Echinatin inhibits tumor growth and synergizes with chemotherapeutic agents against human bladder cancer cells by activating p38 and suppressing Wnt/β-catenin pathways

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system.Due to the poor prognosis and high mortality rate of the disease,it is urgent to develop new drugs with high efficacy and low toxicity to treat BC.Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential.Herein,we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular mechanism.We found that Ecnin vitro inhibited the proliferation,migration,and invasion,arrested the cell cycle at the G2/M phase,and promoted apoptosis in BC cells.Besides,Ecn had no notable cytotoxicity towards human normal cells.We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo .Mechanistically,Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway,while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells.Remarkably,Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells.In summary,our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling pathways.More meaningfully,our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.

B-Site Nanoscale-Ordered Structure Enables Ultra-High Tunable Performance

Tunable devices constructed by ferroelectric thin flms are often desired to possess a low dielectric loss while maintainging a high dielectric tunability over a broad operating temperature range in applications,for example,resonators,filters,or phase shifters.However,it is dificult to simultaneously achieve these characteristics by traditional strategies,such as doping and strain modifying.Here,we demonstrate that the dielectric tunability of the sol-gel-prepared Pb(Sc_(1/2)Nb_(1/2))_(0.9)(Mg_(1/3)Nb_(2/3))_(0.O3)(PSNMN)thin film can be almost doubled from~47%to~80.0%(at 10kHz)at a low electric field(~530kV/cm),and the dielectric loss can be sharply reduced by more than an order of magnitude,from~0.50 to~0.037(at 1 kHz)when the thin flm was annealed in air at 650℃ for 15h under the help of an atmosphere-compensating-block(ACB)made from the proto-PSNMN gel.Moreover,the PSNMN thin flm annealed with ACB also exhibited an extremely high thermally-stable dielectric tunability in an ultrabroad temperature range(>130 K),which could be attributed to the Maxwell-Wagner(MW)effect generated by the interface between the PSNMN disordered matrix and the B-site nanoscale-ordered structure formed during the long-term annealing process.The reduced dielectric loss is mainly benefited from the reduced concentration of oxygen vacancy and the possibie MW efects,and the enhanced dielectric tunability could be ascribed to the weaker domain-pinning effect by oxygen vacancy.The breakthrough provides a new universal strategy to achieve utrahigh tunable performance in A(B'_(1/2)B"_(1/2))O3 ferroelectric thin films with a B-site nanoscale-ordered structure,meanwhile it paves the way for ultraintergrated tunable thin-flm-devices with great phase shifter performance in practical applications.