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1. Axin formation inhibitor 1 aggravates hepatic ischemia‒reperfusion injury by promoting the ubiquitination and degradation of PPARβ

Author

Baolin Qian, Bing Yin, Hongjun Yu, Chaoqun Wang, Shounan Lu, Shanjia Ke, Zihao Li, Xinglong Li, Yongliang Hua, Zhongyu Li, Yongzhi Zhou, Zhanzhi Meng, Yao Fu, Wei Tang, and Yong Ma

Subjects
Science
Abstract

Abstract Hepatic ischemia‒reperfusion injury (HIRI) is a common pathological phenomenon after hepatectomy and liver transplantation. Here, we aim to explore the role of Axin formation inhibitor 1 (Axin1) in HIRI. In this work, we find that the expression of Axin1 is upregulated after HIRI. Cellular experiments confirme that Axin1 knockdown alleviated hypoxia/reoxygenation (H/R)-induced inflammation and apoptosis. Subsequently, we construct a HIRI model based on transgenic hepatocellular-specific Axin1 knockout and overexpression male mice and find that Axin1 deletion alleviated inflammation and apoptosis. Transcriptome sequencing reveal that the genes whose expression differed after Axin1 overexpression are significantly enriched in the PPAR signaling pathway. Furthermore, we demonstrate that Axin1 negatively regulates the expression of PPARβ, thereby activating the NF-κB pathway. Mechanistically, Axin1 binds to PPARβ to enhance the ubiquitination-mediated degradation of PPARβ by the E3 ubiquitin ligase RBBP6. Notably, adenovirus-mediated Axin1 knockdown block I/R damage in mice. Our study results demonstrate that Axin1 exacerbates HIRI by promoting the ubiquitination and degradation of PPARβ, which in turn activates the NF-κB signaling pathway. These results suggest that Axin1 may be a potential therapeutic target for HIRI.

Published
2025
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2. JUNO sensitivity to invisible decay modes of neutrons

Author

JUNO Collaboration, Angel Abusleme, Thomas Adam, Kai Adamowicz, Shakeel Ahmad, Rizwan Ahmed, Sebastiano Aiello, Fengpeng An, Qi An, Giuseppe Andronico, Nikolay Anfimov, Vito Antonelli, Tatiana Antoshkina, João Pedro Athayde Marcondes de André, Didier Auguste, Weidong Bai, Nikita Balashov, Wander Baldini, Andrea Barresi, Davide Basilico, Eric Baussan, Marco Bellato, Marco Beretta, Antonio Bergnoli, Daniel Bick, Lukas Bieger, Svetlana Biktemerova, Thilo Birkenfeld, Iwan Blake, Simon Blyth, Anastasia Bolshakova, Mathieu Bongrand, Dominique Breton, Augusto Brigatti, Riccardo Brugnera, Riccardo Bruno, Antonio Budano, Jose Busto, Anatael Cabrera, Barbara Caccianiga, Hao Cai, Xiao Cai, Yanke Cai, Zhiyan Cai, Stéphane Callier, Steven Calvez, Antonio Cammi, Agustin Campeny, Chuanya Cao, Guofu Cao, Jun Cao, Rossella Caruso, Cédric Cerna, Vanessa Cerrone, Jinfan Chang, Yun Chang, Auttakit Chatrabhuti, Chao Chen, Guoming Chen, Pingping Chen, Shaomin Chen, Xin Chen, Yiming Chen, Yixue Chen, Yu Chen, Zelin Chen, Zhangming Chen, Zhiyuan Chen, Zikang Chen, Jie Cheng, Yaping Cheng, Yu Chin Cheng, Alexander Chepurnov, Alexey Chetverikov, Davide Chiesa, Pietro Chimenti, Yen-Ting Chin, Po-Lin Chou, Ziliang Chu, Artem Chukanov, Gérard Claverie, Catia Clementi, Barbara Clerbaux, Marta Colomer Molla, Selma Conforti Di Lorenzo, Alberto Coppi, Daniele Corti, Simon Csakli, Chenyang Cui, Flavio Dal Corso, Olivia Dalager, Jaydeep Datta, Christophe De La Taille, Zhi Deng, Ziyan Deng, Xiaoyu Ding, Xuefeng Ding, Yayun Ding, Bayu Dirgantara, Carsten Dittrich, Sergey Dmitrievsky, Tadeas Dohnal, Dmitry Dolzhikov, Georgy Donchenko, Jianmeng Dong, Evgeny Doroshkevich, Wei Dou, Marcos Dracos, Frédéric Druillole, Ran Du, Shuxian Du, Yujie Duan, Katherine Dugas, Stefano Dusini, Hongyue Duyang, Jessica Eck, Timo Enqvist, Andrea Fabbri, Ulrike Fahrendholz, Lei Fan, Jian Fang, Wenxing Fang, Dmitry Fedoseev, Li-Cheng Feng, Qichun Feng, Federico Ferraro, Amélie Fournier, Fritsch Fritsch, Haonan Gan, Feng Gao, Alberto Garfagnini, Arsenii Gavrikov, Marco Giammarchi, Nunzio Giudice, Maxim Gonchar, Guanghua Gong, Hui Gong, Yuri Gornushkin, Marco Grassi, Maxim Gromov, Vasily Gromov, Minghao Gu, Xiaofei Gu, Yu Gu, Mengyun Guan, Yuduo Guan, Nunzio Guardone, Rosa Maria Guizzetti, Cong Guo, Wanlei Guo, Caren Hagner, Hechong Han, Ran Han, Yang Han, Jinhong He, Miao He, Wei He, Xinhai He, Tobias Heinz, Patrick Hellmuth, Yuekun Heng, Rafael Herrera, YuenKeung Hor, Shaojing Hou, Yee Hsiung, Bei-Zhen Hu, Hang Hu, Jun Hu, Peng Hu, Shouyang Hu, Tao Hu, Yuxiang Hu, Zhuojun Hu, Guihong Huang, Hanxiong Huang, Jinhao Huang, Junting Huang, Kaixuan Huang, Shengheng Huang, Wenhao Huang, Xin Huang, Xingtao Huang, Yongbo Huang, Jiaqi Hui, Lei Huo, Wenju Huo, Cédric Huss, Safeer Hussain, Leonard Imbert, Ara Ioannisian, Roberto Isocrate, Arshak Jafar, Beatrice Jelmini, Ignacio Jeria, Xiaolu Ji, Huihui Jia, Junji Jia, Siyu Jian, Cailian Jiang, Di Jiang, Guangzheng Jiang, Wei Jiang, Xiaoshan Jiang, Xiaozhao Jiang, Yixuan Jiang, Xiaoping Jing, Cécile Jollet, Li Kang, Rebin Karaparabil, Narine Kazarian, Ali Khan, Amina Khatun, Khanchai Khosonthongkee, Denis Korablev, Konstantin Kouzakov, Alexey Krasnoperov, Sergey Kuleshov, Sindhujha Kumaran, Nikolay Kutovskiy, Loïc Labit, Tobias Lachenmaier, Haojing Lai, Cecilia Landini, Sébastien Leblanc, Frederic Lefevre, Ruiting Lei, Rupert Leitner, Jason Leung, Demin Li, Fei Li, Fule Li, Gaosong Li, Hongjian Li, Huang Li, Jiajun Li, Min Li, Nan Li, Qingjiang Li, Ruhui Li, Rui Li, Shanfeng Li, Shuo Li, Tao Li, Teng Li, Weidong Li, Weiguo Li, Xiaomei Li, Xiaonan Li, Xinglong Li, Yi Li, Yichen Li, Yufeng Li, Zhaohan Li, Zhibing Li, Ziyuan Li, Zonghai Li, An-An Liang, Hao Liang, Jiajun Liao, Yilin Liao, Yuzhong Liao, Ayut Limphirat, Guey-Lin Lin, Shengxin Lin, Tao Lin, Jiajie Ling, Xin Ling, Ivano Lippi, Caimei Liu, Fang Liu, Fengcheng Liu, Haidong Liu, Haotian Liu, Hongbang Liu, Hongjuan Liu, Hongtao Liu, Hongyang Liu, Jianglai Liu, Jiaxi Liu, Jinchang Liu, Min Liu, Qian Liu, Qin Liu, Runxuan Liu, Shenghui Liu, Shubin Liu, Shulin Liu, Xiaowei Liu, Xiwen Liu, Xuewei Liu, Yankai Liu, Zhen Liu, Lorenzo Loi, Alexey Lokhov, Paolo Lombardi, Claudio Lombardo, Kai Loo, Chuan Lu, Haoqi Lu, Jingbin Lu, Junguang Lu, Meishu Lu, Peizhi Lu, Shuxiang Lu, Xianguo Lu, Bayarto Lubsandorzhiev, Sultim Lubsandorzhiev, Livia Ludhova, Arslan Lukanov, Fengjiao Luo, Guang Luo, Jianyi Luo, Shu Luo, Wuming Luo, Xiaojie Luo, Vladimir Lyashuk, Bangzheng Ma, Bing Ma, Qiumei Ma, Si Ma, Xiaoyan Ma, Xubo Ma, Jihane Maalmi, Jingyu Mai, Marco Malabarba, Yury Malyshkin, Roberto Carlos Mandujano, Fabio Mantovani, Xin Mao, Yajun Mao, Stefano M. Mari, Filippo Marini, Agnese Martini, Matthias Mayer, Davit Mayilyan, Ints Mednieks, Yue Meng, Anita Meraviglia, Anselmo Meregaglia, Emanuela Meroni, Lino Miramonti, Nikhil Mohan, Michele Montuschi, Cristobal Morales Reveco, Massimiliano Nastasi, Dmitry V. Naumov, Elena Naumova, Diana Navas-Nicolas, Igor Nemchenok, Minh Thuan Nguyen Thi, Alexey Nikolaev, Feipeng Ning, Zhe Ning, Hiroshi Nunokawa, Lothar Oberauer, Juan Pedro Ochoa-Ricoux, Alexander Olshevskiy, Domizia Orestano, Fausto Ortica, Rainer Othegraven, Alessandro Paoloni, George Parker, Sergio Parmeggiano, Achilleas Patsias, Yatian Pei, Luca Pelicci, Anguo Peng, Haiping Peng, Yu Peng, Zhaoyuan Peng, Elisa Percalli, Willy Perrin, Frédéric Perrot, Pierre-Alexandre Petitjean, Fabrizio Petrucci, Oliver Pilarczyk, Luis Felipe Piñeres Rico, Artyom Popov, Pascal Poussot, Ezio Previtali, Fazhi Qi, Ming Qi, Xiaohui Qi, Sen Qian, Xiaohui Qian, Zhen Qian, Hao Qiao, Zhonghua Qin, Shoukang Qiu, Manhao Qu, Zhenning Qu, Gioacchino Ranucci, Alessandra Re, Abdel Rebii, Mariia Redchuk, Gioele Reina, Bin Ren, Jie Ren, Yuhan Ren, Barbara Ricci, Komkrit Rientong, Mariam Rifai, Mathieu Roche, Narongkiat Rodphai, Aldo Romani, Bedřich Roskovec, Xichao Ruan, Arseniy Rybnikov, Andrey Sadovsky, Paolo Saggese, Deshan Sandanayake, Anut Sangka, Giuseppe Sava, Utane Sawangwit, Michaela Schever, Cédric Schwab, Konstantin Schweizer, Alexandr Selyunin, Andrea Serafini, Mariangela Settimo, Junyu Shao, Vladislav Sharov, Hexi Shi, Jingyan Shi, Yanan Shi, Vitaly Shutov, Andrey Sidorenkov, Fedor Šimkovic, Apeksha Singhal, Chiara Sirignano, Jaruchit Siripak, Monica Sisti, Mikhail Smirnov, Oleg Smirnov, Sergey Sokolov, Julanan Songwadhana, Boonrucksar Soonthornthum, Albert Sotnikov, Warintorn Sreethawong, Achim Stahl, Luca Stanco, Konstantin Stankevich, Hans Steiger, Jochen Steinmann, Tobias Sterr, Matthias Raphael Stock, Virginia Strati, Michail Strizh, Alexander Studenikin, Aoqi Su, Jun Su, Guangbao Sun, Shifeng Sun, Xilei Sun, Yongjie Sun, Yongzhao Sun, Zhengyang Sun, Narumon Suwonjandee, Akira Takenaka, Xiaohan Tan, Jian Tang, Jingzhe Tang, Qiang Tang, Quan Tang, Xiao Tang, Vidhya Thara Hariharan, Igor Tkachev, Tomas Tmej, Marco Danilo Claudio Torri, Andrea Triossi, Wladyslaw Trzaska, Yu-Chen Tung, Cristina Tuve, Nikita Ushakov, Vadim Vedin, Carlo Venettacci, Giuseppe Verde, Maxim Vialkov, Benoit Viaud, Cornelius Moritz Vollbrecht, Katharina von Sturm, Vit Vorobel, Dmitriy Voronin, Lucia Votano, Pablo Walker, Caishen Wang, Chung-Hsiang Wang, En Wang, Guoli Wang, Hanwen Wang, Jian Wang, Jun Wang, Li Wang, Lu Wang, Meng Wang, Mingyuan Wang, Qianchuan Wang, Ruiguang Wang, Sibo Wang, Siguang Wang, Wei Wang, Wenshuai Wang, Xi Wang, Xiangyue Wang, Yangfu Wang, Yaoguang Wang, Yi Wang, Yifang Wang, Yuanqing Wang, Yuyi Wang, Zhe Wang, Zheng Wang, Zhimin Wang, Apimook Watcharangkool, Wei Wei, Wenlu Wei, Yadong Wei, Yuehuan Wei, Liangjian Wen, Jun Weng, Christopher Wiebusch, Rosmarie Wirth, Chengxin Wu, Diru Wu, Qun Wu, Yinhui Wu, Yiyang Wu, Zhi Wu, Michael Wurm, Jacques Wurtz, Christian Wysotzki, Yufei Xi, Dongmei Xia, Shishen Xian, Ziqian Xiang, Fei Xiao, Xiang Xiao, Xiaochuan Xie, Yijun Xie, Yuguang Xie, Zhao Xin, Zhizhong Xing, Benda Xu, Cheng Xu, Donglian Xu, Fanrong Xu, Hangkun Xu, Jiayang Xu, Jilei Xu, Jing Xu, Jinghuan Xu, Meihang Xu, Xunjie Xu, Yin Xu, Yu Xu, Baojun Yan, Qiyu Yan, Taylor Yan, Xiongbo Yan, Yupeng Yan, Changgen Yang, Chengfeng Yang, Fengfan Yang, Jie Yang, Lei Yang, Pengfei Yang, Xiaoyu Yang, Yifan Yang, Yixiang Yang, Zekun Yang, Haifeng Yao, Jiaxuan Ye, Mei Ye, Ziping Ye, Frédéric Yermia, Zhengyun You, Boxiang Yu, Chiye Yu, Chunxu Yu, Guojun Yu, Hongzhao Yu, Miao Yu, Xianghui Yu, Zeyuan Yu, Zezhong Yu, Cenxi Yuan, Chengzhuo Yuan, Ying Yuan, Zhenxiong Yuan, Baobiao Yue, Noman Zafar, Kirill Zamogilnyi, Vitalii Zavadskyi, Fanrui Zeng, Shan Zeng, Tingxuan Zeng, Yuda Zeng, Liang Zhan, Aiqiang Zhang, Bin Zhang, Binting Zhang, Feiyang Zhang, Hangchang Zhang, Haosen Zhang, Honghao Zhang, Jialiang Zhang, Jiawen Zhang, Jie Zhang, Jingbo Zhang, Jinnan Zhang, Junwei Zhang, Lei Zhang, Peng Zhang, Ping Zhang, Qingmin Zhang, Shiqi Zhang, Shu Zhang, Shuihan Zhang, Siyuan Zhang, Tao Zhang, Xiaomei Zhang, Xin Zhang, Xuantong Zhang, Yibing Zhang, Yinhong Zhang, Yiyu Zhang, Yongpeng Zhang, Yu Zhang, Yuanyuan Zhang, Yumei Zhang, Zhenyu Zhang, Zhijian Zhang, Jie Zhao, Rong Zhao, Runze Zhao, Shujun Zhao, Tianhao Zhao, Hua Zheng, Yangheng Zheng, Jing Zhou, Li Zhou, Nan Zhou, Shun Zhou, Tong Zhou, Xiang Zhou, Xing Zhou, Jingsen Zhu, Kangfu Zhu, Kejun Zhu, Zhihang Zhu, Bo Zhuang, Honglin Zhuang, Liang Zong, and Jiaheng Zou

Subjects
Astrophysics, QB460-466, Nuclear and particle physics. Atomic energy. Radioactivity, QC770-798
Abstract

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

Published
2025
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3. Collaborative Optimization of Direct Current Distribution Network Based on Scaled Electric Vehicles Charging and Discharging and Soft Open Points Topology Reconfiguration

Author

Yongqiang Kang, Gang Lu, Meng Chen, Xinglong Li, and Shuaibing Li

Subjects
electric vehicles, DC distribution network, soft open points, topology reconstruction, collaborative optimization, Technology
Abstract

In order to reduce the impact of the performance degradation of a direct current (DC) distribution network system caused by the access of scaled electric vehicles (EVs), this paper proposes a collaborative optimization method for a DC distribution network based on scaled EVs charging and discharging and soft open points (SOPs) topology reconfiguration. Firstly, based on the normal charging of scaled EVs, the EV discharge power model and the discharge response model were established based on the V2G (vehicle-to-grid) characteristic. Based on the characteristics of SOPs regulating voltage and power distribution, the SOP model and its equivalent model of DC system are established to identify the collaborative optimization of scaled EVs charging and discharging and SOPs topology reconstruction. Secondly, the bi-level model that optimizes multi-objects, including distribution network system loss, total voltage deviation and customer benefits, is established. The upper and lower models use the multi-objective particle swarm optimization (MOPSO) algorithm and simulated annealing algorithm to jointly optimize the optimal EV discharge power and the optimal SOP access configuration simultaneously. Finally, the effectiveness of the proposed collaborative optimization method is verified by a modified IEEE 33-node DC system example.

Published
2025
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4. Development of delayed pulmonary toxicities and transcriptional changes in pre-existing interstitial lung disease mice after partial thoracic irradiation

Author

Jiamei Fu, Xinglong Liu, Yuchuan Zhou, Shengnan Zhao, Liang Zeng, Yan Pan, Jianghong Zhang, Kevin M. Prise, Chunlin Shao, and Yaping Xu

Subjects
Animal model, Severe lung injury, Radiation, Interstitial lung disease, Diffuse alveolar damage, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Lung cancer patients with comorbid interstitial lung disease (LC-ILD) have an increased risk of developing severe or even fatal radiation pneumonitis after thoracic radiotherapy. However, the underlying mechanisms of its pathogenesis are still inconclusive. No approved biomarker or medicine is available to prevent pulmonary toxicities in LC-ILD patients. Appropriate management for them remains a challenge for clinicians due to treatment-related complications. Methods To elucidate the histopathological characteristics and molecular mechanisms responsible for this severe toxicity in vivo, C57BL/6J mice were used to develop different lung injury models, including radiation-induced lung injury (RILI), bleomycin-induced pulmonary fibrosis (BIPF), and severe radiation-related lung injury (sRRLI) murine model. Biopsy examination was performed on hematoxylin and eosin (H&E), Masson’s trichrome, and immunohistochemistry-stained lung tissue sections. Changes in lung function were measured. RNA extracted from mouse lung tissues was sequenced on the Illumina Novaseq platform. Results A severe lung injury model after irradiation was built based on pre-existing ILD mice induced by BLM administration. Enhanced lung injury was observed in the sRRLI model, including higher mortality and pulmonary function loss within six months compared to the mono-treatment groups. Autopsy revealed that bilateral diffuse alveolar damage (DAD) with an overlap of exudative, proliferative, and fibrosing patterns was usually presented in the sRRLI model. The histological phenotypes manifested exudative predominated DAD phase in the early phase and proliferating DAD pattern in the late phase. Bioinformatic analysis showed signaling pathways relevant to immune cell migration, epithelial cell development, and extracellular structure organization were commonly activated in different models. Furthermore, the involvement of epithelial cells and the infiltration of macrophages and CD4 + lymphocytes were validated during extensive lung remodeling in the sRRLI group. Conclusions Delayed effects of significantly declined lung function and high mortality were observed in the sRRLI model. DAD with progressive inflammation and fibrosis in bilateral lungs contributed to severe or even fatal complications after partial thoracic irradiation. The hyperactivation of inflammatory responses was clarified during long-term pulmonary toxicities. More studies are needed to investigate potential strategies to prevent and rescue severe lung complications.

Published
2025
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