Comment; Eco-Ethica and Environmental Ethics

千葉大学公共研究センター21世紀プログラム「持続可能な福祉社会に向けた公共研究拠点

Conformational Analysis of <i>o</i>-Phenylenes: Helical Oligomers with Frayed Ends

The o-phenylenes represent a fundamental class of conjugated polymers that, unlike the isomeric p-phenylenes, should exhibit rich conformational behavior. Recently, we reported the synthesis and characterization of a series of o-phenylene oligomers featuring unusual electronic properties, including surprisingly long-range delocalization as measured by UV−vis spectroscopy and hypsochromic shifts in fluorescence maxima with increasing length. To rationalize these properties, we hypothesized that the oligomers predominantly assume a stacked helical conformation in solution. This assertion, however, was supported by only indirect evidence. Here we present a thorough investigation of the conformational behavior of this series of o-phenylenes by dynamic NMR spectroscopy and computational chemistry. EXSY experiments, in combination with other two-dimensional NMR techniques, provided full 1H chemical shift assignments for at least the two most prevalent conformers for each member of the series (hexamer to dodecamer). GIAO density functional theory calculations were then used to relate the NMR data to specific molecular geometries. We have found that the o-phenylenes do indeed assume stacked helical conformations with disorder occurring at the ends. Thus, the o-phenylene motif appears to have great potential as a means to organize arenes into predictable three-dimensional arrangements. Our results also illustrate the power of 1H NMR GIAO predictions in the solution-phase conformational analysis of oligomers, particularly those with a high density of aromatic subunits

Table_4_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_1_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_3_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Table_2_Physical activities and risk of neurodegenerative diseases: A two-sample Mendelian randomization study.DOCX

ObjectivesPhysical activity (PA) is considered beneficial in slowing the progression and improving the neurodegenerative disease prognosis. However, the association between PA and neurodegenerative diseases remains unknown. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to estimate the causal association between PA phenotypes and neurodegenerative diseases.Materials and methodsGenetic variants robustly associated with PA phenotypes, used as instrumental variables, were extracted from public genome-wide association study (GWAS) summary statistics. Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), were considered outcomes. GWAS information was also obtained from the most recent large population study of individuals with European ancestry. Multiple MR methods, pleiotropy tests and sensitivity analyses were performed to obtain a robust and valid estimation.ResultsWe found a positive association between moderate-to-vigorous physical activities and ALS based on the inverse variance weighted MR analysis method (OR: 2.507, 95% CI: 1.218–5.160, p = 0.013). The pleiotropy test and sensitivity analysis confirmed the robustness and validity of these MR results. No causal effects of PA phenotypes were found on PD and AD.ConclusionOur study indicates a causal effect of PA on the risk of neurodegenerative diseases. Genetically predicted increases in self-reported moderate-to-vigorous PA participation could increase the risk of ALS in individuals of European ancestry. Precise and individualized prescriptions of physical activity should be provided to the elderly population.</p

Gold Nanorods-Based Smart Nanoplatforms for Synergic Thermotherapy and Chemotherapy of Tumor Metastasis

The combination therapy of photothermal therapy and chemotherapy as a promising strategy has drawn extensive attention by overcoming the limitations of conventional treatments in tumor therapy. Gold nanorods-based nanoplatforms were herein designed by integrating doxorubicin (DOX)- and polydopamine-coated gold nanorods (GNRs@PDA) for tumor metastasis inhibition and multifunctional drug delivery. The GNRs@PDA–poly­(ethylene glycol) (PEG)–DOX nanocomplex showed robust stability and excellent near-infrared (NIR) photothermal conversion efficiency under laser irradiation. The release of loaded DOX from GNRs@PDA–PEG–DOX nanocomposites was improved in tumor microenvironments. Furthermore, the PDA-functionalized GNR nanocomposites were expected to be potential photoacoustic imaging agents for imaging-guided tumor therapy. Upon NIR laser irradiation, the efficiency of tumor inhibition of GNRs@PDA–PEG–DOX is greater than that of the other group in vitro and in vivo, which was confirmed by immunohistochemistry staining, demonstrating a promising strategy for suppression of tumor metastasis and low long-term systemic toxicity. These results illustrated a promising strategy of tailor-made GNRs@PDA–PEG–DOX nanoplatforms for ablation of tumor and suppression of tumor metastasis in clinical application

High hydrostatic pressure (30 atm) enhances the apoptosis and inhibits the proteoglycan synthesis and extracellular matrix level of human nucleus pulposus cells via promoting the Wnt/β-catenin pathway

Hydrostatic pressure is known to regulate bovine nucleus pulposus cell metabolism, but its mechanism in human nucleus pulposus cells (HNPCs) remains obscure, which attracts our attention and becomes the focus in this study. Specifically, HNPCs were treated with SKL2001 (an agonist in the Wnt/β-catenin pathway) or XAV-939 (an inhibitor of the Wnt/β-catenin pathway), and pressurized under the hydrostatic pressure of 1, 3 and 30 atm. The viability, apoptosis and proteoglycan synthesis of treated HNPC were assessed by CCK-8, flow cytometry and radioisotope incorporation assays. The levels of extracellular matrix, Collagen-II, matrix metalloproteinase 3 (MMP3), Wnt-3a and β-catenin were measured by toluidine blue staining, immunocytochemistry and Western blot. Appropriate hydrostatic stimulation (3 atm) enhanced the viability and proteoglycan synthesis yet inhibited the apoptosis of HNPCs, which also up-regulated extracellular matrix and Collagen-II levels, and down-regulated MMP3, Wnt-3a and β-catenin levels in treated HNPCs. Furthermore, high hydrostatic pressure (30 atm) inhibited the viability and proteoglycan synthesis, and promoted the morphological change and apoptosis of HNPCs, which also down-regulated extracellular matrix and Collagen-II levels and up-regulated MMP3, Wnt-3a and β-catenin levels. Besides, SKL2001 reversed the effects of hydrostatic pressure (3 atm) on inhibiting Wnt-3a, β-catenin, and MMP3 levels and promoting Collagen-II level in HNPC; whereas, XAV-939 reversed the effects of high hydrostatic pressure (30 atm) on promoting MMP3, Wnt-3a, and β-catenin levels and inhibiting Collagen-II level and proteoglycan synthesis of HNPCs. Collectively, high hydrostatic pressure promoted the apoptosis and inhibited the viability of HNPCs via activating the Wnt/β-catenin pathway.</p

Media 1: Directional terahertz beams realized by depth-modulated metallic surface grating structures

Originally published in JOSA B on 01 November 2011 (josab-28-11-2674

Novel Redox Hydrogel by in Situ Gelation of Chitosan as a Result of Template Oxidative Polymerization of Hydroquinone

A new redox hydrogel using poly(hydroquinone) (PHQ) as polymeric redox couple and chitosan as matrix was synthesized by simple exposing an acidic chitosan/hydroquinone (HQ) solution to the air. PHQ was synthesized in situ by oxidative polymerization of HQ using oxygen as an oxidant. The presence of chitosan increases the reaction rate significantly, suggesting chitosan works as a template for the polymerization of HQ. The reaction rate increases linearly with chitosan concentration when molar ratio of chitosan/HQ is less than 0.96 but keeps constant beyond that point. These results suggest a pick-up mechanism for the template polymerization of HQ. The polymerization of HQ further results in the gelation of the aqueous solution, as physical cross-links forms between PHQ and chitosan. The gelation time decreases with increasing chitosan and HQ concentration and also increasing temperature. The resultant hydrogel are redox-active. Cyclic voltammogram of the hydrogel presents two oxidation peaks at 0.62 and 1.23 V and two reduction peaks at −0.79 and −1.66 V (vs Ag/AgCl). The in situ-formed redox hydrogel may find applications in biomedical areas