Boron neutron capture therapy induces cell cycle arrest and cell apoptosis of glioma stem/progenitor cells in vitro

BACKGROUND: Glioma stem cells in the quiescent state are resistant to clinical radiation therapy. An almost inevitable glioma recurrence is due to the persistence of these cells. The high linear energy transfer associated with boron neutron capture therapy (BNCT) could kill quiescent and proliferative cells. METHODS: The present study aimed to evaluate the effects of BNCT on glioma stem/progenitor cells in vitro. The damage induced by BNCT was assessed using cell cycle progression, apoptotic cell ratio and apoptosis-associated proteins expression. RESULTS: The surviving fraction and cell viability of glioma stem/progenitor cells were decreased compared with differentiated glioma cells using the same boronophenylalanine pretreatment and the same dose of neutron flux. BNCT induced cell cycle arrest in the G2/M phase and cell apoptosis via the mitochondrial pathway, with changes in the expression of associated proteins. CONCLUSIONS: Glioma stem/progenitor cells, which are resistant to current clinical radiotherapy, could be effectively killed by BNCT in vitro via cell cycle arrest and apoptosis using a prolonged neutron irradiation, although radiosensitivity of glioma stem/progenitor cells was decreased compared with differentiated glioma cells when using the same dose of thermal neutron exposure and boronophenylalanine pretreatment. Thus, BNCT could offer an appreciable therapeutic advantage to prevent tumor recurrence, and may become a promising treatment in recurrent glioma

A 3D study on the amplification of regional haze and particle growth by local emissions

The role of new particle formation (NPF) events and their contribution to haze formation through subsequent growth in polluted megacities is still controversial. To improve the understanding of the sources, meteorological conditions, and chemistry behind air pollution, we performed simultaneous measurements of aerosol composition and particle number size distributions at ground level and at 260 m in central Beijing, China, during a total of 4 months in 2015-2017. Our measurements show a pronounced decoupling of gas-to-particle conversion between the two heights, leading to different haze processes in terms of particle size distributions and chemical compositions. The development of haze was initiated by the growth of freshly formed particles at both heights, whereas the more severe haze at ground level was connected directly to local primary particles and gaseous precursors leading to higher particle growth rates. The particle growth creates a feedback loop, in which a further development of haze increases the atmospheric stability, which in turn strengthens the persisting apparent decoupling between the two heights and increases the severity of haze at ground level. Moreover, we complemented our field observations with model analyses, which suggest that the growth of NPF-originated particles accounted up to similar to 60% of the accumulation mode particles in the Beijing-Tianjin-Hebei area during haze conditions. The results suggest that a reduction in anthropogenic gaseous precursors, suppressing particle growth, is a critical step for alleviating haze although the number concentration of freshly formed particles (3-40 nm) via NPF does not reduce after emission controls.Peer reviewe

The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251

Abstract Background Zfx is a zinc finger protein of the Zfy family, whose members are highly conserved in vertebrates. Zfx is a shared transcriptional regulator of both embryonic stem cells (ESC) and hematopoietic stem cells (HSC), which suggests a common genetic basis of self-renewal in embryonic and adult stem cells. The level of Zfx expression correlates with aggressiveness and severity in many cancer types, including prostate cancer, breast cancer, and leukemia. However, the importance of Zfx in human glioma is largely unknown. In the present study, we examined the role of Zfx in human glioma. Methods We detected expression levels of Zfx mRNA in U251 cells, U87 cells, U373 cells, and A172 cells by semi-quantitative RT-PCR. To analyze the expression of Zfx mRNA in glioma tissues, we performed real-time quantitative PCR on 35 pathologically confirmed glioma samples (Grade I-4cases, Grade II-13cases, Grade III-11cases, and Grade IV-7cases) and on 5 noncancerous brain tissue samples. We used lentivirus-mediated small interfering RNAs (siRNAs) to knock down Zfx expression in the human malignant glioma cell line U251. Changes in Zfx target gene expression were determined by real-time RT-PCR. Cell proliferation was examined by a High Content Screening assay. DNA synthesis in proliferating cells was determined by BrdU incorporation. Cell cycle distribution and apoptosis were detected by flowcytometric analysis. Results We discovered that Zfx mRNA was expressed in U251 cells, U87 cells, U373 cells, and A172 cells. The expression level of Zfx is significantly higher in gliomas compared to noncancerous brain tissue. Using a lentivirus-based RNAi approach, Zfx expression was significantly inhibited in human glioblastoma U251 cells. The effects of Zfx knockdown on cell proliferation, cell cycle distribution, and apoptosis were assessed. Inhibition of Zfx expression in U251 cells by RNAi significantly impaired cell proliferation, increased apoptosis, and arrested cells in S phase. Conclusions The results of our study demonstrate that the Zfx gene is highly expressed in glioma tissue and in glioma cell lines. Furthermore, Zfx may play a critical role in cell proliferation, cell cycle distribution, and apoptosis of human malignant glioma cells.</p

Unexpected high contribution of in-cloud wet scavenging to nitrogen deposition induced by pumping effect of typhoon landfall in China

Atmospheric nitrogen deposition has large eco-environmental effects such as ocean acidification, eutrophication in coastal areas. However, knowledge of the source and the pathway of N deposition in coastal areas is limited, especially during tropical storms, hindering the accurate quantification of how anthropogenic activities influence the ocean ecosystem. In this study, the Nested Air Quality Prediction Modeling System was used to investigate the wet deposition of N induced by typhoon Hagupit over eastern coastal China from an in- and below-cloud process perspective. Our results reveal for the first time an enhancement mechanism of N deposition related to the ‘pumping effect’ of the typhoon. Different from the non-typhoon conditions, air pollutants in the typhoon-affected regions were pumped into the higher altitudes and deposited via the in-cloud scavenging process in the moving path of the typhoon-affected regions. This study updates our understanding of the source–receptor relationship on atmospheric wet deposition caused by tropical cyclones