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Browsing by Author "Yang, Xin"
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Item Massively-Parallelized, Deterministic Mechanoporation for Intracellular Delivery(American Chemical Society, 2020-02) Dixit, Harish G.; Starr, Renate; Dundon, Morgan L.; Pairs, Pranee I.; Yang, Xin; Zhang, Yanyan; Nampe, Daniel; Ballas, Christopher B.; Tsutsui, Hideaki; Forman, Stephen J.; Brown, Christine E.; Rao, Masaru P.; Medicine, School of MedicineMicrofluidic intracellular delivery approaches based on plasma membrane poration have shown promise for addressing the limitations of conventional cellular engineering techniques in a wide range of applications in biology and medicine. However, the inherent stochasticity of the poration process in many of these approaches often results in a trade-off between delivery efficiency and cellular viability, thus potentially limiting their utility. Herein, we present a novel microfluidic device concept that mitigates this trade-off by providing opportunity for deterministic mechanoporation (DMP) of cells en masse. This is achieved by the impingement of each cell upon a single needle-like penetrator during aspiration-based capture, followed by diffusive influx of exogenous cargo through the resulting membrane pore, once the cells are released by reversal of flow. Massive parallelization enables high throughput operation, while single-site poration allows for delivery of small and large-molecule cargos in difficult-to-transfect cells with efficiencies and viabilities that exceed both conventional and emerging transfection techniques. As such, DMP shows promise for advancing cellular engineering practice in general and engineered cell product manufacturing in particular.Item Mortality and suicide in schizophrenia: 21-year follow-up in rural China(Cambridge University Press, 2020-10-15) Ran, Mao-Sheng; Xiao, Yunyu; Fazel, Seena; Lee, Yeonjin; Luo, Wei; Hu, Shi-Hui; Yang, Xin; Liu, Bo; Brink, Maria; Chan, Sherry Kit Wa; Chen, Eric Yu-Hai; Chan, Cecilia Lai-Wan; School of Social WorkBackground Little is known about the trend and predictors of 21-year mortality and suicide patterns in persons with schizophrenia. Aims To explore the trend and predictors of 21-year mortality and suicide in persons with schizophrenia in rural China. Method This longitudinal follow-up study included 510 persons with schizophrenia who were identified in a mental health survey of individuals (≥15 years old) in 1994 in six townships of Xinjin County, Chengdu, China, and followed up in three waves until 2015. Kaplan–Meier survival analysis and Cox hazard regressions were conducted. Results Of the 510 participants, 196 died (38.4% mortality) between 1994 and 2015; 13.8% of the deaths (n = 27) were due to suicide. Life expectancy was lower for men than for women (50.6 v. 58.5 years). Males consistently showed higher rates of mortality and suicide than females. Older participants had higher mortality (hazard ratio HR = 1.03, 95% CI 1.01–1.05) but lower suicide rates (HR = 0.95, 95% CI 0.93–0.98) than their younger counterparts. Poor family attitudes were associated with all-cause mortality and death due to other causes; no previous hospital admission and a history of suicide attempts independently predicted death by suicide. Conclusions Our findings suggest there is a high mortality and suicide rate in persons with schizophrenia in rural China, with different predictive factors for mortality and suicide. It is important to develop culture-specific, demographically tailored and community-based mental healthcare and to strengthen family intervention to improve the long-term outcome of persons with schizophrenia.Item Notch signaling regulates adipose browning and energy metabolism(Nature Publishing Group, 2014-08) Bi, Pengpeng; Shan, Tizhong; Liu, Weiyi; Yue, Feng; Yang, Xin; Liang, Xin-Rong; Wang, Jinghua; Li, Jie; Carlesso, Nadia; Liu, Xiaoqi; Kuang, Shihuan; Department of Pediatrics, IU School of MedicineBeige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice results in browning of WAT and elevated expression of uncoupling protein 1 (Ucp1), a key regulator of thermogenesis. Consequently, as compared to wild-type mice, Notch mutants exhibit elevated energy expenditure, better glucose tolerance and improved insulin sensitivity and are more resistant to high fat diet-induced obesity. By contrast, adipose-specific activation of Notch1 leads to the opposite phenotypes. At the molecular level, constitutive activation of Notch signaling inhibits, whereas Notch inhibition induces, Ppargc1a and Prdm16 transcription in white adipocytes. Notably, pharmacological inhibition of Notch signaling in obese mice ameliorates obesity, reduces blood glucose and increases Ucp1 expression in white fat. Therefore, Notch signaling may be therapeutically targeted to treat obesity and type 2 diabetes.