EPR properties of mixed-valent μ-oxo and μ-hydroxo dinuclear iron complexes produced by radiolytic reduction at 77 K

 Radiolytic reduction at 77 K of oxo-/hydroxo-bridged dinuclear iron(III) complexes in frozen solutions forms kinetically stabilized, mixed-valent species in high yields that model the mixed-valent sites of non-heme, diiron proteins. The mixed-valent species trapped at 77 K retain ligation geometry similar to the initial diferric clusters. The shapes of the mixed-valent EPR signals depend strongly on the bridging ligands. Spectra of the Fe(II)OFe(III) species reveal an S=1/2 ground state with small g-anisotropy as characterized by the uniaxial component (g _z –g _av /2<0.03) observable at temperatures as high as ∼100 K. In contrast, hydroxo-bridged mixed-valent species are characterized by large g-anisotropy (g _z –g _av /2>0.03) and are observable only below 30 K. Annealing at higher temperatures causes structural relaxation and changes in the EPR characteristics. EPR spectral properties allow the oxo- and hydroxo-bridged, mixed-valent diiron centers to be distinguished from each other and can help characterize the structure of mixed-valent centers in proteins. Received: 27 June 1998 / Accepted: 25 February 1999     

Hydroxysafflor yellow A (HYSA) inhibited the proliferation and differentiation of 3T3-L1 preadipocytes

Hydroxysafflor yellow A (HSYA), a main component of safflor yellow, has been demonstrated to prevent steroid-induced avascular necrosis of femoral head by inhibiting primary bone marrow-derived mesenchymal stromal cells adipogenic differentiation induced by steroid. In this study, we investigate the effect of HSYA on the proliferation and adipogenesis of mouse 3T3-L1 preadipocytes. The effects of HSYA on proliferation and differentiation of 3T3-L1 cells and its possible mechanism were studied by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide spectrophotometry, Oil Red O staining, intracellular triglyceride assays, real-time quantitative RT-PCR, transient transfection and dual luciferase reporter gene methods. HSYA inhibited the proliferation of 3T3-L1 preadipocytes and cell viability greatly decreased in a dose and time dependent manner. HSYA (1 mg/l) notably reduced the amount of intracellular lipid and triglyceride content in adipocytes by 21.3 % (2.13 ± 0.36 vs 2.71 ± 0.40, P < 0.01) and 22.6 % (1.33 ± 0.07 vs 1.72 ± 0.07, P < 0.01) on days 8 following the differentiation, respectively. HSYA (1 mg/l) significantly increased hormone-sensitive lipase (HSL) mRNA expression and promoter activities by 2.4- and 1.55-fold, respectively (P < 0.01), in differentiated 3T3-L1 adipocytes. HSYA inhibits the proliferation and adipogenesis of 3T3-L1 preadipocytes. The inhibitory action of HYSA on adipogenesis may be due to the promotion of lipolytic-specific enzyme HSL expression by increasing HSL promoter activity.     

A Complex Role of Herpes Viruses in the Disease Process of Multiple Sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). Neither the antigenic target(s) nor the cell population(s) responsible for CNS tissue destruction in MS have been fully defined. The objective of this study was to simultaneously determine the antigen (Ag)-specificity and phenotype of un-manipulated intrathecal CD4⁺ and CD8⁺ T cells of patients with relapsing-remitting and progressive MS compared to subjects with other inflammatory neurological diseases. We applied a novel Ag-recognition assay based on co-cultures of freshly obtained cerebrospinal fluid T cells and autologous dendritic cells pre-loaded with complex candidate Ag''s. We observed comparably low T cell responses to complex auto-Ag''s including human myelin, brain homogenate, and cell lysates of apoptotically modified oligodendroglial and neuronal cells in all cohorts and both compartments. Conversely, we detected a strong intrathecal enrichment of Epstein-Barr virus- and human herpes virus 6-specific (but not cytomegalovirus-specific) reactivities of the Th1-phenotype throughout all patients. Qualitatively, the intrathecal enrichment of herpes virus reactivities was more pronounced in MS patients. This enrichment was completely reversed by long-term treatment with the IL-2 modulating antibody daclizumab, which strongly inhibits MS disease activity. Finally, we observed a striking discrepancy between diminished intrathecal T cell proliferation and enhanced cytokine production of herpes virus-specific T cells among progressive MS patients, consistent with the phenotype of terminally differentiated cells. The data suggest that intrathecal administration of novel therapeutic agents targeting immune cells outside of the proliferation cycle may be necessary to effectively eliminate intrathecal inflammation in progressive MS.     

Stable Dynamics Performance and High Efficiency of ABX3‐Type Super‐Alkali Perovskites First Obtained by Introducing H5O2 Cation

Developing new ABX₃‐type perovskites is very important for expanding the family of perovskites and obtaining excellent light absorbing material. One strategy is replacing A site atoms with super‐alkali atoms for the perovskites, but super‐alkali perovskites with stable dynamics performance and high efficiency have not been found until now. Herein, massive super‐alkalis, such as Li₃O, Li₂F, H₅O₂, and so on, are introduced into the cubic CH₃NH₃PbI₃ perovskites, and the perovskites with these super‐alkalis are systematically studied by using ab initio molecular dynamics simulation and density functional theory based first principles calculations. Calculated results indicate that the perovskites with the super‐alkalis including metal atoms show unstable dynamics performance under normal temperature and pressure. On the contrary, the first obtainable super‐alkali perovskites of cubic H₅O₂MBr₃ (M = Ge, Sn, Pb) and H₅O₂PbI₃ show stable dynamics performance. They also show suitable tolerance factors, negative formation energies, tunable direct band gaps, and small effective hole and electron masses. Moreover, the calculated power conversion efficiencies of 23.17% and 22.83% are obtained for the single‐junction solar cells based on the cubic H₅O₂SnBr₃ and H₅O₂PbBr₃ perovskites, respectively.     

Leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry. Part II

Aminopeptidase N (APN) has been proved to be deeply associated with cancer angiogenesis, metastasis and invasion. Therefore, APN gains increasing attention as a promising anti-tumor target. In the current study, we report the design, synthesis, biological evaluation and structure-activity relationship of one new series of leucine ureido derivatives containing the 1,2,3-triazole moiety. Among them, compound 31f was identified as the best APN inhibitor with IC₅₀ value being two orders of magnitude lower than that of the positive control bestatin. Compound 31f possessed selective cytotoxicity to several tumor cell lines over the normal cell line human umbilical vein endothelial cells (HUVECs). Notably, when combined with 5-fluorouracil (5-Fu), 31f exhibited synergistic anti-proliferation effect against several tumor cell lines. At the same concentration, 31f exhibited much better anti-angiogenesis activities than bestatin in the HUVECs capillary tube formation assay and the rat thoracic aorta rings test. In the in vitro anti-invasion assay, 31f also exhibited superior potency over bestatin. Moreover, considerable in vivo antitumor potencies of 31f alone or in combination with 5-Fu were observed without significant toxic signs in a mouse heptoma H22 tumor transplant model.     

基于光纤测温技术的城市地表温度精细化分析

城市景观空间构型与热岛效应关联性较强,研究高时空分辨率的城市不同下垫面地表温度变化,可以更加精细地掌握城市热环境的时空特征。光纤温度传感系统具有实时在线、测温精度高和不受电磁干扰等优点,具备实时、在线、连续开展城市地表温度在线监测的能力。在北京市通州某园区内,选择有太阳辐射的4个时段,对多种类型下垫面的地表温度进行了时间间隔为1 min、空间间隔为1 m的连续4 h、总长度为100 m的实时在线监测。通过对监测时间段内不同类型下垫面地表温度的变化分析,发现这种分布式光纤测温系统能够有效辨识小尺度下地表温度的时间变化性和空间变化性,能有效区分透水和不透水地面,并监测和评估沥青马路地表温度的升温速率以及遮荫效果对地表温度的降温作用。同时,这种监测模式获取的数据能够对地表温度空间序列开展自相关分析,进一步验证了地表温度空间序列在较小尺度上仍然具有自相关性,且距离越近,相关性越大。研究同时表明,光纤测温技术能直接地获取城市热环境的现场真实数据,可以有效应用于小尺度城市热环境的观测与研究。