Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h.

BACKGROUND: Breast cancer is a prevalent disease in women, with high prevalence worldwide. The hypoxic microenvironment of solid tumors develops during the progress of carcinogenesis and leads to greater malignancy and treatment resistance. Recently, accumulating evidence indicates that non-coding RNAs, such as circular RNAs (circRNAs), play a pivotal role in altering cellular functions. However, the underlying mechanisms of circRNAs in breast cancer are still unclear. Therefore, the purpose of this study was to investigate the role of a tumor-suppressive circRNA, circAAGAB, in breast cancer by assuming down-regulation of circAAGAB under hypoxia and the properties of a tumor suppressor. METHODS: Firstly, circAAGAB was identified from expression profiling by next generation sequencing. Next, the stability of circAAGAB increased by interacting with the RNA binding protein FUS. Moreover, cellular and nuclear fractionation showed that most circAAGAB resided in the cytoplasm and that it up-regulated KIAA1522, NKX3-1, and JADE3 by sponging miR-378 h. Lastly, the functions of circAAGAB were explored by identifying its down-stream genes using Affymetrix microarrays and validated by in vitro assays. RESULTS: The results showed that circAAGAB reduced cell colony formation, cell migration, and signaling through p38 MAPK pathway, as well as increased radiosensitivity. CONCLUSION: These findings suggest that the oxygen-responsive circAAGAB acts as a tumor suppressor in breast cancer, and may contribute to the development of a more specific therapeutic regimen for breast cancer.

Continuous polymerase chain reaction microfluidics integrated with a gold-capped nanoslit sensing chip for Epstein-Barr virus detection.

We present the first combination of a microfluidic polymerase chain reaction (PCR) with a gold nanoslit-based surface plasmon resonance (SPR) sensor for detecting the DNA sequence of latent membrane protein 1 (LMP1). The PCR microchannel was produced through a laser scribing technique, and the SPR nanoslit chip was manufactured via hot-embossing nanoimprinting lithography. Afterward, the LMP1 DNA probe was adsorbed onto the SPR chip of the integrated device through electrostatic interactions for further detection. The device can complete the analytical procedure in around 36 min, while the traditional machine requires 105 min to achieve similar signals under the same PCR thermal cycles. The calibration curve with serially diluted LMP1 DNA exhibited the accuracy (R2 > 0.99) and sensitivity (limit of detection: ∼10-11 g/mL) of the device. Moreover, extracted DNA from Epstein-Barr virus (EBV)-positive cells were directly detected through the integrated chip. In brief, this all-in-one chip can amplify gene fragments at the front-end and detect them at the back-end, decreasing the time required for the analysis without compromising accuracy or sensitivity. We believe this label-free, real-time, low-cost device has enormous potential for rapid detection of various viruses, such as EBV and COVID-19.

Portable Nanohybrid Paper-Based Chemiresistive Sensor for Free Chlorine Detection.

Detecting the concentration of free chlorine is important for monitoring the quality of water. In this study, we report a nanohybrid paper-based chemiresistive sensor that can be used with smartphones to detect free chlorine ions. The sensor was fabricated using a simple and standardized coating process. The graphene and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) nanohybrid paper-based sensing device exhibited a more stable and intuitive response to free chlorine than that exhibited by the device using only PEDOT:PSS. The nanohybrid paper-based sensor was sensitive to free chlorine concentrations in a linear range of 0.1-500 ppm, and the limit of detection was 0.18 ppm. The sensor showed specificity for free chloride ions and detection capability in samples. The sensor was integrated as a module with an electric readout system, and the measured signals and results could be displayed in real time on a smartphone. Therefore, the proposed sensing platform is suitable owing to its portability, low cost, ease of use, and capability for on-site water quality measurement.

Antibacterial Application on Staphylococcus aureus Using Antibiotic Agent/Zinc Oxide Nanorod Arrays/Polyethylethylketone Composite Samples.

In this study, zinc oxide (ZnO) nanorod arrays as antibiotic agent carriers were grown on polyetheretherketone (PEEK) substrates using a chemical synthesis method. With the concentration of ammonium hydroxide in the precursor solution kept at 4 M, ZnO nanorod arrays with diameters in the range of 100-400 nm and a loading density of 1.7 mg/cm2 were grown onto the PEEK substrates. Their drug release profiles and the antibacterial properties of the antibiotic agent/ZnO/PEEK samples in the buffer solution were investigated. The results showed that the concentrations of antibiotic agents (ampicillin or vancomycin) released from the samples into the buffer solution were higher than the value of minimum inhibitory concentration of 90% for Staphylococcus aureus within the 96 h test. The bioactivities of ampicillin and vancomycin on substrates also showed around 40% and 80% on the Staphylococcus aureus, respectively. In the antibacterial activity test, sample with the suitable loading amount of antibiotic agent had a good inhibitory effect on the growth of Staphylococcus aureus.

Universal quinone electrodes for long cycle life aqueous rechargeable batteries.

Aqueous rechargeable batteries provide the safety, robustness, affordability, and environmental friendliness necessary for grid storage and electric vehicle operations, but their adoption is plagued by poor cycle life due to the structural and chemical instability of the anode materials. Here we report quinones as stable anode materials by exploiting their structurally stable ion-coordination charge storage mechanism and chemical inertness towards aqueous electrolytes. Upon rational selection/design of quinone structures, we demonstrate three systems that coupled with industrially established cathodes and electrolytes exhibit long cycle life (up to 3,000 cycles/3,500 h), fast kinetics (≥20C), high anode specific capacity (up to 200-395 mAh g-1), and several examples of state-of-the-art specific energy/energy density (up to 76-92 Wh kg-1/ 161-208 Wh l-1) for several operational pH values (-1 to 15), charge carrier species (H+, Li+, Na+, K+, Mg2+), temperature (-35 to 25 °C), and atmosphere (with/without O2), making them a universal anode approach for any aqueous battery technology.

Hydrothermally synthesized PZT film grown in highly concentrated KOH solution with large electromechanical coupling coefficient for resonator.

This paper presents a study of lead zirconate titanate (PZT) films hydrothermally grown on a dome-shaped titanium diaphragm. Few articles in the literature address the implementation of hydrothermal PZT films on curved-diaphragm substrates for resonators. In this study, a 50-µm-thick titanium sheet is embossed using balls of designed dimensions to shape a dome-shaped cavity array. Through single-process hydrothermal synthesis, PZT films are grown on both sides of the processed titanium diaphragm with good adhesion and uniformity. The hydrothermal synthesis process involves a high concentration of potassium hydroxide solution and excess amounts of lead acetate and zirconium oxychloride octahydrate. Varied deposition times and temperatures of PZT films are investigated. The grown films are characterized by X-ray diffraction and scanning electron microscopy. The 10-µm-thick PZT dome-shaped resonators with 60- and 20-µm-thick supporting layers are implemented and further tested. Results for both resonators indicate that large electromechanical coupling coefficients and a series resonance of 95 MHz from 14 MHz can be attained. The device is connected to a complementary metal-oxide-semiconductor integrated circuit for analysis of oscillator applications. The oscillator reaches a Q value of 6300 in air. The resonator exhibits a better sensing stability when loaded with water when compared with air.

A pH sensitive polymeric micelle for co-delivery of doxorubicin and α-TOS for colon cancer therapy.

Combination therapy through simultaneous delivery of two or more therapeutic agents using nanocarriers has emerged as an advanced tactic for cancer treatment. To ensure that two therapeutic agents can be co-delivered and rapidly release their cargo in tumor cells, a biocompatible pH-sensitive copolymer, methoxy poly(ethylene glycol)-b-poly(hydroxypropyl methacrylamide-g-α-tocopheryl succinate-g-histidine) (abbreviated as PTH), was designed and synthesized. The PTH copolymers spontaneously self-assembled into micellar-type nanoparticles in aqueous solutions and are used for co-delivery of therapeutic agents, doxorubicin (Dox) and α-TOS. During micellization, π-π stacking occurred between Dox/α-TOS and imidazole rings of PTH copolymers inducing a regular and tight arrangement of copolymers and drugs to form rod-like micelles, thus efficiently increasing the drug loading and encapsulation efficiency. The micelles enabled the rapid release of both Dox and α-TOS when the pH decreased from 7.4 to 4.5. The protein adsorption assay revealed that low amounts of IgG and BSA were adsorbed on the micelles. In vivo biodistribution demonstrated that the micelles could largely accumulate in the tumor tissues. Furthermore, drug-loaded micelles treated with HCT116 cancer cells exhibited higher cytotoxicity than normal cells, which confirmed that α-TOS exhibited a synergy effect with Dox towards cancer cells, while no recognizable side effects were observed during the treatment from organ function tests.

Vitamin E containing polymer micelles for reducing normal cell cytotoxicity and enhancing chemotherapy efficacy.

An α-tocopheryl succinate (α-TOS) containing diblock copolymer micellar system was used to deliver doxorubicin (Dox), an anticancer drug, for HCT116 colon cancer therapy. The α-TOS containing diblock copolymers were synthesized by conjugation of α-TOS molecules and a mPEG-b-PHEMA hydrophilic diblock copolymer by ester bonds. The Dox-loaded polymeric micelles were then obtained by solvent exchange process. In acidic surroundings such as endosomes or secondary lysosomes, the structures of the Dox-loaded polymeric micelles deformed and released the drug loads. Additionally, Dox-loaded polymeric micelles enhanced the cytotoxicity of Dox and α-TOS to cancer cells in vitro. Dox-loaded polymeric micelles also showed an exceptional tumor inhibiting effect in vivo. This study indicates that the α-TOS containing polymeric micelle system can be used as a drug carrier for cancer therapy.

Diastereoselective synthesis of 2-arylmethylene-6-hydroxyspiro[4.5]deca-7-ones via FeCl3·6H2O-catalyzed spiroannulation/hydride transfer of 6-(5-arylpent-4-yn-1-yl)-7-oxabicyclo[4.1.0]heptan-2-ols.

In the presence of a catalytic amount of FeCl3·6H2O, 6-(5-arylpent-4-yn-1-yl)-7-oxabicyclo[4.1.0]heptan-2-ols underwent attack of the pendant acetylene at the iron-activated oxirane to give a vinylic carbocation. Hydride transfer from the carbinol carbon to the newly formed cation center furnished 2-arylmethylene-6-hydroxyspiro[4.5]deca-7-ones in excellent stereoselectivity and good yields.

Andrographolide sensitizes Ras-transformed cells to radiation in vitro and in vivo.

PURPOSE: Increasing the sensitivity of tumor cells to radiation is a major goal of radiotherapy. The present study investigated the radiosensitizing effects of andrographolide and examined the molecular mechanisms of andrographolide-mediated radiosensitization. METHODS AND MATERIALS: An H-ras-transformed rat kidney epithelial (RK3E) cell line was used to measure the radiosensitizing effects of andrographolide in clonogenic assays, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide assays, and a xenograft tumor growth model. The mechanism of andrographolide-sensitized cell death was analyzed using annexin V staining, caspase 3 activity assays, and terminal transferase uridyl nick end labeling assays. The roles of nuclear factor kappa B (NF-kappaB) and Akt in andrographolide-mediated sensitization were examined using reporter assays, electrophoretic mobility shift assays, and Western blotting. RESULTS: Concurrent andrographolide treatment (10 microM, 3 h) sensitized Ras-transformed cells to radiation in vitro (sensitizer enhancement ratio, 1.73). Andrographolide plus radiation (one dose of 300 mg/kg peritumor andrographolide and one dose of 6 Gy radiation) resulted in significant tumor growth delay (27 +/- 2.5 days) compared with radiation alone (22 +/- 1.5 days; p <.05). Radiation induced apoptotic markers (e.g., caspase-3, membrane reversion, DNA fragmentation), and andrographolide treatment did not promote radiation-induced apoptosis. However, the protein level of activated Akt was significantly reduced by andrographolide. NF-kappaB activity was elevated in irradiated Ras-transformed cells, and andrographolide treatment significantly reduced radiation-induced NF-kappaB activity. CONCLUSION: Andrographolide sensitized Ras-transformed cells to radiation both in vitro and in vivo. Andrographolide-mediated radiosensitization was associated with downregulation of Akt and NF-kappaB activity. These observations indicate that andrographolide is a novel radiosensitizing agent with potential application in cancer radiotherapy.