olloidal nanocrystals bridge the gap between molecules and bulk materials, and enable researchers to probe fundamentals of nanomaterials, surfaces and size-dependent physics 1,2 . Beyond this, they have found a variety of applications from quantum dot emitters in displays 3,4 to photovoltaics 5,6 . Their colloidal nature allows them to be dispersed into solvents for optical studies, which include single-particle measurements 7,8 and assemblies of these materials can be created to investigate collective effects and their use as artificial atoms 9,10 .Fundamentally, most colloidal nanocrystals are composites that consist of an inorganic core and an organic ligand shell. This organic ligand shell enables colloidal stability in solvents 11,12 , prevents inorganic cores from fusing 10,13 , passivates undercoordinated atoms that lead to exciton traps in quantum dots [14][15][16][17] , acts as soft matter in the assembly of artificial solids 9,10,18,19 and provides a platform for the modification of inorganic cores 15,17,20 . Beyond contributing to colloidal nanocrystals properties, they are essential in synthesis.Organic ligands mediate growth by binding to growing nanocrystal surfaces as a surfactant. The group that binds to the nanocrystal surface is referred to as the head group, and the rest of the capping ligand is referred to as the tail group 1,19,21 . Typically, in hydrophobic environments, when growth is terminated by the exhaustion of precursors or reaction quenching, these ligands form an organic shell around each nanocrystal, in which the head groups face into the nanocrystal and the organic tail groups face outward. The nature of the ligands dictates the inorganic nanocrystal surface structure 11,19,21,22 , and has been designed to promote surfaces that minimize electronic trap states in quantum dots 15,17,23,24 . A variety of head groups are used to terminate colloidal nanocrystal surfaces, such as carboxylates, amines, phosphonates, thiols and halides, and often a mixture of capping groups is used [15][16][17]20,[25][26][27][28][29][30][31][32] . The amount, type and impurities of the ligands used in nanocrystal synthesis have implications for the nanocrystal size, shape, crystal structure and stability, as well as for their optical and electronic properties 33,34 .Head groups play a critical role in the control of colloidal nanocrystal growth, and different nanocrystal shapes can be formed by manipulating head group binding. Using combinations of
A Caucasian male with Gaucher disease type 3, treated with continuous enzyme therapy (ET) for 11 years, experienced progressive mesenteric and retroperitoneal lymphadenopathy, lung disease, and neurological involvement leading to death at age 12.5 years. Autopsy showed significant pathology of the brain, lymph nodes, and lungs. Liver and spleen glucosylceramide (GluCer) and glucosylsphingosine (GluS) levels were nearly normal and storage cells were cleared. Clusters of macrophages and very elevated GluCer and GluS levels were in the lungs, and brain parenchymal and perivascular regions. Compared to normal brain GluCer (GC 18:0), GluCer species with long fatty acid acyl chains were increased in the patient’s brain. This profile was similar to that in the patient’s lungs, suggesting these lipids were present in brain perivascular macrophages. In the patient’s brain, generalized astrogliosis, and enhanced LC3, Ubiquitin, and Tau signals were identified in the regions surrounding macrophage clusters, indicating proinflammation, altered autophagy, and neurodegeneration. These findings highlight the altered phenotypes resulting from increased longevity due to ET, as well as those in poorly accessible compartments of brain and lung, which manifested progressive disease involvement despite ET.
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