To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo.METHODSThe thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel diseas...To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo.METHODSThe thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBD patients on a thiopurine, 19 IBD patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBD patients on a thiopurine, 17 IBD patients not on a thiopurine, and 49 healthy screening colonoscopy recipients.RESULTSComplete blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBD patients who were taking thiopurines at the time of sampling. This reduction was restricted to CD3-negative lymphocytes, wherein both natural killer (NK) and B cells were significantly reduced among thiopurine recipients. Among CD19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in CD8+ T cells, mucosa-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells (Tregs) or naïve CD4+ T cells. However, patients with IBD had significantly more circulating FOXP3+, Helios+ Tregs and fewer iNKT and MAIT cells than healthy controls.CONCLUSIONThiopurine use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBD patients.展开更多
With the development of hydropower in the karst area of Southwest China, a series of cascade canyon reservoirs have been formed through the construction of dams. Given that hydrodynamic conditions in canyon reservoirs...With the development of hydropower in the karst area of Southwest China, a series of cascade canyon reservoirs have been formed through the construction of dams. Given that hydrodynamic conditions in canyon reservoirs play a pivotal role in controlling the spatiotemporal distribution of physical and chemical properties of the stored water, hydrodynamic characteristics are of great importance in understanding biogeochemical cycles in those reservoirs. To further this understanding, a field campaign was conducted in the Wujiangdu Reservoir of Guizhou Province. It was found that from the reservoir inlet to the front of the dam, velocity(v) was negativelycorrelated and had a logarithmic relationship with distance along the ship track(s) under dry-season flow conditions[v =-0.104 ln(s) + 0.4756]. Analysis showed that dryseason flow velocity had no significant correlation with water temperature, p H, or dissolved oxygen(DO). However, when velocity decreased to 0.061 m/s, water depth increased abruptly. In addition, DO displayed a sudden drop and the trend in p H changed from increasing to decreasing, while water temperature showed an opposite trend, indicating the existence of a transition zone from the river to the reservoir.展开更多
We have calculated the longitudinal acoustic phonon limited electron mobility of 14 twvo-dimensional semiconductors with composition of MX2, where M （= Mo, W, Sn, Hf, Zr and Pt） is the transition metal, and X is S, ...We have calculated the longitudinal acoustic phonon limited electron mobility of 14 twvo-dimensional semiconductors with composition of MX2, where M （= Mo, W, Sn, Hf, Zr and Pt） is the transition metal, and X is S, Se and Te. We treated the scattering matrix by the deformation potential approximation. We found that out of 14 compounds, MoTe2, HfSe2 and ZrSe2 are promising regarding to their possible high mobility and finite band gap. The phonon limited mobility can be above 2,500 cm^2·V^-1·s^-1 at room temperature.展开更多
基金Supported by Virginia Mason Medical Center,Digestive Disease Institute Research Grant Award,No.0506812-2011
文摘To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo.METHODSThe thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations. Blood cells from 19 IBD patients on a thiopurine, 19 IBD patients not on a thiopurine, and 38 matched healthy control subjects were analyzed by multiple multi-color flow cytometry panels to quantify the immune cell subsets contained therein, both as a percent of cells, and as an absolute cell count. Similar analyses were performed on colon biopsies from 17 IBD patients on a thiopurine, 17 IBD patients not on a thiopurine, and 49 healthy screening colonoscopy recipients.RESULTSComplete blood counts revealed lower lymphocyte, but not monocyte or granulocyte, counts in IBD patients who were taking thiopurines at the time of sampling. This reduction was restricted to CD3-negative lymphocytes, wherein both natural killer (NK) and B cells were significantly reduced among thiopurine recipients. Among CD19+ B cells, the transitional B cells were particularly depleted, being nearly absent in both blood and colon biopsies of thiopurine recipients. No differences were associated with thiopurine use in CD8+ T cells, mucosa-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, gamma/delta T cells, Th1, Th17, regulatory T cells (Tregs) or naïve CD4+ T cells. However, patients with IBD had significantly more circulating FOXP3+, Helios+ Tregs and fewer iNKT and MAIT cells than healthy controls.CONCLUSIONThiopurine use is associated with reduced B and NK cell, but not T cell, subpopulations in the blood of IBD patients.
基金financially supported by the National Key Research and Development Programme of China(2016YFA0601001)the National Natural Science Foundation of China(Grant Nos.U1612441 and 41473082)CAS"Light of West China"Program
文摘With the development of hydropower in the karst area of Southwest China, a series of cascade canyon reservoirs have been formed through the construction of dams. Given that hydrodynamic conditions in canyon reservoirs play a pivotal role in controlling the spatiotemporal distribution of physical and chemical properties of the stored water, hydrodynamic characteristics are of great importance in understanding biogeochemical cycles in those reservoirs. To further this understanding, a field campaign was conducted in the Wujiangdu Reservoir of Guizhou Province. It was found that from the reservoir inlet to the front of the dam, velocity(v) was negativelycorrelated and had a logarithmic relationship with distance along the ship track(s) under dry-season flow conditions[v =-0.104 ln(s) + 0.4756]. Analysis showed that dryseason flow velocity had no significant correlation with water temperature, p H, or dissolved oxygen(DO). However, when velocity decreased to 0.061 m/s, water depth increased abruptly. In addition, DO displayed a sudden drop and the trend in p H changed from increasing to decreasing, while water temperature showed an opposite trend, indicating the existence of a transition zone from the river to the reservoir.
文摘We have calculated the longitudinal acoustic phonon limited electron mobility of 14 twvo-dimensional semiconductors with composition of MX2, where M （= Mo, W, Sn, Hf, Zr and Pt） is the transition metal, and X is S, Se and Te. We treated the scattering matrix by the deformation potential approximation. We found that out of 14 compounds, MoTe2, HfSe2 and ZrSe2 are promising regarding to their possible high mobility and finite band gap. The phonon limited mobility can be above 2,500 cm^2·V^-1·s^-1 at room temperature.
