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International audience; In this study, a specifically designed B4C–TiB2 composite with the typical microstructural feature of a TiB2 network (cages) that encapsulates a B4C matrix was fabricated by the molten-salt and spark plasma sintering (SPS) method. The finite-element (FE) calculation results show that the connected TiB2 cages constitute a thermally conductive network, which effectively improves the overall thermal conductivity of the composite; these results agree well with the experimental results. Moreover, the Vickers indentation results reveal that the TiB2 network (cages) can effectively impinge/block the propagation of cracks, which increases the composite toughness. The composite was subjected to helium (He) ion irradiation to simulate the situation in which the B4C–TiB2 composites serve as neutron absorption material, and for which case a high quantity of He atoms is produced by the B10 (n, α) Li7 nuclear reaction. According to the transmission electron microscopy (TEM) results, the interfaces between TiB2 and B4C act as effective sinks for He atoms, and are preferential nucleation sites for He bubbles. The theoretical and experimental results show that when the B4C–TiB2 composites serve as neutron absorption pellets in nuclear reactors, they exhibit a better resistance to their disintegration than pure B4C pellets. Consequently, the performance of the control rods of nuclear reactors can be improved.

Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET. Funding Agencies|NovartisNovartis; Swedish Research CouncilSwedish Research Council; Swedish Cancer SocietySwedish Cancer Society; Cancer Society in Stockholm; Gustav V Jubilee Foundation; Stockholm County CouncilStockholm County Council; Karolinska InstitutetKarolinska Institutet

Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning. Yet, it remains a challenge due to complexity of the growth process and technical limits of modern characterization tools. We report a combinational use of multiple cutting-edge in situ techniques to study the growth process of octahedral Pt3Ni nanoparticles, which reveal the particle growth and facet formation mechanisms. Our studies confirm the formation of octahedral Pt3Ni initiates from Pt nuclei generation, which is followed by continuous Pt reduction that simultaneously catalyzes Ni reduction, resulting in mixed alloy formation with moderate elemental segregation. Carbon monoxide molecules serve as a facet formation modulator and induce Ni segregation to the surface, which inhibits the (111) facet growth and causes the particle shape to evolve from a spherical cluster to an octahedron as the (001) facet continues to grow., Understanding the growth pathway of faceted alloy nanoparticles at the atomic level is crucial to morphology control and property tuning, but remains a challenge. Here, the authors reveal the particle growth and facet formation mechanisms of octahedral Pt3Ni nanoparticles using multiple cutting-edge in situ techniques.

Active sites play an essential role in heterogeneous catalysis and largely determine the reaction properties. Yet identification and study of the active sites remain challenging owing to their dynamic behaviors during catalysis process and issues with current characterization techniques. This article provides a short review of research progresses in active sites of metal and metal oxide catalysts, which covers the past achievements, current research status, and perspectives in this research field. In particular, the concepts and theories of active sites are introduced. Major experimental and computational approaches that are used in active site study are summarized, with their applications and limitations being discussed. An outlook of future research direction in both experimental and computational catalysis research is provided.