N6-methyladenosine (m6A) is the most commonly occurring internal RNA modification to be found in eukaryotic mRNA and serves an important role in various physiological events. AlkB homolog 5 RNA demethylase (ALKBH5), an m6A demethylase, belongs to the AlkB family of dioxygenases and has been shown to specifically demethylate m6A in RNA, which is associated with a variety of tumors. However, its function in bladder cancer remains largely unclear. In the present study, we found that the expression of ALKBH5 was downregulated in bladder cancer tissues and cell lines. Low expression of ALKBH5 was correlated with the worse prognosis of bladder cancer patients. Furthermore, functional assays revealed that knockdown of ALKBH5 promoted bladder cancer cell proliferation, migration, invasion, and decreased cisplatin chemosensitivity in the 5637 and T24 bladder cancer cell lines in vivo and in vitro , whereas ALKBH5 overexpression led to the opposite results. Finally, ALKBH5 inhibited the progression and sensitized bladder cancer cells to cisplatin through a casein kinase 2 (CK2)α-mediated glycolysis pathway in an m6A-dependent manner. Taken together, these findings might provide fresh insights into bladder cancer therapy.

The rotordynamics of a double-helical gear transmission system is investigated. The equation of motion of the system with bearing and gyroscopic effect is derived by using the finite element method, in which Timoshenko beam finite element is used to represent the shaft, a rigid mass for the gear. Natural frequencies, mode shapes and Campbell diagrams are illustrated to indicate the effects of gear input speed and time varying mesh stiffness. Besides, effects of mesh stiffness on the critical speed of the gear transmission system are analyzed. The numerical results show that the axial force has significant influence on the natural frequency and the mode shape of the double-helical gear transmission system, for which the mix whirling motion dominates the natural characteristics. There are two higher critical speed curves which increase with the mesh stiffness, but one of them is related to the gyroscopic effect.

Background/Aims: Chloroquine was formerly used as an anti-malarial agent drug but has now been proven to be useful for various diseases. This study aimed to investigate the radiosensitizing effect of chloroquine in bladder cancer, with an emphasis on autophagy inhibition and apoptosis induction. Methods: Bladder cancer cell lines were irradiated with or without chloroquine. Cell proliferation was determined by a Cell Counting Kit 8 assay. The radiosensitization effect of chloroquine was evaluated by clonogenic survival and progression of xenograft tumors. Cell apoptosis was detected by flow cytometry and western blot. Radiation-induced DNA double strand break was measured by the staining of γ-H2AX. In addition, autophagy was detected by western blot, immunofluorescence staining, and electron microscopy. Results: The treatment with chloroquine alone inhibited the proliferation of bladder cancer cells in a dose-dependent manner. Low cytotoxic concentrations of chloroquine enhanced the radiation sensitivity of bladder cancer cells with a sensitization enhancement ratio of 1.53 and 1.40. Chloroquine also obviously weakened the repair of radiation-induced DNA damage. A combination of radiation and chloroquine enhanced the apoptosis rate of EJ and T24 cells and down-regulated the expression of Bcl-2 while up-regulating the expression of caspase-3. Additionally, the relevant markers of autophagy were obviously increased in the combined group, meaning that chloroquine inhibited autophagy induced by irradiation. Furthermore, subcutaneous xenograft tumors displayed that the combination of radiation and chloroquine could impede tumorigenesis in vivo. Conclusion: In summary, these results provided support that by inhibiting autophagy and activating apoptosis, chloroquine might be a potentially promising radiosensitizer in the radiation therapy of bladder cancer.

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