Long non-coding RNAs (lncRNAs) regulate gene expression in a variety of ways at epigenetic, chromatin remodeling, transcriptional, and translational levels. Accumulating evidence suggests that lncRNA ...X-inactive specific transcript (lncRNA Xist) serves as an important regulator of cell growth and development. Despites its original roles in X-chromosome dosage compensation, lncRNA Xist also participates in the development of tumor and other human diseases by functioning as a competing endogenous RNA (ceRNA). In this review, we comprehensively summarized recent progress in understanding the cellular functions of lncRNA Xist in mammalian cells and discussed current knowledge regarding the ceRNA network of lncRNA Xist in various diseases. Long non-coding RNAs (lncRNAs) are transcripts that are more than 200 nt in length and without an apparent protein-coding capacity (
Furlan and Rougeulle, 2016
;
Maduro et al., 2016
). These RNAs are believed to be transcribed by the approximately 98–99% non-coding regions of the human genome (
Derrien et al., 2012
;
Fu, 2014
;
Montalbano et al., 2017
;
Slack and Chinnaiyan, 2019
), as well as a large variety of genomic regions, such as exonic, tronic, and intergenic regions. Hence, lncRNAs are also divided into eight categories: Intergenic lncRNAs, Intronic lncRNAs, Enhancer lncRNAs, Promoter lncRNAs, Natural antisense/sense lncRNAs, Small nucleolar RNA-ended lncRNAs (sno-lncRNAs), Bidirectional lncRNAs, and non-poly(A) lncRNAs (
Ma et al., 2013
;
Devaux et al., 2015
;
St Laurent et al., 2015
;
Chen, 2016
;
Quinn and Chang, 2016
;
Richard and Eichhorn, 2018
;
Connerty et al., 2020
). A range of evidence has suggested that lncRNAs function as key regulators in crucial cellular functions, including proliferation, differentiation, apoptosis, migration, and invasion, by regulating the expression level of target genes via epigenomic, transcriptional, or post-transcriptional approaches (
Cao et al., 2018
). Moreover, lncRNAs detected in body fluids were also believed to serve as potential biomarkers for the diagnosis, prognosis, and monitoring of disease progression, and act as novel and potential drug targets for therapeutic exploitation in human disease (
Jiang W. et al., 2018
;
Zhou et al., 2019a
). Long non-coding RNA X-inactive specific transcript (lncRNA Xist) are a set of 15,000–20,000 nt sequences localized in the X chromosome inactivation center (XIC) of chromosome Xq13.2 (
Brown et al., 1992
;
Debrand et al., 1998
;
Kay, 1998
;
Lee et al., 2013
;
da Rocha and Heard, 2017
;
Yang Z. et al., 2018
;
Brockdorff, 2019
). Previous studies have indicated that lncRNA Xist regulate X chromosome inactivation (XCI), resulting in the inheritable silencing of one of the X-chromosomes during female cell development. Also, it serves a vital regulatory function in the whole spectrum of human disease (notably cancer) and can be used as a novel diagnostic and prognostic biomarker and as a potential therapeutic target for human disease in the clinic (
Liu et al., 2018b
;
Deng et al., 2019
;
Dinescu et al., 2019
;
Mutzel and Schulz, 2020
;
Patrat et al., 2020
;
Wang et al., 2020a
). In particular, lncRNA Xist have been demonstrated to be involved in the development of multiple types of tumors including brain tumor, Leukemia, lung cancer, breast cancer, and liver cancer, with the prominent examples outlined in
Table 1
. It was also believed that lncRNA Xist (
Chaligne and Heard, 2014
;
Yang Z. et al., 2018
) contributed to other diseases, such as pulmonary fibrosis, inflammation, neuropathic pain, cardiomyocyte hypertrophy, and osteoarthritis chondrocytes, and more specific details can be found in
Table 2
. This review summarizes the current knowledge on the regulatory mechanisms of lncRNA Xist on both chromosome dosage compensation and pathogenesis (especially cancer) processes, with a focus on the regulatory network of lncRNA Xist in human disease.
In this paper, a microstructure-dependent magneto-electro-elastic functionally graded porous (MEEFGP) beam model is proposed using a variational approach. To account for the microstructure effect, ...the extended modified couple stress theory is incorporated in the new model. In addition, the porosity variation of the two-phase beam model through the thickness direction is also considered. The new developed model is verified in terms of its correctness with a FEM model. Based on the equations of motion and boundary conditions derived by Hamilton’s principle, the static bending and wave propagation behaviors of the new model are analytically determined. The results prove the existence of the microstructure effect and the magneto-electro-elastic multi-field coupling effect. There are significant differences between the new model and the classical model at the microscale. Moreover, the porosity also has an important influence on the mechanical properties of the new model. The results predicted by the new model can provide the theoretical basis for the design of microscale acoustic wave devices and micro-electro-mechanical systems.
Defeathering with rosin results in rosin residue in duck skin, which may present as potential risk to human health. Dehydroabietic acid (DHAA) is a major component of rosin. An indirect competitive ...enzyme-linked immunosorbent assay (ELISA) was developed for determination of DHAA in duck skin. A set of parameters was optimized, including coating antigen concentration, dilution of antiserum, dilution of HRP-IgG antibody, incubation time, and temperature for antigen reaction with antiserum. The indirect competitive ELISA yielded an excellent specificity against DHAA with low cross-reactivity toward other resin acids. The limit of detection and the working concentration range of DHAA in duck skin were 16.4 ng/g and from 40 to 8,060 ng/g, respectively. The indirect competitive ELISA was applied to the determination of DHAA in duck skin samples spiked with DHAA at different contents, and recoveries were found between 78.2 and 97.2%. Finally, DHAA contents in 32 duck samples were quantified by the indirect competitive ELISA and high performance liquid chromatography-fluorescence detector (HPLC-FLD) method. No significant difference was found between DHAA concentrations from indirect competitive ELISA and HPLC-FLD method for all samples, which indicated the indirect competitive ELISA established in this article was of the same accuracy as the HPLC-FLD method. The indirect competitive ELISA was simple, rapid, and reliable, which could be used to identify the duck carcasses defeathered with rosin in the market.
The pivotal roles of miRNAs in carcinogenesis, metastasis, and prognosis have been demonstrated recently in various cancers. This study intended to investigate the specific roles of hsa-miR-654-5p in ...lung cancer, which is, in general, rarely discussed. A series of closed-loop bioinformatic functional analyses were integrated with in vitro experimental validation to explore the overall biological functions and pan-cancer regulation pattern of miR-654-5p. We found that miR-654-5p abundance was significantly elevated in LUAD tissues and correlated with patients’ survival. A total of 275 potential targets of miR-654-5p were then identified and the miR-654-5p-RNF8 regulation axis was validated in vitro as a proof of concept. Furthermore, we revealed the tumor-suppressing roles of miR-654-5p and demonstrated that miR-654-5p inhibited the lung cancer cell epithelial-mesenchymal transition (EMT) process, cell proliferation, and migration using target-based, abundance-based, and ssGSEA-based bioinformatic methods and in vitro validation. Following the construction of a protein–protein interaction network, 11 highly interconnected hub genes were identified and a five-genes risk scoring model was developed to assess their potential prognostic ability. Our study does not only provide a basic miRNA-mRNA-phenotypes reference map for understanding the function of miR-654-5p in different cancers but also reveals the tumor-suppressing roles and prognostic values of miR-654-5p.
Skeletal muscle and thermogenic adipose tissue are both critical for the maintenance of body temperature in mammals. However, whether these two tissues are interconnected to modulate thermogenesis ...and metabolic homeostasis in response to thermal stress remains inconclusive. Here, we report that human and mouse obesity is associated with elevated Musclin levels in both muscle and circulation. Intriguingly, muscle expression of Musclin is markedly increased or decreased when the male mice are housed in thermoneutral or chronic cool conditions, respectively. Beige fat is then identified as the primary site of Musclin action. Muscle-transgenic or AAV-mediated overexpression of Musclin attenuates beige fat thermogenesis, thereby exacerbating diet-induced obesity and metabolic disorders in male mice. Conversely, Musclin inactivation by muscle-specific ablation or neutralizing antibody treatment promotes beige fat thermogenesis and improves metabolic homeostasis in male mice. Mechanistically, Musclin binds to transferrin receptor 1 (Tfr1) and antagonizes Tfr1-mediated cAMP/PKA-dependent thermogenic induction in beige adipocytes. This work defines the temperature-sensitive myokine Musclin as a negative regulator of adipose thermogenesis that exacerbates the deterioration of metabolic health in obese male mice and thus provides a framework for the therapeutic targeting of this endocrine pathway.
Increasing evidences have demonstrated the essentiality of many-body interactions in modeling various systems in physics, biology, and social sciences. Control strategies are useful tools to steer ...real-world complex systems to desired targets. Existing works focus on open-loop control, which relies on predefined control signals, and closed-loop control, which requires an infinite-time duration, on conventional networks expressed by graphs. This work designs closed-loop controllers for higher-order complex networks characterized by simplicial complexes. Protocols including the linear feedback controller and a switching controller, which is a combination of a linear controller and a finite-time controller, are first adapted to higher-order networks to realize successful control tasks, with the rigorous upper bound of the control time theoretically derived and compared. Extensive numerical simulations on benchmark and real-world higher-order complex networks demonstrate the effectiveness of the control protocols and further provide insights on pinning control strategy to higher-order networks. These results shed light on a comprehensive discovery of controlling higher-order complex networks and have also applied values.
Diabetes mellitus is a complex metabolic disease characterized by chronically deregulated blood-glucose levels. To restore glucose homeostasis, therapeutic strategies allowing well-controlled ...production and release of insulinogenic hormones into the blood circulation are required. In this chapter, we describe how mammalian cells can be engineered for applications in diabetes treatment. While closed-loop control systems provide automated and self-sufficient synchronization of glucose sensing and drug production, drug production in open-loop control systems is engineered to depend on exogenous user-defined trigger signals. Rational, robust, and reliable manufacture practices for mammalian cell engineering are essential for industrial-scale mass-production in view of clinical and commercial applications.
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•MBiC@tE achieves an efficient F- electrosorption capacity of 37.9 mgF- gelectrode-1.•Fluoride was removed by the synergistic roles during capacitive control process.•Bismuth active ...units induced Faradaic redox reaction and increased pseudocapacitance.•The complex carbon framework ensured electrical double layer capacitance.•Insights into the phase transition of bismuth during the electrosorption.
Remediation of fluoride in groundwater through electrosorption to cope with its high charge density and the smallest anion radius remains a promising strategy. Composite carbon materials obtained by calcining metal–organic frameworks contribute to the performance of conventional fluoride electrosorption systems. This study provides a redox-active electrode (MBiC@tE) that incorporates the Faradaic ion trapping effect for fluoride removal. Under potential control, MBiC@tE reversibly traps/releases fluoride anions from the aqueous solution through the combined roles of Faradaic pseudocapacitance and electrical double layer capacitance, with an electrosorption capacity of approximately 37.9 mgF- gelectrode-1. The target contaminant anions are directly involved in the Faradaic reaction on the bismuth sites, with the formation of Bi-F bond excited by an electric field, thus resulting in the removal of fluoride as a consequence of the generation of insoluble substance (BiF3). Furthermore, as expected (Bi0 + 3F- ⇌ BiF3 + 3e-), the working electrode exhibits good reversibility and maintains a high fluoride removal capacity even after multiple cycles. This study presents a comprehensive elucidation on the synergistic roles of Faradaic effect and electrical double layer capacitance induced by the electric field, and offers profound insights into the phase transition of bismuth and its affinity for fluoride during the electrosorption.
Age of Information (AoI) is a metric to describe the timeliness of a system proposed in recent years. It measures the freshness of the latest received data from the perspective of the target node in ...the system. This work studies a kind of dynamic data acquisition system for urban security that can update and control the situation of urban environmental security by collecting environmental data. The collected data packets need to be uploaded to the cloud center in time for data update, which has high requirements on the timeliness of the system and freshness of data. However, due to the limited computing capacity of mobile terminals and the pressure of bandwidth for data transmission, problems such as high data execution delay and transmission interruption are caused. Emerging mobile edge computing (MEC), a new model of computing that extends cloud computing capabilities to the edge network, promises to solve these problems. This work focuses on the timeliness of the system, as measured by the average AoI across all mobile terminals. First, a timeliness optimization model is defined, and a multi-agent deep reinforcement learning (DRL) algorithm combined with an attention mechanism is proposed to carry out computing offloading and resource allocation through the continuous interaction between agent and environment; then, in order to improve algorithm performance and data security, the federated learning mode is proposed to train agents; finally, the proposed algorithm is compared with other main baseline algorithms based on deep reinforcement learning. The simulation results show that the proposed algorithm not only outperforms other algorithms in optimizing system timeliness, but also improves the stability of training.
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