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Epidermal growth factor receptor (EGF-R) is an important target in anticancer therapy. Here we report how a novel EGF-R peptide ligand (D4: Leu-Ala-Arg-Leu-Leu-Thr) is identified using a computer-aided design approach from a virtual peptide library of putative EGF-R binding peptides by screening against the EGF-R X-ray crystal structure in silico and in vitro. The selected peptide is conjugated with a polyethylene glycol (PEG) lipid, and the lipid moiety of the peptide-PEG-lipid conjugate is inserted into liposome membranes by a postmodification process. D4 peptide-conjugated liposomes are found to bind to and enter cells by endocytosis specifically and efficiently in vitro in a process apparently mediated by EGF-R high-expressing cancer cells (H1299). In vivo, the D4 peptide-conjugated liposomes are found to accumulate in EGF-R-expressing xenograft tumor tissues up to 80 h after intravenous delivery, in marked contrast to controls. These results demonstrate how structure-based peptide design can be an efficient approach to identify highly novel binding ligands against important receptors. These data could have important consequences for the development of peptide-directed drug delivery systems with engineered specificities and prolonged times of action.

β-relaxation has long been attributed to localized motion of constituent molecules or atoms confined to isolated regions in glasses. However, direct experimental evidence to support this spatially heterogeneous scenario is still missing. Here we report the evolution of nanoscale structural heterogeneity in a metallic glass during β-relaxation by utilizing amplitude-modulation dynamic atomic force microscopy. The successive degeneration of heterogeneity during β-relaxation can be well described by the Kohlrausch–Williams–Watts equation. The characteristic relaxation time and activation energy of the heterogeneity evolution are in accord with those of excess enthalpy release by β-relaxation. Our study correlates β-relaxation with nanoscale spatial heterogeneity and provides direct evidence on the structural origins of β-relaxation in metallic glasses.

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Kawasaki disease (KD) is the most common cause of acquired heart disease in children in developed countries. Although functional and phenotypic changes of immune cells have been reported, a global understanding of immune responses underlying acute KD is unclear. Here, using single-cell RNA sequencing, we profile peripheral blood mononuclear cells from seven patients with acute KD before and after intravenous immunoglobulin therapy and from three age-matched healthy controls. The most differentially expressed genes are identified in monocytes, with high expression of pro-inflammatory mediators, immunoglobulin receptors and low expression of MHC class II genes in acute KD. Single-cell RNA sequencing and flow cytometry analyses, of cells from an additional 16 KD patients, show that although the percentage of total B cells is substantially decreased after therapy, the percentage of plasma cells among the B cells is significantly increased. The percentage of CD8+ T cells is decreased in acute KD, notably effector memory CD8+ T cells compared with healthy controls. Oligoclonal expansions of both B cell receptors and T cell receptors are observed after therapy. We identify biological processes potentially underlying the changes of each cell type. The single-cell landscape of both innate and adaptive immune responses provides insights into pathogenesis and therapy of KD.

The HER performance of MoS2 is enhanced dramatically by doping single Ni atoms into Mo sites.

The failure of superhard materials is often associated with stress-induced amorphization. However, the underlying mechanisms of the structural evolution remain largely unknown. Here, we report the experimental measurements of the onset of shear amorphization in single-crystal boron carbide by nanoindentation and transmission electron microscopy. We verified that rate-dependent loading discontinuity, i.e., pop-in, in nanoindentation load-displacement curves results from the formation of nanosized amorphous bands via shear amorphization. Stochastic analysis of the pop-in events reveals an exceptionally small activation volume, slow nucleation rate, and lower activation energy of the shear amorphization, suggesting that the high-pressure structural transition is activated and initiated by dislocation nucleation. This dislocation-mediated amorphization has important implications in understanding the failure mechanisms of superhard materials at stresses far below their theoretical strengths.