RESUMO
Lactoferrin (LF) is a soluble glycoprotein of the transferring family found in most biological fluids, functioning as a major first line defense molecule against infection in mammals. It also shows certain anti-tumor activity, but its clinical application in tumor therapy is limited because high dosage is required. In this study, we demonstrate that M860, a monoclonal antibody against human LF (hLF), could significantly increase the anti-tumor potential of low dosage hLF by forming LF-containing immune complex (IC). Human monocytes primed with LF-IC, but not hLF or M860 alone, or control ICs, showed strong tumoricidal activity on leukemia cell lines Jurkat and Raji through induction of secreted Granzyme B (GzB). LF-IC is able to colligate membrane-bound CD14 (a TLR4 co-receptor) and FcγRIIa (a low affinity activating Fcγ receptor) on the surface of human monocytes, thereby triggering the Syk-PI3K-AKT-mTOR pathway leading to GzB production. Our work identifies a novel pathway for LF-mediated tumoricidal activity and may extend the clinical application of LF in tumor therapy.
Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Granzimas/biossíntese , Lactoferrina/antagonistas & inibidores , Biomarcadores , Sinergismo Farmacológico , Expressão Gênica , Granzimas/genética , Humanos , Lactoferrina/administração & dosagem , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quinase Syk/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
P2-type layered oxides for rechargeable sodium-ion batteries have drawn a lot of attention because of their excellent electrochemical performance. However, these types of cathodes usually suffer from poor cyclic stability. To overcome this disadvantage, in this work, novel ball-shaped concentration-gradient oxide Na0.67Ni0.17Co0.17Mn0.66O2 with P2 structure modified by Mn-rich surface is successfully prepared using co-precipitation method. The concentration of Mn increased from the inner core to the surface, endowing the material with an excellent cyclic stability. The cathode exhibits enhanced electrochemical properties than that of the sample synthesized by solid-state method and concentration-constant material. It shows 143.2 mAh/g initial discharge capacity and retains 131 mAh/g between 2 V and 4.5 V after 100 rounds. The significant improvement in the electrochemical properties of the sample benefits from the unique concentration-gradient structure, and the Mn-rich surface that effectively stabilizes the basic P2 structure. The relatively higher Ni content in the core leads to a slight improvement in the discharge capacity of the sample. This strategy may provide new insights for preparing layered cathodes for sodium-ion batteries with high electrochemical performance.
RESUMO
Swelling caused by gas generated from municipal solid waste incineration fly ash (MSWIFA) when it is mixed with alkali limits its uses. Besides, the leaching of anion salts and heavy metals contained in MSWIFA poses a high risk to environment. This study presents the feasibility of a one-step alkaline washing, one-step thermal quenching and two-step combination of alkaline washing and thermal quenching pretreatment methods in altering the key properties of MSWIFA for promoting its reusability. It was found that apart from H2(gas), NH3(gas) was also generated during the alkaline washing of the MSWIFA. Besides, pretreatments led to the reduction in particle size, the increase in pore volume and specific surface area of the MSWIFA, as well as the removal of chloride and sulfate anions. All the pretreatment methods were effective in reducing leaching of heavy metals to below levels of nonhazardous waste except Cd and Pb with alkaline washing. Furthermore, both the chemical Frattini test and the mechanical activity index test showed improvement in pozzolanic activities of the MSWIFA after the pretreatments. Overall, the combined pretreatment method was most effective in eliminating gas emission, and reducing leaching of metal ions and anions from the ash, while enhancing the pozzolanic activity of the ash.