Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this ...study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
Synopsis
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis.
LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511.
LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1.
Graphical Abstract
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
Energy harvesting modules play an increasingly important role in the development of autonomous self‐powered microelectronic devices. MXenes (i.e., 2D transition metal carbide/nitride) have recently ...emerged as promising candidates for energy applications due to their excellent electronic conductivity, large specific surface area, and tunable properties. Herein, a perspective on using MXenes to harvest energy from various sources in the environment is presented. First, the characteristics of MXenes that facilitate energy capturing are systematically introduced and the preparation strategies of MXenes and their derived nanostructures tailored toward such applications are summarized. Subsequently, the harvesting mechanism of different energy sources (e.g., solar energy, thermoelectric energy, triboelectric energy, piezoelectric energy, salinity‐gradient energy, electrokinetic energy, ultrasound energy, and humidity energy) are discussed. Then, the recent progress of MXene‐based nanostructures in energy harvesting, as well as their applications, is introduced. Finally, opinions on the existing challenges and future directions of MXene‐based nanostructure for energy harvesting are presented.
The progress in employing MXenes in energy harvesting applications is summarized. Different energy sources, including solar, ultrasound, electrokinetic, salinity‐gradient, piezoelectric, triboelectric, thermoelectric, and humidity energy, are discussed separately. The future challenges and promising directions of MXene research for energy harvesting are presented.
Diffuse large B cell lymphoma (DLBCL) is a common and fatal hematological malignancy. Long noncoding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNA ...biomarker in DLBCL needs to be investigated badly, as well as its function and molecular mechanism. To further explore, microarray analysis was performed to identify the differentially expressed lncRNAs in DLBCL tissues. To investigate the biological functions of SMAD5-AS1, we performed gain- and loss-of-function experiments in vitro and in vivo. Furthermore, bioinformatics analysis, dual-luciferase reporter assays, Argonaute 2-RNA immunoprecipitation (AGO2-RIP), RNA pull-down assay, quantitative PCR arrays, western blot assay, TOPFlash/FOPFlash reporter assay, and rescue experiments were conducted to explore the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We found that SMAD5-AS1 was down-regulated in DLBCL tissues and cell lines. Functionally, SMAD5-AS1 downregulation promoted cell proliferation in vitro and in vivo, whereas SMAD5-AS1 overexpression could lead to the opposite effects in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-135b-5p was a direct target of SMAD5-AS1, which was validated by dual-luciferase reporter assays, AGO2-RIP, RNA pull-down assay, and rescue experiments. Also, dual-luciferase reporter assays and rescue experiments demonstrated that miR-135b-5p targeted the adenomatous polyposis coli (APC) gene directly. SMAD5-AS1/miR-135b-5p inhibits the cell proliferation via inactivating the classic Wnt/β-catenin pathway in the form of APC dependency. Our results indicated that SMAD5-AS1 inhibits DLBCL proliferation by sponging miR-135b-5p to up-regulate APC expression and inactivate classic Wnt/β-catenin pathway, suggesting that SMAD5-AS1 may act as a potential biomarker and therapeutic target for DLBCL.
As a sub-field of video content analysis, action recognition has received extensive attention in recent years, which aims to recognize human actions in videos. Compared with a single image, video has ...a temporal dimension. Therefore, it is of great significance to extract the spatio-temporal information from videos for action recognition. In this paper, an efficient network to extract spatio-temporal information with relatively low computational load (dubbed MEST) is proposed. Firstly, a motion encoder to capture short-term motion cues between consecutive frames is developed, followed by a channel-wise spatio-temporal module to model long-term feature information. Moreover, the weight standardization method is applied to the convolution layers followed by batch normalization layers to expedite the training process and facilitate convergence. Experiments are conducted on five public datasets of action recognition, Something-Something-V1 and -V2, Jester, UCF101 and HMDB51, where MEST exhibits competitive performance compared to other popular methods. The results demonstrate the effectiveness of our network in terms of accuracy, computational cost and network scales.
DNA methylation at the 5-position of cytosine (5mC) plays vital roles in mammalian development. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), and the two DNMT families, DNMT3 and ...DNMT1, are responsible for methylation establishment and maintenance, respectively. Since their discovery, biochemical and structural studies have revealed the key mechanisms underlying how DNMTs catalyze de novo and maintenance DNA methylation. In particular, recent development of low-input genomic and epigenomic technologies has deepened our understanding of DNA methylation regulation in germ lines and early stage embryos. In this review, we first describe the methylation machinery including the DNMTs and their essential cofactors. We then discuss how DNMTs are recruited to or excluded from certain genomic elements. Lastly, we summarize recent understanding of the regulation of DNA methylation dynamics in mammalian germ lines and early embryos with a focus on both mice and humans.
Printed electronics are an important enabling technology for the development of low‐cost, large‐area, and flexible optoelectronic devices. Transparent conductive films (TCFs) made from ...solution‐processable transparent conductive materials, such as metal nanoparticles/nanowires, carbon nanotubes, graphene, and conductive polymers, can simultaneously exhibit high mechanical flexibility, low cost, and better photoelectric properties compared to the commonly used sputtered indium‐tin‐oxide‐based TCFs, and are thus receiving great attention. This Review summarizes recent advances of large‐area flexible TCFs enabled by several roll‐to‐roll‐compatible printed techniques including inkjet printing, screen printing, offset printing, and gravure printing using the emerging transparent conductive materials. The preparation of TCFs including ink formulation, substrate treatment, patterning, and postprocessing, and their potential applications in solar cells, organic light‐emitting diodes, and touch panels are discussed in detail. The rational combination of a variety of printed techniques with emerging transparent conductive materials is believed to extend the opportunities for the development of printed electronics within the realm of flexible electronics and beyond.
The recent advances of large‐area flexible transparent conductive films (TCFs) enabled by several roll‐to‐roll‐compatible printing techniques including inkjet printing, screen printing, offset printing, and gravure printing using emerging transparent conductive materials are summarized, with the hope of providing timely references for the fabrication of low‐cost/large‐area flexible TCFs and advancing the field of flexible electronics in general.
Aims
The emerging of drug resistant Pseudomonas aeruginosa is a critical challenge and renders an urgent action to discover innovative antimicrobial interventions. One of these interventions is to ...disrupt the pseudomonas quinolone signal (pqs) quorum sensing (QS) system, which governs multiple virulence traits and biofilm formation. This study aimed to investigate the QS inhibitory activity of a series of new PqsR inhibitors bearing a quinoline scaffold against Ps. aeruginosa.
Methods and Results
The results showed that compound 1 suppressed the expression of QS‐related genes and showed the best inhibitory activity to the pqs system of wild‐type Ps. aeruginosa PAO1 with an IC50 of 20.22 μmol L−1. The virulence factors including pyocyanin, total protease, elastase and rhamnolipid were significantly suppressed in a concentration‐dependent manner with the compound. In addition, compound 1 in combination with tetracycline inhibited synergistically the bacterial growth and suppressed the biofilm formation of PAO1. The molecular docking studies also suggested that compound 1 could potentially interact with the ligand‐binding domain of the Lys‐R type transcriptional regulator PqsR as a competitive antagonist.
Conclusions
The quinoline‐based derivatives were found to interrupt the quorum sensing system via the pqs pathway and thus the production of virulence factors was inhibited and the antimicrobial susceptibility of Ps. aeruginosa was enhanced.
Significance and Impact of Study
The study showed that the quinoline‐based derivatives could be used as an anti‐virulence agent for treating Ps. aeruginosa infections.
In the booming development of flexible electronics represented by electronic skins, soft robots, and human–machine interfaces, 3D printing of hydrogels, an approach used by the biofabrication ...community, is drawing attention from researchers working on hydrogel‐based stretchable ionotronic devices. Such devices can greatly benefit from the excellent patterning capability of 3D printing in three dimensions, as well as the free design complexity and easy upscale potential. Compared to the advanced stage of 3D bioprinting, 3D printing of hydrogel ionotronic devices is in its infancy due to the difficulty in balancing printability, ionic conductivity, shape fidelity, stretchability, and other functionalities. In this review, a guideline is provided on how to utilize the power of 3D printing in building high‐performance hydrogel‐based stretchable ionotronic devices mainly from a materials’ point of view, highlighting the systematic approach to balancing the printability, printing quality, and performance of printed devices. Various 3D printing methods for hydrogels are introduced, and then the ink design principles, balancing printing quality, printed functions, such as elastic conductivity, self‐healing ability, and device (e.g., flexible sensors, shape‐morphing actuators, soft robots, electroluminescent devices, and electrochemical biosensors) performances are discussed. In conclusion, perspectives on the future directions of this exciting field are presented.
Hydrogel ionotronics prepared via 3D printing have received intensive attention due to the combination of high biocompatibility, stimuli‐responsiveness, rapid prototyping, and delicated patterns. Herein, recent advances in 3D printed hydrogel devices are reviewed, highlighting strategies to enhance printing quality (printability, resolution, and shape fidelity), properties (elastic conductivity, and self‐healing ability), and performances of various ionotronic devices.
DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in ...methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.
Illustrations on the problems of current BBR losses. Each row shows the optimization results in different iterations with certain loss function. The Black denotes the anchor box. The Blue denotes the ...target box. The fist row denotes GIOU. The second row denotes CIOU. The third row denotes the proposed EIOU. EIOU attains more quick convergence speed and more accurate regression results. Display omitted
•We reveal the flaws of ℓn-norm and IOU-based losses for object detection.•We design a regression version of focal loss to emphasize the most promising anchors.•We conduct extensive experiments to validate the superiority of the proposed methods.
In object detection, bounding box regression (BBR) is a crucial step that determines the object localization performance. However, we find that most previous loss functions for BBR have two main drawbacks: (i) Both ℓn-norm and IOU-based loss functions are inefficient to depict the objective of BBR, which leads to slow convergence and inaccurate regression results. (ii) Most of the loss functions ignore the imbalance problem in BBR that the large number of anchor boxes which have small overlaps with the target boxes contribute most to the optimization of BBR. To mitigate the adverse effects caused thereby, we perform thorough studies to exploit the potential of BBR losses in this paper. Firstly, an Efficient Intersection over Union (EIOU) loss is proposed, which explicitly measures the discrepancies of three geometric factors in BBR, i.e., the overlap area, the central point and the side length. After that, we state the Effective Example Mining (EEM) problem and propose a regression version of focal loss to make the regression process focus on high-quality anchor boxes. Finally, the above two parts are combined to obtain a new loss function, namely Focal-EIOU loss. Extensive experiments on both synthetic and real datasets are performed. Notable superiorities on both the convergence speed and the localization accuracy can be achieved over other BBR losses.
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