An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is described here, which involves introduction of a chiral group, formation and separation of diasteroisomers and final transformation of an amide to an ester. The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis of their intermediates.
To investigate the effects of letherally total body irradiation (TBI) on distribution of T-lymphocyte subtypes and their cytokine expression.The BALB/c mice were divided randomly into ⁶⁰Co gamma rays TBI group and control group. Mice were sacrificed 7 days after irradiation. The lymphocytes in spleens, mesenteric lymphonodes, livers and bone marrow were collected and counted. Changes of CD4(+) T and CD8(+) T cell subsets as well as the expressions of IFN-γ and IL-17 were analyzed by flow cytometry.(1)Compared with control group, the total number of lymphocytes in marrow, spleen, lymph node and liver distinctively decreased in TBI group [(5.34±1.14)×10⁵ vs (3.08±1.13)×10⁷, (2.10±0.54)×10⁵ vs (2.71±0.83)×10⁷, (5.89±1.07)×10⁵ vs (7.92±1.15)×10⁷ and (3.45±1.01)×10⁵ vs (7.44±0.79)×10⁶, respectively, and the significant differences were observed between two groups in each organ (P<0.05)]. (2)The level of IFN-γ produced by CD4(+) T in spleen, lymph node and liver elevated in TBI group compared to control group, which were (20.77±2.03)% vs (3.69±3.13)%, (6.28±0.46)% vs (1.11±0.17)%, (27.24±5.79)% vs (9.01±1.24)% respectively, the differences between two groups in each organ were significant (P<0.05). (3)Percentages of IFN-γ(+)CD8(+) T in spleen, lymph node and liver in TBI group increased compared to control group [(52.40±9.26)% vs (43.06±1.04)%, (33.56±5.02)% vs (21.83±4.22)%, and (44.27±8.97)% vs (19.32±3.11)%, respectively, and the differences between two groups in each tissue were significant (P<0.05)]. (4)However, IL-17A expressions in CD4(+) T and CD8(+) T cells from spleen and liver were lower than those in control group.TBI induced the reduction of lymphocytes and the expansion of IFN-γ producing Th1 and Tc1 effector cells in mice.
KRAS activation is driven by GTP binding, leading to increased flexibility and dynamic network reorganization. This study highlights the critical roles of switch I, switch II, and P-loop in mediating allosteric signaling pathways.
1. The expression of insulin-like growth factor-1 (IGF1) and myostatin (MSTN) mRNA in breast and leg muscle was quantified in 70-d-old Taihu and Wanxi geese by using a Multiplex Competitive Fluorescent–PCR method and the correlations between mRNA levels and carcass traits were analysed.2. IGF1 mRNA expression in breast muscle in Taihu geese was significantly higher than that in Wanxi geese and the MSTN mRNA level in leg muscle in Taihu geese was significantly higher than that in Wanxi geese.3. There was no significant difference in breast muscle MSTN or leg muscle IGF1 mRNA expression between the two breeds.4. Within the same breed, the IGF1 mRNA expression in leg muscle of male geese was significantly higher than that in female geese, and MSTN mRNA expression in leg muscle was significantly higher than that in breast muscle.5. There was no difference in the IGF1 mRNA expression between tissues.6. There was a positive correlation between IGF1 mRNA and MSTN mRNA and a negative correlation between IGF1 mRNA expression of breast muscle and leg muscle ratio.7. In Wanxi geese, MSTN mRNA expression in leg muscle was negatively associated with body weight and leg muscle weight.
This study aimed to evaluate the efficacy and safety of calcium ionophore during assisted oocyte activation (AOA). This meta-analysis contained randomized controlled trials and prospective observational and retrospective trials. The summary odds ratio (OR) with 95% confidence intervals (CIs) was calculated for clinical pregnancy rate and live birth rate. Both fixed and random effects models were applied. A total of 22 studies were included into this meta-analysis. Seventeen of the included studies showed that calcium ionophore increased the clinical pregnancy rate (OR, 2.14; 95% CI, 1.38-3.31). Similarly, 14 studies indicated that AOA with calcium ionophore during intracytoplasmic sperm injection (ICSI) improved the live birth rate considerably (OR, 2.65; 95% CI, 1.53-4.60). Moreover, fertilization, blastocyst formation, and implantation rate were higher after using AOA with calcium ionophore combined with ICSI. In addition, calcium ionophore did not increase top-quality embryo rate, cleavage rate, miscarriage rate, congenital birth defects, and neonatal sex ratio. Therefore, calcium ionophore followed by ICSI not only significantly improved live birth and overall pregnancy, but also did not affect the incidence of miscarriage, congenital birth defects, and neonatal sex ratio. This meta-analysis indicated that using calcium ionophore to activate oocytes was beneficial for couples with poor fertilization rates following ICSI.
This study was purposed to explore the cellular source of IL-22 in graft versus host disease (GVHD) mouse following allo-genetic bone marrow transplantation. BALB/c and C57BL/6 mice were used as recipients and donors, respectively. GVHD model was established by irradiated BABL/c mice inoculated with mixed suspension of C57BL/6 bone marrow cells and splenic lymphocytes. The mice were divided into normal group (normal), total body irradiated group (TBI), bone marrow cell-transplanted group (BMT), and the combination of bone marrow cell and splenic lymphocytes-induced GVHD group (BS). The level of IL-22 in plasma was detected by ELISA. The cellular source of IL-22 and IL-22(+) subsets were detected by flow cytometry. The results showed that compared with normal mice, the level of IL-22 in plasma from BS mice was the highest (P < 0.01). All the lymphocytes of spleen, lymph nodes and peripheral blood from BS mice could produce IL-22, in which the percentage of IL-22(+)CD4(+) T cell was higher than that of IL-22(+)CD8(+) T cells. Not only Th22 cells but also Th1 and Th17 cells were the cellular source of IL-22 in GVHD mice. It is concluded that the high level of IL-22 has been found in mice with GVHD, which mainly originates from IFN-γ(-)IL-17(-)IL-22(+) Th22 cells.
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