We prepared an asymmetric liquid crystal dimer possessing a terminal hydroxyl group, 2-{4-{7-4-(4-cyanophenyl)phenyloxyheptyloxy}phenyl}-5-(6-hydroxyhexyloxy)pyrimidine, and investigated the phase ...transition behaviour using polarising optical microscopy and differential scanning calorimetry. The compound exhibited an enantiotropic nematic phase. On cooling, two distinct domains were formed during the nematic-to-crystal phase transition. During heating, one domain melted at 126.4°C to the N phase, whereas the other domain changed to the N phase at 144.6°C. Therefore, the crystal and nematic phases coexisted at a temperature of 18.2 K. The coexistence behaviour characteristics depend on the cooling rate. We discuss the manner in which intermolecular interactions affect the phase transition behaviour.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
We prepared a homologous series of achiral liquid crystal trimers (
I-
n
) in which two phenylpyrimidine units and one biphenyl unit were connected
via
flexible spacers, and investigated the physical ...properties. All the trimers possessing odd-numbered methylene spacers exhibited soft crystalline chiral conglomerate phases. X-ray diffraction measurements reveal that they have an intercalated layer structure. On the other hand, the trimers possessing even-numbered spacers showed nematic and smectic C phases. We investigated the surface structures of odd-membered trimers in the soft crystalline phases using scanning electron microscopy. Trimers
I-3
and
I-5
were found to form cylindrical tubes, whereas trimers
I-7
,
I-9
and
I-11
toroidal pits. We discuss the formation of diverse supramolecular architectures in terms of the anisotropy of the chirality transfer.
Achiral linear trimers possessing odd-numbered spacers exhibited soft crystalline chiral conglomerate phases. The trimers with shorter spacers were found to form cylindrical tubes, whereas those with longer spacers toroidal pits.
Chiral conglomerates of domains with opposite handedness have attracted much attention from researchers. We prepared a homologous series of achiral liquid crystal trimers in which two ...phenylpyrimidine units and one biphenyl unit were connected
via
flexible methylene spacers. We investigated their phase transition behaviour. Some trimers possessing odd-numbered spacers were found to exhibit a nematic phase and a dark chiral conglomerate phase possessing a layered structure. The chiral characteristics were confirmed by uncrossing the polarizers in opposite directions. The layer spacing detected using X-ray diffraction was about 80% of the molecular length. The structure-property relations indicate that intermolecular interactions cause a conformational change in the trimers possessing flexible odd-numbered methylene spacers to form helical conformers with axial chirality, which might induce chiral segregation and layer deformation to drive the chiral conglomerates.
The liquid crystal trimers form an achiral ground-state conformation in the nematic phase; however, by intermolecular interactions between cores they adopt a twisted chiral conformation to exhibit the spontaneous mirror symmetry breaking in the low-temperature DC phase.
Dark conglomerates of domains with opposite handedness, which are designated as dark conglomerate phases (DC phases), have attracted much attention. After designing an achiral liquid crystal trimer, ...4,4′-bis{7-4-(5-octyloxypyrimidin-2-yl)phenyloxyheptyloxy}biphenyl (
1
), which exhibits only a nematic phase, we prepared binary mixtures with some typical rod-like nematic liquid crystals,
i.e.
, 4′-hexyloxy-4-cyanobiphenyl (
6OCB
), 2-(4-hexyloxyphenyl)-5-pentyloxypyrimidine (
PPY
), or 4-methyloxyphenyl 4-hexyloxycyclohexanecarboxylate (
PCA
), and investigated their phase transition behaviour. The binary mixtures containing 55-90 mol% of
6OCB
were found to exhibit a nematic phase and a DC phase of chiral domains with opposite handedness. However, neither
PPY
nor
PCA
induced such a chiral conglomerate phase in the mixture with trimer
1
. We discuss how core-core interactions contribute to produce such a chiral conglomerate phase.
Interactions between a phenylpyrimidine unit of trimer
1
and a cyanobiphenyl unit of
6OCB
can produce a twist conformation of the central biphenyl of the trimer, which induces chiral segregation and layer deformation to drive the chiral conglomerates.
Experimental colitis studies, including T cell-mediated colitis, indicate that IL-23 rather than IL-12 orchestrates intestinal inflammation in inflammatory bowel disease (IBD). Previous studies have ...identified the roles of IL-12 and IL-23 using mice deficient for their specific subunits, p35 and p19, respectively. However, these studies do not completely reflect the difference in roles between IL-12 and IL-23, especially since the discovery of novel IL-12 family cytokines, which also include p35 or p19 subunits. Here, to clarify the contribution of IL-12 and IL-23 in T cell-mediated colitis, we compared the efficacy of a monoclonal antibody (mAb) to an IL-23-specific receptor subunit with that of an anti-IL-12/23p40 mAb in a naive CD4+ T cell transfer model of experimental colitis, which is associated with enhanced Th1 and Th17 responses. Both antibodies almost completely prevented the development of colitis and showed reduced associated histological changes, including mucosal hyperplasia, infiltration of inflammatory cells and loss of goblet cells. The anti-IL-23 receptor mAb inhibited not only the systemic Th17-response but also the Th1-response, both of which were up-regulated in this model. These results suggest that IL-23, but not IL-12, signaling is critical for the development of colitis. Blockade of IL-23 signaling is a promising therapeutic approach for IBD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Roots of Aconitum plants (A. japonicum and A. carmichaelii) have been used as traditional Japanese Kampo medicine. They are listed in The Japanese Pharmacopoeia as raw materials of Kampo medicine, ...“Bushi”. In commercial plantations of A. japonicum in Iwate Prefecture, blighting and wilting symptoms were observed in 2016. Diseased stems were water-soaked, dark brown, and displayed both white mycelium and brown sclerotia on the basal parts of the stems. Based on morphological traits, internal transcribed spacer sequence analysis, and pathogenicity tests, the causative fungus was identified as Sclerotium rolfsii (Sexual morph: Athelia rolfsii). S. rolfsii on A. carmichaelii has been reported in China, but not on A. japonicum. To the best of our knowledge, this is the first report of S. rolfsii causing southern blight disease in A. japonicum in Japan or elsewhere in the world.
Interleukin (IL)-23 is thought to be critical in the pathogenesis of psoriasis, and anti-IL-23 monoclonal antibodies (mAbs) have been approved for the treatment of psoriasis. We speculated that an ...anti-IL-23 receptor mAb might have greater efficacy than an anti-IL-23 mAb in the treatment of local inflamed lesions with high IL-23 levels. We previously generated an anti-human IL-23 receptor mAb, AS2762900-00, which potently blocked IL-23-induced cell proliferation, regardless of the concentration of IL-23. Here, we evaluated the therapeutic potential of AS2762900-00 in the treatment of psoriasis. Compared with untreated control, AS2762900-00 significantly reduced the epidermal thickness of lesions in a clinically relevant psoriatic human skin xenograft model. The expression of inflammatory genes including genes downstream of IL-23 signaling in the lesion tended to be lower in the AS2762900-00 group than the untreated group, suggesting that the inhibitory effects of AS2762900-00 in the psoriatic human skin xenograft model might occur via blockade of IL-23 signaling pathways. Further, AS2762900-00 showed an inhibitory effect on signal transducer and activator of transcription 3 (STAT3) phosphorylation as a downstream signal of IL-23 receptor activation in whole blood from patients with psoriasis. We also confirmed that AS2762900-00 inhibited IL-23-induced STAT3 phosphorylation in a concentration-dependent manner using whole blood from healthy donors. These data suggest that AS2762900-00 is a promising drug candidate for the treatment of psoriasis. In addition, STAT3 phosphorylation in whole blood may be a useful biomarker for the evaluation of the pharmacodynamic effects of AS2762900-00 in healthy volunteers in clinical development.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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