<Advanced Energy Utilization Division> Molecular Nanotechnology Research Section

3-1. Research Activities in 202

Generation of Novel Polycyclic Aromatic Compounds by Tandem Cyclization of Macrocyclic Aryleneethynylenes

This is the author's version of a work that was accepted for publication in Chemistry - A European Journal. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Chemistry - A European Journal, VOLUME：18, ISSUE：4, DATE：2012-08-22, DOI: 10.1002/chem.201201061.This is the author's version of a work that was accepted for publication in Angewandte Chemie International Edition. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Angewandte Chemie International Edition, VOLUME：52, ISSUE：15, DATE：2013-02-28, DOI：10.1002/anie.201210233.This is the author's version of a work that was accepted for publication in Angewandte Chemie International Edition. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Angewandte Chemie International Edition, VOLUME：54, ISSUE：7, DATE：2015-01-14, DOI：10.1002/anie.201410791

Bridging pico-to-nanonewtons with a ratiometric force probe for monitoring nanoscale polymer physics before damage

ピンと張られた分子鎖を定量する「羽ばたき型蛍光Force Probe」の開発 --高分子材料の中で力のかかった分子鎖の比率を蛍光イメージングで計測する--. 京都大学プレスリリース. 2022-01-14.Understanding the transmission of nanoscale forces in the pico-to-nanonewton range is important in polymer physics. While physical approaches have limitations in analyzing the local force distribution in condensed environments, chemical analysis using force probes is promising. However, there are stringent requirements for probing the local forces generated before structural damage. The magnitude of those forces corresponds to the range below covalent bond scission (from 200 pN to several nN) and above thermal fluctuation (several pN). Here, we report a conformationally flexible dual-fluorescence force probe with a theoretically estimated threshold of approximately 100 pN. This probe enables ratiometric analysis of the distribution of local forces in a stretched polymer chain network. Without changing the intrinsic properties of the polymer, the force distribution was reversibly monitored in real time. Chemical control of the probe location demonstrated that the local stress concentration is twice as biased at crosslinkers than at main chains, particularly in a strain-hardening region. Due to the high sensitivity, the percentage of the stressed force probes was estimated to be more than 1000 times higher than the activation rate of a conventional mechanophore

Bridging Pico-to-Nanonewtons with a Ratiometric Force Probe for Monitoring Nanoscale Polymer Physics Before Damage

Understanding the transmission of nanoscale forces in the pico-to-nanonewton range is important in polymer physics. While physical approaches have limitations in analyzing the local force distribution in condensed environments, chemical analysis using force probes is promising. However, there are stringent requirements for probing the local forces generated before structural damage. The magnitude of those forces corresponds to the range below covalent bond scission (from 200 pN to several nN) and above thermal fluctuation (several pN). Here, we report a conformationally flexible dual-fluorescence force probe with a theoretically estimated threshold of approximately 100 pN. This probe enables ratiometric analysis of the distribution of local forces in a stretched polymer chain network. Without changing the intrinsic properties of the polymer, the force distribution was reversibly monitored in real time. Chemical control of the probe location demonstrated that the local stress concentration is twice as biased at crosslinkers than at main chains, particularly in a strain-hardening region. Due to the high sensitivity, the percentage of stressed force probes was estimated to be more than 1000 times higher than the activation rate of a conventional mechanophore.Comment: 21 pages and 5 figures in the main text, and 73 pages and 68 figures in the supplementary material

Gamma-glutamyl transpeptidase (γ-GTP) has an ambivalent association with hypertension and atherosclerosis among elderly Japanese men: a cross-sectional study

Background: Even though there is bidirectional association between hypertension and atherosclerosis, atherosclerosis itself is involved in the process of endothelial repair. To clarify the association of endothelial repair with hypertension, a cross-sectional study was conducted. Methods: We conducted a cross-sectional study of 562 elderly Japanese men aged 60-69. As gamma-glutamyl transpeptidase (γ-GTP) could act as a marker of oxidative stress that injures endothelial cell and higher levels of CD34-positive cell indicate a higher activity of endothelial repair, we therefore performed a CD34-positive level specific analysis of γ-GTP on atherosclerosis and hypertension. Results: In the present study population, hypertension was independently and positively associated with atherosclerosis (multivariable odds ratio (OR) = 2.09 (1.30, 3.35)). Among participants with high CD34-positive cells, γ-GTP showed significant and positive association with atherosclerosis (OR of the log-transformed value of γ-GTP (OR) = 2.26 (1.32, 3.86)) but not with hypertension (OR = 0.77 (0.51, 1.17)). Among participants with low CD34-positive cells, even γ-GTP showed no significant association with atherosclerosis (OR = 0.92 (0.51, 1.68)), but was significantly and positively associated with hypertension (OR = 1.99 (1.27, 3.12)). Conclusions: γ-GTP revealed to have ambivalent association with hypertension and atherosclerosis. Active endothelial repair that is associated with atherosclerosis might have beneficial association with hypertension

Circulating CD34+ cells and active arterial wall thickening among elderly men: A prospective study

Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60?69 years who participated in a general health check-up at least twice from 2014?2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects

Association between circulating CD34‑positive cell count and height loss among older men

Height loss starting in middle age is reportedly signifcantly associated with death due to cardiovascular disease. Impaired blood fow is the main pathology in cardiovascular disease. Hematopoietic stem cells such as CD34-positive cells play an important role in maintaining the microcirculation and preventing impaired blood fow by activating endothelial repair and angiogenesis. Therefore, circulating CD34-positive cell count could be associated with height loss. To clarify the association between circulating CD34-positive cell count and height loss, we conducted a follow-up study of 363 Japanese men aged 60–69 years over 2 years. Height loss was defned as being in the highest quartile of height decrease per year. Independent of known cardiovascular risk factors, circulating CD34-positive cell count was signifcantly inversely associated with height loss. The fully adjusted odds ratio (OR) and 95% confdence interval (CI) of height loss for circulating CD34-positive cell count (logarithmic values) was 0.49 (0.32, 0.74). This study suggests that a lower capacity to maintain the microcirculation due to a fewer CD34-positive cells might afect height loss

Association between high psychological distress and poor oral health-related quality of life (OHQoL) in Japanese community-dwelling people: the Nagasaki Islands Study

Background: We investigated the association between psychological distress and oral health status/oral health-related quality of life (OHQoL) in Japanese community-dwelling people. Methods: We conducted a cross-sectional study using data from the Nagasaki Islands Study. A total of 1183 (455 men and 728 women)has been analyzed in this study. Psychological distress was measured using the Kessler Psychological Distress Scale (K6). Oral health status was measured by dental examination. The OHQoL was measured using the General Oral Health Assessment Index (GOHAI). We defined the total score of ?5 points on the K6 as high psychological distress (high-K6 group). Results: The multiple linear regression analysis to identify the GOHAI showed that gender, K6, the total number of teeth, the number of dental caries, and visiting a dental clinic within the past 6 months significantly associated with the GOHAI. Among all of these variables, high-K6 (? 5)was a substantial contributing factor of the GOHAI (β = ? 0.23, 95% Cl ? 2.31 to ?1.41, p < 0.0001).Conclusions: It is likely that the individual with high psychological distress was strongly related to poor OHQoL even in the general population

Identification of risk factors for elevated serum IgG4 levels in subjects in a large-scale health checkup cohort study

Introduction: To allow the identification of IgG4-related disease (IgG4-RD) from a subclinical phase as it is important to understand the risk of elevated serum IgG4 levels. We planned to evaluate serum IgG4 levels in the participants of the Nagasaki Islands Study (NaIS), a large-scale health checkup cohort study.Methods: This study included 3,240 individuals who participated in the NaIS between 2016 and 2018 and consented to participate in the study. Serum IgG4, IgG, and IgE levels and human leukocyte antigen (HLA) genotyping results of the NaIS subjects as well as lifestyle habits and peripheral blood test results were analyzed. The magnetic bead panel assay (MBA) and the standard nephelometry immunoassay (NIA) were used to measure serum IgG4 levels. The data were evaluated using multivariate analysis to identify lifestyle and genetic factors associated with elevated serum IgG4 levels.Results: Serum IgG4 levels measured with the NIA and MBA showed a tight positive correlation between the two groups (correlation coefficient 0.942). The median age of the participants in the NaIS was 69 years [63–77]. The median serum IgG4 level was 30.2 mg/dL [IQR 12.5–59.8]. Overall, 1019 (32.1%) patients had a history of smoking. When the subjects were stratified into three groups based on the smoking intensity (pack-year), the serum IgG4 level was significantly higher among those with a higher smoking intensity. Accordingly, the multivariate analysis identified a significant relationship between smoking status and serum IgG4 elevation.Conclusion: In this study, smoking was identified as a lifestyle factor correlating positively with elevated serum IgG4 levels

Enantiopure distorted ribbon-shaped nanographene combining two-photon absorptionbased upconversion and circularly polarized luminescence

Herein we describe a distorted ribbon-shaped nanographene exhibiting unprecedented combination of optical properties in graphene-related materials, namely upconversion based on two-photon absorption (TPA-UC) together with circularly polarized luminescence (CPL). The compound is a graphene molecule of ca. 2 nm length and 1 nm width with edge defects that promote the distortion of the otherwise planar lattice. The edge defects are an aromatic saddle-shaped ketone unit and a [5]carbohelicene moiety. This system is shown to combine two-photon absorption and circularly polarized luminescence and a remarkably long emission lifetime of 21.5 ns. The [5]helicene is responsible for the chiroptical activity while the push–pull geometry and the extended network of sp2 carbons are factors favoring the nonlinear absorption. Electronic structure theoretical calculations support the interpretation of the results.This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (ERC-2015-STG-677023). We also thank the Ministerio de Economía y Competitividad (MINECO, Spain) (CTQ2015-70283-P, CTQ2014-53598-R, MAT2014-54231-C4-1P, FIS2016-77578-R) and the “Unidad de Excelencia Química Aplicada a Biomedicina y Medioambiente (UGR)”. A. G. C., C. S. S. and C. M. C. acknowledge funding from MINECO (Spain) for RyC-2013-12943, IJCI-2014-19291 and BES-2016-076371 contracts, respectively. I. R. M. thanks UGR (Spain) for a postdoctoral scholarship. I. M. and E. M. thank the Fundação para a Ciência e a Tecnologia for financial support (IF/00759/2013 and post-doc grant SFRH/BPD/75782/2011). We thank the CSIRC-Alhambra for supercomputing facilities