Long non-coding RNAs (lncRNAs) are essential factors that regulate tumor development and metastasis via diverse molecular mechanisms in a broad type of cancers. However, the pathological roles of ...lncRNAs in gallbladder carcinoma (GBC) remain largely unknown. Here we discovered a novel lncRNA termed lncRNA Highly expressed in GBC (lncRNA-HGBC) which was upregulated in GBC tissue and aimed to investigate its role and regulatory mechanism in the development and progression of GBC.
The expression level of lncRNA-HGBC in GBC tissue and different cell lines was determined by quantitative real-time PCR. The full length of lncRNA-HGBC was obtained by 5' and 3' rapid amplification of the cDNA ends (RACE). Cellular localization of lncRNA-HGBC was detected by fluorescence in situ hybridization (FISH) assays and subcellular fractionation assay. In vitro and in vivo assays were preformed to explore the biological effects of lncRNA-HGBC in GBC cells. RNA pull-down assay, mass spectrometry, and RNA immunoprecipitation (RIP) assay were used to identify lncRNA-HGBC-interacting proteins. Dual luciferase reporter assays, AGO2-RIP, and MS2-RIP assays were performed to verify the interaction between lncRNA-HGBC and miR-502-3p.
We found that lncRNA-HGBC was upregulated in GBC and its upregulation could predict poor survival. Overexpression or knockdown of lncRNA-HGBC in GBC cell lines resulted in increased or decreased, respectively, cell proliferation and invasion in vitro and in xenografted tumors. LncRNA-HGBC specifically bound to RNA binding protein Hu Antigen R (HuR) that in turn stabilized lncRNA-HGBC. LncRNA-HGBC functioned as a competitive endogenous RNA to bind to miR-502-3p that inhibits target gene SET. Overexpression, knockdown or mutation of lncRNA-HGBC altered the inhibitory effects of miR-502-3p on SET expression and downstream activation of AKT. Clinically, lncRNA-HGBC expression was negatively correlated with miR-502-3p, but positively correlated with SET and HuR in GBC tissue.
Our study demonstrates that lncRNA-HGBC promotes GBC metastasis via activation of the miR-502-3p-SET-AKT cascade, pointing to lncRNA-HGBC as a new prognostic predictor and a therapeutic target.
Tea culture is an excellent traditional culture in China, and its integration into higher vocational aesthetic education can promote the overall development of students. This paper takes the higher ...vocational colleges and universities in H city as an example, constructs the correlation index of the integration and development of tea culture and aesthetic education, and explores the key factors of the integration and development of tea culture and aesthetic education by combining the gray correlation method. At the same time, the students’ portraits are constructed, the constructed user portraits are clustered using the K-mean algorithm, combined with the improved collaborative filtering algorithm, and the resources related to tea culture and aesthetic education in higher vocational colleges and universities are accurately recommended. The improved model is also applied to the city to analyze the resource recommendation effect of tea culture and aesthetic education and explore the development path of integration of tea culture and aesthetic education in higher vocational colleges. The results show that the gray correlation between the integration of tea culture and aesthetic education in higher vocational colleges and universities, and the educational foundation, educational level, student ability, and educational needs are within (0.642, 0.808). The similarity between the users recommending aesthetic education resources is above 0.7, the similarity between the users recommending tea culture and aesthetic education resources and the users recommending tea culture resources is above 0.8, and the content recommended by each user achieves the desired effect (100%). The effective promotion of tea culture and aesthetic education in higher vocational colleges and universities is achieved through the accurate recommendation of relevant resources for students’ needs.
A facile and efficient method to produce optically pure benzofuroindolines, especially those without 3‐substituents that are susceptible to rearomatization, through 3+2 annulation of indoles with ...quinones is described. The suitable combination of a BOX ligand CuII hydrate complex and freshly activated molecular sieves functions to give controllably dynamic release of water, which enables the success of this reaction. This reaction can be performed on a gram scale with only 0.5 mol % catalyst loading.
Thinking outside the BOX: A CuII‐catalyzed asymmetric 3+2 annulation of indoles with quinones provides diverse access to the optically pure benzofuroindolines, including those without 3‐substituents that are susceptible to rearomatization, for the first time. The use of a BOX ligand copper hydrate complex in combination with activated molecular sieves for the controlled release of H2O leads to reproducibly high yields and excellent enantioselectivity.
As the most powerful antigen-presenting cell type, dendritic cells (DCs) can induce potent antigen-specific immune responses in vivo, hence becoming optimal cell population for vaccination purposes. ...DCs can be derived ex vivo in quantity and manipulated extensively to be endowed with adequate immune-stimulating capacity. After pulsing with cancer antigens in various ways, the matured DCs are administrated back into the patient. DCs home to lymphoid organs to present antigens to and activate specific lymphocytes that react to a given cancer. Ex vivo pulsed DC vaccines have been vigorously investigated for decades, registering encouraging results in relevant immunotherapeutic clinical trials, while facing some solid challenges. With more details in DC biology understood, new theory proposed, and novel technology introduced (featuring recently emerged mRNA vaccine technology), it is becoming increasingly likely that ex vivo pulsed DC vaccine will fulfill its potential in cancer immunotherapy.
Suspended single‐hole transistors (SHTs) can also serve as nanoelectromechanical resonators, providing an ideal platform for investigating interactions between mechanical vibrations and charge ...carriers. Demonstrating such a device in silicon (Si) is of particular interest, due to the strong piezoresistive effect of Si and potential applications in Si‐based quantum computation. Here, a suspended Si SHT also acting as a nanoelectromechanical beam resonator is demonstrated. The resonant frequency and zero‐point motion of the device are ≈3 GHz and 0.2 pm, respectively, reaching the best level among similar devices demonstrated with Si‐containing materials. The mechanical vibration is transduced to electrical readout by the SHT. The signal transduction mechanism is dominated by the piezoresistive effect. A giant apparent effective piezoresistive gauge factor with strong correlation to single‐hole tunneling is extracted in this device. The results show the great potential of the device in interfacing charge carriers with mechanical vibrations, as well as investigating potential quantum behavior of the vibration phonon mode.
A silicon single‐hole transistor, a promising candidate for next‐generation electronics, is suspended to function as a nanoelectromechanical resonator, demonstrating a record‐high resonant frequency and large zero‐point motion. The mechanical‐to‐electrical signal transducing is dominated by the piezoresistive effect with a giant piezoresistive gauge factor strongly correlated to single‐hole tunneling, providing great potential in interfacing charge carriers with mechanical vibrations.
Gefitinib resistance in triple negative breast cancer (TNBC) is a growing important concern. Glutathione peroxidase 4 (GPX4) is a main regulator of ferroptosis, which is pivotal for TNBC cell growth. ...We investigated GPX4-mediated ferroptosis in gefitinib sensitivity in TNBC. Gefitinib resistant TNBC cells MDA-MB-231/Gef and HS578T/Gef were constructed and treated with lentivirus sh-GPX4 and ferroptosis inhibitor ferrostatin-1. GPX4 expression, cell viability and apoptosis were detected. Malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS) levels were evaluated. The levels of ferroptosis-related proteins were detected. Subcutaneous tumor model was established in nude mice, and gefitinib was intraperitoneally injected to evaluate tumor growth, apoptosis, and Ki-67 expression. GPX4 was increased in gefitinib-resistant cells. After silencing GPX4, the inhibition rate of cell viability was increased, the limitation of colony formation ability was reduced, apoptosis rate was increased, and the sensitivity of cells to gefitinib was improved. After silencing GPX4, MDA and ROS production were increased, while GSH was decreased. Silencing GPX4 promoted ferroptosis. Inhibition of GPX4 promoted gefitinib sensitivity by promoting cell ferroptosis.
experiments also revealed that inhibition of GPX4 enhanced the anticancer effect of gefitinib through promoting ferroptosis. Overall, inhibition of GPX4 stimulated ferroptosis and enhanced TNBC cell sensitivity to gefitinib.
Vibrational modes in mechanical resonators provide a promising candidate to interface and manipulate classical and quantum information. The observation of coherent dynamics between distant mechanical ...resonators can be a key step toward scalable phononbased applications. Here we report tunable coherent phonon dynamics with an architecture comprising three graphene mechanical resonators coupled in series, where all resonators can be manipulated by electrical signals on control gates. We demonstrate coherent Rabi oscillations between spatially separated resonators indirectly coupled via an intermediate resonator serving as a phonon cavity. The Rabi frequency fits well with the microwave burst power on the control gate. We also observe Ramsey interference, where the oscillation frequency corresponds to the indirect coupling strength between these resonators. Such coherent processes indicate that information encoded in vibrational modes can be transferred and stored between spatially separated resonators, which can open the venue of on-demand phonon-based information processing.
Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological activities. However, the precise mechanisms of the anti-proliferation and anti-metastatic effects of baicalein on ...gallbladder cancer (GBC) remain poorly understood. Therefore, the aim of this study was to assess the anti-proliferation and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In the present study, we found that treatment with baicalein induced a significant inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996 cells, two widely used gallbladder cancer cell lines. Additionally, treatment with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated for the first time that baicalein inhibited GBC cell growth and metastasis via down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In conclusion, our studies suggest that baicalein may be a potential phytochemical flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or predictive target for GBC.
An Anisotropic Critical State Theory (ACST) for granular media is presented, which accounts for the role of anisotropic fabric at critical state. It enhances the requirements of critical values for ...the stress and void ratio of the classical Critical State Theory (CST) by an additional requirement of critical value for an appropriate measure of fabric-anisotropy. A fabric tensor and its evolution toward a critical value, norm-wise and direction-wise, is introduced motivated by micromechanical and experimental studies. On the basis of a scalar-valued fabric-anisotropy variable relating the evolving fabric tensor to the loading direction, a dilatancy state line is defined in the void ratio—pressure plane which determines a dilatancy state parameter ζ that characterizes the contracting or dilating trends of the current state. When the fabric-anisotropy variable reaches its critical state value, the dilatancy state line becomes identical to the critical state line and the ζ identical to the well-known state parameter ψ. An immediate corollary is the uniqueness of the critical state line, for which a thermodynamic proof is provided on the basis of the Gibbs condition. Static liquefaction is obtained when ζ=0 with the stress ratio reaching its critical value but not the void ratio and the fabric. Simulations of anisotropic material response by a triaxial model are used to illustrate the effectiveness of the novel ACST.
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