Severe plastic deformation for producing superfunctional ultrafine-grained and heterostructured materials: An interdisciplinary review

Ultrafine-grained and heterostructured materials are currently of high interest due to their superior mechanical and functional properties. Severe plastic deformation (SPD) is one of the most effective methods to produce such materials with unique microstructure-property relationships. In this review paper, after summarizing the recent progress in developing various SPD methods for processing bulk, surface and powder of materials, the main structural and microstructural features of SPD-processed materials are explained including lattice defects, grain boundaries and phase transformations. The properties and potential applications of SPD-processed materials are then reviewed in detail including tensile properties, creep, superplasticity, hydrogen embrittlement resistance, electrical conductivity, magnetic properties, optical properties, solar energy harvesting, photocatalysis, electrocatalysis, hydrolysis, hydrogen storage, hydrogen production, CO2 conversion, corrosion resistance and biocompatibility. It is shown that achieving such properties is not limited to pure metals and conventional metallic alloys, and a wide range of materials are currently processed by SPD, including high-entropy alloys, glasses, semiconductors, ceramics and polymers. It is particularly emphasized that SPD has moved from a simple metal processing tool to a powerful means for the discovery and synthesis of new superfunctional metallic and nonmetallic materials. The article ends by declaring that the borders of SPD have been extended from materials science and it has become an interdisciplinary tool to address scientific questions such as the mechanisms of geological and astronomical phenomena and the origin of life

NG2 antigen is involved in leukemia invasiveness and central nervous system infiltration in MLL-rearranged infant B-ALL

Mixed-lineage leukemia (MLL)-rearranged (MLLr) infant B-cell acute lymphoblastic leukemia (iMLLr-B-ALL) has a dismal prognosis and is associated with a pro-B/mixed phenotype, therapy refractoriness and frequent central nervous system (CNS) disease/relapse. Neuron-glial antigen 2 (NG2) is specifically expressed in MLLr leukemias and is used in leukemia immunophenotyping because of its predictive value for MLLr acute leukemias. NG2 is involved in melanoma metastasis and brain development; however, its role in MLL-mediated leukemogenesis remains elusive. Here we evaluated whether NG2 distinguishes leukemia-initiating/propagating cells (L-ICs) and/or CNS-infiltrating cells (CNS-ICs) in iMLLr-B-ALL. Clinical data from the Interfant cohort of iMLLr-B-ALL demonstrated that high NG2 expression associates with lower event-free survival, higher number of circulating blasts and more frequent CNS disease/relapse. Serial xenotransplantation of primary MLL-AF4+ leukemias indicated that NG2 is a malleable marker that does not enrich for L-IC or CNS-IC in iMLLr-B-All. However, NG2 expression was highly upregulated in blasts infiltrating extramedullar hematopoietic sites and CNS, and specific blockage of NG2 resulted in almost complete loss of engraftment. Indeed, gene expression profiling of primary blasts and primografts revealed a migratory signature of NG2+ blasts. This study provides new insights on the biology of NG2 in iMLLr-B-ALL and suggests NG2 as a potential therapeutic target to reduce the risk of CNS disease/relapse and to provide safer CNS-directed therapies for iMLLr-B-ALL.This work was supported by the European Research Council (CoG-2014-646903) and the Spanish Ministry of Economy-Competitiveness (SAF-SAF2013-43065) to PM, the Asociación Española Contra el Cáncer to CB and the ISCIII/FEDER (PI14/01191-PI13/00168) to CB and JCRM. PM acknowledges the financial support from the Obra Social La Caixa-Fundaciò Josep Carreras, the Inocente-Inocente Foundation and Generalitat de Catalunya. CP and DRM were funded by PFIS scholarships from the ISCIII. VA has financial support from L’Oreal-UNESCO. PM is investigator of the Spanish Cell Therapy cooperative network (TERCEL). We thank Antonio Agraz/Ignacio Varela (IBBTEC, Santander) for assisting in microarray analysis. We also thank Dr Patricia Pérez-Galán and Gael Roue (IDIBAPS, Barcelona, Spain) for helpful discussions on NG2 blocking experiments