Novel Inhibitor of Mixed-Lineage Kinase Domain-Like Protein: The Antifibrotic Effects of a Necroptosis Antagonist.

The pseudokinase mixed-lineage kinase domain-like protein plays a crucial role in programmed cell death via necroptosis. We developed a novel mixed-lineage kinase domain-like inhibitor, P28, which demonstrated potent necroptosis inhibition and antifibrotic effects. P28 treatment directly inhibited mixed-lineage kinase domain-like phosphorylation and oligomerization after necroptosis induction, inhibited immune cell death after necroptosis, and reduced the expression of adhesion molecules. Additionally, P28 treatment reduced the level of activation of hepatic stellate cells and the expression of hepatic fibrosis markers induced by necroptosis stimulation. Unlike the necrosulfonamide treatment, the P28 treatment did not induce cytotoxicity. Finally, the cysteine covalent bonding of P28 was confirmed by liquid chromatography-tandem mass spectrometry.

Atomic-Resolution Imaging of Small Organic Molecules on Graphene.

Here, we demonstrate atomic-resolution scanning transmission electron microscopy (STEM) imaging of light elements in small organic molecules on graphene. We use low-dose, room-temperature, aberration-corrected STEM to image 2D monolayer and bilayer molecular crystals, followed by advanced image processing methods to create high-quality composite images from ∼102-104 individual molecules. In metalated porphyrin and phthalocyanine derivatives, these images contain an elementally sensitive contrast with up to 1.3 Å resolution─sufficient to distinguish individual carbon and nitrogen atoms. Importantly, our methods can be applied to molecules with low masses (∼0.6 kDa) and nanocrystalline domains containing just a few hundred molecules, making it possible to study systems for which large crystals cannot easily be grown. Our approach is enabled by low-background graphene substrates, which we show increase the molecules' critical dose by 2-7×. These results indicate a new route for low-dose, atomic-resolution electron microscopy imaging to solve the structures of small organic molecules.

Enhanced Photoluminescence of Multiple Two-Dimensional van der Waals Heterostructures Fabricated by Layer-by-Layer Oxidation of MoS2.

Monolayer transition metal dichalcogenides (TMDs) are promising for optoelectronics because of their high optical quantum yield and strong light-matter interaction. In particular, the van der Waals (vdW) heterostructures consisting of monolayer TMDs sandwiched by large gap hexagonal boron nitride have shown great potential for novel optoelectronic devices. However, a complicated stacking process limits scalability and practical applications. Furthermore, even though lots of efforts, such as fabrication of vdW heterointerfaces, modification of the surface, and structural phase transition, have been devoted to preserve or modulate the properties of TMDs, high environmental sensitivity and damage-prone characteristics of TMDs make it difficult to achieve a controllable technique for surface/interface engineering. Here, we demonstrate a novel way to fabricate multiple two-dimensional (2D) vdW heterostructures consisting of alternately stacked MoS2 and MoOx with enhanced photoluminescence (PL). We directly oxidized multilayer MoS2 to a MoOx/1 L-MoS2 heterostructure with atomic layer precision through a customized oxygen plasma system. The monolayer MoS2 covered by MoOx showed an enhanced PL intensity 3.2 and 6.5 times higher in average than the as-exfoliated 1 L- and 2 L-MoS2 because of preserved crystallinity and compensated dedoping by MoOx. By using layer-by-layer oxidation and transfer processes, we fabricated the heterostructures of MoOx/MoS2/MoOx/MoS2, where the MoS2 monolayers are separated by MoOx. The heterostructures showed the multiplied PL intensity as the number of embedded MoS2 layers increases because of suppression of the nonradiative trion formation and interlayer decoupling between stacked MoS2 layers. Our work shows a novel way toward the fabrication of 2D material-based multiple vdW heterostructures and our layer-by-layer oxidation process is beneficial for the fabrication of high performance 2D optoelectronic devices.

Phase Formation Behavior and Thermoelectric Transport Properties of P-Type YbxFe3CoSb12 Prepared by Melt Spinning and Spark Plasma Sintering.

Formation of multiple phases is considered an effective approach for enhancing the performance of thermoelectric materials since it can reduce the thermal conductivity and improve the power factor. Herein, we report the in-situ generation of a submicron-scale (~500 nm) heterograin structure in p-type Yb-filled (Fe,Co)4Sb12 skutterudites during the melt spinning process. Mixed grains of YbxFe3-yCo1+ySb12 and YbzFe3+yCo1-ySb12 were formed in melt spun ribbons due to uneven distribution of cations. By the formation of interfaces between two different grains, the power factor was enhanced due to the formation of an energy barrier for carrier transport, and simultaneously the lattice thermal conductivity was reduced due to the intensified boundary phonon scattering. A high thermoelectric figure of merit zT of 0.66 was obtained at 700 K.

On-Demand Electromagnetic Hotspot Generation in Surface-Enhanced Raman Scattering Substrates via "Add-On" Plasmonic Patch.

Electromagnetic hotspots at the interstices of plasmonic assemblies are recognized to be the most potent sites for surface-enhanced Raman scattering (SERS). We demonstrate a novel "add-on" electromagnetic hotspot formation technique, which significantly improves the sensitivity of conventional SERS substrates composed of individual plasmonic nanostructures. The novel approach demonstrated here involves the transfer of "plasmonic patch", a transparent, flexible, and conformal elastomeric film adsorbed with plasmonic nanostructures, onto a conventional SERS substrate. The addition of the plasmonic patch onto a conventional SERS substrate following the analyte capture results in the formation of electromagnetic hotspots and hence a large SERS enhancement. The application of the plasmonic patch improves the sensitivity and limit of detection of conventional SERS substrates by up to ∼100-fold. The transfer of the plasmonic patch also effectively transforms the SERS-inactive gold mirror to a highly SERS-active "particle-on-mirror" system. Furthermore, we demonstrate that the "add-on" technique can be effectively utilized for the vapor-phase detection of explosives such as trinitrotoluene (TNT) using peptide recognition elements. We believe that the on-demand hotspot formation approach presented here represents a highly versatile and ubiquitously applicable technology readily expandable to any existing SERS substrate without employing complicated modification.

Quantitative Imaging of Organic Ligand Density on Anisotropic Inorganic Nanocrystals.

A longstanding challenge in nanoparticle characterization is to understand anisotropic distributions of organic ligands at the surface of inorganic nanoparticles. Here, we show that using electron energy loss spectroscopy in an aberration-corrected scanning transmission electron microscope we can directly visualize and quantify ligand distributions on gold nanorods (AuNRs). These experiments analyze dozens of particles on graphene substrates, providing insight into how ligand binding densities vary within and between individual nanoparticles. We demonstrate that the distribution of cetyltrimethylammonium bromide (CTAB) on AuNRs is anisotropic, with a 30% decrease in ligand density at the poles of the nanoparticles. In contrast, the distribution of (16-mercaptohexadecyl)trimethylammonium bromide (MTAB) is more uniform. These results are consistent with literature reported higher reactivity at the ends of CTAB-coated AuNRs. Our results demonstrate the impact of electron spectroscopy to probe molecular distributions at soft-hard interfaces and how they produce spatially heterogeneous properties in colloidal nanoparticles.