Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence and mortality among malignant tumors worldwide. CRC patients with metastasis in the liver, lung or other ...distant sites always have poor prognosis. Thus, there is an urgent need to discover the underlying mechanisms of metastatic colorectal cancer (mCRC) and to develop optimal therapy for mCRC. Transforming growth factor-β (TGF-β) signaling plays a significant role in various physiologic and pathologic processes, and aberrant TGF-β signal transduction contributes to mCRC progression. In this review, we summarize the alterations of the TGF-β signaling pathway in mCRC patients, the functional mechanisms of TGF-β signaling, its promotion of epithelial-mesenchymal transition, its facilitation of angiogenesis, its suppression of anti-tumor activity of immune cells in the microenvironment and its contribution to stemness of CRC cells. We also discuss the possible applications of TGF-β signaling in mCRC diagnosis, prognosis and targeted therapies in clinical trials. Hopefully, these research advances in TGF-β signaling in mCRC will improve the development of new strategies that can be combined with molecular targeted therapy, immunotherapy and traditional therapies to achieve better efficacy and benefit mCRC patients in the near future.
The rapid development of the information age brings convenience to human life, but it also brings great challenges to information processing technology. Multimedia enhancement technology is an ...organic combination of multimedia technology and information processing technology, and it is also an important way of modern multimedia image information processing. However, its usefulness and effectiveness are increasingly negatively affected by the open information environment. The processing effect is also unable to meet the development requirements of the visual field. In order to improve this problem, this paper studied the image transmission and processing system of network-controlled robot on the basis of analyzing the characteristics of the problems existing in the current stage of multimedia technology. On this basis, a new image processing variational model was established and applied to multimedia enhancement technology, which improved the efficiency and effect of image information processing. Finally, the feasibility of its application function and performance was tested by experiments. The test results showed that in the difficult mode of the image processing task, the refresh time of the model in this paper in the multimedia enhancement technology was 1.13 s in total, which was not much different from the test results in the easy mode. Also, in the load stress test, the comprehensive test values under full-function operation and partial-function operation were 42.04% and 20.92%, respectively. Compared with the traditional model, the model in this paper has stronger carrying capacity in multimedia enhancement technology and has better processing ability and stability.
Aiming at the problems of traditional optimization algorithms for reconfiguring distribution networks, which easily fall into a local optimum, have difficulty finding a global optimum, and suffer ...from low computational efficiency, the proposed algorithm named Chaotic Particle Swarm Chicken Swarm Fusion Optimization (CPSCSFO) is used to optimize the reconfiguration of the distribution network with distributed generation (DG). This article works to solve the problems mentioned above from the following three aspects: Firstly, chaotic formula is used to improve the initialization of the particles and optimize the optimal position. This increases individual randomness while avoiding local optimality for inert particles. Secondly, chicken swarm optimization (CSO) and particle swarm optimization (PSO) are combined. The multi-population nature of the CSO algorithm is used to increase the global search capability, and, at the same time, the information exchange between groups is completed to extend the particle search range, which ensures the independence and excellence of each particle group. Thirdly, the node hierarchy method is introduced to calculate the power flow. The branching loop matrix and the node hierarchy strategy are used to detect the network topology. In this way, improper solutions can be reduced, and the efficiency of the algorithm can be improved. This paper has demonstrated better performance by CPSCSFO based on simulation results. The network loss has been reduced and the voltage level of each node in the optimal reconfiguration with distributed power supply has been improved; the network loss in the optimal reconfiguration with DG is 69.59% lower than that reconfiguration before. The voltage level of each node is increased, the minimum node voltage is increased by 3.44% and a better convergence speed is presented. As a result, the quality of network operation and the distribution network is greatly improved and provides guidance for building a safer, more economical and reliable distribution network.
Polycomb group (PcG) proteins, which are important epigenetic regulators, play essential roles in the regulatory networks involved in plant growth, development, and environmental stress responses. ...Currently, as far as we know, no comprehensive and systematic study has been carried out on the PcG family in Medicago truncatula. In the present study, we identified 64 PcG genes with distinct gene structures from the M. truncatula genome. All of the PcG genes were distributed unevenly over eight chromosomes, of which 26 genes underwent gene duplication. The prediction of protein interaction network indicated that 34 M. truncatula PcG proteins exhibited protein–protein interactions, and MtMSI1;4 and MtVRN2 had the largest number of protein–protein interactions. Based on phylogenetic analysis, we divided 375 PcG proteins from 27 species into three groups and nine subgroups. Group I and Group III were composed of five components from the PRC1 complex, and Group II was composed of four components from the PRC2 complex. Additionally, we found that seven PcG proteins in M. truncatula were closely related to the corresponding proteins of Cicer arietinum. Syntenic analysis revealed that PcG proteins had evolved more conservatively in dicots than in monocots. M. truncatula had the most collinearity relationships with Glycine max (36 genes), while collinearity with three monocots was rare (eight genes). The analysis of various types of expression data suggested that PcG genes were involved in the regulation and response process of M. truncatula in multiple developmental stages, in different tissues, and for various environmental stimuli. Meanwhile, many differentially expressed genes (DEGs) were identified in the RNA-seq data, which had potential research value in further studies on gene function verification. These findings provide novel and detailed information on the M. truncatula PcG family, and in the future it would be helpful to carry out related research on the PcG family in other legumes.
Little is known about the molecular mechanism of the R2R3-MYB transcriptional repressors involved in plant phenylpropanoid metabolism. Here, we describe one R2R3-type MYB repressor, FtMYB11 from ...Fagopyrum tataricum. It contains the SID-like motif GGDFNFDL and it is regulated by both the importin protein ‘Sensitive to ABA and Drought 2’ (SAD2) and the jasmonates signalling cascade repressor JAZ protein.
Yeast two hybrid and bimolecular fluorescence complementation assays demonstrated that FtMYB11 interacts with SAD2 and FtJAZ1. Protoplast transactivation assays demonstrated that FtMYB11 acts synergistically with FtSAD2 or FtJAZ1 and directly represses its target genes via the MYB-core element AATAGTT.
Changing the Asp122 residue to Asn in the SID-like motif results in cytoplasmic localization of FtMYB11 because of loss of interaction with SAD2, while changing the Asp126 residue to Asn results in the loss of interaction with FtJAZ1. Overexpression of FtMYB11 or FtMYB11
D126N in F. tataricum hairy roots resulted in reduced accumulation of rutin, while overexpression of FtMYB11
D122N in hairy roots did not lead to such a change.
The results indicate that FtMYB11 acts as a regulator via interacting with FtSAD2 or FtJAZ1 to repress phenylpropanoid biosynthesis, and this repression depends on two conserved Asp residues of its SID-like motif.
Proanthocyanidins (PA), also known as condensed tannins, contribute to important forage legumes traits including disease resistance and forage quality. PA in forage plants has both positive and ...negative effects on feed digestibility and animal performance. The analytical methods and their applicability in measuring the contents of PA in forage plants are essential to studies on their nutritional effects. In spite of important breakthroughs in our understanding of the PA biosynthesis, important questions still remain to be answered such as the PA polymerization and transport. Recent advances in the understanding of transcription factor-mediated gene regulation mechanisms in anthocyanin and PA biosynthetic pathway in model plants suggest new approaches for the metabolic engineering of PA in forage plants. The present review will attempt to present the state-of-the-art of research in these areas and provide an update on the production and metabolic engineering of PA in forage plants. We hope that this will contribute to a better understanding of the ways in which PA production to manipulate the content of PA for beneficial effects in forage plants.
The APETALA2/ethylene response factor (AP2/ERF) family are important regulatory factors involved in plants' response to environmental stimuli. However, their roles in salt tolerance in Lotus ...corniculatus remain unclear.
Here, the key salt-responsive transcription factor LcERF056 was cloned and characterised. LcERF056 belonging to the B3-1 (IX) subfamily of ERFs was considerably upregulated by salt treatment. LcERF056-fused GFP was exclusively localised to nuclei. Furthermore, LcERF056- overexpression (OE) transgenic Arabidopsis and L. corniculatus lines exhibited significantly high tolerance to salt treatment compared with wild-type (WT) or RNA interference expression (RNAi) transgenic lines at the phenotypic and physiological levels. Transcriptome analysis of OE, RNAi, and WT lines showed that LcERF056 regulated the downstream genes involved in several metabolic pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) and yeast one-hybrid (Y1H) assay demonstrated that LcERF056 could bind to cis-element GCC box or DRE of reactive oxygen species (ROS)-related genes such as lipid-transfer protein, peroxidase and ribosomal protein.
Our results suggested that the key regulator LcERF056 plays important roles in salt tolerance in L. corniculatus by modulating ROS-related genes. Therefore, it may be a useful target for engineering salt-tolerant L. corniculatus or other crops.
Objective: Interleukin-17 (IL-17), produced by T helper (Th)-17 cells, is a potent regulator of bone homeostasis. Osteoblasts are key cells that orchestrate inflammatory bone destruction and bone ...remodeling. This study examines the effect of different concentrations of IL-17 on osteogenesis and receptor activator of nuclear factor-kappa B ligand (RANKL) expression of primary osteoblasts.
Methods: First, the growth of primary osteoblasts was evaluated. Second, we assessed the effects of IL-17 on the level of autophagy and the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway. Next, osteogenic activity in different concentrations of IL-17 was tested. Finally, the specific JAK2/STAT3 signaling pathway inhibitor AG490 and autophagy inhibitor 3-MA were used to investigate the involvement of this pathway and autophagy in IL-17-induced regulation of RANKL expression.
Results: Initially, we found that IL-17 treatment promoted growth of osteoblasts in a time- and dose-dependent manner. Next, we showed that low levels of IL-17 promoted autophagy activity, whereas the opposite was observed at high levels of IL-17. Moreover, high levels of IL-17 activated the JAK2/STAT3 signaling pathway, although this effect was reversed by upregulation of autophagy. Furthermore, our findings indicated that high concentrations of IL-17 promoted the differentiation, calcification, and RANKL expression of murine osteoblasts via activation of the JAK2/STAT3 pathway. Importantly, downregulation of autophagy at high IL-17 concentrations further enhanced RANKL expression via suppressing the JAK2/STAT3 cascade.
Conclusion: Overall, our findings demonstrate, for the first time, that IL-17 modulates RANKL expression of osteoblasts through an autophagy-JAK2-STAT3 signaling pathway, thus affecting bone metabolism.
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•Dual effects of lipopolysaccharide were found on osteoclastogenesis in vitro.•Lipopolysaccharide promoted osteoclasts differentiation only from RANKL primed cells.•Effects of ...autophagy and Wnt signaling were demonstrated in lipopolysaccharide induced osteoclastogenensis.•A crosstalk between autophagy and Wnt signaling was elucidated during osteoclast differentiation.
Periodontitis thereby the alveolar bone loss induced by inflammation, is a wide-spread phenomenon around the world. It is an ongoing challenge faced by clinicians worldwide. This study aimed to identify the effects of lipopolysaccharide (LPS) on osteoclasts (OCs) differentiation in vitro and to investigate its molecular mechanism. For bone marrow derived macrophages (considered as Pro-OCs), LPS impaired their differentiation into OCs in a dose-dependent manner. In contrast, it promoted Pre-OCs (referred to receptor activator of nuclear factor-κB ligand (RANKL) pretreated Pro-OCs) and differentiated to OCs with increased maximum diameter, quantity, the covering area and the fusion index in vitro. It also facilitated OCs proliferation, bone resorption and OCs related genes expression. Furthermore, it was revealed that LPS enhanced OCs genesis from Pre-OCs via activating autophagy pathway consequently elevated the accumulation of TRAP, Cts K and NFATC1, specific genes of OCs. The members of Wnt signaling were expressed as at lower states during the LPS induced OCs formation, but they could be rescued in the presence of autophagy inhibitor. The most promising observation was the direct interaction of LC3B and Dvl2, indicating that the crosstalk between above pathways existed in OCs. Taken together, we consider that LPS activates autophagy which negatively regulates Wnt signaling via autophagic degradation of Dvl2 is significant for osteoclastogenesis from Pre-OCs in vitro. Our study sheds light on the fact that autophagy inhibitors will become a new, potentially applicable therapeutic option in the treatment of periodontal bone loss.
Periodontal disease (PD), as an age-related disease, prevalent in middle-aged and elderly population, is characterized as inflammatory periodontal tissue loss, including gingival inflammation and ...alveolar bone resorption. However, the definite mechanism of aging-related inflammation in PD pathology needs further investigation. Our study is aimed at exploring the effect of inflamm-aging-related cytokines of interleukin-17 (IL-17) and interferon-γ (IFN-γ) on osteoclastogenesis in vitro and periodontal destruction in vivo. For receptor activator of nuclear factor-κB ligand- (RANKL-) primed bone marrow macrophages (BMMs), IL-17 and IFN-γ enhanced osteoclastogenesis, with the expression of osteoclastogenic mRNA (TRAP, c-Fos, MMP-9, Ctsk, and NFATc1) and protein (c-Fos and MMP-9) upregulated. Ligament-induced rat models were established to investigate the role of IL-17 and IFN-γ on experimental periodontitis. Both IL-17 and IFN-γ could enhance the local inflammation in gingival tissues. Although there might be an antagonistic interaction between IL-17 and IFN-γ, IL-17 and IFN-γ could facilitate alveolar bone loss and osteoclast differentiation.
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