A Review of EFL Formulaic Language Acquisition and Teaching intervention

This paper reviews EFL formulaic language research in international and Chinese domestic academia from the perspectives of language acquisition and language teaching. Current studies have some limitations due to different types of reasons. For example, a lack of representativeness in the selection of target items, a lack of attention to learner’s differences, and a scanty of high-quality EFL formulaic sequences instruction research. Future research can pay more attention to learners’ differences that may affect the acquisition and learning process of the formulaic language, with the aim of exploring effective methods and approaches to improve the competence of EFL learners and promoting the optimization of theories exploring the teaching of EFL formulaic language

Optimizing Sparse Matrix-Vector Multiplications on an ARMv8-based Many-Core Architecture

Sparse matrix–vector multiplications (SpMV) are common in scientific and HPC applications but are hard to be optimized. While the ARMv8-based processor IP is emerging as an alternative to the traditional x64 HPC processor design, there is little study on SpMV performance on such new many-cores. To design efficient HPC software and hardware, we need to understand how well SpMV performs. This work develops a quantitative approach to characterize SpMV performance on a recent ARMv8-based many-core architecture, Phytium FT-2000 Plus (FTP). We perform extensive experiments involved over 9500 distinct profiling runs on 956 sparse datasets and five mainstream sparse matrix storage formats, and compare FTP against the Intel Knights Landing many-core. We experimentally show that picking the optimal sparse matrix storage format and parameters is non-trivial as the correct decision requires expert knowledge of the input matrix and the hardware. We address the problem by proposing a machine learning based model that predicts the best storage format and parameters using input matrix features. The model automatically specializes to the many-core architectures we considered. The experimental results show that our approach achieves on average 93% of the best-available performance without incurring runtime profiling overhead

Adaptive Optimization of Sparse Matrix-Vector Multiplication on Emerging Many-Core Architectures

Sparse matrix vector multiplication (SpMV) is one of the most common operations in scientific and high-performance applications, and is often responsible for the application performance bottleneck. While the sparse matrix representation has a significant impact on the resulting application performance, choosing the right representation typically relies on expert knowledge and trial and error. This paper provides the first comprehensive study on the impact of sparse matrix representations on two emerging many-core architectures: the Intel's Knights Landing (KNL) XeonPhi and the ARM-based FT-2000Plus (FTP). Our large-scale experiments involved over 9,500 distinct profiling runs performed on 956 sparse datasets and five mainstream SpMV representations. We show that the best sparse matrix representation depends on the underlying architecture and the program input. To help developers to choose the optimal matrix representation, we employ machine learning to develop a predictive model. Our model is first trained offline using a set of training examples. The learned model can be used to predict the best matrix representation for any unseen input for a given architecture. We show that our model delivers on average 95% and 91% of the best available performance on KNL and FTP respectively, and it achieves this with no runtime profiling overhead

HSPA12A Is Required for Adipocyte Differentiation and Diet-Induced Obesity Through a Positive Feedback Regulation With PPARγ

Obesity is one of the most serious public health problems. Peroxisome proliferator-activated receptor γ (PPARγ) plays the master role in adipocyte differentiation for obesity development. However, optimum anti-obesity drug has yet been developed, mandating more investigation to identify novel regulator in obesity pathogenesis. Heat shock protein 12A (HSPA12A) encodes a novel member of the HSP70 family. Here, we report that obese patients showed increased adipose HSPA12A expression, which was positively correlated with increase of body mass index. Intriguingly, knockout of HSPA12A (Hspa12a−/−) in mice attenuated high-fat diet (HFD)-induced weight gain, adiposity, hyperlipidemia, and hyperglycemia compared to their wild type (WT) littermates. Increased insulin sensitivity was observed in Hspa12a−/− mice compared to WT mice. The HFD-induced upregulation of PPARγ and its target adipogenic genes in white adipose tissues (WAT) of Hspa12a−/− mice were also attenuated. Loss- and gain-of-function studies revealed that the differentiation of primary adipocyte precursors, as well as the expression of PPARγ and target adipogenic genes during the differentiation, was suppressed by HSPA12A deficiency whereas promoted by HSPA12A overexpression. Importantly, PPARγ inhibition by GW9662 reversed the HSPA12A-mediated adipocyte differentiation. On the other hand, HSPA12A expression was downregulated by PPARγ inhibition but upregulated by PPARγ activation in primary adipocytes. A direct binding of PPARγ to the PPAR response element in the Hspa12a promoter region was confirmed by chromatin immunoprecipitation assay, and this binding was increased after differentiation of primary adipocytes. These findings indicate that HSPA12A is a novel regulator of adipocyte differentiation and diet-induced obesity through a positive feedback regulation with PPARγ. HSPA12A inhibition might represent a viable strategy for the management of obesity in humans

MicroRNA-214 Protects Against Hypoxia/Reoxygenation Induced Cell Damage and Myocardial Ischemia/Reperfusion Injury via Suppression of PTEN and Bim1 Expression

Background: Myocardial apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Activation of PI3K/Akt signaling protects the myocardium from I/R injury. This study investigated the role of miR-214 in hypoxia/ reoxygenation (H/R)-induced cell damage in vitro and myocardial I/R injury in vivo. Methods and Results: H9C2 cardiomyoblasts were transfected with lentivirus expressing miR-214 (LmiR-214) or lentivirus expressing scrambled miR-control (LmiR-control) respectively, to establish cell lines of LmiR-214 and LmiR-control. The cells were subjected to hypoxia for 4 h followed by reoxygenation for 24 h. Transfection of LmiR-214 suppresses PTEN expression, significantly increases the levels of Akt phosphorylation, markedly attenuates LDH release, and enhances the viability of the cells subjected to H/R. In vivo transfection of mouse hearts with LmiR-214 significantly attenuates I/R induced cardiac dysfunction and reduces I/Rinduced myocardial infarct size. LmiR-214 transfection significantly attenuates I/Rinduced myocardial apoptosis and caspase-3/7 and caspase-8 activity. Increased expression of miR-214 by transfection of LmiR-214 suppresses PTEN expression, increases the levels of phosphorylated Akt, represses Bim1 expression and induces Bad phosphorylation in the myocardium. In addition, in vitro data shows transfection of miR-214 mimics to H9C2 cells suppresses the expression and translocation of Bim1 from cytosol to mitochondria and induces Bad phosphorylation. Conclusions: Our in vitro and in vivo data suggests that miR-214 protects cells from H/R induced damage and attenuates I/R induced myocardial injury. The mechanisms involve activation of PI3K/Akt signaling by targeting PTEN expression, induction of Bad phosphorylation, and suppression of Bim1 expression, resulting in decreases in I/R-induced myocardial apoptosis

One-pot synthesis of responsive catalytic Au@PVP hybrid nanogels

NSFC [21274118]; FRFCU [2012121016]; NFFTBS [J1030415]; NCETFJResponsive catalytic hybrid nanogels with Au nanoparticle cores and a polyvinylpyrrolidone (PVP) based gel shell are prepared through a novel one-pot approach. The embedded Au nanoparticles demonstrate both a pH-modulated catalytic activity and anti-aggregation properties upon recycling

HSPA12A Attenuates Lipopolysaccharide-Induced Liver Injury Through Inhibiting Caspase-11-Mediated Hepatocyte Pyroptosis via PGC-1α-Dependent Acyloxyacyl Hydrolase Expression

Liver dysfunction is strongly associated with poor survival of sepsis patients. Cytosolic lipopolysaccharide (LPS) sensing by Caspase-4/5/11 for pyroptosis activation is a major driver of the development of sepsis. Studies in macrophages and endothelial cells have demonstrated that LPS is inactivated by acyloxyacyl hydrolase (AOAH) and leading to desensitizing Caspase-4/5/11 to LPS. However, little is known about the cytosolic LPS-induced pyroptosis in hepatocytes during sepsis. Heat shock protein 12A (HSPA12A) is a novel member of the HSP70 family. Here, we report that LPS increased HSPA12A nuclear translocation in hepatocytes, while knockout of HSPA12A (Hspa12a−/−) in mice promoted LPS-induced acute liver injury. We also noticed that the LPS-induced Caspase-11 activation and its cleavage of gasdermin D (GSDMD) to produce the membrane pore-forming GSDMDNterm (markers of pyroptosis) were greater in livers of Hspa12a−/− mice compared with its wild type controls. Loss- and gain-of-function studies showed that HSPA12A deficiency promoted, whereas HSPA12A overexpression inhibited, cytosolic LPS accumulation, Caspase-11 activation and GSDMDNterm generation in primary hepatocytes following LPS incubation. Notably, LPS-induced AOAH expression was suppressed by HSPA12A deficiency, whereas AOAH overexpression reversed the HSPA12A deficiency-induced promotion of LPS-evoked and Caspase-11-mediated pyroptosis of hepatocytes. In-depth molecular analysis showed that HSPA12A interacted directly with peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and increased its nuclear translocation, thereby inducing AOAH expression for cytosolic LPS inactivation, which ultimately leading to inhibition of the Caspase-11 mediated pyroptosis of hepatocytes. Taken together, these findings revealed HSPA12A as a novel player against LPS-induced liver injury by inhibiting cytosolic LPS-induced hepatocyte pyroptosis via PGC-1α-mediated AOAH expression. Therefore, targeting hepatocyte HSPA12A represents a viable strategy for the management of liver injury in sepsis patients

The TLR9 ligand, CpG-ODN, Induces Protection Against Cerebral Ischemia/Reperfusion Injury via Activation of pi3k/Akt Signaling.

Toll-like receptors (TLRs) have been shown to be involved in cerebral ischemia/reperfusion (I/R) injury. TLR9 is located in intracellular compartments and recognizes CpG-DNA. This study examined the effect of CpG-ODN on cerebral I/R injury. C57BL/6 mice were treated with CpG-ODN by i.p. injection 1 hour before the mice were subjected to cerebral ischemia (60 minutes) followed by reperfusion (24 hours). Scrambled-ODN served as control-ODN. Untreated mice, subjected to cerebral I/R, served as I/R control. The effect of inhibitory CpG-ODN (iCpG-ODN) on cerebral I/R injury was also examined. In addition, we examined the therapeutic effect of CpG-ODN on cerebral I/R injury by administration of CpG-ODN 15 minutes after cerebral ischemia. CpG-ODN administration significantly decreased cerebral I/R-induced infarct volume by 69.7% (6.4±1.80% vs 21.0±2.85%, P\u3c0.05), improved neurological scores, and increased survival rate, when compared with the untreated I/R group. Therapeutic administration of CpG-ODN also significantly reduced infarct volume by 44.7% (12.6±2.03% vs 22.8±2.54%, P\u3c0.05) compared with untreated I/R mice. Neither control-ODN, nor iCpG-ODN altered I/R-induced cerebral injury or neurological deficits. Nissl staining showed that CpG-ODN treatment preserved neuronal morphology in the ischemic hippocampus. Immunoblot showed that CpG-ODN administration increased Bcl-2 levels by 41% and attenuated I/R-increased levels of Bax and caspase-3 activity in ischemic brain tissues. Importantly, CpG-ODN treatment induced Akt and GSK-3β phosphorylation in brain tissue and cultured microglial cells. PI3K inhibition with LY294002 abolished CpG-ODN-induced protection. CpG-ODN significantly reduces cerebral I/R injury via a PI3K/Akt-dependent mechanism. Our data also indicate that CpG-ODN may be useful in the therapy of cerebral I/R injury

Activation of Myocardial Phosphoinositide-3-Kinase p110α Ameliorates Cardiac Dysfunction and Improves Survival in Polymicrobial Sepsis

Phosphoinositide-3-kinase (PI3K)/Akt dependent signaling has been shown to improve outcome in sepsis/septic shock. There is also ample evidence that PI3K/Akt dependent signaling plays a crucial role in maintaining normal cardiac function. We hypothesized that PI3K/Akt signaling may ameliorate septic shock by attenuating sepsis-induced cardiac dysfunction. Cardiac function and survival were evaluated in transgenic mice with cardiac myocyte specific expression of constitutively active PI3K isoform, p110α (caPI3K Tg). caPI3K Tg and wild type (WT) mice were subjected to cecal ligation/puncture (CLP) induced sepsis. Wild type CLP mice showed dramatic cardiac dysfunction at 6 hrs. Septic cardiomyopathy was significantly attenuated in caPI3K CLP mice. The time to 100% mortality was 46 hrs in WT CLP mice. In contrast, 80% of the caPI3K mice survived at 46 hrs after CLP (p30 days (