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体内時計の評価系の開発と光応答の理解によるヒト体内時計を光で調節する系の基盤確立

Research Project

Project/Area Number 20H04565
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90150:Medical assistive technology-related
Research InstitutionKomatsu University

Principal Investigator

平山 順  公立小松大学, 保健医療学部, 教授 (90510363)

Co-Investigator(Kenkyū-buntansha) 野川 雅道  公立小松大学, 保健医療学部, 准教授 (40292445)
古澤 之裕  富山県立大学, 工学部, 准教授 (80632306)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2023: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2022: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Keywords体内時計 / 細胞時計 / 生体信号 / 光 / ゼブラフィッシュ / 実験モデル動物 / 遺伝子改変個体 / ウェアラブルセンサ / 血中酸素飽和度 / 静脈血酸素飽和度 / 深部体温 / 光制御
Outline of Research at the Start

体内時計は、睡眠といった多様な生理機能に日周変動を作り出し、その時刻を外環境に同調させる恒常性維持機構である。この制御には、体内時計自体の時刻が光情報を利用し、自然界の昼夜の変化に同調(光同調)することが必須である。要介護者と高齢者では、体内時計の光同調が不安定になり易いため、夜間の徘徊(睡眠障害)やせん妄(意識障害)といった介護者に大きな負担となる病態が頻発する。この解決策として、在宅で簡便に使用できるヒト体内時計を人工光を用いて調節するシステムを構築することが本研究の目的である。

Outline of Annual Research Achievements

体内時計は、多様な生理機能に観察される約24時間の周期変動を作り出す生命現象であり「光を利用し自然界の昼夜の変化に対し体内環境を最適化する」という重要な生理的な役割を担っている。この機能には、体内時計自体の時刻が光情報を利用し自然界の昼夜の変化に同調(光同調)することが必須である。要介護者と高齢者では、体内時計の光同調が不安定になり易く、睡眠障害や意識障害といった介護者に負担となる病態が頻発する。この解決のために「簡便に使用できるヒト体内時計を人工光により正常化する系の開発」が求められている。しかし、1)非侵襲的で安価なヒト体内時計の評価系の構築が困難であること、および 2)体内時計の光同調機構の理解が不十分であることから、ヒト体内時計の光調節系は確立されていない。この背景より、本研究は、1)細胞時計の光同調を制御する新規のシグナル分子の探索(計画1)、および2)体内時計の評価系の開発と光調節系の基盤確立(計画2)を目的としている。計画1の研究成果は、光による細胞時計の同調が細胞内の酸化状態の調節を介していることを見出し、この調節に関わる酸化状態の変化に応答する分子群を選定したことである。また睡眠調節ホルモンのメラトニンが、その抗酸化作用を介して細胞時計とその代謝制御を調節することを提唱した。計画2の研究成果は、ヒト体内時計を評価する系を構築するために生体信号の日周変動を計測する系を確立したことである。またこの評価系に基づいて、人工光によりヒト体内時計の時刻を調節する系の構築を開始した。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

実験モデル動物を用いた細胞時計の光同調を制御するシグナル分子の探索と同定したシグナル分子の遺伝子改変個体の作出・解析が実施できた。また、生体信号の日周変動を計測する系の構築が計画通りに進んでいる。

Strategy for Future Research Activity

これまでの実験モデル同b津を用いた解析と生体計測に関する解析を継続して行う。特に、後者に関する成果の論文化をめざしていく。

Report

(3 results)
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (35 results)

All 2023 2022 2021 2020 Other

All Journal Article (27 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 27 results,  Open Access: 21 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Remarks (4 results)

  • [Journal Article] Kynurenine promotes Calcitonin secretion and reduces cortisol in the Japanese flounder Paralichthys olivaceus2023

    • Author(s)
      Ikari T, Furusawa Y, Tabuchi Y, Maruyama Y, Hattori A, Kitani Y, Toyota K, Nagami A, Hirayama J, Watanabe K, Shigematsu A, Rafiuddin MA, Ogiso S, Fukushi K, Kuroda K, Hatano K, Sekiguchi T, Kawashima R, Srivastav AK, Nishiuchi T, Sakatoku A, Yoshida M, Matsubara H, Suzuki N
    • Journal Title

      Sci. Rep.

      Volume: In press

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nocturnal melatonin increases glucose uptake via insulin-independent action in goldfish brain2023

    • Author(s)
      Watanabe K, Nakano M, Maruyama Y, Hirayama J, Suzuki N, Hattori A
    • Journal Title

      Front. Endocrinol.

      Volume: In press

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deep ocean water alters the cholesterol and mineral metabolism of squid Todarodes pacificus and suppresses its weight loss2023

    • Author(s)
      Hatano Kaito、Yoshida Masa-Aki、Hirayama Jun、Kitani Yoichiro、Hattori Atsuhiko、Ogiso Shouzo、Watabe Yukina、Sekiguchi Toshio、Tabuchi Yoshiaki、Urata Makoto、Matsumoto Kyoko、Sakatoku Akihiro、Srivastav Ajai K.、Toyota Kenji、Matsubara Hajime、Suzuki Nobuo
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 7591-7591

    • DOI

      10.1038/s41598-023-34443-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] daptation to the shallow sea floor environment of a species of marine worms, Oligobrachia mashikoi, generally inhabiting deep-sea water.2023

    • Author(s)
      Shouzo Ogiso, Kazuki Watanabe, Yusuke Maruyama, Hiroshi Miyake, Kaito Hatano, Jun Hirayama, Atsuhiko Hattori, Yukina Watabe, Toshio Sekiguchi, Yoichiro Kitani, Yukihiro Furusawa, Yoshiaki Tabuchi, Hajime Matsubara, Mana Nakagiri, Kenji Toyota, Yuichi Sasayama, Nobuo Suzuki.
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 6299-6299

    • DOI

      10.1038/s41598-023-33309-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Use of biosignal measurements for circadian clock evaluation2023

    • Author(s)
      Kawashima R, Suzuki I, Watanabe K, Fukuda T, Nogawa M, Hirayama J
    • Journal Title

      Advances in Health and Disease. (Edited by Lowell T. Duncan) Nova Science Publishers.

      Volume: 66(In press)

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Integrator complex subunit 15 controls mRNA splicing and is critical for eye development2023

    • Author(s)
      Noriyuki Azuma, Tadashi Yokoi, Taku Tanaka, Emiko Matsuzaka, Yuki Saida, Sachiko Nishina, Miho Terao, Shuji Takada, Maki Fukami, Kohji Okamura, Kayoko Maehara, Tokiwa Yamasaki, Jun Hirayama, Hiroshi Nishina, Hiroshi Handa, and Yuki Yamaguchi
    • Journal Title

      Hum. Mol. Genet.

      Volume: ddad034 Issue: 12 Pages: 2032-2045

    • DOI

      10.1093/hmg/ddad034

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Possible involvement of Calcitonin I and II in calcium metabolism of the female reproductive physiology of goldfish (Carassius auratus).2023

    • Author(s)
      Kuroda K, Hatano K, Kawamura R, Fukushima A, Sasayama Y, Tabuchi Y, Furusawa Y, Ikegame M, Hattori A, Hirayama J, Fukuda T, Uekura S, Matsubara H, Kawago U, Sekiguchi T, Srivastav A.K, Suzuki N
    • Journal Title

      Int. Aquat. Res.

      Volume: 15 Pages: 15-26

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diurnal rhythm of indole compounds synthesized in polychaete Perinereis aibuhitensis (Grube,1878) heads2023

    • Author(s)
      Ogiso S, Maruyama Y, Hattori A, Hirayama J, Yamaguchi K, Shimizu N, Suzuki N
    • Journal Title

      Aquacult. Sci.

      Volume: In press

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fluorene is Highly Toxic to Zoea Larvae of the Red-Clawed Crab Chiromantes haematocheir2023

    • Author(s)
      Kawamura R, Rafiuddin AM, Toyota K, Honda M, Amornsakun T, Tabuchi Y, Hattori A, Harumi T, Hirayama J, Urata M, Matsumoto K, Nishimoto S, Srivastav AK, Suzuki N, Matsubara H
    • Journal Title

      Int. J. Zoolog. Investig.

      Volume: 9 Issue: 1 Pages: 1-7

    • DOI

      10.33745/ijzi.2023.v09i01.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physiological consequences of space flight, including abnormal bone metabolism, space radiation injury, and circadian clock dysregulation: Implications of melatonin use and regulation as a countermeasure2022

    • Author(s)
      Hirayama Jun、Hattori Atsuhiko、Takahashi Akihisa、Furusawa Yukihiro、Tabuchi Yoshiaki、Shibata Masahiro、Nagamatsu Aiko、Yano Sachiko、Maruyama Yusuke、Matsubara Hajime、Sekiguchi Toshio、Suzuki Nobuo
    • Journal Title

      Journal of Pineal Research

      Volume: 74 Issue: 1

    • DOI

      10.1111/jpi.12834

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Editorial: The circadian circus ? how our clocks keep us ticking2022

    • Author(s)
      Hughes Alun Thomas Lloyd、Attarian Hrayr P.、Hirayama Jun
    • Journal Title

      Frontiers in Neuroscience

      Volume: 16

    • DOI

      10.3389/fnins.2022.973727

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Functional analysis of a matrix peptide involved in calcification of the exoskeleton of the kuruma prawn, Marsupenaeus japonicus2022

    • Author(s)
      Sekimoto Aika、Ohira Tsuyoshi、Shigematsu Atsushi、Okumura Takuji、Mekuchi Miyuki、Toyota Kenji、Mishima Hiroyuki、Kawamura Ryoya、Hatano Kaito、Kawago Umi、Kitani Yoichiro、Sekiguchi Toshio、Amornsakun Thumronk、Hirayama Jun、Hattori Atsuhiko、Matsubara Hajime、Suzuki Nobuo
    • Journal Title

      Aquaculture

      Volume: 559 Pages: 738437-738437

    • DOI

      10.1016/j.aquaculture.2022.738437

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hydroxylated benzo[c]phenanthrene metabolites cause osteoblast apoptosis and skeletal abnormalities in fish2022

    • Author(s)
      Suzuki Nobuo, Honda Masato, Sekiguchi Toshio, Toriba Akira, Tang Ning, Edward Nagato Go, Zhang Lulu, Hayakawa Kazuichi, et all.
    • Journal Title

      Ecotoxicology and Environmental Safety

      Volume: 234 Pages: 113401-113401

    • DOI

      10.1016/j.ecoenv.2022.113401

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteoclastic and Osteoblastic Responses to Hypergravity and Microgravity: Analysis Using Goldfish Scales as a Bone Model2022

    • Author(s)
      Yamamoto Tatsuki、Ikegame Mika、Furusawa Yukihiro、Tabuchi Yoshiaki、Hatano Kaito、Watanabe Kazuki、Kawago Umi、Hirayama Jun、Yano Sachiko、Sekiguchi Toshio、Kitamura Kei-ichiro、Endo Masato、Nagami Arata、Matsubara Hajime、Maruyama Yusuke、Hattori Atsuhiko、Suzuki Nobuo
    • Journal Title

      Zoological Science

      Volume: 39 Issue: 4 Pages: 388-396

    • DOI

      10.2108/zs210107

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of the thermal responses in Japanese pearl oysters, Pinctada fucata martensii2022

    • Author(s)
      Hatano K, Kawamura R, Watabe Y, Ogiso S, Nagami A, Matsubara H, Urata M, Matsumoto K, Yachiguchi K, Shimizu N, Hirayama J, Furusawa Y, Tabuchi Y, Srivastav AK, Suzuki N
    • Journal Title

      Int. J. Zool. Inv.

      Volume: 8 Pages: 371-378

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Light-Inducible Genes <i>Per2</i>, <i>Cry1a</i>, and <i>Cry2a</i> Regulate Oxidative Status in Zebrafish2021

    • Author(s)
      Alifu Yikelamu、Kofuji Satoshi、Sunaga Sachi、Kusaba Mizuki、Hirayama Jun、Nishina Hiroshi
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 44 Issue: 8 Pages: 1160-1165

    • DOI

      10.1248/bpb.b21-00432

    • NAID

      130008070607

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2021-08-01
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influences of the priming procedure and saline circulation conditions on polyvinylpyrrolidone in vitro elution from polysulfone membrane dialyzers2021

    • Author(s)
      Sato Yoshinori、Horiuchi Hayato、Fukasawa Shinji、Takesawa Shingo、Hirayama Jun
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 28 Pages: 101140-101140

    • DOI

      10.1016/j.bbrep.2021.101140

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Data on the in vitro elution of substances from three types of polysulfone membrane dialyzers as well as a non-polysulfone cellulose triacetate membrane dialyzer evaluated using ultraviolet absorption2021

    • Author(s)
      Sato Yoshinori、Horiuchi Hayato、Fukasawa Shinji、Takesawa Shingo、Hirayama Jun
    • Journal Title

      Data in Brief

      Volume: 39 Pages: 107490-107490

    • DOI

      10.1016/j.dib.2021.107490

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral administration of melatonin increases plasma calcium and magnesium and improves bone metabolism in aged male mice2021

    • Author(s)
      Igarashi-Migitaka Junko、Maruyama Yusuke、Seki Azusa、Hirayama Jun、Kamijo-Ikemori Atsuko、Hirata Kazuaki、Kawamura Ryoya、Matsubara Hajime、Srivastav Ajai K、Tabuchi Yoshiaki、Mishima Hiroyuki、Hattori Atsuhiko、Suzuki Nobuo
    • Journal Title

      Melatonin Research

      Volume: 4 Issue: 4 Pages: 581-591

    • DOI

      10.32794/mr112500113

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] In Vivo Suppression of Osteoclastic and Osteoblastic Activities of Goldfish Scales in Water Containing Cadmium2021

    • Author(s)
      Suzuki N, Kawago U, Honda M, Srivastav AK, Amornsakun T, Matsumoto K, Hirayama J, Matsubara H, Shimizu N, Sekiguchi T, Sasayama Y, Tabuchi Y, Hattori A, Shimasaki Y, Oshima Y
    • Journal Title

      Journal of the Faculty of Agriculture, Kyushu University

      Volume: 66 Issue: 2 Pages: 199-203

    • DOI

      10.15017/4486551

    • NAID

      120007143908

    • ISSN
      0023-6152
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glyoxal‐induced formation of advanced glycation end‐products in type 1 collagen decreases both its strength and flexibility in vitro2021

    • Author(s)
      Kitamura Kei‐ichiro、Hirayama Jun、Tabuchi Yoshiaki、Minami Takao、Matsubara Hajime、Hattori Atsuhiko、Suzuki Nobuo
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 12 Issue: 9 Pages: 1555-1559

    • DOI

      10.1111/jdi.13528

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic response to low-intensity ultrasound on mouse ST2 bone marrow stromal cells2021

    • Author(s)
      Tabuchi Yoshiaki、Hasegawa Hideyuki、Suzuki Nobuo、Furusawa Yukihiro、Hirano Tetsushi、Nagaoka Ryo、Hirayama Jun、Hoshi Nobuhiko、Mochizuki Takashi
    • Journal Title

      Molecular Medicine Reports

      Volume: 23 Issue: 3 Pages: 173-173

    • DOI

      10.3892/mmr.2020.11812

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight2020

    • Author(s)
      Yamamoto, T., Ikegame, M., Hirayama, J., Kitamura, K., Tabuchi, Y., Furusawa, Y., Sekiguchi, T., Endo, M., Mishima, H., Seki, A., Yano, S., Matsubara H., Hattori, A. and Suzuki, N.
    • Journal Title

      Biomedical Research

      Volume: 41 Issue: 6 Pages: 279-288

    • DOI

      10.2220/biomedres.41.279

    • NAID

      130007948844

    • ISSN
      0388-6107, 1880-313X
    • Year and Date
      2020-12-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] De novo transcriptome analysis and gene expression profiling of fish scales isolated from Carassius auratus during space flight: Impact of melatonin on gene expression in response to space radiation2020

    • Author(s)
      Furusawa Yukihiro、Yamamoto Tatsuki、Hattori Atsuhiko、Suzuki Nobuo、Hirayama Jun、Sekiguchi Toshio、Tabuchi Yoshiaki
    • Journal Title

      Molecular Medicine Reports

      Volume: 22 Pages: 2627-2636

    • DOI

      10.3892/mmr.2020.11363

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral administration of melatonin contained in drinking water increased bone strength in naturally aged mice2020

    • Author(s)
      Igarashi-Migitaka Junko、Seki Azusa、Ikegame Mika、Honda Masato、Sekiguchi Toshio、Mishima Hiroyuki、Shimizu Nobuaki、Matsubara Hajime、Srivastav Ajai K.、Hirayama Jun、Maruyama Yusuke、Kamijo-Ikemori Atsuko、Hirata Kazuaki、Hattori Atsuhiko、Suzuki Nobuo
    • Journal Title

      Acta Histochemica

      Volume: 122 Issue: 6 Pages: 151596-151596

    • DOI

      10.1016/j.acthis.2020.151596

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The use of chemical compounds to identify the regulatory mechanisms of vertebrate circadian clocks.2020

    • Author(s)
      Nishimura A, Izawa J, Hattori A, Suzuki N, Hirayama J# #Corresponding author
    • Journal Title

      Curr Drug Targets.

      Volume: 21 Issue: 5 Pages: 425-432

    • DOI

      10.2174/1389450120666190926143120

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of RANKL-producing cells and osteoclastic activation by the addition of exogenous RANKL in the regenerating scales of goldfish.2020

    • Author(s)
      Yamamoto, T., Ikegame, M., Kawago, U., Tabuchi, Y., Hirayama, J., Sekiguchi, T., Furusawa, Y., Yachiguchi, K., Matsubara, H., Urata, M., Hattori, A. and Suzuki, N.
    • Journal Title

      Biological Science in Space

      Volume: 34 Issue: 0 Pages: 34-40

    • DOI

      10.2187/bss.34.34

    • NAID

      130007884615

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Shedding light on vertebrate circadian clocks2022

    • Author(s)
      Hirayama Jun
    • Organizer
      2022 UTAR (Malaysia) - KU (Japan) Interaction Day(Web開催)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 体内時計の光制御の理解に基づく体内時計を光で調節する系の基盤確立2021

    • Author(s)
      平山 順
    • Organizer
      2021年度 照明学会全国大会(Web開催)
    • Related Report
      2021 Annual Research Report
  • [Presentation] グリオキサールによる終末糖化産物の形成は、1型コラーゲンの強度と柔軟性を低下させる2021

    • Author(s)
      平山 順 北村 敬一郎 鈴木 信雄
    • Organizer
      第31回日本メイラード学会年会(Web開催)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Regulation of behavioral rhythms and locomotor activity by light-inducible components of the circadian clock in zebrafish2021

    • Author(s)
      平山 順
    • Organizer
      第126回日本解剖学会総会・全国学術集会 第98回日本生理学会大会 合同大会: 解剖と生理の時計 (Web開催
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Remarks] 公立小松大学 教員紹介ページ

    • URL

      https://www.komatsu-u.ac.jp/academics/teacher/#rinsyo

    • Related Report
      2022 Annual Research Report
  • [Remarks] 公立小松大学 教員紹介ページ

    • URL

      https://www.komatsu-u.ac.jp/academics/teacher/pdf/jun_hirayama.pdf

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
  • [Remarks] プレスリリース資料(日本語)

    • URL

      https://www.tmd.ac.jp/archive-tmdu/kouhou/20190118_1.pdf

    • Related Report
      2020 Annual Research Report
  • [Remarks] プレスリリース資料(英語)

    • URL

      https://www.eurekalert.org/pub_releases/2019-02/tmad-slo020619.php

    • Related Report
      2020 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2023-12-25  

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