分类: 生物学 >> 生物物理学 >> 神经科学 提交时间: 2016-05-05
摘要: Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. We therefore established a pre-clinical model in aged C57BL/6 mice and aimed to investigate the effects of surgical stress and psychological stress on learning and memory function and the possible roles of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. The surgical stress was induced by abdominal surgery under local anesthesia, and the psychological stress was induced by a communication box. Cognitive functions and markers of the AKT/mTOR pathway were assessed at 1, 3 and 7 days following the stress. The impairments of learning and memory function existed for up to 7 days following surgical stress and surgical stress plus psychological stress, whereas the psychological stress did not affect the cognitive function alone or combined with surgical stress. Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD. (C) 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
分类: 物理学 分类: 物理学 >> 基本粒子与场物理学 提交时间: 2016-12-28
摘要: In minimal supersymmetric standard model the R-parity violating interactions can induce anomalous top pair productions at the LHC through the t-channel process d_R \bar d_R -> t_L \bar t_L by exchanging a slepton or u-channel process d_R \bar d_R -> t_R \
分类: 动力与电气工程 >> 工程热物理学 提交时间: 2017-06-22 合作期刊: 《热科学学报》
摘要: In order to expand the study on flow instability of supercritical circulating fluidized bed (CFB) boiler, a new numerical computational model considering the heat storage of the tube wall metal was presented in this paper. The lumped parameter method was proposed for wall temperature calculation and the single channel model was adopted for the analysis of flow instability. Based on the time-domain method, a new numerical computational program suitable for the analysis of flow instability in the water wall of supercritical CFB boiler with annular furnace was established. To verify the code, calculation results were respectively compared with data of commercial software. According to the comparisons, the new code was proved to be reasonable and accurate for practical engineering application in analysis of flow instability. Based on the new program, the flow instability of supercritical CFB boiler with annular furnace was simulated by time-domain method. When 1.2 times heat load disturbance was applied on the loop, results showed that the inlet flow rate, outlet flow rate and wall temperature fluctuated with time eventually remained at constant values, suggesting that the hydrodynamic flow was stable. The results also showed that in the case of considering the heat storage, the flow in the water wall is easier to return to stable state than without considering heat storage.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: Cancers remain a major public health problem worldwide, which still require profound research in both the basic and preclinical fields. Patient-derived xenograft(PDX) models are created when cancerous cells or tissues from patients' primary tumors are implanted into immunodeficient mice to simulate human tumor biology in vivo, which have been extensively used in cancer research. The routes of implantation appeared to affect the outcome of PDX research, and there has been increasing applications of patient-derived orthotopic xenograft (PDOX) models. In this review, we firstly summarize the methodology to establish PDX models and then go over recent application and function of PDX models in basic cancer research on the areas of cancer characterization, initiation, proliferation, metastasis, and tumor microenvironment and in preclinical explorations of anti-cancer targets, drugs, and therapeutic strategies and finally give our perspectives on the future prospects of PDX models.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: Chimeric antigen receptor (CAR) T-cell immunotherapies have shown unprecedented success in treating leukemia but limited clinical efficacy in solid tumors. Here, we generated 1928zT2 and m28zT2, targeting CD19 and mesothelin, respectively, by introducing the Toll/interleukin-1 receptor domain of Toll-like receptor 2 (TLR2) to 1928z and m28z. T cells expressing 1928zT2 or m28zT2 showed improved expansion, persistency and effector function against CD19+ leukemia or mesothelin+ solid tumors respectively in vitro and in vivo. In a patient with relapsed B-cell acute lymphoblastic leukemia, a single dose of 5 * 104/kg 1928zT2 T cells resulted in robust expansion and leukemia eradication and led to complete remission. Hence, our results demonstrate that TLR2 signaling can contribute to the efficacy of CAR T cells. Further clinical trials are warranted to establish the safety and efficacy of this approach.Leukemia advance online publication, 25 August 2017; doi:10.1038/leu.2017.249.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide. This peptide was followed by the luciferase coding sequence to recapitulate the expression of the Ucp1 gene at the transcriptional and translational levels. With this mouse, we discovered a cold-sensitive brown/beige adipose depot underneath the skin of the ears, which we named uBAT. Because of the sensitivity and high dynamic range of luciferase activity, the Ucp1-2A-luciferase mouse is useful for both in vitro quantitative determination and in vivo visualization of nonshivering thermogenesis. With the use of this model, we identified and characterized axitinib, an oral small-molecule tyrosine kinase inhibitor, as an effective browning agent.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: The Chang'E 5 (CE-5) samples represent the youngest mare basalt ever known and provide an access into the late lunar evolution. Recent studies have revealed that CE-5 basalts are the most evolved lunar basalt, yet controversy remains over the nature of their mantle sources. Here we combine Fe and Mg isotope analyses with a comprehensive study of petrology and mineralogy on two CE-5 basalt clasts. These two clasts have a very low Mg# (~29) and show similar Mg isotope compositions with Apollo low-Ti mare basalts as well as intermediate TiO2 and Fe isotope compositions between low-Ti and high-Ti mare basalts. Fractional crystallization or evaporation during impact cannot produce such geochemical signatures which otherwise indicate a hybrid mantle source that incorporates both early- and late-stage lunar magma ocean (LMO) cumulates. Such a hybrid mantle source would be also compatible with the KREEP-like REE pattern of CE-5 basalts. Overall, our new Fe-Mg isotope data highlight the role of late LMO cumulate for the generation of young lunar volcanism.
分类: 天文学 >> 天文学 提交时间: 2023-02-19
摘要: The Chang'E 5 (CE-5) samples represent the youngest mare basalt ever known and provide an access into the late lunar evolution. Recent studies have revealed that CE-5 basalts are the most evolved lunar basalt, yet controversy remains over the nature of their mantle sources. Here we combine Fe and Mg isotope analyses with a comprehensive study of petrology and mineralogy on two CE-5 basalt clasts. These two clasts have a very low Mg# (~29) and show similar Mg isotope compositions with Apollo low-Ti mare basalts as well as intermediate TiO2 and Fe isotope compositions between low-Ti and high-Ti mare basalts. Fractional crystallization or evaporation during impact cannot produce such geochemical signatures which otherwise indicate a hybrid mantle source that incorporates both early- and late-stage lunar magma ocean (LMO) cumulates. Such a hybrid mantle source would be also compatible with the KREEP-like REE pattern of CE-5 basalts. Overall, our new Fe-Mg isotope data highlight the role of late LMO cumulate for the generation of young lunar volcanism.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: Background: The adapter proteins Appl1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine domain, and leucine zipper motif 1) and Appl2 are highly homologous and involved in several signaling pathways. While previous studies have shown that Appl1 plays a pivotal role in adiponectin signaling and insulin secretion, the physiological functions of Appl2 are largely unknown. Results: In the present study, the role of Appl2 in sepsis shock was investigated by using Appl2 knockout (KO) mice. When challenged with lipopolysaccharides (LPS), Appl2 KO mice exhibited more severe symptoms of endotoxin shock, accompanied by increased production of proinflammatory cytokines. In comparison with the wild-type control, deletion of Appl2 led to higher levels of TNF-alpha and IL-1 beta in primary macrophages. In addition, phosphorylation of Akt and its downstream effector NF-kappa B was significantly enhanced. By co-immunoprecipitation, we found that Appl2 and Appl1 interacted with each other and formed a complex with PI3K regulatory subunit p85 alpha, which is an upstream regulator of Akt. Consistent with these results, deletion of Appl1 in macrophages exhibited characteristics of reduced Akt activation and decreased the production of TNF alpha and IL-1 beta when challenged by LPS. Conclusions: Results of the present study demonstrated that Appl2 is a critical negative regulator of innate immune response via inhibition of PI3K/Akt/NF-kappa B signaling pathway by forming a complex with Appl1 and PI3K.Conclusions: Results of the present study demonstrated that Appl2 is a critical negative regulator of innate immune response via inhibition of PI3K/Akt/NF-kappa B signaling pathway by forming a complex with Appl1 and PI3K.
分类: 生物学 >> 生态学 提交时间: 2017-11-17
摘要: In recent years, immunotherapies, such as those involving chimeric antigen receptor (CAR) T cells, have become increasingly promising approaches to non-small-cell lung cancer (NSCLC) treatment. In this study, we explored the antitumor potential of prostate stem cell antigen (PSCA)-redirected CAR T and mucin 1 (MUC1)-redirected CAR T cells in tumor models of NSCLC. First, we generated patient-derived xenograft (PDX) mouse models of human NSCLC that maintained the antigenic profiles of primary tumors. Next, we demonstrated the expression of PSCA and MUC1 in NSCLC, followed by the generation and confirmation of the specificity and efficacy of PSCA-and MUC1-targeting CAR T cells against NSCLC cell lines in vitro. Finally, we demonstrated that PSCA-targeting CAR T cellscould efficiently suppress NSCLC tumor growth in PDX mice and synergistically eliminate PSCA(+)MUC1(+) tumors when combined with MUC1-targeting CAR Tcells. Taken together, our studies demonstrate that PSCA and MUC1 are both promising CAR T cell targets in NSCLC and that the combinatorial targeting ofthese antigens could further enhance the antitumor efficacy of CAR T cells.