Concurrent optimisation of structural topology and fibre paths for 3D printing of continuous fibre composites based on chain primitive projection

This study proposes a novel topology optimisation method based on the Geometry Projection Topology Optimisation method (GPTO) with the consideration of manufacturing constraints for the 3D printing of continuous fibre reinforced polymer composite structures. The proposed method uses connecting bars in chains to represent the continuous fibre filaments in the composite structure, as opposed to the use of separate bars as primitives. Thus, the method is termed as Chain Projection Topology Optimisation (CPTO), in which the chain-like primitives are equivalent to clusters of real printing paths. The 3D printing paths can be acquired by splitting the primitives evenly, which simplified the printing path design procedure to a great extent. In addition, manufacturing constraints can be easily imposed on the primitives, making it superior to density-based topology optimisation methods. An MBB beam, a cantilever beam, and a bridge case are optimised to demonstrate the CPTO’s efficiency. It was found that the designs by CPTO possess comparable mechanical properties when compared to those by the Solid Orthotropic Material Penalization (SOMP) method while guaranteeing the composite structures are suitable for 3D printing and contain less microscopic defects in the printed fibre filaments

A modified equally-spaced method (MEQS) for fibre placement in additive manufacturing of topology-optimised continuous carbon fibre-reinforced polymer composite structures

This study proposes a modified equally-spaced (MEQS) method for the path design of continuous fibres in additive manufacturing (AM) of topologically optimised composite structures. The MEQS method addresses the low fibre infill rate issue of the traditional Equally-Spaced (EQS) method by utilising the Offset method to generate looped printing paths around the internal cavities and gaps between continuous fibre paths. The developed MEQS method was first illustrated against EQS and Offset methods using an open-hole composite plate in which topology and material orientation were simultaneously optimised using the discrete–continuous parameterisation (DCP) method. Actual printing path-based finite element modelling showed that the MEQS method achieves a 25.32% increase in stiffness compared to the Offset method. Experimental testing of the additively manufactured open-hole composite plates showed that the MEQS method improves the stiffness and strength by 15.52% and 27.38%, respectively, compared to the Offset method. The proposed MEQS was further demonstrated through two other case studies by finite element modelling, showing that the stiffness of MEQS has increased by an average of 66.71% and 14.95% compared to EQS and Offset, respectively

Profile and clinical implication of circular RNAs in human papillary thyroid carcinoma

Background Differently expressed circular RNAs (circRNAs) have been reported to play a considerable role in tumor behavior; however, the expression profile and biological function of circRNAs in papillary thyroid carcinoma (PTC) remains unknown. Thus, the study was aimed to characterize the circRNA expression profile to comprehensively understand the biological behavior of PTC. Methods We investigated the expression profile of circRNAs using circRNA microarray in three pairs of PTC and adjacent normal tissues. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to validate eight candidate circRNAs in 40 paired PTC tumors and adjacent normal samples. Next, we employed a bioinformatics tool to identify putative miRNA and circRNA-associated downstream genes, followed by constructing a network map of circRNA-miRNA-mRNA interactions and exploring the potential role of the candidate circRNAs. Results In total, 206 up- and 177 downregulated circRNAs were identified in PTC tissues (fold change >1.5; P < 0.05). The expression levels of eight candidate circRNAs confirmed by qRT-PCR were significantly different between the PTC and normal samples. The downstream genes of candidate circRNAs participated in various biological processes and signaling pathways. The most up and downregulated circRNAs were hsa_circRNA_007148 and hsa_circRNA_047771. The lower expression level of hsa_circRNA_047771 was associated BRAFV600 mutation, lymph node metastasis (LNM), as well as with advanced TNM stage (all P < 0.05). The higher expression level of hsa_circRNA_007148 was significantly correlated with LNM (P < 0.05). The areas under receiver operating curve were 0.876 (95% CI [0.78–0.94]) for hsa_circRNA_047771 and 0.846 (95% CI [0.75–0.96]) for hsa_circRNA_007148. Discussion The study suggests that dysregulated circRNAs play a critical role in PTC pathogenesis. PTC-related hsa_circRNA_047771 and hsa_circRNA_007148 may serve as potential diagnostic biomarkers and prognostic predictors for PTC patients

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial KATP Channel Activation in Isolated Rat Hearts

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (KATP) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective KATP channel blocker glibenclamide (GLI) and a selective mitochondrial KATP (mKATP) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dtmax, and -dP/dtmin throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5±2.5% in EGCG 1 µM and 4.0±1.7% in EGCG 10 µM, P<0.001 vs. control 27.2±1.4%). This anti-infarct effect was totally abrogated by 10 µM GLI (24.6±1.5%, P<0.001 vs. EGCG). Similarly, 100 µM HD also aborted the anti-infarct effect of EGCG (24.1±1.2%, P<0.001 vs. EGCG ). These data support a role for the KATP channels in EGCG-induced cardioprotection. The mKATP channels play a crucial role in the cardioprotection by EGCG

p38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice

Muscle wasting is the key manifestation of cancer-associated cachexia, a lethal metabolic disorder seen in over 50% of cancer patients. Autophagy is activated in cachectic muscle of cancer hosts along with the ubiquitin-proteasome pathway (UPP), contributing to accelerated protein degradation and muscle wasting. However, established signaling mechanism that activates autophagy in response to fasting or denervation does not seem to mediate cancer-provoked autophagy in skeletal myocytes. Here, we show that p38β MAPK mediates autophagy activation in cachectic muscle of tumor-bearing mice via novel mechanisms. Complementary genetic and pharmacological manipulations reveal that activation of p38β MAPK, but not p38α MAPK, is necessary and sufficient for Lewis lung carcinoma (LLC)-induced autophagy activation in skeletal muscle cells. Particularly, muscle-specific knockout of p38β MAPK abrogates LLC tumor-induced activation of autophagy and UPP, sparing tumor-bearing mice from muscle wasting. Mechanistically, p38β MAPK-mediated activation of transcription factor C/EBPβ is required for LLC-induced autophagy activation, and upregulation of autophagy-related genes LC3b and Gabarapl1. Surprisingly, ULK1 activation (phosphorylation at S555) by cancer requires p38β MAPK, rather than AMPK. Activated ULK1 forms a complex with p38β MAPK in myocytes, which is markedly increased by a tumor burden. Overexpression of a constitutively active p38β MAPK in HEK293 cells increases phosphorylation at S555 and other amino acid residues of ULK1, but not several of AMPK-mediated sites. Finally, ULK1 activation is abrogated in tumor-bearing mice with muscle-specific knockout of p38β MAPK. Thus, p38β MAPK appears a key mediator of cancer-provoked autophagy activation, and a therapeutic target of cancer-induced muscle wasting

MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

Erratum: https://link.springer.com/article/10.1007/s10863-014-9597-1MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.Funding support from Medical Research Council, United Kingdom; National Institutes of Health, United States; British Heart Foundation, United Kingdo

Association of sleep duration with apolipoproteins and the apolipoprotein B/A1 ratio: the China health and nutrition survey

Abstract Background Short sleep duration has been related to established cardiovascular risk factors, likely obesity, diabetes, hypertension and dyslipidaemia. However, to the best of our knowledge, the associations between sleep duration and apolipoprotein concentrations and their ratios have not been investigated to date. This study aimed to explore the independent relationship of sleep duration with apolipoprotein (apo) A1, apoB and the apoB/apoA1 ratio in a Chinese adult population. Methods Data from 7381 participants, aged 18 to 75 years, from the National Health and Nutrition Survey 2009 were analysed in this cross-sectional study. Participants were divided into 3 categories according to sleep duration: ≤6, 7–8, and ≥9 h. Logistic regression analysis with odds ratios was employed to assess the association between sleep duration and apo profile. Results Using 7–8 h of sleep as a reference, short sleep duration was associated with significantly increased odds of elevated apoB (OR =1.75, 95% CI 1.12–2.72), whereas long sleep duration was correlated with a decreased (but not statistically significant) risk for elevated apoB (OR =0.86, 95% CI 0.54–1.38) among females after controlling for covariates. Among males, long sleep duration was only marginally related to decreased odds ratios for elevated apoB/apoA1 ratio after adjustment for covariates (OR =0.78, 95% CI 0.6–0.99). Conclusions These results indicate that short sleep duration is strongly associated with an increased risk of elevated apoB levels in women and that long sleep duration is correlated with decreased apoB/apoA1 levels in men. Sleep hygiene management could serve to treat and prevent cardiovascular diseases by altering unfavourable apo profile

MEMS Inertial Sensors Based Gait Analysis for Rehabilitation Assessment via Multi-Sensor Fusion

Gait and posture are regular activities which are fully controlled by the sensorimotor cortex. In this study, fluctuations of joint angle and asymmetry of foot elevation in human walking stride records are analyzed to assess gait in healthy adults and patients affected with gait disorders. This paper aims to build a low-cost, intelligent and lightweight wearable gait analysis platform based on the emerging body sensor networks, which can be used for rehabilitation assessment of patients with gait impairments. A calibration method for accelerometer and magnetometer was proposed to deal with ubiquitous orthoronal error and magnetic disturbance. Proportional integral controller based complementary filter and error correction of gait parameters have been defined with a multi-sensor data fusion algorithm. The purpose of the current work is to investigate the effectiveness of obtained gait data in differentiating healthy subjects and patients with gait impairments. Preliminary clinical gait experiments results showed that the proposed system can be effective in auxiliary diagnosis and rehabilitation plan formulation compared to existing methods, which indicated that the proposed method has great potential as an auxiliary for medical rehabilitation assessment