Emerging evidence indicates that tumor cells release a large amount of exosomes loaded with cargos during tumorigenesis. Exosome secretion is a multi-step process regulated by certain related ...molecules. Long non-coding RNAs (lncRNAs) play an important role in hepatocellular carcinoma (HCC) progression. However, the role of lncRNA HOTAIR in regulating exosome secretion in HCC cells remains unclear.
We analyzed the relationship between HOTAIR expression and exosome secretion-related genes using gene set enrichment analysis (GSEA). Nanoparticle tracking analysis was performed to validate the effect of HOTAIR on exosome secretion. The transport of multivesicular bodies (MVBs) after overexpression of HOTAIR was detected by transmission electron microscopy and confocal microscopy analysis of cluster determinant 63 (CD63) with synaptosome associated protein 23 (SNAP23). The mechanism of HOTAIR's regulation of Ras-related protein Rab-35 (RAB35), vesicle associated membrane protein 3 (VAMP3), and SNAP23 was assessed using confocal co-localization analysis, phosphorylation assays, and rescue experiments.
We found an enrichment of exosome secretion-related genes in the HOTAIR high expression group. HOTAIR promoted the release of exosomes by inducing MVB transport to the plasma membrane. HOTAIR regulated RAB35 expression and localization, which controlled the docking process. Moreover, HOTAIR facilitated the final step of fusion by influencing VAMP3 and SNAP23 colocalization. In addition, we validated that HOTAIR induced the phosphorylation of SNAP23 via mammalian target of rapamycin (mTOR) signaling.
Our study demonstrated a novel function of lncRNA HOTAIR in promoting exosome secretion from HCC cells and provided a new understanding of lncRNAs in tumor cell biology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The success of targeted drug therapy for cancer patients has attracted extensive attention from academia and society. However, the rapid development of acquired drug resistance is becoming a major ...challenge. Autophagy, as an essential homeostatic and catabolic process, is crucial for the degradation or recycling of proteins and cellular components. Autophagy has a crucial role in several cellular functions and its dysregulation is associated with tumorigenesis, tumor–stroma interactions, and resistance to cancer therapy. A growing body of evidence shows that in multiple types of cancer, autophagy is also a key regulator in the tumor microenvironment and the cellular drug response. However, our understanding of the process of autophagy remains incompletely. In this review, we identify the role of autophagy and describe recent advances in the identification of the mechanism by which autophagy is implicated in drug resistance, with a focus on the mode of action, and validation as potential therapeutics.
Long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually because of the great importance in different cancers. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is a novel ...lncRNA and has been reported to promote multiple cancer progression. However, the biological roles of NEAT1 in hepatocellular carcinoma (HCC) is not cleared nowadays. In the present research, the level of NEAT1 was found to be upregulated in HCC by The Cancer Genome Atlas. In addition, NEAT1 expression is negatively correlated with the survival rate in HCC. Further investigation revealed that NEAT1 upregulation inhibited sorafenib efficacy and promoted autophagy. We found that NEAT1 could be a sponge for microRNA‐204 (miR‐204) and inhibits its level to upregulate ATG3 expression. In addition to the above, we demonstrated that miR‐204 mimics also attenuated tumor autophagy. And rescue assays demonstrated that NEAT1 promotes HCC autophagy through modulating miR‐204/ATG3 pathway. Collectively, this study first demonstrated that a novel NEAT1/miR‐204/ATG3 signaling regulates HCC progression.
Nuclear enriched abundant transcript 1 (NEAT1) could be a sponge for microRNA‐204 (miR‐204) and inhibits its level to upregulate ATG3 expression. We demonstrated that miR‐204 mimics also attenuated tumor autophagy. And rescue assays demonstrated that NEAT1 promotes hepatocellular carcinoma (HCC) autophagy through modulating miR‐204/ATG3 pathway.
This paper begins by exploring the challenge of event-triggered state estimations in nonlinear systems, grappling with packet dropout and correlated noise. A communication mechanism is introduced ...that determines whether to transmit measurement values based on whether event-triggered conditions are violated, thereby minimizing redundant communication data. In designing the filter, noise decorrelation is initially conducted, followed by the integration of the event-triggered mechanism and the unreliable network transmission system for state estimator development. Subsequently, by combining the three-degree spherical-radial cubature rule, the numerical implementation steps of the proposed state estimation framework are outlined. The performance estimation analysis highlights that by adjusting the event-triggered threshold appropriately, the estimation performance and transmission rate can be effectively balanced. It is established that when there is a lower bound on the packet dropout rate, the covariance matrix of the state estimation error remains bounded, and the stochastic stability of the state estimation error is also confirmed. Ultimately, the algorithm and conclusions that are proposed in this paper are validated through a simulation example of a target tracking system.
Hypoxia is a remarkable trait of the tumor microenvironment (TME). When facing selective pressure, tumor cells show various adaptive characteristics, such as changes in the expression of cancer ...hallmarks (increased proliferation, suppressed apoptosis, immune evasion, and so on) and more frequent cell communication. Because of the adaptation of cancer cells to hypoxia, exploring the association between cell communication mediators and hypoxia has become increasingly important. Exosomes are important information carriers in cell-to-cell communication. Abundant evidence has proven that hypoxia effects in the TME are mediated by exosomes, with the occasional formation of feedback loops. In this review, we equally focus on the biogenesis and heterogeneity of cancer-derived exosomes and their functions under hypoxia and describe the known and potential mechanism ascribed to exosomes and hypoxia. Notably, we call attention to the size change of hypoxic cancer cell-derived exosomes, a characteristic long neglected, and propose some possible effects of this size change. Finally, jointly considering recent developments in the understanding of exosomes and tumors, we describe noteworthy problems in this field that urgently need to be solved for better research and clinical application.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Red phosphorus-carbon nanotube (P@CNT) composites were synthesized as anodes for advanced lithium ion batteries via a facile solution-based method at room temperature. In these composites, the ...entangled P@CNT nanostructure reduced the aggregation of both components and allowed their complete utilization in a synergetic manner. The highly conductive and porous CNT framework, along with the nanoscale red P particles intimately anchored on the CNT surface, conferred the composite with excellent ion/electron transport properties. Volume expansion within the red P particles was mitigated by their amorphous and nanoscale features, which can be well buffered by the soft CNTs, therefore maintaining an integrated electrode structure during cycling. When used as an anode in lithium ion batteries, the composite exhibited a reversible capacity of 960 mAh·g
−1
(based on the overall weight of the composite) after 120 cycles at 200 mA·g
−1
. The composite also delivered excellent high-rate capability with capacities of 886, 847, and 784 mAh·g
−1
at current densities of 2,000, 4,000, and 10,000 mA·g
−1
, respectively, which reveals its potential as a high performance anode for lithium ion batteries.
The low mechanical efficiency of metal belt's continuously variable transmission (CVT) limits its application in new energy vehicles. To further improve CVT efficiency and reduce the energy ...consumption of electric vehicles (EVs) with CVT, this paper proposes a pure electric CVT configuration and a clamping force control strategy. The slip characteristics of CVT are obtained through a bench test, the dynamic model of CVT slip is established, and a clamping force fuzzy control strategy is designed. The strategy is studied by simulation under extreme conditions and standard driving cycles. The simulation results show that the proposed clamping force control strategy has good adaptability. Under extreme conditions, this strategy can ensure that CVT does not undergo macro slip, while reducing the clamping force by 12.86-21.65%. Energy consumption per 100 km is 14.90 kWh in NEDC, which is 6.67% lower compared with the traditional strategy. CVT average efficiency and average transmission efficiency increased by 3.71% and 6.40%. The research results demonstrate that adjusting the CVT clamping force through fuzzy control based on the slip rate can improve the CVT efficiency and energy economy of EVs, which provides a certain reference for CVT clamping force control strategy development and the application of CVT on EVs.
Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. ...However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H
clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation.
Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription-PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues.
Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3).
Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.
In order to reduce the sea clutter interference in the detection of sea surface targets, we propose a bistatic sea clutter suppression method based on compressed sensing optimization in this paper. ...The proposed method mitigates the interference effect by reconstructing and cancelling out the sea clutter. Since the fixed sparse base is not always completely applicable for the sparse representation of sea clutter, we propose a sparse base optimization algorithm based on transfer learning to convert the fixed sparse base into an adaptive one. Moreover, we introduce a sensing matrix optimization algorithm to decrease the cross-correlation coefficient between the measurement matrix and the sparse base matrix, which can enhance the signal reconstruction quality. Finally, we use the orthogonal matching pursuit algorithm to reconstruct the sea clutter and employ the reconstructed results to cancel and suppress the sea clutter. The simulation results demonstrate that the proposed method outperforms the traditional methods such as the root time-domain cancellation method and the singular value decomposition method (SVD). Therefore, the proposed method has great practical significance for the detection of bistatic sea surface targets.
Background
Gastric band operation and sleeve gastrectomy are increasingly popular bariatric surgeries for weight loss. The purpose of this study is to investigate the changes in plasma ghrelin levels ...and hypothalamic ghrelin receptor expression with weight loss achieved through these surgeries.
Methods
Twenty-four high fat diet-induced obese rats were used to investigate the effects of gastric band and sleeve operation on Body Mass Index, fat mass, plasma ghrelin levels, and hypothalamic growth hormone secretagogue receptor 1a (GHS-R 1a) protein expression in hypothalamus. In comparison, data of patients who received laparoscopic adjustable gastric banding (LAGB) and laparoscopic sleeve gastrectomy (LSG) in our hospital in 2005 were also summarized.
Results
Body weights and fat mass decreased significantly in rats that received operation. Plasma ghrelin concentrations in the sleeve group were 0.4-fold of control rats and about 2-fold of control in the gastric band group. GHS-R1a protein expression in hypothalamus was 1.5-fold in the sleeve group compared with control group, while it was only 0.9-fold in the gastric band group. Clinical data showed that patients in the LSG group lost 60% excess body weights in 2 years follow-up. After operation, fasting plasma ghrelin concentrations in LAGB was significantly higher than the LSG group.
Conclusion
Both LAGB and LSG can decrease patients’ excess body weights and fat mass. Plasma ghrelin levels are down-regulated with LSG operation but up-regulated with LAGB operation. Hypothalamic GHS-R1a expression is elevated in sleeve gastrectomy.
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