Effects of Eltrombopag on In Vitro Macrophage Polarization in Pediatric Immune Thrombocytopenia

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug.     

AP2M1 Supports TGF-β Signals to Promote Collagen Expression by Inhibiting Caveolin Expression

The extracellular matrix (ECM) is important for normal development and disease states, including inflammation and fibrosis. To understand the complex regulation of ECM, we performed a suppressor screening using Caenorhabditis elegans expressing the mutant ROL-6 collagen protein. One cuticle mutant has a mutation in dpy-23 that encodes the μ2 adaptin (AP2M1) of clathrin-associated protein complex II (AP-2). The subsequent suppressor screening for dpy-23 revealed the lon-2 mutation. LON-2 functions to regulate body size through negative regulation of the tumor growth factor-beta (TGF-β) signaling pathway responsible for ECM production. RNA-seq analysis showed a dominant change in the expression of collagen genes and cuticle components. We noted an increase in the cav-1 gene encoding caveolin-1, which functions in clathrin-independent endocytosis. By knockdown of cav-1, the reduced TGF-β signal was significantly restored in the dpy-23 mutant. In conclusion, the dpy-23 mutation upregulated cav-1 expression in the hypodermis, and increased CAV-1 resulted in a decrease of TβRI. Finally, the reduction of collagen expression including rol-6 by the reduced TGF-β signal influenced the cuticle formation of the dpy-23 mutant. These findings could help us to understand the complex process of ECM regulation in organism development and disease conditions.     

Reformate-enriched gasoline-ethanol blends: Volatility criteria and azeotrope formation

Four hydrocarbon-base gasolines (BG) were formulated from the local refinery streams; isomerate, reformate, and light naphtha. The formulations were enriched in reformate. Each of these BG formulations was blended with 10 vol% of anhydrous ethanol. From ASTM-D86 distillation data, eight distillation curves were constructed and the trend line equations of these distillation curves were developed. Also, the area under each distillation curve (AUDC) was calculated through calculus definite integration technique. Subsequently, the area due to azeotrope formation (ADAF) for each BG-ethanol blend was estimated. In this paper, the influence of increasing reformate proportions on the created positive azeotrope, was studied. Also the influence of increasing reformate proportions on vapor pressure, Temperature for the vapor-liquid ratio of 20, T50 and octane number was studied. The results show that the R² values of the distillation curve equations prove the reliability of the fits. Also, increasing reformate proportion in the fuel blend improves the octane number while increasing reformate proportion decreases the volatility of the fuel formulation.     

Electron Paramagnetic Resonance and Magnetic Circular Dichroism Spectra of the Nitrogenase M Cluster Precursor Suggest Sulfur Migration upon Oxidation: A Proposal for Substrate and Inhibitor Binding

The active site of the nitrogen-fixing enzyme Mo-nitrogenase is the M cluster ([MoFe₇S₉C ⋅ R-homocitrate]), also known as the FeMo cofactor or FeMoco. The biosynthesis of this highly complex metallocluster involves a series of proteins. Among them, NifB, a radical-SAM enzyme, is instrumental in the assembly of the L cluster ([Fe₈S₉C]), a precursor and all-iron core of the M cluster. In the absence of sulfite, NifB assembles a precursor form of the L cluster called the L* cluster ([Fe₈S₈C]), which lacks the final ninth sulfur. EPR and MCD spectroscopies are used to probe the electronic structures of the paramagnetic, oxidized forms of both the L and L* clusters, labeled L^Ox and [ L* ] ^Ox . This study shows that both L^Ox and [ L* ] ^Ox have nearly identical EPR and MCD spectra, thus suggesting that the two clusters have identical structures upon oxidation; in other words, a sulfur migrates away from L^Ox following oxidation, thereby rendering the cluster identical to [ L* ] ^Ox . It is proposed that a similar migration could occur to the M cluster upon oxidation, and that this is an instrumental part of both M cluster formation and nitrogenase substrate/inhibitor binding.     

仅外墙板为装配式建筑的施工细节

装配式建筑相较于传统建筑,具有节能减排、绿色环保、快速施工、工业化生产和缩短工期等优势,能有效改善我国现阶段建筑业劳动力低、技术创新弱、建筑品质不高的局面,推动建造方式的改变,并能大幅提高企业信息化、可视化管控管理水平,并通过预制装配式产业链的整合,催生相关新产业和服务业,可以使产业链上各企业的核心竞争力得到提高。全产业标准化,规格化,使得信息流、资金流和物流得到有效整合。     

月柿提取物体外抗氧化活性研究

目的以月柿提取物为原料,研究其对2,2-联苯基-1-苦基肼基(1,1-diphenyl-2-picrylhydrazyl,DPPH)自由基的清除能力,并测定其多酚类物质没食子酸的含量。方法检测波长为518 nm,反应时间为40 min条件下,以IC_(50)值(清除率为50%时,抗氧化剂的浓度值)作为抗氧化能力评价指标,并采用高效液相色谱法测定其没食子酸含量。结果月柿提取物对于DPPH自由基有良好的清除作用,其IC50值为0.1868 mg/mL,与常用抗氧化剂作用相当,且月柿提取物中没食子酸含量为1.65 g/kg。结论月柿提取物具有很强抗氧化活性,作为化妆品及功能性食品原料有广阔的开发前景。     

Synthesis of red mud derived M-type barium hexaferrites with tuneable coercivity

Hexagonal ferrites can be employed in a multitude of applications, the most common hexaferrites are the M ferrites such as BaFe₁₂O₁₉ (barium hexaferrite, BaM). It is known that if Fe³⁺ is substituted with a combination of Ti⁴⁺/Co²⁺ the coercivity of BaM can be reduced to produce soft M ferrites with easily switchable magnetisation. They can be utilised as powders, films or bulk ceramics, and can be manufactured from a wide variety of synthesis methods. The production of hexaferrites usually requires commercial raw materials, but if an industrial waste can be utilised, this will help to ease waste disposal and storage costs, valorise a waste material and encourage circular economy. In this study, bauxite residue (red mud) from the production of alumina was used to synthesise M-type hexaferrites, using a simple ceramic process. BaCO₃, or BaCO₃+Co₃O₄, were added to the red mud, blended and heated at 1000 °C to produce the M-type hexaferrites. Without cobalt addition up to 81.1 wt% M ferrite was produced, and with Co addition up to 74.3 wt% M ferrite was formed. Without cobalt, the M ferrite phase closely resembled BaFe₉Al₃O₁₉, and was a hard ferrite with a magnetisation of 12–19 A m²/kg for the whole powder (up to 23.6 A m²/kg for the M ferrite phase) and a coercivity of ~290 kA/m. When cobalt was added, secondary titanate phases vanished, and Ti⁴⁺/Co²⁺ partially substituted very soft M ferrite was formed with a low coercivity of ~16 kA/m but a higher magnetisation of 24.5 A m²/kg for the whole powder (up to 34.9 A m²/kg for the M ferrite phase). Therefore, not only can good quality magnetic materials be easily produced from this common waste material, but its magnetic properties can be tuned by varying the 2 + ions added during the process.     

Effects of ionic radius on phase evolution in Ln-Al co-doped Ca1-xLnxZrTi2-xAlxO7 (Ln = La,Nd, Gd,Ho, Yb) solid solutions

Zirconolite ceramic has been considered as a promising matrix to dispose high-level radioactive waste due to its excellent performance in immobilizing radionuclides. In this work, a series of zirconate solid solutions with stoichiometric Ca_1-xLn_xZrTi_2-xAl_xO₇ (Ln = La, Nd, Gd, Ho, Yb; x?=?0.1–1) were systematically studied to investigate the radius effect on their phase evolution. Powder X-ray diffraction (XRD) and scanning electron microscopy with energy dispersive X-Ray spectrometry (SEM-EDX) were used to characterize the products. XRD and SEM results show that complete solid solutions of Ln and Al in zirconolite phase for Ca_1-xLn_xZrTi_2-xAl_xO₇ cannot found. In the Ca_1-xLa_xZrTi_2-xAl_xO₇ ceramics, single zirconolite phase cannot form, instead of multiple phases, such as zirconolite-2M, zirconia, perovskite and LaTi₂Al₉O₁₉. In the Nd-Al co-doping ceramics, nearly single zirconolite-2M and zirconolite-3O were found at x?≤?0.6 and 0.8?≤?x?≤?0.9, respectively. The miscibility gap between zirconolite-2M and 3O was found at x?=?0.7. Single zirconolite-2M formed in the Gd-Al, Ho-Al and Yb-Al co-doped ceramics can only be detected in a compositional range of 0.1?≤?x?≤?0.8. Higher incorporation contents in these three series can form an additional phase cubic zirconia which is usually a ceramic waste form for radionuclides. Based on the XRD data, lattice parameters of zirconolite-2M and zirconolite-3O were calculated by Pawley refinement method. The evolution of lattice parameters of zirconolite-2M shows great difference between different lanthanide ions, indicating different substitution mechanisms in the Ln-Al co-doped zirconolite-2M.