As a promising functional material, hydrogels have attracted extensive attention, especially in flexible wearable sensor fields, but it remains a great challenge to facilely integrate excellent ...mechanical properties, self-adhesion, and strain sensitivity into a single hydrogel. In this work, we present high in strength, stretchable, conformable, and self-adhesive chitosan/poly(acrylic acid) double-network nanocomposite hydrogels for application in epidermal strain sensor via in situ polymerization of acrylic acid in chitosan acid aqueous solution with tannic acid-coated cellulose nanocrystal (TA@CNC) acting as nanofillers to reinforce tensile properties, followed by a soaking process in a saturated NaCl solution to cross-link chitosan chains. With addition of a small amount of TA@CNC, the double-network nanocomposite hydrogels became highly adhesive and mechanically compliant, which were critical factors for the development of conformable and resilient wearable epidermal sensors. The salt-soaking process was applied to cross-link chitosan chains by shielded electrostatic repulsions between positively charged amino groups, drastically enhancing the mechanical properties of the hydrogels. The obtained double-network nanocomposite hydrogels exhibited excellent tunable mechanical properties that could be conveniently tailored with fracture stress and fracture strain ranging from 0.39 to 1.2 MPa and 370 to 800%, respectively. Besides, the hydrogels could be tightly attached onto diverse substrates, including wood, glass, plastic, polytetrafluoroethylene, glass, metal, and skin, demonstrating high adhesion strength and compliant adhesion behavior. In addition, benefiting from the abundant free ions from strong electrolytes, the flexible hydrogel sensors demonstrated stable conductivity and strain sensitivity, which could monitor both large human motions and subtle motions. Furthermore, the antibacterial property originating from chitosan made the hydrogels suitable for wearable epidermal sensors. The facile soaking strategy proposed in this work would be promising in fabricating high-strength multifunctional conductive hydrogels used for wearable epidermal devices.
The use of an initial state value function and an optimal strategy are used in this paper to solve educational problems based on deep reinforcement learning. Deep reinforcement learning’s approximate ...function is defined, and the matrix model is created by training tuning using learning methods like gradient descent. To analyze the modeling process of reinforcement learning, reward values are added to the Markov decision transfer matrix and the expected value of cumulative returns is calculated. The weights are trained using the Bellman equation to enhance the algorithm’s stability. In evaluating the effect of reform and innovation in Civic Education, the teacher education concept is rated as 10 points. The reform and innovation of civic education, combined with deep reinforcement learning, can promote the reform of education and teaching modes, improving the efficiency and quality of education.
In multi-target tracking, the sequential Monte Carlo probability hypothesis density (SMC-PHD) filter is a practical algorithm. Influenced by outliers under unknown heavy-tailed measurement noise, the ...SMC-PHD filter suffers severe performance degradation. In this paper, a robust SMC-PHD (RSMC-PHD) filter is proposed. In the proposed filter, Student-t distribution is introduced to describe the unknown heavy-tailed measurement noise where the degrees of freedom (DOF) and the scale matrix of the Student-t distribution are respectively modeled as a Gamma distribution and an inverse Wishart distribution. Furthermore, the variational Bayesian (VB) technique is employed to infer the unknown DOF and scale matrix parameters while the recursion estimation framework of the RSMC-PHD filter is derived. In addition, considering that the introduced Student- t distribution might lead to an overestimation of the target number, a strategy is applied to modify the updated weight of each particle. Simulation results demonstrate that the proposed filter is effective with unknown heavy-tailed measurement noise.
Abstract
DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly ...selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.
Graphical Abstract
Graphical Abstract
Thiazole orange-based small molecules engineered to possess the functional property of two-directional and multi-site interactions with G4–DNA structures achieving excellent G4-target selectivity and in vivo antitumor activity against breast cancer.
Energy efficiency (EE) takes a significant place in the upcoming sixth generation (6G) mobile networks. Cell-free systems have demonstrated impressive performance and attracted much attention in ...academia and industry. Various types and numbers of access points (APs) can be deployed in heterogeneous cell-free systems, operating at millimeter-wave (mmWave) frequencies. But, the instantaneous EE cannot give a full insight into these systems. To tackle this issue, in this paper, we study the ergodic EE of mmWave heterogeneous cell-free systems. Since the derivation of a general closed-form expression for the ergodic EE is intractable, a semi-closed form expression was achieved via discretization, and its effects were investigated. Based on this expression, two specific cases of gain were obtained to describe the EE performance of the mmWave heterogeneous cell-free systems: the first determines the necessity to employ mmWave heterogeneous cell-free systems, and the second guides their deployment. Our simulation results validate the effectiveness of the two gain cases.
PD-L1 is critical for tumor cell escape from immune surveillance by inhibiting T cell function via the PD-1 receptor. Accumulating evidence demonstrates that anti-PD-L1 monoclonal antibodies might ...potently enhance antitumor effects in various tumors, but the effect of PD-L1 on colorectal cancer stem cells (CSCs) remains unclear. We observed high PD-L1 expression in CD133+CD44+ colorectal CSCs and CSC-enriched tumorspheres. Altering PD-L1 expression promoted colorectal CSC self-renewal by increasing the expression of stemness genes, the CD133+CD44+ cell population sizes and the ability to form tumorspheres. Additionally, PD-L1 expression was markedly increased in chemoresistant colorectal cancer (CRC) cells in vitro and in vivo. More importantly, PD-L1 enhanced CRC cell tumorigenicity in nude mice; the inoculation of 1 × 104 cells resulted in high tumor formation efficiency. Mechanistically, PD-L1 directly interacted with HMGA1, and HMGA1 upregulation by PD-L1 activated HMGA1-dependent pathways, including the PI3K/Akt and MEK/ERK pathways, and promoted CSC expansion. HMGA1 downregulation rescued the PD-L1-induced phenotypes, highlighting the role of HMGA1 in PD-L1-mediated colorectal CSC self-renewal. Moreover, PD-L1 expression was correlated with the expression of CSC markers and HMGA1 in clinical CRC specimens. Thus, PD-L1 could crucially contribute to the maintenance of CSC self-renewal by activating HMGA1-dependent signaling pathways.
•PD-L1 promotes the expansion of colorectal CSCs by increasing HMGA1-dependent signaling.•PD-L1 promotes colorectal CSCs self-renewal in vitro and in vivo.•PD-L1 correlates with chemoresistance.•We used mass spectrometry, CO-IP and GST-pull down to identify a new protein (HMGA1) that PD-L1 interacts with directly.
Background Mesenchymal stem cell (MSC)-based therapy is currently considered to be an effective treatment strategy for diabetes and hepatic disorders, such as liver cirrhosis and non-alcoholic fatty ...liver disease. Exosomes are important mediators of cellular connections, and increasing evidence has suggested that exosomes derived from MSCs may be used as direct therapeutic agents; their mechanisms of action, however, remain largely unclear. Here, we evaluated the efficacy and molecular mechanisms of human umbilical cord MSC-derived exosomes (HucMDEs) on hepatic glucose and lipid metabolism in type 2 diabetes mellitus (T2DM). Methods HucMDEs were used to treat T2DM rats, as well as palmitic acid (PA)-treated L-O2 cells, in order to determine the effects of HucMDEs on hepatic glucose and lipid metabolism. To evaluate the changes in autophagy and potential signaling pathways, autophagy-related proteins (BECN1, microtubule-associated protein 1 light chain 3 beta MAP 1LC3B), autophagy-related genes (ATGs, ATG5, and ATG7), AMP-activated protein kinase (AMPK), and phosphorylated AMPK (p-AMPK) were assessed by Western blotting. Results HucMDEs promoted hepatic glycolysis, glycogen storage, and lipolysis, and reduced gluconeogenesis. Additionally, autophagy potentially contributed to the effects of HucMDE treatment. Transmission electron microscopy revealed an increased formation of autophagosomes in HucMDE-treated groups, and the autophagy marker proteins, BECN1 and MAP 1LC3B, were also increased. Moreover, autophagy inhibitor 3-methyladenine significantly reduced the effects of HucMDEs on glucose and lipid metabolism in T2DM rats. Based on its phosphorylation status, we found that the AMPK signaling pathway was activated and induced autophagy in T2DM rats and PA-treated L-O2 cells. Meanwhile, the transfection of AMPK siRNA or application of the AMPK inhibitor, Comp C, weakened the therapeutic effects of HucMDEs on glucose and lipid metabolism. Conclusions These findings demonstrate that HucMDEs improved hepatic glucose and lipid metabolism in T2DM rats by activating autophagy via the AMPK pathway, which provides novel evidence suggesting the potential for HucMDEs in clinically treating T2DM patients. Keywords: Exosome, Mesenchymal stem cell, Glucose metabolism, Type 2 diabetes mellitus, Autophagy
A visible light-promoted hydrosilylation of alkynes has been explored and achieved using 1 mol % organic dye Eosin Y as the photocatalyst and a catalytic amount of thiol as the radical quencher. The ...corresponding alkenylsilanes were provided with high regio- and stereoselectivites in the reactions of various terminal and internal alkynes. The experimental evidence shows that the reaction is preferentially initiated by a single electron transfer process, and a photoredox pathway is suggested.
In this study, C-dots were facilely synthesized via microwave irradiation using citric acid and ethylenediamine as carbon precursors. The fluorescence emissions of the C-dots could be selectively ...quenched by Fe3+, and the degree of quenching was linearly related to the concentrations of Fe3+ presented. This phenomenon was utilized to develop a sensitive fluorescence assay for Fe3+ detection with broad linear range (0–250, 250–1200 μmol/L) and low detection limit (1.68 μmol/L). Most importantly, the assay demonstrated high reliability towards samples in deionized water, tap water and lake water, which should find potential applications for Fe3+ monitoring in complicated environments.
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