IL-10 is a critical immunoregulatory cytokine expressed in virtually all immune cell types. Maintaining a delicate balance between effective immune response and tolerance requires meticulous and ...dynamic control of IL-10 expression both epigenetically and transcriptionally. In this Review, we describe the epigenetic mechanisms controlling IL-10 expression, including chromatin remodeling, 3D chromatin loops, histone modification and DNA methylation. We discuss the role of transcription factors in directing chromatin modifications, with a special highlight on the emerging concept of pioneer transcription factors in setting up the chromatin landscape in T helper cells for IL-10 induction. Besides summarizing the recent progress on transcriptional regulation in specialized IL-10 producers such as type 1 regulatory T cells, regulatory B cells and regulatory innate lymphoid cells, we also discuss common transcriptional mechanisms for IL-10 regulation that are shared with other IL-10 producing cells.
Since nuclear factor of κ‐light chain of enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF‐κB ...for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF‐κB activation have also been illuminated, the cascades of signaling events leading to NF‐κB activity and key components of the NF‐κB pathway are also identified. It has been suggested NF‐κB plays an important role in human diseases, especially inflammation‐related diseases. These studies make the NF‐κB an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF‐κB, as well as the basic mechanisms of NF‐κB signaling pathway activation. We will also review the effects of dysregulated NF‐κB on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF‐κB for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF‐κB in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF‐κB for inflammatory diseases and cancer treatment, with minimal side effects.
This year (2021) marks the 35th anniversary of the discovery of NF‐κB. With so many years of in‐depth research on NF‐κB, people have realized that the NF‐κB signaling pathway plays an important role in inflammation, immunity, cell survival and proliferation. This review summarizes the relevant knowledge of the NF‐κB signaling pathway, inflammation, and cancer. The progression of the translational study and drug development targeting NF‐κB for inflammatory diseases and cancer treatment and the potential obstacles will also be discussed.
Location selection of electric vehicle charging stations (LSEVCS) is a complex multi-attribute group decision-making (MAGDM) problem involving multiple experts and multiple conflicting attributes. ...Spherical fuzzy sets (SFSs) can deeply excavate fuzziness and uncertainty in MAGDM. In this paper, we first propose some new spherical fuzzy distance measures based on Dice and Jaccard indexes to detect the differences between SFSs or inputs. Secondly, considering risk preferences of decision makers, we integrate cumulative prospect theory (CPT) and combined compromise solutions (CoCoSo) method to develop a spherical fuzzy CoCoSo based on CPT (SF-CPT–CoCoSo) model for settling MAGDM issues. At the same time, we extend the improved CRiteria Importance Through Intercriteria Correlation (CRITIC) method, called the distance correlation-based CRITIC (D-CRITIC) method, to reasonably obtain unknown attribute weights under SFSs. Finally, this paper applies the developed model for LSEVCS to verify its practicability. Moreover, sensitivity analysis and comparative discussion with existing methods further demonstrate the robustness and effectiveness of the SF-CPT–CoCoSo model.
As a new improvement of fuzzy sets (FSs), spherical fuzzy sets (SFSs) can provide a wider space for decision-makers (DMs) to express their preference information. Spherical fuzzy aggregation ...operators are a vital tool for multiple attribute group decision-making (MAGDM) in spherical fuzzy environment (SFE). Thus, the main work of this paper is to develop some new aggregation operators (AOs) to fuse spherical fuzzy information. First, based on Dombi operators and Heronian mean (HM) operator, we develop spherical fuzzy Dombi Heronian mean (SFDHM) operator, spherical fuzzy Dombi weighted Heronian mean (SFDWHM) operator, spherical fuzzy Dombi geometric Heronian mean (SFDGHM) operator and spherical fuzzy Dombi weighted geometric Heronian mean (SFDWGHM) operator. Second, considering the influence of extreme data on decision results, we utilize the merit of power average (PA) operator to further develop spherical fuzzy Dombi power Heronian mean (SFDPHM) operator, spherical fuzzy Dombi weighted power Heronian mean (SFDWPHM) operator, spherical fuzzy Dombi power geometric Heronian mean (SFDPGHM) operator and spherical fuzzy Dombi weighted power geometric Heronian mean (SFDWPGHM) operator. In the meantime, we discuss some desirable properties of these operators. Furthermore, we establish some novel MAGDM methods to aggregate spherical fuzzy numbers (SFNs) by utilizing the presented AOs. Finally, an example of enterprise resource planning (ERP) systems selection is employed to verify the applicability of the established approaches, and the effectiveness and superiority of the designed methods are proved by further comparison with the existing methods.
The electric eel is a unique species that has evolved three electric organs. Since the 1950s, electric eels have generally been assumed to use these three organs to generate two forms of electric ...organ discharge (EOD): high-voltage EOD for predation and defense and low-voltage EOD for electrolocation and communication. However, why electric eels evolved three electric organs to generate two forms of EOD and how these three organs work together to generate these two forms of EOD have not been clear until now. Here, we present the third form of independent EOD of electric eels: middle-voltage EOD. We suggest that every form of EOD is generated by one electric organ independently and reveal the typical discharge order of the three electric organs. We also discuss hybrid EODs, which are combinations of these three independent EODs. This new finding indicates that the electric eel discharge behavior and physiology and the evolutionary purpose of the three electric organs are more complex than previously assumed. The purpose of the middle-voltage EOD still requires clarification.
Advanced sensing and measurement technology is the key to realizing the transparent power grid and electric internet of things. Meanwhile, sensors, as an indispensable part of the smart grid, can ...monitor, collect, process, and transmit various types of data information of the power system in real-time. In this way, it is possible to further control the power system. Among them, partial discharge (PD) sensors are of great importance in the fields of online monitoring of insulation condition, intelligent equipment control, and power maintenance of power systems. Therefore, this paper intends to focus on advanced sensing materials and study new materials for the improvement for partial discharge sensors. As two-dimensional material, graphene is introduced. The electromagnetic properties of graphene partial discharge sensor electrode plate material are analyzed theoretically. By studying the influence of different chemical potential, relaxation time, temperature, and frequency, we obtain the changing curve of conductivity, dielectric constant, and refractive index. A linear regression model based on the least-squares method was developed for the three electromagnetic properties. Finally, the simulation and experiment verified that the graphene partial discharge sensor has better absorption of the partial discharge signal. This study can apply to the design of graphene partial discharge sensors.
The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of signaling pathways involved in ...immune responses. Most TRIM proteins have E3 ubiquitin ligase activity, mediating polyubiquitination of target proteins. Emerging evidence demonstrates that TRIM proteins play important roles in innate immunity by regulating pattern recognition receptors, vital adaptor proteins, kinases, and transcription factors in innate immune signaling pathways. Additionally, the critical roles of TRIM proteins in adaptive immunity, especially in T cell development and activation, are increasingly appreciated. In this review, we aim to summarize the studies on TRIMs in both innate and adaptive immunity, focusing on their E3 ubiquitin ligase functions in pattern recognition receptor signaling pathways and T cell functions, shedding light on the developing new strategies for modulating innate and adaptive immune responses against invading pathogens and avoiding autoimmunity.
Traditional Chinese medicine has growing importance in the treatment of ischemia stroke due to its abundance and low drug resistance. In this study, we aim to investigate the therapeutic potential of ...daucosterol palmitate against ischemia stroke, as well as its neuro-protective mechanism. The dose-response effects of daucosterol palmitate in the protection from brain damage were evaluated in a cerebral ischemia/reperfusion (I/R) rat model. The correlation of neuro-protective effects of daucosterol palmitate with apoptosis inhibition was examined and the possible signaling targets were identified. Our findings revealed that daucosterol palmitate treatment after 2 h’ ischemia significantly lowered brain damage, and neuronal cell apoptosis caused by I/R injury in a dose-response mode (20, 40 and 80 mg/kg). Western blot analysis indicated that daucosterol palmitate could reverse the effects of I/R injury on protein expression of PI3K and mTOR, and phosphorylation of Akt. Contrarily, inactivation of PI3K using wortmannin dramatically antagonized the effect of daucosterol palmitate for I/R injury. With these findings, it supports the application potential of daucosterol palmitate in the treatment of ischemia stroke. Besides, the PI3K/Akt/mTOR pathway might be potential cellular targets for daucosterol palmitate.
Recently, in online social networks (OSNs), the least cost influence (LCI) problem has become one of the central research topics. It aims at identifying a minimum number of seed users who can trigger ...a wide cascade of information propagation. Most of existing literature investigated the LCI problem only based on an individual network. However, nowadays users often join several OSNs such that information could be spread across different networks simultaneously. Therefore, in order to obtain the best set of seed users, it is crucial to consider the role of overlapping users under this circumstances. In this article, we propose a unified framework to represent and analyze the influence diffusion in multiplex networks. More specifically, we tackle the LCI problem by mapping a set of networks into a single one via lossless and lossy coupling schemes. The lossless coupling scheme preserves all properties of original networks to achieve high-quality solutions, while the lossy coupling scheme offers an attractive alternative when the running time and memory consumption are of primary concern. Various experiments conducted on both real and synthesized datasets have validated the effectiveness of the coupling schemes, which also provide some interesting insights into the process of influence propagation in multiplex networks.
The immune system plays pivotal roles in the occurrence and progression of cancers. As blockade of immune-checkpoint has been proven effective at improving anti-tumor immune response in multiple ...tumor types, the tumor immunotherapy still faces many challenges. Emerging evidence indicates lymphoid organ-like structures, also called tertiary lymphoid organs (TLOs) or ectopic lymphoid organs (ELOs), have been identified in cancers, as the result of lymphoid neoorganogenesis. The prognostic value of TLOs in cancer patients has been evaluated with debates, however, such well-organized lymphoid structures in the site of cancer indicate TLOs are the important modulators of cancer immunological microenvironment. TLOs have attracted remarkable efforts to investigate their neoorganogenesis and function in immune responses, aiming to develop new strategies for cancer immunotherapy. In this review, we summarize the current understandings about the molecular and cellular mechanisms governing the formation and function of TLOs in immune responses against cancer.
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