based on micro-ring resonators. Any input polarization states can be actively converted to the standard transverse-electric (TE) mode under the phase manipulation. Experimental results show that the insertion loss is less than 0.8 dB and the polarization dependent loss (PDL) is around 0.5 dB. The proposed device also exhibits excellent performances in wavelength tunability over the C band and 35 Gbps data transmission.

An Admittance Control Method Based on Parameters Fuzzification for Humanoid Steering Wheel Manipulation.

Developing a human bionic manipulator to achieve certain humanoid behavioral skills is a rising problem. Enabling robots to operate the steering wheel to drive the vehicle is a challenging task. To address the problem, this work designs a novel 7-DOF (degree of freedom) humanoid manipulator based on the arm structure of human bionics. The 3-2-2 structural arrangement of the motors and the structural modifications at the wrist allow the manipulator to act more similar to a man. Meanwhile, to manipulate the steering wheel stably and compliantly, an admittance control approach is firstly applied for this case. Considering that the system parameters vary in configuration, we further introduce parameter fuzzification for admittance control. Designed simulations were carried out in Coppeliasim to verify the proposed control approach. As the result shows, the improved method could realize compliant force control under extreme configurations. It demonstrates that the humanoid manipulator can twist the steering wheel stably even in extreme configurations. It is the first exploration to operate a steering wheel similar to a human with a manipulator by using admittance control.

Maize MITOGEN-ACTIVATED PROTEIN KINASE 20 mediates high-temperature-regulated stomatal movement.

High temperature induces stomatal opening; however, uncontrolled stomatal opening is dangerous for plants in response to high temperature. We identified a high-temperature sensitive (hts) mutant from the ethyl methane sulfonate (EMS)-induced maize (Zea mays) mutant library that is linked to a single base change in MITOGEN-ACTIVATED PROTEIN KINASE 20 (ZmMPK20). Our data demonstrated that hts mutants exhibit substantially increased stomatal opening and water loss rate, as well as decreased thermotolerance, compared to wild-type plants under high temperature. ZmMPK20-knockout mutants showed similar phenotypes as hts mutants. Overexpression of ZmMPK20 decreased stomatal apertures, water loss rate, and enhanced plant thermotolerance. Additional experiments showed that ZmMPK20 interacts with MAP KINASE KINASE 9 (ZmMKK9) and E3 ubiquitin ligase RPM1 INTERACTING PROTEIN 2 (ZmRIN2), a maize homolog of Arabidopsis (Arabidopsis thaliana) RIN2. ZmMPK20 prevented ZmRIN2 degradation by inhibiting ZmRIN2 self-ubiquitination. ZmMKK9 phosphorylated ZmMPK20 and enhanced the inhibitory effect of ZmMPK20 on ZmRIN2 degradation. Moreover, we employed virus-induced gene silencing (VIGS) to silence ZmMKK9 and ZmRIN2 in maize and heterologously overexpressed ZmMKK9 or ZmRIN2 in Arabidopsis. Our findings demonstrated that ZmMKK9 and ZmRIN2 play negative regulatory roles in high-temperature-induced stomatal opening. Accordingly, we propose that the ZmMKK9-ZmMPK20-ZmRIN2 cascade negatively regulates high-temperature-induced stomatal opening and balances water loss and leaf temperature, thus enhancing plant thermotolerance.

Campaign-style governance of air pollution in China? A comprehensive analysis of the central environmental protection inspection.

Central environmental protection inspection (CEPI) is a major institutional innovation in China's environmental governance, but its effectiveness in improving air quality is still unclear. However, the effectiveness of CEPI is of great significance and can be regarded as an important reference for deepening the reform of environmental governance system in China. This article takes the CEPI as a quasi-natural experiment and uses the regression discontinuity design (RDD) and the difference-in-differences (DID) methods to examine the effectiveness of this policy. The study found that the first round of CEPI reduced the air pollution of cities in the inspected provinces in a short time. Moreover, this positive policy effect persisted in the aftermath of the inspection, but this long-term effect is mainly reflected in PM10 and SO2. Heterogeneity analysis showed that CEPI was only effective in reducing air pollutants of industry-oriented cities, cities in Central and Eastern China, and cities with large or small population size. The moderating effect analysis indicated that a healthy relationship (close and clean) between the local governments and businesses was conducive to reducing air pollution. The research confirmed the presence of "selective" reduction of air pollutants in the long run caused by CEPI, thereby providing new inspiration for the improvement of campaign-style environmental governance and the follow-up CEPI work.

High-performance TM-pass polarizer based on anti-symmetric Bragg gratings.

We present an all-silicon transverse-magnetic-pass (TM-pass) polarizer based on anti-symmetric Bragg gratings. We obtain wide operation bandwidth and high polarization extinction ratio (PER) by maximizing the coupling between the forward TE0 mode and the backward TE1 mode through the reduction of the bridge element width. In the meantime, low insertion loss (IL) is acquired with long tapered structures and the exclusion of the center grating part. Experimental results indicate IL below 0.74 dB and PER over 40 dB covering the wavelength ranges of 1275-1360 nm and 1500-1523 nm, while the average IL within these ranges is as low as 0.27 dB. Additionally, simulation results suggest that the performance can be further improved by introducing chirp in the period of Bragg gratings, thus achieving IL < 0.11 dB and PER > 60 dB over a wide range of 280 nm (1290-1570 nm).

Epidemiology and survival outcomes in adenosquamous carcinoma: a population-based study.

BACKGROUND: The relationship between the location of the primary tumor and survival of adenosquamous carcinoma (ASC) remains poorly understood. This study aimed to evaluate the impact of primary tumor location on the survival outcome of patients with ASC. METHODS: Patients with ASC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database with ≥ 150 cases per tumor location. The Kaplan-Meier method was used to generate survival curves and differences among them were compared using the log-rank test. On the other hand, Cox proportional hazards models were used to evaluate factors that had independent predictive effects on cancer-specific survival (CSS). RESULTS: A total of 14,829 eligible patients with ASC were included in this study. Lung and bronchus ASC accounted for 51.1%, followed by the cervix uteri (17.0%), corpus uteri (13.9%), pancreas (4.9%), esophagus (3.1%), gallbladder (2.5%), stomach (2.2%), colon and rectum (2.0%), head and neck (1.8%), and breast ASC (1.3%). The 5-year CSS of breast, cervix uteri, colon and rectum, corpus uteri, esophagus, gallbladder, head and neck, lung and bronchus, pancreas, and stomach ASC was 76.9%, 66.0%, 34.8%, 72.9%, 12.0%, 10.8%, 45.0%, 24.7%, 4.3%, and 17.3%, respectively. COX analysis demonstrated that the primary tumor location was an independent prognostic factor for CSS. Besides, the breast, uterine corpus, and cervix as well as head and neck ASC were significantly associated with better prognosis, while pancreas and gallbladder ASC were significantly associated with poor CSS; stomach and colorectal were roughly the same as ASC prognosis. CONCLUSION: Our study showed that the CSS of patients with ASC depends on the location of the primary tumor. Besides, tumor location is an important factor that should guide the use of chemotherapy and radiation.

Dual-Arm Robot Trajectory Planning Based on Deep Reinforcement Learning under Complex Environment.

In this article, the trajectory planning of the two manipulators of the dual-arm robot is studied to approach the patient in a complex environment with deep reinforcement learning algorithms. The shape of the human body and bed is complex which may lead to the collision between the human and the robot. Because the sparse reward the robot obtains from the environment may not support the robot to accomplish the task, a neural network is trained to control the manipulators of the robot to prepare to hold the patient up by using a proximal policy optimization algorithm with a continuous reward function. Firstly, considering the realistic scene, the 3D simulation environment is built to conduct the research. Secondly, inspired by the idea of the artificial potential field, a new reward and punishment function was proposed to help the robot obtain enough rewards to explore the environment. The function is consisting of four parts which include the reward guidance function, collision detection, obstacle avoidance function, and time function. Where the reward guidance function is used to guide the robot to approach the targets to hold the patient, the collision detection and obstacle avoidance function are complementary to each other and are used to avoid obstacles, and the time function is used to reduce the number of training episode. Finally, after the robot is trained to reach the targets, the training results are analyzed. Compared with the DDPG algorithm, the PPO algorithm reduces about 4 million steps for training to converge. Moreover, compared with the other reward and punishment functions, the function used in this paper will obtain many more rewards at the same training time. Apart from that, it will take much less time to converge, and the episode length will be shorter; so, the advantage of the algorithm used in this paper is verified.

Effects of Sacubitril/Valsartan on the Expression of CaMKII/Cav1.2 in Atrial Fibrillation Stimulation Rabbit Model.

Methods: Overall, 18 rabbits were randomly divided into control, pacing (600 beats/min), and pacing+sac/val groups. The rabbits in the pacing+sac/val cohort received oral sac/val (10 mg/kg twice daily) across the 21-day investigation period. After three weeks, the atrial effective refractory period (AERP) and AF induction rate were compared. HL-1 cultures were exposed to fast pacing (24 h) with and without LBQ657 (active sacubitril form)/valsartan. Western blots were used for detecting Cav1.2 and CaMKII expression within atrial muscles of the rabbits and HL-1 cultures of AF model. Results: In comparison to the sham cohort, the AF induction rate was markedly increased together with AERP reduction within pacing cohort. Such changes were markedly rescued through sac/val treatment in pacing+sac/val cohort. The proteomic expression profiles of CaMKII and Cav1.2 showed that the CaMKII expression was markedly upregulated, while Cav1.2 expression was downregulated in the pacing cohort. Importantly, these effects were absent in pacing+sac/val cohort. Conclusion: Results of this study show that sac/val treatment regulates the expression of CaMKII/Cav1.2 and could alter this pathway in atrial rapid electrical stimulation models. Therefore, this investigation could contribute to a novel strategy in AF therapeutics in clinical settings.

Sacubitril/valsartan attenuates atrial electrical and structural remodelling in a rabbit model of atrial fibrillation.

Atrial structural and electrical remodelling play important roles in atrial fibrillation (AF). Sacubitril/valsartan attenuates cardiac remodelling in heart failure. However, the effect of sacubitril/valsartan on AF is unclear. The aim of this study was to evaluate the effect of sacubitril/valsartan on atrial electrical and structural remodelling in AF and investigate the underlying mechanism of action. Thirty-three rabbits were randomized into sham, RAP, and sac/val groups. HL-1 cells were subjected to control treatment or rapid pacing with or without LBQ657 and valsartan. Echocardiography, atrial electrophysiology, and histological examination were performed. The concentration of Ca2+ and expression levels of calcineurin, NFAT, p-NFAT, Cav1.2, collagen Ⅰ and Ⅲ, ANP, BNP, CNP, NT-proBNP, and ST2 in HL-1 cells, and IcaL in left atrial cells, were determined. We observed that compared to that in the sham group, the atrium and right ventricle were enlarged, myocardial fibrosis was markedly higher, AF inducibility was significantly elevated, and atrial effective refractory periods were shortened in the RAP group. These effects were significantly reversed by sacubitril/valsartan. Compared to that in the sham group, collagen Ⅰ and Ⅲ, NT-proBNP, ST2, calcineurin, and NFAT were significantly up-regulated, while p-NFAT and Cav1.2 were down-regulated in the RAP group, and sacubitril/valsartan inhibited these changes. Ca2+ concentration increased and ICaL density decreased in in vivo and in vitro AF models, reversed by sacubitril/valsartan. Sacubitril/valsartan attenuates atrial electrical remodelling and ameliorates structure remodelling in AF. This study paves the way for the possibility of clinical use of sacubitril/valsartan in AF patients.

Shegan-Mahuang Decoction ameliorates asthmatic airway hyperresponsiveness by downregulating Th2/Th17 cells but upregulating CD4+FoxP3+ Tregs.

ETHNOPHARMACOLOGICAL RELEVANCE: Shegan-Mahuang Decoction (SMD), also named Yakammaoto or Shegan-Mahuang Tang, is a classic formula of traditional Chinese medicine with nine herbs, including Asarum sieboldii Miq., Aster tataricus L.f., Ephedra sinica Stapf, Belamcanda chinensis (L.) Redouté, Pinellia ternata (Thunb.) Breit., Schisandra chinensis (Turcz.) Baill., Tussilago farfara L., Zingiber officinale Roscoe, and Ziziphus jujuba Mill. SMD was originally discovered by Zhang Zhongjing in Eastern Han dynasty. It has been widely used as traditional medicine to treat flu-like symptoms in China and Japan for around twenty centuries. It was also utilized for the treatment of the early stage of acute asthma. However, the immune mechanisms underlying its therapeutic effects remain unknown. AIM OF THE STUDY: This study was set to investigate the effects of SMD on asthmatic airway hyperresponsiveness and its impacts on adaptive immunity in a mouse model of asthma. MATERIALS AND METHODS: The HPLC fingerprint profile of the water extract of SMD recorded 22 peaks, including those equivalent to guanosine, chlorogenic acid, tectoridin, 6-gingerol and wuweizisu B, as described previously (Yen et al., 2014). Airway hyperresponsiveness was assessed by measuring the airway resistance. Cellular infiltration was measured via H&E staining and immunochemistry while gene expression was analyzed using real-time RT-PCR. Treg frequency was determined through flow analysis whereas cytokine production in the supernatant was evaluated using ELISA. Finally, mTOR and NF-kB signalings were analyzed via Western blotting. RESULTS: We found that SMD largely corrected the imbalance of Th cell subsets in asthmatic mice with a significant inhibition of Th2 and Th17 cytokine production, thereby reducing asthmatic airway hyperresponsiveness. Moreover, lung function tests showed that SMD reduced airway hyperresponsiveness while immunohistochemical analyses demonstrated that SMD attenuated pulmonary infiltration of CD3+ and CD4+ T cells. Further, we observed a significant increase in the proportion of CD4+Foxp3+ Tregs in SMD-treated asthmatic mice. We also found that SMD downregulated gene expression of GATA3 and ROR-γt in murine lung tissue. In addition, both mTOR- and NF-kB-related protein expressions were reduced in the lung tissue of SMD-treated mice. SMD inhibited Th2/Th17 cytokine production by CD4+ T cells and also their mTOR activity in vitro. CONCLUSIONS: Our findings demonstrate that SMD attenuates asthmatic airway hyperresponsiveness by hindering Th2/Th17 differentiation, promoting CD4+FoxP3+ Treg generation and suppressing mTOR and NF-kB activities.

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The combination of field trial and indoor incubation experiment were conducted to examine the long-term effects of one-time application of bio-organic fertilizer on soil organic carbon (C) components, organic C mineralization, and enzyme activity in cucumber continuous cropping. Compared with CK, bio-organic fertilizer application significantly increased the content of soil organic C, activated C pool, slow-release C pool and inert C pool during four continuous cucumber planting seasons. With the increases of the number of consecutive crops, the proportion of soil inert carbon gradually increased. After four continuous seasons of cucumber planting, the cumulative and daily mineralization rate of soil organic C in the bio-organic fertilizer treatment increased by 17.3%-31.0% and 7.8%-43.0%, respectively. In the stage of cucumber ripening, bio-organic fertilizer application increased the activities of continuous soil urease, catalase, sucrose and neutral phosphatase by 10.5%-62.1%, 4.8%-25.5%, 3.9%-21.4% and 4.6%-66.4%. The activities of those four enzymes increased with the increases of the application amount of organic fertilizer. Results from the correlation and path analysis showed that the activity of the four enzymes were significantly correlated with the dynamics of organic carbon components in soil cucumber continuous cropping process. Soil urease and invertase activities significantly affected organic carbon mineralization during the continuous cropping process of cucumber. Application of bio-organic fertilizer could increase soil organic carbon content and enzyme activity, improve inert carbon ratio of soil organic carbon pools, cumulative and mineralization rate of organic carbon in continuous cropping process, thereby enhance soil carbon sequestration capacity.

Novel copy number variation of the KLF3 gene is associated with growth traits in beef cattle.

Copy number variation (CNV) related to complex traits, such as disease and quantitative phenotype, is considered an important and wealthy source of genetic and phenotypic diversity. It suggests that the copy number variation of function gene maybe leads to the phenotypic changes. Kupple like factor 3 (KLF3) gene is a vital transcription factor associated with the growth and development of muscle and adipose tissue. It has been mapped in a CNV region by animal genome re-sequencing. In this study, we detected the distribution diversity of KLF3 gene copy numbers in six Chinese cattle breeds (QC, NY, XN, PN, QDM and JX) and associated the phenotypic traits with it. Then, we analyzed the KLF3 gene transcription expression level in different tissues of Jiaxian (JX) cattle. Furthermore, we detected mRNA expression level of muscle and fat tissues of Jiaxian cattle (JX), Angus × Jiaxian (AJ). The results showed that the copy number in CNV loss was more frequent in QC than others. And we revealed a positive effect of KLF3 CNV on growth traits, such as body mass and heart girth (P < 0.05). In a word, we ascertained the significance between CNVs of KLF3 gene and growth traits in different cattle breeds, and our data indicates that the CNVs of KLF3 gene may as a marker for the future molecular breeding of Chinese beef cattle.

DNA methylation status of CRABP2 promoter down-regulates its expression.

As an important epigenetic modification DNA methylation is catalyzed by DNA methylation transferases (DNMTs) and occurs mainly in CpG islands. DNA methylation plays an important role in regulates gene expression, cell differentiation, genetic imprinting and tumor therapy. Retinoic acid-binding proteins (RAC) is vital for the absorption, transport, metabolism and maintenance of homeostasis of retinoic acid, which in turn regulates the differentiation and proliferation of cells by regulating the transcription of many target genes, therefore, these proteins influence differentiation and proliferation of adipocytes and muscle fibroblasts. Thus, cellular retinoic acid binding protein 2 (CRABP2) may be a candidate gene which affects beef quality, yield and fat deposition. The aim of this study was to evaluate the expression and the methylation pattern on the differentially methylated region (DMR) of the promoter of CRABP2. The DNA methylation pattern was tested by bisulfite sequencing polymerase chain reaction (BSP), the quantitative real-time PCR (qPCR) was used to analysis the expression of CRABP2 gene. The results showed that the DNA methylation level was higher in purebred cattle breed than that in hybrid cattle breeds which was negative correlation with the expression of the gen. These results indicate that the methylation status of the CRABP2 DMR can regulate mRNA expression. What's more, there are different methylation and expression patterns in different breeds and tissues which may influence the phenotype, and the results may be a useful parameter to investigate the function of CRABP2 in muscle and fat developmental in Chinese cattle.

Associations of GBP2 gene copy number variations with growth traits and transcriptional expression in Chinese cattle.

Copy number variations (CNVs) recently have been recognized as another important genetic variability followed single nucleotide polymorphisms (SNPs). The guanylate binding protein 2 (GBP2) gene plays an important role in cell proliferation. This study was performed to determine the presence of GBP2 CNV (relative to Angus cattle) in 466 individuals representing six main cattle breeds from China, identify its relationship with growth, and explore the biological effects of gene expression. There were two CNV regions in the GBP2 gene, for three types, CNV1 loss type (relative to Angus cattle) was more frequent in XN than other breeds, and CNV2 loss type (relative to Angus cattle) was more frequent in XN and CDM than other breeds. Though the GBP2 gene copy number presented no correlation with the transcriptional expression of JX (P > .05), but the transcriptional expression in heart is higher than other tissues, and the copy number in muscles and fat of JX is higher than others breeds. Statistical analysis revealed that the GBP2 gene CNV1 and CNV2 were significantly associated with growth traits (P < .05). In conclusion, this research established the correlations between CNVs of GBP2 gene and growth traits in different cattle breeds, and our results suggested that the CNVs in GBP2 gene may be considered markers for the molecular breeding of Chinese beef cattle.

Correlation between ZBED6 Gene Upstream CpG Island methylation and mRNA expression in cattle.

DNA methylation is essential for the regulation of gene expression and important roles in muscle development. To assess the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in ZBED6, we simultaneously examined DNA methylation and expression in six tissues from two different developmental stages (fetal bovine and adult bovine). The DNA methylation pattern was compared using bisulfite sequencing polymerase chain reaction (BSP) and combined bisulfite restriction analysis (COBRA). The result of quantitative real-time PCR (qPCR) analysis showed that ZBED6 has a broad tissue distribution and is highly expressed in adult bovine (P < 0.05 or P < 0.01). The DNA methylation level was significantly different in liver, lung and spleen between the two cattle groups (P < 0.05 or P < 0.01). The adult bovine group exhibited a significantly higher mRNA level and lower DNA methylation level than the fetal bovine group in liver, lung, and spleen. No significant association was detected between DNA methylation level and muscle, heart, and kidney at two different stages. In this study, the statistical analyses indicated that DNA methylation patterns are associated with mRNA level in some tissues, these results may be a useful parameter to investigate muscle developmental in cattle and as a model for studies in other species, potentially contributing to an improvement of growth performance selection in beef cattle breeding program.

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR-α/sirtuin 1/PGC-1α pathway.

BACKGROUND AND PURPOSE: Atrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. EXPERIMENTAL APPROACH: The expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min(-1) for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. KEY RESULTS: The PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. CONCLUSION AND IMPLICATIONS: Fenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF.

Overexpression of Fibulin-5 Attenuates Ischemia/Reperfusion Injury After Middle Cerebral Artery Occlusion in Rats.

Ischemia/reperfusion (I/R) injury after middle cerebral artery occlusion (MCAO) induces detrimental processes such as oxidative stress, inflammation, and apoptosis. All parts of the neurovascular unit are involved in these pathological processes. Fibulin-5 is a 66-kD glycoprotein secreted by various vascular cells, including vascular smooth muscle cells (SMCs), fibroblasts, and endothelial cells. As an extracellular matrix protein involved in cell adhesion, fibulin-5 has been widely studied in tumor growth and invasion. However, the effects of fibulin-5 on brain injury following ischemia/reperfusion have not been reported. In this study, we examined the effect of overexpressed fibulin-5 on reactive oxygen species (ROS) production. Fibulin-5 overexpression attenuated ROS expression, which in turn decreased apoptosis and blood-brain barrier (BBB) permeability following MCAO and reperfusion. Fibulin-5 also improved neurological deficits but had no effect on infarction volume. T2-weighted MRI and electron microscopy further confirmed brain edema reduction and decreased BBB disruption in fibulin-5 overexpression recombinant adenovirus (Ad-FBLN) treated rats. In addition, tight junction protein occludin was significantly degraded and matrix metalloproteinase 9 (MMP-9) immunoreactivity was significantly increased. Fibulin-5-mediated ROS decrease was not due to increased total superoxide dismutase levels but was instead correlated with the activation of Rac-1 pathway. The findings highlight the importance of antioxidant mechanism underlying cerebral ischemia/reperfusion.

Systematic review of clinical practice guidelines related to multiple sclerosis.

BACKGROUND: High quality clinical practice guidelines (CPGs) can provide clinicians with explicit recommendations on how to manage health conditions and bridge the gap between research and clinical practice. Unfortunately, the quality of CPGs for multiple sclerosis (MS) has not been evaluated. OBJECTIVE: To evaluate the methodological quality of CPGs on MS using the AGREE II instrument. METHODS: According to the inclusion and exclusion criteria, we searched four databases and two websites related to CPGs, including the Cochrane library, PubMed, EMBASE, DynaMed, the National Guideline Clearinghouse (NGC), and Chinese Biomedical Literature database (CBM). The searches were performed on September 20th 2013. All CPGs on MS were evaluated by the AGREE II instrument. The software used for analysis was SPSS 17.0. RESULTS: A total of 27 CPGs on MS met inclusion criteria. The overall agreement among reviews was good or substantial (ICC was above 0.70). The mean scores for each of all six domains were presented as follows: scope and purpose (mean ± SD: 59.05 ± 16.13), stakeholder involvement (mean ± SD: 29.53 ± 17.67), rigor of development (mean ± SD: 31.52 ± 21.50), clarity of presentation (mean ± SD: 60.39 ± 13.73), applicability (mean ± SD: 27.08 ± 17.66), editorial independence (mean ± SD: 28.70 ± 22.03). CONCLUSIONS: The methodological quality of CPGs for MS was acceptable for scope, purpose and clarity of presentation. The developers of CPGs need to pay more attention to editorial independence, applicability, rigor of development and stakeholder involvement during the development process. The AGREE II instrument should be adopted by guideline developers.