NFYB-induced high expression of E2F1 contributes to oxaliplatin resistance in colorectal cancer via the enhancement of CHK1 signaling.

As a third-generation platinum drug, oxaliplatin has been widely applied in colorectal cancer (CRC); however, acquired resistance to oxaliplatin has become a major obstacle. In the present study, we found that the nuclear transcription factor Y subunit beta (NFYB) and E2F transcription factor 1 (E2F1) expression levels were significantly higher in oxaliplatin-resistant DLD1 and RKO CRC (OR-CRC) cells than in non-resistant cells. Additionally, highly expressed NFYB transactivated the E2F1 gene, which is important to maintain oxaliplatin resistance in OR-CRC cells. And Sirt1-dependent deacetylation suppresses the proapoptotic activity of E2F1 in OR-CRC cells. Through profiling the transcriptome of OR-CRC cells following E2F1 knockdown, CHK1 was identified as a target of E2F1. Deprivation of CHK1 sensitized OR-CRC cells to oxaliplatin. In vitro and in vivo phenotype experiments confirmed that an intact NFYB-E2F1-CHK1 axis was required to suppress oxaliplatin-induced apoptosis and maintain the tumorigenicity in OR-CRC cells. Knockdown of E2F1 in OR-CRC cells also decreased the expression of Pol κ, which was essential for CHK1 activation. Consistently, a high level of NFYB, E2F1, or CHK1 predicted poor survival in CRC patients, especially with oxaliplatin treatment. Collectively, the NFYB-E2F1 pathway displays a crucial role in the chemoresistance of OR-CRC by inducing the expression and activation of CHK1, providing a possible therapeutic target for oxaliplatin resistance in CRC.

Demonstration of a microwave photonic synthetic aperture radar based on photonic-assisted signal generation and stretch processing.

A microwave photonic synthetic aperture radar (MWP SAR) is developed and experimentally demonstrated. In the transmitter, microwave photonic frequency doubling is used to generate a linearly-frequency-modulated (LFM) radar signal; while in the receiver, photonic stretch processing is employed to receive the reflection signal. The presented MWP SAR operates in Ku band with a bandwidth of 600MHz, and is evaluated through a series of inverse SAR imaging tests both in a microwave anechoic chamber and in a field trial. Its imaging performance verifies that the proposed MWP SAR works perfect and shows the potential of overcoming the conventional radar bandwidth bottleneck.

Histone deacetylase 5 promotes the migration and invasion of hepatocellular carcinoma via increasing the transcription of hypoxia-inducible factor-1α under hypoxia condition.

Hypoxia plays a critical role in the progression and metastasis of hepatocellular carcinoma by activating the key transcription factor, hypoxia-inducible factor-1. This study aims to identify the novel mechanisms underlying the dysregulation of hypoxia-inducible factor-1α in hepatocellular carcinoma. We found that histone deacetylase 5, a highly expressed histone deacetylase in hepatocellular carcinoma, strengthened the migration and invasion of hepatocellular carcinoma cells under hypoxia but not normoxia condition. Furthermore, histone deacetylase 5 induced the transcription of hypoxia-inducible factor-1α by silencing homeodomain-interacting protein kinase-2 expression, which was also dependent on hypoxia. And then knockdown of hypoxia-inducible factor-1α decreased the expressions of mesenchymal markers, N-cadherin, and Vimentin, as well as matrix metalloproteinases, MMP7 and MMP9; however, the epithelial marker, E-cadherin, increased. Phenotype experiments showed that the migration and invasion of hepatocellular carcinoma cells were impaired by knockdown of histone deacetylase 5 or hypoxia-inducible factor-1α but rescued when eliminating homeodomain-interacting protein kinase-2 in hepatocellular carcinoma cells, which suggested the critical role of histone deacetylase 5-homeodomain-interacting protein kinase-2-hypoxia-inducible factor-1α pathway in hypoxia-induced metastasis. Finally, clinical analysis confirmed the positive correlation between histone deacetylase 5 and hypoxia-inducible factor-1α in hepatocellular carcinoma specimens and a relatively poor prognosis for the patients with high levels of histone deacetylase 5 and hypoxia-inducible factor-1α. Taken together, our findings demonstrated a novel mechanism underlying the crosstalk between histone deacetylase 5 and hypoxia-inducible factor-1 in hepatocellular carcinoma.

[Establishment and application of school-based health promotion and intervention model of schistosomiasis in lake-type endemic area].

OBJECTIVE: To establish an intervention model of school health promotion, and apply it in developing "schistosomiasis-free schools". METHODS: At the pilot stage, all students of Henghu primary school and Banshan primary school in Xinjian County of Jiangxi Province were selected as experiment group and control group, respectively. A baseline survey covered knowledge and attitude on schistosomiasis control, water contact behaviors and Schistosoma japonicum infection rate. Two health promotion intervention models, i.e. "information communication + training of protection skill + reward & punishment" (model A, 1993-1999) and "information communication + behavior participation + encouragement" (model B, 2000-2007), were implemented in Henghu school. The effect of two models was compared by infection rate. At the application stage, all students of 8 schools in Xinjian County, Nanchang County, and Jinxian County were chosen for evaluation of the effectiveness of Model B with same methods and index. RESULTS: Before intervention there was no significant statistical difference on the passed rate of anti-schistosomiasis knowledge, correct rate of anti-schistosomiasis attitude, frequency of infested water exposure and the infection rate between Henghu and Banshan schools (P > 0.05). In Henghu school, the intervention showed significant effect on the scores of knowledge and attitude after one year (P < 0.01), raised from 9.0% and 55.1% before intervention to 94.4% and 98.9% after intervention, respectively. The frequency of infested water exposure and the infection rate significantly decreased from 14.6% and 13.5% before intervention to 1.9% and 2.3%, respectively (P < 0.01). In 2-7 years after intervention, there were only one or two schistosomiasis cases each year. At the application stage, no schistosomiasis cases were found among Model B target population in two successive years after intervention. CONCLUSION: The practice of Model B can be extended to other schools in endemic area to develop "schistosomiasis-free schools".