A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity.

BACKGROUND: Osteosarcoma (OS) is one of most commonly diagnosed bone cancer. Circular RNAs (circRNAs) are a class of highly stable non-coding RNA, the majority of which have not been characterized functionally. The underlying function and molecular mechanisms of circRNAs in OS have not been fully demonstrated. METHOD: Microarray analysis was performed to identify circRNAs that are differentially-expressed between OS and corresponding normal tissues. The biological function of circKEAP1 was confirmed in vitro and in vivo. Mass spectrometry and western blot assays were used to identify the circKEAP1-encoded protein KEAP1-259aa. The molecular mechanism of circKEAP1 was investigated by RNA sequencing and RNA immunoprecipitation analyses. RESULTS: Here, we identified a tumor suppressor circKEAP1, originating from the back-splicing of exon2 of the KEAP1 gene. Clinically, circKEAP1 is downregulated in OS tumors and associated with better survival in cancer patients. N6-methyladenosine (m6A) at a specific adenosine leads to low expression of circKEAP1. Further analysis revealed that circKEAP1 contained a 777 nt long ORF and encoded a truncated protein KEAP1-259aa that reduces cell proliferation, invasion and tumorsphere formation of OS cells. Mechanistically, KEAP1-259aa bound to vimentin in the cytoplasm to promote vimentin proteasome degradation by interacting with the E3 ligase ARIH1. Moreover, circKEAP1 interacted with RIG-I to activate anti-tumor immunity via the IFN-γ pathway. CONCLUSION: Taken together, our findings characterize a tumor suppressor circKEAP1 as a key tumor suppressor regulating of OS cell stemness, proliferation and migration, providing potential therapeutic targets for treatment of OS.

Transcriptional upregulation of MAPK15 by NF-κB signaling boosts the efficacy of combination therapy with cisplatin and TNF-α.

The efficacy of cisplatin in treating advanced non-small cell lung cancer is limited mainly because of insensitivity and/or acquired resistance. MAPK15, previously shown by us to enhance the sensitivity of the anti-cancer drug arsenic trioxide, could also enhance the sensitivity of other anti-cancer drugs. Here, we explore the potential role of MAPK15 in chemosensitivity to cisplatin in human lung cancer cells. Our results indicated that the expression level of MAPK15 was positively correlated with cisplatin sensitivity through affecting the DNA repair capacity of cisplatin-treated cells. The expression of MAPK15 was transcriptionally regulated by the TNF-α-activated NF-κB signaling pathway, and TNF-α synergized with cisplatin, in a MAPK15-dependent manner, to exert cytotoxicity in vitro and in vivo. Therefore, levels of TNF-α dictate the responsiveness/sensitivity of lung cancer cells to cisplatin by transcriptionally upregulating MAPK15 to enhance chemosensitivity, suggesting manipulation of MAPK15 as a strategy to improve the therapeutic efficacy of chemotherapeutic drugs.

CeO2 Nanocrystal Decorated TiO2 Nanobelt with Enhanced Photocatalytic Performance.

In this work, CeO2 nanocrystal-decorated TiO2 nanobelt for forming a CeO2@TiO2 heterostructure. CeO2 plays a dual role in improving photocatalytic activity, not only by promoting the separation and transfer of photogenerated charge carriers, but also by increasing visible light absorption of the photocatalyst as a photosensitizer. The as-prepared CeO2@TiO2 heterostructure demonstrates the performance of organic degradation and H2 production (about 17 µmol/h/g, which is about 2.5 times higher than that of pure TiO2 nanobelts). Our work provides a facile and controllable synthesis method for high performance photocatalyst, which will have potential applications in synthesis clean/solar fuel, and photocatalytic water treatment.

Excitation Management of Lead-Free Perovskite Nanocrystals Through Doping.

Despite their low toxicity and phase stability, lead-free double perovskite nanocrystals, Cs2AgInCl6 in specific, have suffered from low quantum yield of photoluminescence. This is mainly due to two reasons, including (i) the quenching effect from metal silver which was usually formed at high temperature from Ag+ reduction in the presence of organic amines and (ii) the parity-forbidden transition of pristine double perovskites. Here, we reported a room-temperature synthesis of Cs2AgInCl6 nanocrystals in an inverse microemulsion system, where Ag+ reduction was largely suppressed. By codoping Bi and Na ions, dark self-trapping excitons (STEs) were converted into bright ones, enabling a bright phosphor of photoluminescence quantum yield up to 56%. Importantly, the doping approach at room temperature relaxed the parity-forbidden transition (1S0 → 3P2) of Bi-6s2 orbitals, revealing a fine structure of a triband excitation profile. Such spin-rule relaxation was ascribed to symmetry breaking of the doped lattice, which was evidenced by Raman spectroscopy. In a proof-of-concept experiment, the bright nanocrystals were used as a color-converting ink, which enabled a stable white light light-emitting diode to operate in various environments, even under water, for long-term service.

Fabrication of a Sensitive Strain and Pressure Sensor from Gold Nanoparticle-Assembled 3D-Interconnected Graphene Microchannel-Embedded PDMS.

Manufacture of uniform, sensitive, and durable microtextured sensing materials is one of the greatest challenges for pressure sensors and electronic skins. Reported in this article is a gold nanoparticle-assembled, 3D-interconnected, graphene microchannel-embedded PDMS (3D GMC-PDMS) film for strain and pressure sensors. The film consists of porous nickel foam with its inner walls coated by multilayer graphene. Embedding in PDMS with etching removal of the Ni yields a 3D GMC-PDMS. Coating the inner walls with Au nanoparticles yields an Au nanoparticle-assembled 3D GMC-PDMS (AuNPs-GMC-PDMS) film, which is useful as an ultrasensitive pressure and strain sensor. This sensor exhibits a wide detection range (∼50 kPa) and ultrahigh sensitivity of 5.37, 1.56, and 0.5 kPa-1 in the ranges of <1, 1-10, and 10-50 kPa, respectively. Its lower detection limit is 4.4 Pa, its response time is 20 ms, and its strain factor is up to 15. Comparison of a AuNPs-GMC-PDMS film with a 3D GMC-PDMS film reveals a sensitivity improvement of 40 times in the 0-1 kPa pressure range and a gauge factor of more than 4 times in the 0-30% tensile strain range. The device has broad applications as a traditional or wearable medical sensor.

Resveratrol Promotes Tumor Microvessel Growth via Endoglin and Extracellular Signal-Regulated Kinase Signaling Pathway and Enhances the Anticancer Efficacy of Gemcitabine against Lung Cancer.

The synergistic anticancer effect of gemcitabine (GEM) and resveratrol (RSVL) has been noted in certain cancer types. However, whether the same phenomenon would occur in lung cancer is unclear. Here, we uncovered the molecular mechanism by which RSVL enhances the anticancer effect of GEM against lung cancer cells both in vitro and in vivo. We established human lung adenocarcinoma HCC827 xenografts in nude mice and treated them with GEM and RSVL to detect their synergistic effect in vivo. Tumor tissue sections from nude mice were subjected to hematoxylin and eosin staining for blood vessel morphological observation, and immunohistochemistry was conducted to detect CD31-positive staining blood vessels. We also established the HCC827-human umbilical vein endothelial cell (HUVEC) co-culture model to observe the tubule network formation. Human angiogenesis antibody array was used to screen the angiogenesis-related proteins in RSVL-treated HCC827. RSVL suppressed the expression of endoglin (ENG) and increased tumor microvessel growth and blood perfusion into tumor. Co-treatment of RSVL and GEM led to more tumor growth suppression than treatment of GEM alone. Mechanistically, using the HCC827-HUVEC co-culture model, we showed that RSVL-suppressed ENG expression was accompanied with augmented levels of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 and increased tubule network formation, which may explain why RSVL promoted tumor microvessel growth in vivo. RSVL promoted tumor microvessel growth via ENG and ERK and enhanced the anticancer efficacy of GEM. Our results suggest that intake of RSVL may be beneficial during lung cancer chemotherapy.

Enhanced Antibacterial Photocatalytic Activity of Porous Few-Layer C3N4.

Nowadays, antibacterial photocatalytic activity of semiconductors has attracted great attention due to its excellent stability, good biocompatibility and no disinfection byproducts. Herein, a porous few-layer C3N4 was successfully fabricated via a simple and low-cost bottom-up method. The asprepared porous few-layer C3N4 exhibits large specific surface areas, which is about 4.8 times than bulk C3N4. Under the light (<430 nm) irradiation, reactive oxygen species (ROS) (singlet oxygen (1O2), hydroxyl radicals (·OH), and superoxide (O·-2)) can be generated. The porous few-layer C3N4 was used as an antibacterial agent to kill gram-positive bacterium S. Aureus with an anibacterial efficiency up to 99.7%. The log removal rate of the porous few-layer C3N4 is more than 50 times than the bulk C3N4. The material shows a potential application in water purification and antibacterial photocatalytic therapy.

Electrochemical detection of DNA hybridization based on three-dimensional ZnO nanowires/graphite hybrid microfiber structure.

In the present work, zinc oxide (ZnO) nanowire (NWs)/graphite microfiber hybrid electrodes were used for the detection of DNA hybridization. ZnO NWs were in-situ synthesized onto graphite fibers using the hydrothermal technique, and the result was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) as well as transmission electron microscope (TEM). An electrochemical sensor for the analysis of DNA hybridization was developed based on immobilizing DNA probes onto the ZnO NWs/graphite microfiber electrodes surface via electrostatic interaction. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) were used to corroborate the fabrication of the sensor. Based on the results, ZnO NWs/graphite microfiber hybrid electrodes showed a great hybridization capacity for the determination of target DNA. A wide dynamic detection range from 1.0 × 10-14 M to 1.0 × 10-7 M with an ultralow detection limit of 3.3 × 10-15 M was achieved for detecting the target DNA. Moreover, it showed good selectivity and stability during the detection process.

Hybrid nanostructures of pit-rich TiO2 nanocrystals with Ru loading and N doping for enhanced solar water splitting.

A general method was elaborately developed for the synthesis of pit-rich metal oxide (TiO2, ZrO2 and HfO2) nanocrystals with metallocene dichlorides as precursors. Benefiting from the synergies in numerous pits, Schottky junctions and nitrogen doping, the hybrid nanostructures of pit-rich TiO2 nanocrystals with Ru loading and N doping exhibited enhanced solar water splitting.

TiO2/TiN core/shell nanobelts for efficient solar hydrogen generation.

TiO2/TiN core/shell NBs are successfully synthesized, and used as highly efficient photocatalytic H2 evolution catalysts (120 µmol h-1 g-1) from methanol solution. The TiN shell plays dual roles by extending the light absorption range and also promoting the separation/transfer of photoexcited charge carriers as an electron collector.