Exosomes participate in cancer progression and metastasis by transferring bioactive molecules between cancer and various cells in the local and distant microenvironments. Such intercellular ...cross‐talk results in changes in multiple cellular and biological functions in recipient cells. Several hallmarks of cancer have reportedly been impacted by this exosome‐mediated cell‐to‐cell communication, including modulating immune responses, reprogramming stromal cells, remodeling the architecture of the extracellular matrix, or even endowing cancer cells with characteristics of drug resistance. Selectively, loading specific oncogenic molecules into exosomes highlights exosomes as potential diagnostic biomarkers as well as therapeutic targets. In addition, exosome‐based drug delivery strategies in preclinical and clinical trials have been shown to dramatically decrease cancer development. In the present review, we summarize the significant aspects of exosomes in cancer development that can provide novel strategies for potential clinical applications.
Exosomes in cancer development.
Long noncoding RNAs (IncRNAs) have been implicated in a variety of physiological and pathological processes, including cancer. In prostate cancer, prostate cancer gene expression marker 1 (PCGEM1) is ...an androgen-induced prostate-specific IncRNA whose overexpression is highly associated with prostate tumors. PCGEM1's tumorigenie potential has been recently shown to be in part due to its ability to activate androgen receptor (AR). Here, we report a novel function of PCGEM1 that provides growth advantages for cancer cells by regulating tumor metabolism via c-Myc activation. PCGEM1 promotes glucose uptake for aerobic glycolysis, coupling with the pentose phosphate shunt to facilitate biosynthesis of nucleotide and lipid, and generates NADPH for redox homeostasis. We show that PCGEM1 regulates metabolism at a transcriptional level that affects multiple metabolic pathways, including glucose and g Iutamine metabolism, the pentose phosphate pathway, nucleotide and fatty acid biosynthesis, and the tricarboxylic acid cycle. The PCGEM1-mediated gene regulation takes place in part through AR activation, but predominantly through c-Myc activation, regardless of hormone or AR status. Significantly, PCGEM1 binds directly to target promoters, physically interacts with c-Myc, promotes chromatin recruitment of c-Myc, and enhances its transactivation activity. We also identified a c-Myc binding domain on PCGEM1 that contributes to the PCGEM1-dependent c-Myc activation and target induction. Together, our data uncover PCGEM1 as a key transcriptional regulator of central metabolic pathways in prostate cancer cells. By being a coactivator for both c-Myc and AR, PCGEM1 reprograms the androgen network and the central metabolism in a tumor-specific way, making it a promising target for therapeutic intervention.
Long noncoding RNAs (lncRNAs) have been implicated in hypoxia/HIF-1-associated cancer progression through largely unknown mechanisms. Here we identify MIR31HG as a hypoxia-inducible lncRNA and ...therefore we name it LncHIFCAR (long noncoding HIF-1α co-activating RNA); we describe its oncogenic role as a HIF-1α co-activator that regulates the HIF-1 transcriptional network, crucial for cancer development. Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1α transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1α via direct binding and facilitates the recruitment of HIF-1α and p300 cofactor to the target promoters. Our results uncover an lncRNA-mediated mechanism for HIF-1 activation and establish the clinical values of LncHIFCAR in prognosis and potential therapeutic strategy for oral carcinoma.
Human action recognition in 3D skeleton sequences has attracted a lot of research attention. Recently, long short-term memory (LSTM) networks have shown promising performance in this task due to ...their strengths in modeling the dependencies and dynamics in sequential data. As not all skeletal joints are informative for action recognition, and the irrelevant joints often bring noise which can degrade the performance, we need to pay more attention to the informative ones. However, the original LSTM network does not have explicit attention ability. In this paper, we propose a new class of LSTM network, global context-aware attention LSTM, for skeleton-based action recognition, which is capable of selectively focusing on the informative joints in each frame by using a global context memory cell. To further improve the attention capability, we also introduce a recurrent attention mechanism, with which the attention performance of our network can be enhanced progressively. Besides, a two-stream framework, which leverages coarse-grained attention and fine-grained attention, is also introduced. The proposed method achieves state-of-the-art performance on five challenging datasets for skeleton-based action recognition.
Feature Boosting Network For 3D Pose Estimation Liu, Jun; Ding, Henghui; Shahroudy, Amir ...
IEEE transactions on pattern analysis and machine intelligence,
02/2020, Volume:
42, Issue:
2
Journal Article
Peer reviewed
Open access
In this paper, a feature boosting network is proposed for estimating 3D hand pose and 3D body pose from a single RGB image. In this method, the features learned by the convolutional layers are ...boosted with a new long short-term dependence-aware (LSTD) module, which enables the intermediate convolutional feature maps to perceive the graphical long short-term dependency among different hand (or body) parts using the designed Graphical ConvLSTM. Learning a set of features that are reliable and discriminatively representative of the pose of a hand (or body) part is difficult due to the ambiguities, texture and illumination variation, and self-occlusion in the real application of 3D pose estimation. To improve the reliability of the features for representing each body part and enhance the LSTD module, we further introduce a context consistency gate (CCG) in this paper, with which the convolutional feature maps are modulated according to their consistency with the context representations. We evaluate the proposed method on challenging benchmark datasets for 3D hand pose estimation and 3D full body pose estimation. Experimental results show the effectiveness of our method that achieves state-of-the-art performance on both of the tasks.
The high similarities of different real-world vehicles and great diversities of the acquisition views pose grand challenges to vehicle re-identification (ReID), which traditionally maps the vehicle ...images into a high-dimensional embedding space for distance optimization, vehicle discrimination, and identification. To improve the discriminative capability and robustness of the ReID algorithm, we propose a novel end-to-end embedding adversarial learning network (EALN) that is capable of generating samples localized in the embedding space. Instead of selecting abundant hard negatives from the training set, which is extremely difficult if not impossible, with our embedding adversarial learning scheme, the automatically generated hard negative samples in the specified embedding space can greatly improve the capability of the network for discriminating similar vehicles. Moreover, the more challenging cross-view vehicle ReID problem, which requires the ReID algorithm to be robust with different query views, can also benefit from such a scheme based on the artificially generated cross-view samples. We demonstrate the promise of EALN through extensive experiments and show the effectiveness of hard negative and cross-view generation in facilitating vehicle ReID based on the comparisons with the state-of-the-art schemes.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. Metabolic reprogramming is considered a new hallmark of cancer, but it remains unclearly described ...in HCC. The dysregulation of the PI3K/AKT/mTOR signaling pathway is common in HCC and is, therefore, a topic of further research and the concern of developing a novel target for liver cancer therapy. In this review, we illustrate mechanisms by which this signaling network is accountable for regulating HCC cellular metabolism, including glucose metabolism, lipid metabolism, amino acid metabolism, pyrimidine metabolism, and oxidative metabolism, and summarize the ongoing clinical trials based on the inhibition of the PI3K/AKT/mTOR pathway in HCC.
In this study, using coconut fibers as raw material, activated carbon fibers were prepared
via
carbonization and KOH activation processes. The morphology, composition, specific surface area, pore ...structure and thermal stability of the resulting activated carbon fibers were systematically characterized. It was found that the activation process increases the specific surface area of carbon fibers to a greater extent
via
formation of a large number of micropores (0.7-1.8 nm) and a certain amount of slit-shaped mesopores (2-9 nm). The specific surface area and the pore volume of the activated carbon fibers reach 1556 m
2
g
−1
and 0.72 cm
3
g
−1
, respectively. The activation process can also decompose the tar deposits formed after the carbonization process by pyrolysis, making the surface of the activated carbon fibers smoother. To study the adsorption properties of the as-prepared activated carbon fibers, the adsorption capacities and adsorption kinetics of various organic dyes including methylene blue, Congo red and neutral red were investigated. The adsorption capacities of the dyes increased with the increasing initial dye concentrations, and varied greatly with the pH value of the system. In methylene blue and neutral red systems, the adsorption capacities reach the maximum at pH 9, and in the Congo red system, it reaches the maximum at pH 3. The adsorption capacities of the activated carbon fibers in methylene blue, Congo red and neutral red systems reached equilibrium at 150, 120, and 120 min, and the maximum adsorption capacities were 21.3, 22.1, and 20.7 mg g
−1
, respectively. The kinetics of the adsorption process was investigated using three models including pseudo-first-order, pseudo-second-order and intraparticle diffusion models. The results indicated that the dynamic adsorption processes of coconut-based activated carbon fibers to methylene blue, Congo red and neutral red were all in accordance with the second-order kinetic model, and the equations are as follows:
t
/
Q
t
= 0.1028 +
t
/21.3220,
t
/
Q
t
= 0.1128 +
t
/21.5982 and
t
/
Q
t
= 0.0210 +
t
/20.6612.
Activated carbon fibers with high micropore volume and large specific surface area were prepared from abundant and low-cost coconut fibers, which show excellent adsorption performances towards various dyes.
Key points
In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently ...unknown.
Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.
Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.
Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.
Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress.
In cold environments, most homeothermic animals increase their food intake to supply more energy to maintain body temperature, whereas most poikilothermic animals such as fishes decrease or even stop feeding under cold stress. However, the physiological value of fasting during cold resistance in poikilotherms has not been explained. Here, we show that moderate fasting largely enhanced cold resistance in fish. By using pharmacological (fenofibrate, mildronate, chloroquine and rapamycin) and nutritional approaches (fatty acids diets and amino acids diets) in wild‐type or specific gene knock‐out zebrafish models (carnitine palmitoyltransferase‐1b‐deficient strain, CPT1b−/−, or autophagy‐related protein 12‐deficient strain, ATG12−/−), we verified that fasting‐stimulated lipid catabolism and autophagy played essential roles in the improved cold resistance. Moreover, suppression of the mechanistic target of rapamycin (mTOR) pathway by using rapamycin mostly mimicked the beneficial effects of fasting in promoting cold resistance as either the physiological phenotype or transcriptomic pattern. However, these beneficial effects were largely reduced when the mTOR pathway was activated through high dietary leucine supplementation. We conclude that fasting helps fish to resist cold stress by modulating lipid catabolism and autophagy, which correlates with the mTOR signalling pathway. Therefore, fasting can act as a protective strategy of fish in resisting coldness.
Key points
In a cold environment, mammals increase their food intake while fish decrease or stop feeding. However, the physiological value of fasting during cold resistance in fish is currently unknown.
Fasting for more than 48 h enhanced acute cold resistance in zebrafish, which correlated with lipid catabolism and cell damage attenuation.
Lipid catabolism and autophagy were necessary for cold resistance in fish and the inhibition of mitochondrial fatty acid β‐oxidation or autophagy weakened the fasting‐induced cold resistance.
Repression of mechanistic target of rapamycin (mTOR) signalling pathway by rapamycin largely mimicked the beneficial effects of fasting in promoting cold resistance, suggesting mTOR signalling may be involved in the fasting‐induced cold resistance in fish.
Our study demonstrates that fasting may be a protective strategy for fish to survive under cold stress.
A nickel‐catalyzed three‐component reaction for the synthesis of difluoroalkylated compounds through tandem difluoroalkylation‐arylation of enamides has been developed. The reaction tolerates a ...variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The significant advantages of this protocol are the low‐cost nickel catalyst, synthetic convenience, excellent functional‐group compatibility and high reaction efficiency.
All about efficiency: The title reaction tolerates a variety of arylboronic acids and widely available difluoroalkyl bromides, and even the relatively inert substrate chlorodifluoroacetate. The protocol provides a highly efficient method for the catalytic synthesis of difluoroalkylated compounds.
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