分类: 生物学 >> 生物物理学 提交时间: 2016-05-11
摘要: Group 3 innate lymphoid cells (ILC3s) have demonstrated roles in promoting antibacterial immunity, maintaining epithelial barrier function, and supporting tissue repair. ILC3 alterations are associated with chronic inflammation and inflammatory disease; however, the characteristics and relevant regulatory mechanisms of this cell population in HIV-1 infection are poorly understood due in part to a lack of a robust model. Here, we determined that functional human ILC3s develop in lymphoid organs of humanized mice and that persistent HIV-1 infection in this model depletes ILC3s, as observed in chronic HIV-1-infected patients. In HIV-1-infected mice, effective antiretroviral therapy reversed the loss of ILC3s. HIV-1-dependent reduction of ILC3s required plasmacytoid dendritic cells (pDCs), IFN-I, and the CD95/FasL pathway, as targeted depletion or blockade of these prevented HIV-1-induced ILC3 depletion in vivo and in vitro, respectively. Finally, we determined that HIV-1 infection induces CD95 expression on ILC3s via a pDC- and IFN-I-dependent mechanism that sensitizes ILC3s to undergo CD95/FasL-mediated apoptosis. We conclude that chronic HIV-1 infection depletes ILC3s through pDC activation, induction of IFN-I, and CD95-mediated apoptosis.
分类: 生物学 >> 植物学 提交时间: 2017-07-14
摘要: Three new cycloheximide congeners, 2,3-dehydro--epi-isocycloheximide (1), (E)- and (Z)-2,3-dehydro-anhydrocycloheximides (2 and 3), together with three known compounds, anhydroisoheximide (4), cycloheximide (5), and isocycloheximide (6), were obtained from the cultures of Streptomyces sp. SC0581. Their structures were elucidated by extensive spectroscopic analysis in combination with theoretical conformational analysis and ECD computations. The photoinduced interconversion between 2 and 3 was observed and verified and the possible reaction path and mechanism were proposed by theoretical computations. The antifungal and cytotoxic activities of 1–6 were evaluated and suggested that 2,3-dehydrogenation results in the loss of the activities and supported the OH- is important to the activities of cycloheximide congeners.
分类: 核科学技术 >> 裂变堆工程技术 提交时间: 2021-12-31
摘要: The advantages of once-through molten salt reactors include readily available fuel, low nuclear proliferation risk, and low technical difficulty. It is potentially the most easily commercialized fuel cycle mode for molten salt reactors. However, there are some problems in the parameter selection of once-through molten salt reactors, and the relevant burnup optimization work requires further analysis. This study examined a once-through graphite moderated molten salt reactor using enriched uranium and thorium. The fuel volume fraction (VF), initial heavy nuclei concentration (HN0), feeding uranium enrichment (EFU), volume of the reactor core, and fuel type were changed to obtain the optimal conditions for burnup. We found an optimal region for VF and HN0 in each scheme, and the location and size of the optimal region changed with the degree of EFU, core volume, and fuel type. The recommended core schemes provide a reference for the core design of a once-through molten salt reactor.
分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Extensive accumulation of neurofibrillary tangles (NFTs) consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimers disease. However, no PET probe is currently available for selective detection of NFTs in the living human brain. [18F]-THK523 was developed as a potential in vivo imaging probe for tau pathology. In this paper, we report a new protected precursor, 2-((2-(4-(( tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (THK-7), instead of 2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (BF241), and an improved automated radiosynthesis of [18F]-THK523 and the study on chemical kinetics of the labeling reaction of [18F]-THK523, with high-yield (705%, n=6, decay-corrected to end of bombardment), and high radiochemical purity (>90%) and specific activity (2.5 0.5 Ci/mol) from protected precursor on fully automated module at the end of radiosynthesis (4555 min). The chemical kinetics for [18F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.
分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimers disease (AD). The existence of neurofibrillary tangles (NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD. However, no clinically approved positron emission tomography (PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.