Video Coding for Machines: Compact Visual Representation Compression for Intelligent Collaborative Analytics.

As an emerging research practice leveraging recent advanced AI techniques, e.g. deep models based prediction and generation, Video Coding for Machines (VCM) is committed to bridging to an extent separate research tracks of video/image compression and feature compression, and attempts to optimize compactness and efficiency jointly from a unified perspective of high accuracy machine vision and full fidelity human vision. With the rapid advances of deep feature representation and visual data compression in mind, in this paper, we summarize VCM methodology and philosophy based on existing academia and industrial efforts. The development of VCM follows a general rate-distortion optimization, and the categorization of key modules or techniques is established including feature-assisted coding, scalable coding, intermediate feature compression/optimization, and machine vision targeted codec, from broader perspectives of vision tasks, analytics resources, etc. From previous works, it is demonstrated that, although existing works attempt to reveal the nature of scalable representation in bits when dealing with machine and human vision tasks, there remains a rare study in the generality of low bit rate representation, and accordingly how to support a variety of visual analytic tasks. Therefore, we investigate a novel visual information compression for the analytics taxonomy problem to strengthen the capability of compact visual representations extracted from multiple tasks for visual analytics. A new perspective of task relationships versus compression is revisited. By keeping in mind the transferability among different machine vision tasks (e.g. high-level semantic and mid-level geometry-related), we aim to support multiple tasks jointly at low bit rates. In particular, to narrow the dimensionality gap between neural network generated features extracted from pixels and a variety of machine vision features/labels (e.g. scene class, segmentation labels), a codebook hyperprior is designed to compress the neural network-generated features. As demonstrated in our experiments, this new hyperprior model is expected to improve feature compression efficiency by estimating the signal entropy more accurately, which enables further investigation of the granularity of abstracting compact features among different tasks.

ATP9A deficiency causes ADHD and aberrant endosomal recycling via modulating RAB5 and RAB11 activity.

ATP9A, a lipid flippase of the class II P4-ATPases, is involved in cellular vesicle trafficking. Its homozygous variants are linked to neurodevelopmental disorders in humans. However, its physiological function, the underlying mechanism as well as its pathophysiological relevance in humans and animals are still largely unknown. Here, we report two independent families in which the nonsense mutations c.433C>T/c.658C>T/c.983G>A (p. Arg145*/p. Arg220*/p. Trp328*) in ATP9A (NM_006045.3) cause autosomal recessive hypotonia, intellectual disability (ID) and attention deficit hyperactivity disorder (ADHD). Atp9a null mice show decreased muscle strength, memory deficits and hyperkinetic movement disorder, recapitulating the symptoms observed in patients. Abnormal neurite morphology and impaired synaptic transmission are found in the primary motor cortex and hippocampus of the Atp9a null mice. ATP9A is also required for maintaining neuronal neurite morphology and the viability of neural cells in vitro. It mainly localizes to endosomes and plays a pivotal role in endosomal recycling pathway by modulating small GTPase RAB5 and RAB11 activation. However, ATP9A pathogenic mutants have aberrant subcellular localization and cause abnormal endosomal recycling. These findings provide strong evidence that ATP9A deficiency leads to neurodevelopmental disorders and synaptic dysfunctions in both humans and mice, and establishes novel regulatory roles for ATP9A in RAB5 and RAB11 activity-dependent endosomal recycling pathway and neurological diseases.

Establishment of a Zebrafish Xenograft Model for in Vivo Investigation of Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a unique malignant tumor of the head and neck. Despite higher survival rates by the combination of radiotherapy and chemotherapy, the recurrence or metastasis of NPC still occurs at about 10%. Therefore, there is urgent demand to develop more effective in vivo models for preclinical trials to investigate the mechanisms of NPC development and progression and to explore better treatment approaches. In this study, we transplanted human NPC CNE1 cells into zebrafish embryos to establish a xenograft model of NPC, where the proliferation and invasion behaviors of NPC cells were investigated in vivo. Combining in vitro and in vivo analyses, we found that activating transcription factor 7 (ATF7) was involved in the occurrence and development of NPC regulated by peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1). The zebrafish NPC xenograft model established here thereby provides an in vivo tool for exploring the occurrence and development of NPC, which may help to identify new tumor markers and develop new therapeutic strategies for the treatment of NPC.

Towards Low Light Enhancement With RAW Images.

In this paper, we make the first benchmark effort to elaborate on the superiority of using RAW images in the low light enhancement and develop a novel alternative route to utilize RAW images in a more flexible and practical way. Inspired by a full consideration on the typical image processing pipeline, we are inspired to develop a new evaluation framework, Factorized Enhancement Model (FEM), which decomposes the properties of RAW images into measurable factors and provides a tool for exploring how properties of RAW images affect the enhancement performance empirically. The empirical benchmark results show that the Linearity of data and Exposure Time recorded in meta-data play the most critical role, which brings distinct performance gains in various measures over the approaches taking the sRGB images as input. With the insights obtained from the benchmark results in mind, a RAW-guiding Exposure Enhancement Network (REENet) is developed, which makes trade-offs between the advantages and inaccessibility of RAW images in real applications in a way of using RAW images only in the training phase. REENet projects sRGB images into linear RAW domains to apply constraints with corresponding RAW images to reduce the difficulty of modeling training. After that, in the testing phase, our REENet does not rely on RAW images. Experimental results demonstrate not only the superiority of REENet to state-of-the-art sRGB-based methods and but also the effectiveness of the RAW guidance and all components.

Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum-Mitochondria Contact and Mitochondrial Functions in Stress-Induced Hypertension Rats.

Exposure to stress plays a detrimental role in the pathogenesis of hypertension via neuroinflammation pathways. Microglial neuroinflammation in the rostral ventrolateral medulla (RVLM) exacerbates stress-induced hypertension (SIH) by increasing sympathetic hyperactivity. Mitochondria of microglia are the regulators of innate immune response. Sigma-1R (σ-1R) localizes to the mitochondria-associated membranes (MAMs) and regulates endoplasmic reticulum (ER) and mitochondria communication, in part through its chaperone activity. The present study aims to investigate the protective role of σ-1R on microglial-mediated neuroinflammation. Stress-induced hypertension (SIH) was induced in rats using electric foot shocks and intermittent noise. Arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured to evaluate the sympathetic nervous system (SNS) activities. SKF10047 (100 µM), an agonist of σ-1R, was administrated to rats, then σ-1R localization and MAM alterations were detected by immuno-electron microscopy. Mitochondrial calcium homeostasis was examined in primary microglia and/or BV-2 microglia cells. The effect of SKF10047 treatment on the mitochondrial respiratory function of cultured microglia was measured using a Seahorse Extracellular Flux Analyzer. Confocal microscopic images were performed to indicate mitochondrial dynamics. Stress reduces σ-1R's localization at the MAMs, leading to decreased ER-mitochondria contact and IP3R-GRP75-VDAC calcium transport complexes expression in the RVLM of rats. SKF10047 promotes the length and coverage of MAMs in the prorenin-treated microglia. Prorenin treatment increases mitoROS levels, and inhibits Ca2+ signalling between the two organelles, therefore negatively affects ATP production in BV2 cells, and these effects are reversed by SKF10047 treatment. We found mitochondrial hyperfusion and microglial M1 polarization in prorenin-treated microglia. SKF10047 suppresses microglial M1 polarization and RVLM neuroinflammation, subsequently ameliorates sympathetic hyperactivity in stress-induced hypertensive rats. Sigma-1 receptor activation suppresses microglia M1 polarization and neuroinflammation via regulating endoplasmic reticulum-mitochondria contact and mitochondrial functions in stress-induced hypertension rats.

Molecular machineries and physiological relevance of ER-mediated membrane contacts.

Membrane contact sites (MCSs) are defined as regions where two organelles are closely apposed, and most MCSs associated with each other via protein-protein or protein-lipid interactions. A number of key molecular machinery systems participate in mediating substance exchange and signal transduction, both of which are essential processes in terms of cellular physiology and pathophysiology. The endoplasmic reticulum (ER) is the largest reticulum network within the cell and has extensive communication with other cellular organelles, including the plasma membrane (PM), mitochondria, Golgi, endosomes and lipid droplets (LDs). The contacts and reactions between them are largely mediated by various protein tethers and lipids. Ions, lipids and even proteins can be transported between the ER and neighboring organelles or recruited to the contact site to exert their functions. This review focuses on the key molecules involved in the formation of different contact sites as well as their biological functions.

Sparse Gradient Regularized Deep Retinex Network for Robust Low-Light Image Enhancement.

Due to the absence of a desirable objective for low-light image enhancement, previous data-driven methods may provide undesirable enhanced results including amplified noise, degraded contrast and biased colors. In this work, inspired by Retinex theory, we design an end-to-end signal prior-guided layer separation and data-driven mapping network with layer-specified constraints for single-image low-light enhancement. A Sparse Gradient Minimization sub-Network (SGM-Net) is constructed to remove the low-amplitude structures and preserve major edge information, which facilitates extracting paired illumination maps of low/normal-light images. After the learned decomposition, two sub-networks (Enhance-Net and Restore-Net) are utilized to predict the enhanced illumination and reflectance maps, respectively, which helps stretch the contrast of the illumination map and remove intensive noise in the reflectance map. The effects of all these configured constraints, including the signal structure regularization and losses, combine together reciprocally, which leads to good reconstruction results in overall visual quality. The evaluation on both synthetic and real images, particularly on those containing intensive noise, compression artifacts and their interleaved artifacts, shows the effectiveness of our novel models, which significantly outperforms the state-of-the-art methods.

The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses.

Energy deprivation activates the cellular energy sensor AMP-activated protein kinase (AMPK), which in turn induces macroautophagy/autophagy. The mitochondrial-associated ER membrane (MAM) plays a key role in mitochondrial division and autophagy, and the mitochondrial fusion protein MFN2 (mitofusin 2) tethers the MAM, but the mechanism by which AMPK and MFN2 regulate autophagy in response to energy stress remains unclear. Here, we found that energy stress not only triggers mitochondrial fission and autophagy, but more importantly increases the number of MAMs, a process that requires AMPK. Interestingly, under energy stress, considerable amounts of AMPK translocate from cytosol to the MAM and the mitochondrion as mitochondrial fission occurs. Unexpectedly, AMPK interacts directly with MFN2. The autophagic ability of mouse embryonic fibroblasts (MEFs) lacking MFN2 (mfn2-/-) is significantly attenuated in response to energy stress as compared to wild-type MEFs (WT MEFs), while re-expression of MFN2 in mfn2-/- cells rescues the autophagy defects of these cells. The abundance of MAMs is also greatly reduced in MFN2-deficient cells. Functional experiments show that the oxygen consumption rate and the glycolytic function of cells lacking MFN2 but not MFN1 are obviously attenuated, and MFN2 is important for cell survival under energy stress. In conclusion, our study establishes the molecular link between the energy sensor AMPK and the MAM tether MFN2, and reveals the important role of AMPK and MFN2 in energy stress-induced autophagy and MAM dynamics.Abbreviations: ACTB, actin beta; AMPK, AMP-activated protein kinase; BECN1, beclin 1; CANX, calnexin; ER, endoplasmic reticulum; HRP, horseradish peroxidase; EM, electron microscopy; FL, full-length; KD, kinase dead, KO, knockout; MAb, monoclonal antibody; MAMs, mitochondria-associated membranes; MAP1LC3/LC3B, microtubule associated protein 1 light chain 3; MFN2, mitofusin 2; OPA1, OPA1 mitochondrial dynamin like GTPase; PAb, polyclonal antibody; PtdIns3K, class III phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; SD, standard deviation; TEM, transmission electron microscopy; TOMM20, translocase of outer mitochondrial membrane 20; ULK1, unc-51 like autophagy activating kinase 1; MEF, mouse embryonic fibroblast; WT, wildtype.

Tropolone derivatives with hepatoprotective and antiproliferative activities from the aerial parts of Chenopodium album Linn.

Chenopodium album Linn is used as the traditional Chinese medicine for treating cough, anorexia, piles, dysentery, diarrhea, and kills small worms in China. Nine new tropolones (1-9), and fourteen known tropolone derivatives (10-23) were elucidated by comprehensive spectroscopic data analysis and references from C. album Linn for the first time. Compounds (1-4) and compounds (13-14) displayed notably hepatoprotective activities in intro for lowering AST levels (19.63 ± 2.34 to 29.87 ± 1.27 U•L-1) and ALT levels (15.21 ± 1.18 to 20.29 ± 2.11 U•L-1) in HepG2 cells treated with H2O2. Compounds (8-9) and compounds (15-17) exhibited moderate antiproliferative activities in vitro against the human tumor cell lines with IC50 values ranging from 0.5 ± 0.2 to 15.5 ± 2.7 µM. A preliminary structure activity relationship was summarized and discussed scientifically, which provided new clues to design novel hepatoprotective and antiproliferative drugs based on the tropolone derivatives.

Mitochondrial Quality Control in Cardiomyocytes: A Critical Role in the Progression of Cardiovascular Diseases.

Mitochondria serve as an energy plant and participate in a variety of signaling pathways to regulate cellular metabolism, survival and immunity. Mitochondrial dysfunction, in particular in cardiomyocytes, is associated with the development and progression of cardiovascular disease, resulting in heart failure, cardiomyopathy, and cardiac ischemia/reperfusion injury. Therefore, mitochondrial quality control processes, including post-translational modifications of mitochondrial proteins, mitochondrial dynamics, mitophagy, and formation of mitochondrial-driven vesicles, play a critical role in maintenance of mitochondrial and even cellular homeostasis in physiological or pathological conditions. Accumulating evidence suggests that mitochondrial quality control in cardiomyocytes is able to improve cardiac function, rescue dying cardiomyocytes, and prevent the deterioration of cardiovascular disease upon external environmental stress. In this review, we discuss recent progress in understanding mitochondrial quality control in cardiomyocytes. We also evaluate potential targets to prevent or treat cardiovascular diseases, and highlight future research directions which will help uncover additional mechanisms underlying mitochondrial homeostasis in cardiomyocytes.

Recent progress in the role of autophagy in neurological diseases.

Autophagy (here refers to macroautophagy) is a catabolic pathway by which large protein aggregates and damaged organelles are first sequestered into a double-membraned structure called autophago-some and then delivered to lysosome for destruction. Recently, tremen-dous progress has been made to elucidate the molecular mechanism and functions of this essential cellular metabolic process. In addition to being either a rubbish clearing system or a cellular surviving program in response to different stresses, autophagy plays important roles in a large number of pathophysiological conditions, such as cancer, diabetes, and especially neurodegenerative disorders. Here we review recent progress in the role of autophagy in neurological diseases and discuss how dysregulation of autophagy initiation, autophagosome formation, maturation, and/or au-tophagosome-lysosomal fusion step contributes to the pathogenesis of these disorders in the nervous system.

Fabrication of superparamagnetic magnetite/poly(styrene-co-12-acryloxy-9-octadecenoic acid) nanocomposite microspheres with controllable structure.

We herein report a novel and facile approach to the fabrication of the superparamagnetic magnetite/poly(styrene-co-12-acryloxy-9-octadecenoic acid) nanocomposite microspheres with controllable structure via gamma-ray radiation induced inverse emulsion polymerization under room temperature and at ambient pressure. 12-Acryloxy-9-octadecenoic acid (AOA, containing part of sodium salts Na-AOA) as a surfactant can also copolymerize with the styrene. It is interesting that just by changing the added amount of styrene, the magnetic hollow spheres with different wall thickness and various sizes of core, up to the magnetic solid spheres, can be obtained. The final products were thoroughly characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron diffraction (TEM), field-emission scanning electron microscopy (FESEM), thermogravimetric analysis (TGA) which showed the formation of magnetite/poly(styrene-co-AOA) nanocomposite microspheres. Magnetic hysteresis loop measurements showed that the magnetic nanocomposite microspheres exhibited superparamagnetism, which should make them have potential applications in biotechnology and biomedicine. Furthermore, we also proposed a possible formation mechanism of these magnetic microspheres with different morphologies.