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Browsing by Author "Zhao, Lei"
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Item Design, synthesis and in vitro anti-Zika virus evaluation of novel Sinefungin derivatives(Elsevier, 2018-09) Tao, Zeyu; Cao, Ruiyuan; Yan, Yunzheng; Huang, Guocheng; Lv, Kai; Li, Wei; Geng, Yunhe; Zhao, Lei; Wang, Apeng; He, Qinhao; Yang, Jingjing; Fan, Shiyong; Huang, Menghao; Guo, Huiyuan; Zhong, Wu; Lu, Mingliang; Medicine, School of MedicineWe report herein the design and synthesis of a series of novel Sinefungin (SIN) derivatives, based on the structures of SIN and its analogue EPZ004777. Our results reveal that target compounds 1ad-af, 1ba-bb and 1bf-bh show better activity (IC50 = 4.56–20.16 μM) than EPZ004777 (IC50 = 35.19 μM). Surprisingly, SIN was founded to be not as active (IC50 > 50 μM) as we and other research groups predicted. Interestingly, the intermediates 9a-b and 11b display potent anti-ZIKV potency (IC50 = 6.33–29.98 μM), and compound 9a also exhibits acceptable cytotoxicity (CC50 > 200 μM), suggesting their promising potential to be leads for further development.Item Genomic Analysis of Human Brain Metastases Treated with Stereotactic Radiosurgery Under the Phase-II Clinical Trial (NCT03398694) Reveals DNA Damage Repair at the Peripheral Tumor Edge(medRxiv, 2023-04-24) Shireman, Jack M.; White, Quinn; Agrawal, Namita; Ni, Zijian; Chen, Grace; Zhao, Lei; Gonugunta, Nikita; Wang, Xiaohu; Mccarthy, Liam; Kasulabada, Varshitha; Pattnaik, Akshita; Ahmed, Atique U.; Miller, James; Kulwin, Charles; Cohen-Gadol, Aaron; Payner, Troy; Lin, Chih-Ta; Savage, Jesse J.; Lane, Brandon; Shiue, Kevin; Kamer, Aaron; Shah, Mitesh; Iyer, Gopal; Watson, Gordon; Kendziorski, Christina; Dey, Mahua; Radiation Oncology, School of MedicineStereotactic Radiosurgery (SRS) is one of the leading treatment modalities for oligo brain metastasis (BM), however no comprehensive genomic data assessing the effect of radiation on BM in humans exist. Leveraging a unique opportunity, as part of the clinical trial (NCT03398694), we collected post-SRS, delivered via Gamma-knife or LINAC, tumor samples from core and peripheral-edges of the resected tumor to characterize the genomic effects of overall SRS as well as the SRS delivery modality. Using these rare patient samples, we show that SRS results in significant genomic changes at DNA and RNA levels throughout the tumor. Mutations and expression profiles of peripheral tumor samples indicated interaction with surrounding brain tissue as well as elevated DNA damage repair. Central samples show GSEA enrichment for cellular apoptosis while peripheral samples carried an increase in tumor suppressor mutations. There are significant differences in the transcriptomic profile at the periphery between Gamma-knife vs LINAC.Item Spatial transmission and meteorological determinants of tuberculosis incidence in Qinghai Province, China: a spatial clustering panel analysis(Springer (Biomed Central Ltd.), 2016-06-02) Rao, Hua-Xiang; Zhang, Xi; Zhao, Lei; Yu, Juan; Ren, Wen; Zhang, Xue-Lei; Ma, Yong-Cheng; Shi, Yan; Ma, Bin-Zhong; Wang, Xiang; Wei, Zhen; Wang, Hua-Fang; Qiu, Li-Xia; Department of Epidemiology, Richard M. Fairbanks School of Public HealthBACKGROUND: Tuberculosis (TB) is the notifiable infectious disease with the second highest incidence in the Qinghai province, a province with poor primary health care infrastructure. Understanding the spatial distribution of TB and related environmental factors is necessary for developing effective strategies to control and further eliminate TB. METHODS: Our TB incidence data and meteorological data were extracted from the China Information System of Disease Control and Prevention and statistical yearbooks, respectively. We calculated the global and local Moran's I by using spatial autocorrelation analysis to detect the spatial clustering of TB incidence each year. A spatial panel data model was applied to examine the associations of meteorological factors with TB incidence after adjustment of spatial individual effects and spatial autocorrelation. RESULTS: The Local Moran's I method detected 11 counties with a significantly high-high spatial clustering (average annual incidence: 294/100 000) and 17 counties with a significantly low-low spatial clustering (average annual incidence: 68/100 000) of TB annual incidence within the examined five-year period; the global Moran's I values ranged from 0.40 to 0.58 (all P-values < 0.05). The TB incidence was positively associated with the temperature, precipitation, and wind speed (all P-values < 0.05), which were confirmed by the spatial panel data model. Each 10 °C, 2 cm, and 1 m/s increase in temperature, precipitation, and wind speed associated with 9 % and 3 % decrements and a 7 % increment in the TB incidence, respectively. CONCLUSIONS: High TB incidence areas were mainly concentrated in south-western Qinghai, while low TB incidence areas clustered in eastern and north-western Qinghai. Areas with low temperature and precipitation and with strong wind speeds tended to have higher TB incidences.