A CRM1 Inhibitor Alleviates Cardiac Hypertrophy and Increases the Nuclear Distribution of NT-PGC-1α in NRVMs

Chromosomal maintenance 1 (CRM1) inhibitors display antihypertrophic effects and control protein trafficking between the nucleus and the cytoplasm. PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1alpha) is a type of transcriptional coactivator that predominantly resides in the nucleus and is downregulated during heart failure. NT-PGC-1α is an alternative splicing variant of PGC-1α that is primarily distributed in the cytoplasm. We hypothesized that the use of a CRM1 inhibitor could shuttle NT-PGC-1α into the nucleus and activate PGC-1α target genes to potentially improve cardiac function in a mouse model of myocardial infarction (MI). We showed that PGC-1α and NT-PGC-1α were decreased in MI-induced heart failure mice. Phenylephrine and angiotensin II were applied to induce hypertrophy in neonatal rat ventricular myocytes (NRVMs). The antihypertrophic effects of the CRM1-inhibitor Selinexor was verified through profiling the expression of β-MHC and through visualizing the cell cross-sectional area. NRVMs were transfected with adenovirus-NT-PGC-1α or adenovirus-NLS (nucleus localization sequence)-NT-PGC-1α and then exposed to Selinexor. Confocal microscopy was then used to observe the shuttling of NT-PGC-1α. After NT-PGC-1α was shuttled into the nucleus, there was increased expression of its related genes, including PPAR-α, Tfam, ERR-γ, CPT1b, PDK4, and Nrf2. The effects of Selinexor on post-MI C57BL/6j mice were determined by echocardiography and qPCR. We found that Selinexor showed antihypertrophic effects but did not influence the ejection fraction of MI-mice. Interestingly, the antihypertrophic effects of Selinexor might be independent of NT-PGC-1α transportation

A novel heteromorphic ensemble algorithm for hand pose recognition

Imagining recognition of behaviors from video sequences for a machine is full of challenges but meaningful. This work aims to predict students’ behavior in an experimental class, which relies on the symmetry idea from reality to annotated reality centered on the feature space. A heteromorphic ensemble algorithm is proposed to make the obtained features more aggregated and reduce the computational burden. Namely, the deep learning models are improved to obtain feature vectors representing gestures from video frames and the classification algorithm is optimized for behavior recognition. So, the symmetric idea is realized by decomposing the task into three schemas including hand detection and cropping, hand joints feature extraction, and gesture classification. Firstly, a new detector method named YOLOv4-specific tiny detection (STD) is proposed by reconstituting the YOLOv4-tiny model, which could produce two outputs with some attention mechanism leveraging context information. Secondly, the efficient pyramid squeeze attention (EPSA) net is integrated into EvoNorm-S0 and the spatial pyramid pool (SPP) layer to obtain the hand joint position information. Lastly, the D–S theory is used to fuse two classifiers, support vector machine (SVM) and random forest (RF), to produce a mixed classifier named S–R. Eventually, the synergetic effects of our algorithm are shown by experiments on self-created datasets with a high average recognition accuracy of 89.6%

Mitofusin 2 Participates in Mitophagy and Mitochondrial Fusion Against Angiotensin II-Induced Cardiomyocyte Injury

BackgroundMitochondrial dynamics play a critical role in mitochondrial function. The mitofusin 2 (MFN2) gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion to maintain and operate the mitochondrial network. Moreover, MFN2 is essential for mitophagy. In Ang II-induced cardiac remodeling, the combined effects of MFN2-mediated mitochondrial fusion and mitophagy are unclear. This study was designed to explore a novel strategy for preventing cardiomyocyte injury via modulation of mitochondrial dynamics.MethodsWe studied the function of MFN2 in mitochondrial fusion and mitophagy in Ang II-stimulated cardiomyocyte injury. Cardiomyocyte injury experiments, including reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), and apoptosis rate of cardiomyocytes were performed. The mitochondrial morphology in cardiomyocytes was examined via transmission electron microscopy (TEM) and confocal microscopy. Autophagic levels in response to Ang II were examined by immunoblotting of autophagy-related proteins. Moreover, PINK1/MFN2/Parkin pathway-related proteins were examined.ResultsWith stimulation by Ang II, MFN2 expression was progressively reduced. MFN2 deficiency impaired mitochondrial quality, resulting in exacerbated mitochondrial damage induced by Ang II. The Ang II-induced increases in ROS production and apoptosis rate were alleviated by MFN2 overexpression. Moreover, MFN2 alleviated the Ang II-induced reduction in MMP. MFN2 promoted mitochondrial fusion, and MFN2 promoted Parkin translocation and phosphorylation, leading to mitochondrial autophagy. The effects of MFN2 overexpression were reversed by autophagy inhibitors.ConclusionMitofusin 2 promotes Parkin translocation and phosphorylation, leading to mitophagy to clear damaged mitochondria. However, the beneficial effects of MFN2 were reversed by autophagy inhibitors. Additionally, MFN2 participates in mitochondrial fusion to maintain mitochondrial quality. Thus, MFN2 participated in mitophagy and mitochondrial fusion against Ang II-induced cardiomyocyte injury

Nanomechanical Resonators: Toward Atomic Scale

The quest for realizing and manipulating ever smaller man-made movable structures and dynamical machines has spurred tremendous endeavors, led to important discoveries, and inspired researchers to venture to new grounds. Scientific feats and technological milestones of miniaturization of mechanical structures have been widely accomplished by advances in machining and sculpturing ever shrinking features out of bulk materials such as silicon. With the flourishing multidisciplinary field of low-dimensional nanomaterials, including one-dimensional (1D) nanowires/nanotubes, and two-dimensional (2D) atomic layers such as graphene/phosphorene, growing interests and sustained efforts have been devoted to creating mechanical devices toward the ultimate limit of miniaturization— genuinely down to the molecular or even atomic scale. These ultrasmall movable structures, particularly nanomechanical resonators that exploit the vibratory motion in these 1D and 2D nano-to-atomic-scale structures, offer exceptional device-level attributes, such as ultralow mass, ultrawide frequency tuning range, broad dynamic range, and ultralow power consumption, thus holding strong promises for both fundamental studies and engineering applications. In this Review, we offer a comprehensive overview and summary of this vibrant field, present the state-of-the-art devices and evaluate their specifications and performance, outline important achievements, and postulate future directions for studying these miniscule yet intriguing molecular-scale machines

Nanomechanical Resonators: Toward Atomic Scale

The quest for realizing and manipulating ever smaller man-made movable structures and dynamical machines has spurred tremendous endeavors, led to important discoveries, and inspired researchers to venture to previously unexplored grounds. Scientific feats and technological milestones of miniaturization of mechanical structures have been widely accomplished by advances in machining and sculpturing ever shrinking features out of bulk materials such as silicon. With the flourishing multidisciplinary field of low-dimensional nanomaterials, including one-dimensional (1D) nanowires/nanotubes and two-dimensional (2D) atomic layers such as graphene/ phosphorene, growing interests and sustained effort have been devoted to creating mechanical devices toward the ultimate limit of miniaturization--genuinely down to the molecular or even atomic scale. These ultrasmall movable structures, particularly nanomechanical resonators that exploit the vibratory motion in these 1D and 2D nano-to-atomic-scale structures, offer exceptional device-level attributes, such as ultralow mass, ultrawide frequency tuning range, broad dynamic range, and ultralow power consumption, thus holding strong promises for both fundamental studies and engineering applications. In this Review, we offer a comprehensive overview and summary of this vibrant field, present the state-of-the-art devices and evaluate their specifications and performance, outline important achievements, and postulate future directions for studying these miniscule yet intriguing molecular-scale machines

Episode of ventricular fibrillation in patient with coronary artery ectasia during coronary angiography

Key Clinical Message There was an 83‐year‐old man having coronary artery disease associated with coronary artery ectasia who occurred ventricular fibrillation suddenly during coronary artery angiography. As Kawasaki disease was suspected to the most likely reason which led to coronary artery lesion

On-chip mechanical computing: status, challenges, and opportunities

ABSTRACT: With increasing challenges towards continued scaling and improvement in performance faced by electronic computing, mechanical computing has started to attract growing interests. Taking advantage of the mechanical degree of freedom in solid state devices, micro/nano-electromechanical systems (MEMS/NEMS) could provide alternative solutions for future computing and memory systems with ultralow power consumption, compatibility with harsh environments, and high reconfigurability. In this review, MEMS/NEMS-enabled memories and logic processors were surveyed, and the prospects and challenges for future on-chip mechanical computing were also analyzed

Effect of cooling rate on microstructure and properties of SiCP/A359 composites

The microstructure and properties of stirred cast SiCP/A359 composites under different cooling rates were studied. The strengthening mechanism of the composite material under three cooling rates was analyzed, and the failure mechanism of the composite material was elucidated by means of in-situ tension and EBSD testing. The results showed that increasing the cooling rate simultaneously refined the grains, secondary dendrites, and eutectic silicon, resulting in improved distribution uniformity of SiC and the stacking fault density of eutectic silicon. Additionally, the relationship between the secondary dendrite arm spacing (SDAS) and cooling rate (v) of the SiCP/A359 composite was described using the equation SDAS = 56.02v^(-0.3). There was a positive correlation between cooling rate and yield strength, with particle strengthening being the main contributor to the strength of composites with high cooling rates, resulting in significantly higher strength than samples with low cooling rates. The geometrically necessary dislocations (GND) density at the eutectic Si-Al boundary was found to be higher than other positions after the material was loaded, and the main crack propagated mainly along the eutectic region. Secondary cracks, including SiC cracking, eutectic silicon cracking, interface separation, and shrinkage cracking, may become part of the main crack by bridging

Strengthening effects of GP zone induced by SiCp size variations in Al–Si–Mg matrix composites

In this work, SiCp reinforced Al–Si–Mg matrix composites were prepared by stirring casting with different SiCp sizes. The effect of SiCp sizes on the microstructure and mechanical properties was investigated, and different strengthening effects were systematically calculated and analyzed. With the decrease of SiCp sizes, the microstructure of composites is refined and the plasticity is improved significantly. The refined SiCp also leads to a more intense grain refinement strengthening and thermal expansion mismatch strengthening. However, an abnormal decrease of yield strength is discovered with the refinement of SiCp, which is due to the influence of SiCp on GP zones strengthening in the matrix. As SiCp sizes decreasing, the increased SiCp/Al interfaces capture more Mg atoms, and then inhibits the formation of GP zones in the α-Al. Therefore, the refined SiCp weaken the precipitation strengthening in composites. These acicular Mg–Si GP zones exhibit a preferentially growing direction along Al and present a same structure as α-Al with coherent interfaces which pin dislocations and provide precipitation strengthening. The high density of GP zones also increases nano-hardness and elastic modulus of α-Al, which improves the wear resistance of SiCp/Al–Si–Mg composites. Therefore, it is suggested that the interaction between the SiCp and precipitates in matrix should also be considered to obtain a suitable strengthening effect in the design of SiCp/Al alloy composites