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Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.

In order to overcome the power measurement error caused by switch leakage of time division multiplier, in this paper, the mechanism of switch leakage of no-beats time division multiplier was analyzed, and switch leak was tested. On the basis of this, power compensation circuit on zero point correction based on voltage feedback and voltage frequency conversion method is designed, subsequently the compensation effect was tested respectively. Test results show that the zero compensation method based on voltage frequency conversion method is better, the zero error decreased to 0.0022%, the accuracy of the power measurement was improved.

The incidence of stage Ib ~ IIa of cervical adenocarcinoma accounts about 60 to 70 % of all patients. This study aims to investigate the prognostic significance of protein estrogen receptor alpha (ERα) and transforming growth factor beta 1 (TGF-β1) level in different glandular epithelia of the cervix. In this study, immunohistochemistry was used to detect ERα and TGF-β1 in carcinomas and incisal margins of 66 cases with cervical adenocarcinoma, 20 cases with normal cervix, and 20 cases with chronic cervicitis. Uni- and multivariate analysis was applied to evaluate the prognostic significance of TGF-β1 and ERα in carcinomas. The results indicated that the positive expression of TGF-β1 in carcinomas was 71.21 %, significantly higher compared to that in the normal cervix (35 %) and chronic cervicitis (55 %) (χ 2 = 8.901, P = 0.012). Similarly, the positive expression of ERα in the carcinomas was 68.18 %, significantly higher compared to the normal cervix (35 %) and chronic cervicitis (50 %) (χ 2 = 7.693, P = 0.021). Both TGF-β1 and ERα in the carcinomas were associated with the vaginal recurrence, infection of HPV, depth of infiltration, and lymphatic metastasis (P

On the basis of introducing the working principle of the electrical fast transient pulse/burst generator, the method of combination of AC inverting and DC boosting is adopted to design a kind of DC high voltage power supply used for the electrical fast transient pulse/burst generator after the further study about the key technology of the high voltage DC power supply according to the requirements of IEC61000-4-4. The experiments show that the power output voltage reaches 5 KV, meanwhile the range of output voltage is from 0.1 KV to 5.0 KV within the linearity is about 5%, the electric power can be up to 250 watts. Above all, the design meets the requirements of the high voltage power supply for the electrical fast transient pulse/burst generator.

With the improvement of output frequency of electric fast transients (EFT) burst generator, amplitude attenuation of pulse train appeared in the high frequency. Therefore, the method of pulse width programmed digitally ,and realized by Field Programmable Gate Array (FPGA) device was put forward to overcome burst amplitude attenuation. The technology of direct digital frequency synthesis was used to adjust the output signal frequency changes. The linear array memory with one bit was adopted to store square-wave waveform, the output signal duty cycle is digital adjustable, which is achieved by changing the waveform data in the linear array memory. Brust generator is designed by using VHDL languages in the QUARTUS II 6.0 simulation platform. The simulation and experiment results show that when the frequency of the output signal reaches 1 MHz, frequency resolution arrives at 6Hz, error of pulse width is less than 10 ns.

OBJECTIVE: The effects of celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, on HeLa cervical cancer cell growth and radiosensitivity were investigated. METHODS: Cytotoxicity was quantified using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay and effects on radiosensitivity were assessed using the lethal dose, quasithreshold dose, fraction surviving after 2 Gy irradiation and the radiosensitization ratio (SER, based on average lethal dose) determined using a single-hit multitarget model. RESULTS: Celecoxib inhibited HeLa cell proliferation in a concentration- and time-dependent manner, with a half-maximal inhibitory concentration at 72 h of 44 μmol/l. Treatment with 20 μmol/l celecoxib for 72 h before irradiation was associated with an SER of 2.01. The SER of irradiated cells was 2.41 when treated with 40 μmol/l celecoxib before irradiation, 1.89 when treated simultaneously and 1.44 when treated after irradiation. Celecoxib down-regulated COX-2 and vascular endothelial growth factor C (VEGF-C) expression evaluated immunohistochemically. CONCLUSION: Celecoxib pretreatment radiosensitizes HeLa cells via a mechanism dependent on down-regulation of COX-2 and VEGF-C.