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Genome-wide CRISPR screens identify PTPN21 and WDR26 as modulators of the mitochondrial stress-induced ISR

Life Metabolism 2024年第4期3卷 55-61页

作者： Wen Li Mingyue Dong Kaiyu Gao Jialiang Guan Ying Liu State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Beijing Advanced Innovation Center for Genomics Beijing 100871China PKU-Tsinghua-NIBS Graduate Program Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China

Dear Editor,Organisms have evolved mitochondrial stress response pathways to surveil mitochondrial function and activate repair programs upon detection of mitochondrial dysfunction[1].Failure to respond to mitochondrial perturbation has been implicated in aging and age-related diseases[2,3].Mitochondrial perturbation in mammals primarily activates the integrated stress response(ISR).

关键词： stress diseases primarily

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Monte Carlo-Based Identification of Electron and Proton Edges for Calibration of Miniaturized Tissue Equivalent Proportional Counter

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SSRN 2022年

作者： Eom, Mingi Youn, Sukwon Ye, Sung-Joon Program in Biomedical Radiation Sciences Department of Transdisciplinary Studies Graduate School of Convergence Science and Technology Seoul National University Seoul Korea Republic of Department of Applied Bioengineering Research Institute of Convergence Science Graduate School of Convergence Science and Technology Seoul National University Seoul Korea Republic of Advanced Institutes of Convergence Technology Seoul National University Suwon Korea Republic of

A miniaturized tissue equivalent proportional counter (mini-TEPC) cannot accommodate an internal alpha source for calibration. Instead, electron and proton edges on Monte Carlo (MC)-generated lineal energy spectra can be identified as makers for this purpose. A mini-TEPC of 1 mm-diameter and-length cylinder was assumed to be irradiated with 137Cs or 252Cf source and to have the tissue size of 1 or 2 µm. The electron edge marker, yδδ (maximum of second derivative of the fitted function) from Geant4 and MCNP6 was close to each other and comparable to the analytical values. The proton edges from the two codes were comparable, especially in yδδ but showed a difference from the analytical values. The lineal energy spectra from Geant4 and MCNP6 simulations were somewhat different in their peak locations. However, MC simulations of realistic detector and source geometry would provide practical channel positions of electron and proton edges for calibration of mini-TEPC. © 2022, The Authors. All rights reserved.

关键词： Electrons

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Accuracy Enhancement of L-Band EPR Tooth Dosimetry by Implementing Multiple Harmonic Detection

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SSRN 2024年

作者： Oh, Jeonghun Koo, Chang Uk Park, Jong In Choi, Kwon Lee, Junyoung Hirata, Hiroshi Ye, Sung-Joon Program in Biomedical Radiation Sciences Graduate School of Convergence Science and Technology Seoul National University Seoul08826 Korea Republic of Ionizing Radiation Metrology Group Korea Research Institute of Standards and Science Daejeon34113 Korea Republic of Research Institute for Convergence Science Seoul National University Seoul08826 Korea Republic of Division of Bioengineering and Bioinformatics Faculty of Information Science and Technology Hokkaido University Sapporo060–0814 Japan Department of Applied Bioengineering Graduate School of Convergence Science and Technology Seoul National University Seoul08826 Korea Republic of Advanced Institute of Convergence Technology Seoul National University Suwon16629 Korea Republic of Biomedical Research Institute Seoul National University Hospital Seoul03080 Korea Republic of

In a large-scale radiation accident, the swift classification of individuals exposed to high levels of radiation is crucial to minimize casualties. In-vivo tooth dosimetry using L-band electron paramagnetic resonance (EPR) spectroscopy is a promising method for this purpose, as it can estimate individual exposure levels rapidly and non-invasively. However, the accuracy of dose estimation associated with this technique remains a great challenge. To enhance the accuracy, digital multiple harmonic detection (MHD) was incorporated into a home-built L-band EPR spectrometer. This approach enabled the utilization of information present in higher harmonics of EPR signals, which has been often discarded in traditional EPR spectroscopy. Acquired multiple harmonic spectra were reconstructed to the first derivative spectrum to merge information and mitigate the signal broadening. The modulation amplitude varied in a range of 0.3 to 0.7 mT to maximize the accuracy. In a 0.5-minute measurement at 0.6 mT, the standard error of inverse prediction (SEIP) was reduced to 0.57 Gy from 0.71 Gy. The statistical significancy of the enhancement was validated. In conclusion, the accuracy enhanced by this MHD can contribute to improving the efficiency of triage systems in the aftermath of a mass radiation accident. © 2024, The Authors. All rights reserved.

关键词： Paramagnetic resonance

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An ultra thin,bright,and sensitive interactive tactile display based on organic mechanoluminescence for dual-mode handwriting identification

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InfoMat 2024年第6期6卷 76-87页

作者： Tingting Hou Wenlang Li Haoyu Wang Yuantian Zheng Chaojie Chen Haoran Zhang Kai Chen Huilin Xie Xin Li Shaoshuai He Siwei Zhang Dengfeng Peng Cheng Yang Jacky W.Y.Lam Ben Zhong Tang Yunlong Zi Department of Mechanical and Automation Engineering The Chinese University of Hong KongHong Kongthe People's Republic of China Department of Chemistry Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction and Institute for Advanced StudyThe Hong Kong University of Science and TechnologyHong Kongthe People's Republic of China Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Physics and Optoelectronic EngineeringShenzhen UniversityShenzhenthe People's Republic of China Thrust of Sustainable Energy and Environment The Hong Kong University of Science and Technology(Guangzhou)Guangzhouthe People's Republic of China The Hong Kong University of Science and Technology Interdisciplinary Program Office Hong Kong SARthe People's Republic of China Institute of Materials Research Tsinghua Shenzhen International Graduate SchoolTsinghua UniversityShenzhenthe People's Republic of China School of Science and Engineering Shenzhen Institute of Aggregate Science and TechnologyThe Chinese University of Hong KongShenzhenthe People's Republic of China HKUST Shenzhen-Hong Kong Collaborative Innovation Research Institute Shenzhenthe People's Republic of China Guangzhou HKUST Fok Ying Tung Research Institute Guangzhouthe People's Republic of China

Visible light-based human–machine interactive media is capable of transmitting electrical readouts to machines and providing intuitive feedback to users ***,many inorganic mechanoluminescent(ML)materials-based interactive media,typically ZnS-loaded phosphors(ZLPs),have been successfully ***,organic ML materials-based solutions were rarely exploited despite their huge merits of strong structural modification,abundant luminescence property,low cost,easy preparation,and so ***,we propose a novel interactive tactile display(ITD)based on organic ML materials(Cz-A6-dye)and triboelectric nanogenerator,with ultra-brightness(130%enhancement)and ultra-low threshold pressure(57%reduction)as compared to *** proposed ITD achieves the conversion of weak mechanical stimuli into visible light and electrical signals simultaneously,without extra power ***,the relationship between the luminous performance of organic ML materials and mechanical force is quantified,benefiting from the uniform ML layer *** by convolutional neural networks,the high-accuracy recognition(97.1%)for handwriting and identity of users is realized at the same ***,the ITD has great potential for intelligent wearable electronics and classified military applications.

关键词： interactive media organic mechanoluminescence triboelectric nanogenerators

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Third-Order Optical Properties of Ag Nanocubes and Ag-Au Hollow Nanostructures Investigated by Femtosecond Z-Scan Measurements

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SSRN 2024年

作者： Sousa, Claudevan A. Melo, Antonio F.A.A. Silva, Nefe J.B. Silva, Tânia Patrícia Silva E. Viana, Bartolomeu C. Santos, Francisco Eroni P. Garcia, Hans Department of Physics UFPI - Universidade Federal do Piauí PI Teresina64049-550 Brazil Materials Engineering Graduate Program Federal Institute of Education Science and Technology of Piauí Central Campus PI Teresina64000-040 Brazil Interdisciplinary Laboratory for Advanced Materials BioMatLab group Materials Science & Engineering Graduate Program UFPI - Universidade Federal do Piauí PI Teresina64049-550 Brazil

In this work, we reported experimental investigations on third-order optical properties of aqueous colloidal dispersions of silver nanocubes (Ag-NCs) and Ag-Au hollow nanostructures. The hollow bimetallic are nanoboxes, that were synthesized by galvanic substitution using silver nanocubes as templates, inserting silver with gold in molar ratios of 1.5 and 3.0 mL. This process adjusted tuning the Surface Plasmon Resonance (SPR) compared to the original Ag-NCs nanocubes. Femtosecond Z-scan measurements performed at 1040 nm, 350fs and laser intensities from 99.7 - 279 GW/cm2 shows negative nonlinear refraction for both nanocube and nanoboxes colloids, attributed to hot electron generation. Solvent effects are simultaneously suppressed of the nanostructures. On the other hand, the non-linear absorption observed for bimetallic nanoboxes shows the presence of saturated absorption (SA), but the Ag-NCs do not show a non-linear absorption signal. Therefore, our experimental results provide a reliable reference for the application of these bimetallic nanostructures as active media in nonlinear photonic devices. © 2024, The Authors. All rights reserved.

关键词： Surface plasmon resonance

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EXCESSIVE SUCROSE EXACERBATES HIGH FAT DIET-INDUCED HEPATIC INFLAMMATION AND FIBROSIS PROMOTING OSTEOARTHRITIS IN MICE MODEL

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Osteoarthritis and Cartilage 2025年 33卷 S139-S140页

作者： Yunhui Min Yunji Heo Dinesh Suminda Godagama Gamaarachchige minhye Kim myeongyeon shin Md. M. Ansari Young-Ok Son Interdisciplinary Graduate Program in Advanced Convergence Technology and Science Jeju National University Jeju Korea (the Republic of) Department of Animal Biotechnology Faculty of Biotechnology College of Applied Life Sciences Jeju National University Jeju-si Jeju-do Korea (the Republic of) Interdisciplinary Graduate Program in Advanced Convergence Technology and Science Jeju national University Jeju-si Jeju-do Korea (the Republic of)

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A novel N6-Deoxyadenine methyltransferase METL-9 modulates *** immunity via dichotomous mechanisms

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细胞研究（英文版） 2023年第8期33卷 628-639页

作者： Chengchuan Ma Tingling Xue Qi Peng Jie Zhang Jialiang Guan Wanqiu Ding Yi Li Peixue Xia Liankui Zhou Tianyu Zhao Sheng Wang Li Quan Chuan-Yun Li Ying Liu State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina Peking-Tsinghua Center for Life Sciences Peking UniversityBeijingChina Beijing Advanced Innovation Center for Genomics BeijingChina Research Center for Stem Cell and Regenerative Medicine Institute of Blood TransfusionChinese Academy of Medical Sciences and Peking Union Medical CollegeChengduSichuanChina State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina Peking-Tsinghua Center for Life Sciences Peking UniversityBeijingChina Laboratory of Bloinformatics and Genomic Medicine Institute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina PKU-Tsinghua-NIBS Graduate Program Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijingChina State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina Shanghai Zelixir Biotech Company Ltd. ShanghaiChina State Key Laboratory of Membrane Biology New Cornerstone Science LaboratoryInstitute of Molecular MedicineCollege of Future TechnologyPeking UniversityBeijingChina Peking-Tsinghua Center for Life Sciences Peking UniversityBeijingChina Beijing Advanced Innovation Center for Genomics BeijingChina

N6-Methyldeoxyadenine(6mA)has been rediscovered as a DNA modification with potential biological function in ***,the physiological function and regulatory mechanisms regarding the establishment,maintenance and removal of 6mA in eukaryotes are still poorly *** we show that genomic 6mA levels change in response to pathogenic infection in Caenorhabditis elegans(***).We further identify METL-9 as the methyltransferase that catalyzes DNA 6mA modifications upon pathogen *** of METL-9 impairs the induction of innate immune response genes and renders the animals more susceptible to pathogen ***,METL-9 functions through both 6mA-dependent and-independent mechanisms to transcriptionally regulate innate *** findings reveal that 6mA is a functional DNA modification in immunomodulation in ***.

关键词： DNA methylation Methylation analysis

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Biomedical data and AI

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science China Life sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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PD-1 blockade-unresponsive human tumor-infiltrating CD8^(+)T cells are marked by loss of CD28 expression and rescued by IL-15

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Cellular & Molecular Immunology 2021年第2期18卷 385-397页

作者： Kyung Hwan Kim Hong Kwan Kim Hyung-Don Kim Chang Gon Kim Hoyoung Lee Ji Won Han Seong Jin Choi Seongju Jeong Minwoo Jeon Hyunglae Kim Jiae Koh Bo Mi Ku Su-Hyung Park Myung-Ju Ahn Eui-Cheol Shin Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeonRepublic of Korea Department of Thoracic and Cardiovascular Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Biomedical Science and Engineering Interdisciplinary Program Korea Advanced Institute of Science and TechnologyDaejeonRepublic of Korea Research Institute for Future Medicine Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Department of Radiation Oncology Yonsei Cancer CenterYonsei University College of MedicineSeoulRepublic of Korea Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea

Blockade of programmed death-1(PD-1)reinvigorates exhausted CD8^(+)T cells,resulting in tumor regression in cancer ***,reinvigoration of exhausted CD8^(+)T cells following PD-1 blockade was shown to be CD28-dependent in mouse ***,we examined the role of CD28 in anti-PD-1 antibody-induced human T cell reinvigoration using tumor-infiltrating CD8^(+)T cells(CD8^(+)TILs)obtained from non-small-cell lung cancer ***-cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8^(+)***,we found that human CD28^(+)CD8^(+)but not CD28^(–)CD8^(+)TILs responded to PD-1 blockade irrespective of B7/CD28 blockade,indicating that CD28 costimulation in human CD8^(+)TILs is dispensable for PD-1 blockade-induced reinvigoration and that loss of CD28 expression serves as a marker of anti-PD-1 antibody-unresponsive CD8^(+)*** and phenotypically,PD-1 blockade-unresponsive human CD28^(–)PD-1^(+)CD8^(+)TILs exhibited characteristics of terminally exhausted CD8^(+)T cells with low TCF1 ***,CD28^(–)PD-1^(+)CD8^(+)TILs had preserved machinery to respond to IL-15,and IL-15 treatment enhanced the proliferation of CD28^(–)PD-1^(+)CD8^(+)TILs as well as CD28^(+)PD-1^(+)CD8^(+)*** together,these results show that loss of CD28 expression is a marker of PD-1 blockade-unresponsive human CD8^(+)TILs with a TCF1–signature and provide mechanistic insights into combining IL-15 with anti-PD-1 antibodies.

关键词： anti-PD-1 T cells TCF1 CD28 IL-15

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Single-cell protein-DNA interactomics and multiomics tools for deciphering genome regulation

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National science Open 2023年第3期2卷 64-82页

作者： Haiqing Xiong Runyu Wang Aibin He State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Peking University-Tsinghua University-National Institute of Biological Science Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Institute of Molecular Medicine College of Future TechnologyPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China

The emergence of single-cell genomic and transcriptomic sequencing accelerates the development of single-cell epigenomic technologies,providing an unprecedented opportunity for decoding cell fate decisions largely encoded in the *** advances in single-cell multimodality epigenomic technologies facilitate directly interrogating the reg-ulatory relationship between multi-layer molecular information in the same *** this review,we discuss recent progress in development of single-cell multimodality epigenomic technologies and applications in elucidating cellular diversifications in development and diseases,with a focus on protein-DNA interactomics and regulatory links between epigenome and ***,we provide perspective on the future direction of single-cell multiomics tool development as well as challenges facing ahead.

关键词： single-cell protein-DNA interaction single-cell multiomics single-cell epigenomics epigenome genome regulation

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