A Fluid Liquid‐Crystal Material with Highly Polar Order

An anomalously large dielectric permittivity of ≈10⁴ is found in the mesophase temperature range (MP phase) wherein high fluidity is observed for a liquid‐crystal compound having a 1,3‐dioxane unit in the mesogenic core (DIO). In this temperature range, no sharp X‐ray diffraction peak is observed at both small and wide Bragg angles, similar to that for a nematic phase; however, an inhomogeneous sandy texture or broken Schlieren one is observed via polarizing optical microscopy, unlike that for a conventional nematic phase. DIO exhibits polarization switching with a large polarization value, i.e., P = 4.4 µC cm^?2, and a parallelogram‐shaped polarization–electric field hysteresis loop in the MP phase. The inhomogeneously aligned DIO in the absence of an electric field adopts a uniform orientation along an applied electric field when field‐induced polarization switching occurs. Furthermore, sufficiently larger second‐harmonic generation is observed for DIO in the MP phase. Second‐harmonic‐generation interferometry clearly shows that the sense of polarization is inverted when the +/? sign of the applied electric field in MP is reversed. These results suggest that a unidirectional, ferroelectric‐like parallel polar arrangement of the molecules is generated along the director in the MP phase.     

Molecular Bases of Human Malformation Syndromes Involving the SHH Pathway: GLIA/R Balance and Cardinal Phenotypes

Human hereditary malformation syndromes are caused by mutations in the genes of the signal transduction molecules involved in fetal development. Among them, the Sonic hedgehog (SHH) signaling pathway is the most important, and many syndromes result from its disruption. In this review, we summarize the molecular mechanisms and role in embryonic morphogenesis of the SHH pathway, then classify the phenotype of each malformation syndrome associated with mutations of major molecules in the pathway. The output of the SHH pathway is shown as GLI activity, which is generated by SHH in a concentration-dependent manner, i.e., the sum of activating form of GLI (GLIA) and repressive form of GLI (GLIR). Which gene is mutated and whether the mutation is loss-of-function or gain-of-function determine in which concentration range of SHH the imbalance occurs. In human malformation syndromes, too much or too little GLI activity produces symmetric phenotypes affecting brain size, craniofacial (midface) dysmorphism, and orientation of polydactyly with respect to the axis of the limb. The symptoms of each syndrome can be explained by the GLIA/R balance model.     

Rapid In Situ Synthesis of Spherical Microflower Pt/C Catalyst Via Spray‐drying for High Performance Fuel Cell Application

A facile route for the rapid in situ synthesis of platinum nanoparticles on spherical microflower carbon has been developed. An aqueous precursor slurry containing carbon black, polystyrene latex (PSL), polyvinyl alcohol, and platinum salt was spray‐dried, followed by calcination to simultaneously reduce platinum salt and to decompose PSL particles. Prepared Pt/C catalyst showed high‐performance electrocatalytic activity with excellent durability. The mass activity and specific activity values were 132.26 mA mg^–1 Pt and 207.62 μA cm^–2 Pt, respectively. This work presents a future direction for the production of high‐performance Pt/C catalyst in an industrial scale.     

The Detection of Immunity against WT1 and SMAD4P130L of EpCAM+ Cancer Cells in Malignant Pleural Effusion

Malignant pleural effusion (MPE) provides a liquid tumor microenvironment model that includes cancer cells and immune cells. However, the characteristics of tumor antigen-specific CD8⁺ T cells have not been investigated in detail. Here, we analyzed MPE samples taken from a patient with pancreatic cancer who received a dendritic cell vaccine targeting Wilms’ Tumor 1 (WT1) antigen over the disease course (two points at MPE^1st and 2^nd, two months after MPE1^st). Epithelial cell adhesion molecule (EpCAM)⁺ cancer cells (PD-L1⁻ or T cell immunoglobulin mucin-3, TIM-3⁻), both PD-1 or TIM-3 positive CD8⁺ T cells, and CD14⁺CD68⁺CD163⁺TIM-3⁺ macrophages increased from the MPE^1st to MPE^2nd. The ratio of WT1-specific cytotoxic lymphocytes (WT1-CTLs) to MPE CD8⁺ T cells and IFN-γ secretion of WT1-CTLs were reduced with disease progression. Coincidentally, the fraction of central memory T (T_CM) of WT1-CTLs was decreased. On the other hand, CD8⁺ T cells in response to SMAD4^P130L, which is homogeneously expressed in EpCAM⁺ cancer cells, were detected using in vitro expansion with the HLA-A*11:01 restrictive SVCVNLYH neoantigen. Furthermore, the CD8⁺ T cell response to SMAD4^P130L was diminished following remarkably decreased numbers of CD8⁺ T_CM in MPE samples. In conclusion, CD8⁺ T cells responding to WT1 or SMAD4^P130L neoantigen expressed in EpCAM⁺ pancreatic cancer cells were detected in MPE. A tumor antigen-specific immune response would provide novel insight into the MPE microenvironment.     

Preparation and characterization of active Ni/MgO in oxidative steam reforming of n-C4H10

Oxidative steam reforming of n-C₄H₁₀ over MgO-supported Ni catalysts is described. The Ni/MgO catalysts were prepared by the impregnation method from aqueous Ni(NO₃)₂ precursor solutions at two pH values. Ni/MgO prepared at pH 7 exhibited considerably higher activity than Ni/MgO prepared from a conventional acidic aqueous precursor solution (pH 3.5). The H₂ formation rate for the modified Ni/MgO was up to 2.3 times that for conventional Ni/MgO under a high space velocity of 1660 L(h g)⁻¹. Furthermore, after reduction at high temperature (1273 K), the modified Ni/MgO showed a higher H₂ formation rate than did Rh/MgO. The superior performance of the modified Ni/MgO was ascribed to stronger resistance to oxidation of Ni⁰ due to the formation of relatively large Ni⁰ particles.     

Constrained Nanoparticles Deliver siRNA and sgRNA to T Cells In Vivo without Targeting Ligands

T cells help regulate immunity, which makes them an important target for RNA therapies. While nanoparticles carrying RNA have been directed to T cells in vivo using protein‐ and aptamer‐based targeting ligands, systemic delivery to T cells without targeting ligands remains challenging. Given that T cells endocytose lipoprotein particles and enveloped viruses, two natural systems with structures that can be similar to lipid nanoparticles (LNPs), it is hypothesized that LNPs devoid of targeting ligands can deliver RNA to T cells in vivo. To test this hypothesis, the delivery of siRNA to 9 cell types in vivo by 168 nanoparticles using a novel siGFP‐based barcoding system and bioinformatics is quantified. It is found that nanomaterials containing conformationally constrained lipids form stable LNPs, herein named constrained lipid nanoparticles (cLNPs). cLNPs deliver siRNA and sgRNA to T cells at doses as low as 0.5 mg kg^?1 and, unlike previously reported LNPs, do not preferentially target hepatocytes. Delivery occurs via a chemical composition‐dependent, size‐independent mechanism. These data suggest that the degree to which lipids are constrained alters nanoparticle targeting, and also suggest that natural lipid trafficking pathways can promote T cell delivery, offering an alternative to active targeting approaches.     

Detection of a new Fusarium masked mycotoxin in wheat grain by high-resolution LC-Orbitrap™ MS

A new Fusarium mycotoxin glucoside, fusarenon X-glucoside (FUXGlc), is reported for the first time in wheat grain that was artificially infected with Fusarium fungi. This new glucoside was identified using LC Orbitrap high-resolution mass spectrometry (LC-Orbitrap MS) analysis on the basis of accurate mass measurement of characteristic ions and MS/MS fragmentation patterns. Although the absolute structure of FUXGlc was not clarified by LC-MS, 3-OH glucosylation seems to be the most probable structure based on the fragment profile and considering that deoxynivalenol-3-glucoside (DON3Glc) was reported as the predominant glucosylated derivative of the structurally similar mycotoxin, deoxynivalenol (DON). Another mycotoxin glucoside, nivalenol-glucoside (NIVGlc) was also found in the same grain sample. According to the semi-quantification by LC-Orbitrap MS, more than 15% of FUX and NIV were estimated to be converted into respective glucosides. The existence of these masked mycotoxins should be taken into account in risk assessment, since they could be transformed back to the corresponding mycotoxins under certain conditions; for example, through various food processing operations or in the digestive tract of mammals after ingestion.