Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC₅₀<10⁻⁴ M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.     

Microwave dielectric properties of SrLa[Ga1−x(Mg0.5Ti0.5)x]O4 and SrLa[Ga1−x(Zn0.5Ti0.5)x]O4 (x = 0.2-0.8) ceramics

SrLa[Ga_1−x(R_0.5Ti_0.5)_x]O₄ (R = Mg, Zn) ceramics were prepared by a standard solid state sintering method. The single-phase ceramics with K₂NiF₄-type layered perovskite structure and I4/mmm space group were obtained, indicating that SrLa(R_0.5Ti_0.5) and SrLaGaO₄ can form the unlimited solid solutions. With increasing x for R = Mg and Zn, ε_r increases monotonously, the Qf value first increases and then decreases, while τ_f increases from a negative to a positive value. The optimized microwave dielectric properties were obtained as following: ε_r = 23.3, Qf = 89 400 GHz, τ_f = −0.8 ppm/°C for SrLa[Ga_0.6(Mg_0.5Ti_0.5)_0.4]O₄ and ε_r = 23.3, Qf = 76 200 GHz, τ_f = 0.2 ppm/°C for SrLa[Ga_0.7(Zn_0.5Ti_0.5)_0.3]O₄, indicating that the present solid solution ceramics are the promising candidates as microwave resonator materials for the telecommunication applications.     

Y_2P_4O_(13):Eu~(3+)荧光材料的制备及其性能

采用湿化学法制备了Eu~(3+)掺杂Y_2P_4O_(13)荧光材料,通过X射线粉末衍射(XRD)、傅里叶变换红外光谱(FT-IR)和荧光光谱(FL)等手段表征制备产物的物相结构、荧光性能,并对合成原料中稀土与磷的比例(n(Y+Eu)/n(P))和pH调节剂种类对制备样品的物相结构及性能的影响进行分析。结果表明:合成原料中n(Y+Eu)/n(P)比值和pH调节剂种类直接影响着制备产物的物相结构与性能。在n(Y+Eu)/n(P)=12.1、以NH_4HCO_3为pH调节剂调节pH为6的条件下可获得正交晶系的Eu~(3+)掺杂Y_2P_4O_(13)荧光材料。所制备的Y_2P_4O_(13):2at%Eu~(3+)荧光材料在395nm光的激发下可发射出橙红光。     

Stable isotope and fatty acid compositions of monovarietal olive oils: Implications of ripening stage and climate effects as determinants in traceability studies

The quantitative variability of isotopic and fatty acid compositions in extra virgin olive oil was investigated in relation to variety, olive ripeness index and geographical origin. The study was carried out in two environments of Umbria region (central Italy), differing in annual/seasonal temperatures and rainfalls. Significant correlation was found between oil isotope compositions and climatic seasonal changes during fruit ripening. Moreover, significant isotopic differences among cultivars were related to the period of maximum oil accumulation in the fruits and to the fatty acid profile. A carbon kinetic isotopic effect could be associated with the fatty acid elongation from palmitic to stearic acid and to the unsaturation step leading from oleic to linoleic. No correlation was found between stable isotope and fatty acid compositions during fruit ripening. The analyzed cultivar and ripening effects on oil traceability issues are discussed in order to focus the resolution power of stable isotope methodologies and the possibility to distinguish monovarietal oils from the same area.     

Quantification of Mixtures of C2 and C3 Hydroxy Acids and Products of Glycerol Oxidation by High-Performance Liquid Chromatography and Quantitative 13C NMR

The aim of this study was to develop an improved general method for detecting and quantifying mixtures of hydroxy acids and other products of glycerol oxidation in aqueous media, to prevent the confusions that can occur due to similarities and interactions between these compounds depending on media conditions. Standard potential products of glycerol oxidation—glycerol, glyceraldehyde, dihydroxyacetone, glyceric acid, lactic acid, glycolic acid, glyoxylic acid, oxalic acid, tartronic acid, and mesoxalic acid—were analyzed by high-performance liquid chromatography (HPLC) and quantitative ¹³C nuclear magnetic resonance (NMR), in mixtures of known composition. The results obtained were concordant with the known compositions tested. HPLC was more accurate than quantitative ¹³C NMR for simple mixtures, but ¹³C NMR was required for complex mixtures containing dihydroxyacetone and glycerol, oxalic acid and mesoxalic acid, or glyoxylic acid and tartronic acid, pairs of compounds not well separated or detected by HPLC. As proof-of-concept, an unknown mixture generated by glycerol oxidation was analyzed by HPLC and quantitative ¹³C NMR. The results obtained were concordant and allowed accurate determination of the composition of the sample, which contained mesoxalic acid as the major product, with oxalic acid, tartronic acid, and glyceric acid as by-products.     

AC-13级配钢渣沥青混合料粘弹塑本构模型研究

为了研究钢渣沥青混合料非线性粘弹塑性变形特性,提出Schapery模型与改进Swchartz模型组合的积分型粘弹塑本构模型。采用钢渣替换AC-13级配中粒径2.36 mm以上的石灰石粗骨料,制作得到钢渣沥青混合料试件。设计并开展一系列的单轴压缩蠕变实验,通过应力递增蠕变回复实验,获得不同应力条件下材料的弹性、粘弹性应变和粘塑性应变,进而拟合确定本构模型参数。利用0.4 MPa、1.0 MPa下的蠕变回复实验验证模型有效性。结果表明,模型不仅能准确刻画钢渣沥青混合料蠕变过程中的弹性、粘弹性与粘塑性变形,还可用于预测不同应力水平下钢渣沥青混合料蠕变变形规律。     

Strengthening boron carbide through lithium dopant

The high strength of boron carbide (B₄C) is essential in its engineering applications such as wear-resistance and body armors. Here, by employing density functional theory simulations, we demonstrated that the strength of B₄C can be enhanced by doping lithium to boron-rich boron carbide (B₁₃C₂) to form r-LiB₁₃C₂. The bonding analysis on r-LiB₁₃C₂ indicates that the electron counting rule (or Wade's rule) is satisfied in r-LiB₁₃C₂ whose formula can be written as r-Li⁺(B₁₂)^2-(CB⁺C). The shear deformation on r-LiB₁₃C₂ indicates that its ideal shear strength is larger than that of B₄C because of the existing of Li dopant. The failure process of r-LiB₁₃C₂ under ideal shear deformation initiates from breaking the icosahedral-icosahedral B-B bonds. Then these B atoms react with the middle B in the C-B-C chain, resulting in the disintegration of icosahedral clusters and brittle failure. More interesting, the nanotwinned r-LiB₁₃C₂ is even stronger than r-LiB₁₃C₂ because of the directional nature of covalent bonding at the twin boundaries. This suggests that the nanotwinned r-LiB₁₃C₂ has a significant enhanced strength compared to B₄C. Our simulation results illustrate the deformation mechanism of Li-doped boron carbide and its nanotwinned microstructure. We proposed to improve the strength of boron carbide by doping Li into B₁₃C₂ and increasing its twin densities.     

2017～2018年宁波市出生儿童13价肺炎球菌结合疫苗接种率分析

目的分析2017~2018年宁波市出生儿童13价肺炎球菌结合疫苗(13-valent pneumococcal conjugate vaccine,PCV13)的接种率。方法收集宁波市“免疫预防管理信息系统”中2017~2018年出生儿童的PCV13接种信息,采用描述性流行病学方法进行统计分析。结果宁波市2017~2018年出生儿童221921人,接种PCV13有25124人,≥1剂次接种率为11.32%,其中至少接种3针PCV13的有19212人,≥3剂次接种率为8.66%。25124名<2岁儿童中,首针疫苗接种年龄≤1、2、3、4和≥5月龄者分别为5428、11287、5556、2608和245人,分别占21.60%、44.93%、22.11%、10.38%和0.98%。不同地区、户籍类型、出生年份儿童PCV13≥1和≥3剂次接种率差异均有统计学意义(P均<0.001),不同地区、性别、户籍类型、出生年份儿童PCV13首针疫苗接种年龄差异有统计学意义(P均<0.01)。结论宁波市儿童PCV13接种率处于较低水平,建议将PCV13纳入国家免疫规划项目。     

Physiochemical structure of semicoke derived from co-carbonization of coal and sawdust blends

The substitution of coal blending with sawdust had been widely investigated for metallurgical coke production. In this paper, the physiochemical structures of the semicoke derived from sawdust/coals blends co-coking were characterized by several analytical techniques including FTIR-ATR, XPS, NMR, OM, and SEM. Meanwhile, the influence of the sawdust on the physicochemical properties of the sawdust/coals blends were also investigated. Results indicated that partial substitution of coal blending with sawdust benefited from the formation of colloid and optical anisotropy due to the positive synergetic effect, whereas high proportion of sawdust (>10 wt%) inhibited the agglomeration of semi-coke. On the other hand, the semicoke consisted primarily of aromatic carbons replaced by the oxygen linked to carbons and aliphatic carbons when the coal blending was replaced by high proportion of sawdust, causing a less polyaromatic graphite-like structure formation in the semicoke.     

Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo

Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 μg) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1α)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-κB) crosstalk triggered by PMA enhanced PKCα-ERK1/2-NF-κB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1α and NF-κB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.