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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular cell Biology Sungkyunkwan University School of MedicineSuwonKorea single cell network research center Sungkyunkwan University School of MedicineSuwonKorea research Institute of Aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative diseases.However,the molecular mechanisms underlying neuromuscular dysfunction are currently unclear.Recent studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle maintenance.In the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using Hb9-Cre.mnKO exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and lethality.Prmt1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve injury.The transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and mitochondria.Consistently,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor neurons.Furthermore,Prmt1 inhibition in motor neurons elicited mitochondrial dysfunction.Our findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle loss.Thus,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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A hierarchical enhanced data-driven battery pack capacity estimation framework for real-world operating conditions with fewer labeled data

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Journal of Energy Chemistry 2024年第4期91卷 417-432页

作者： Sijia Yang Caiping Zhang Haoze Chen Jinyu Wang Dinghong Chen Linjing Zhang Weige Zhang National Active Distribution network Technology research center(NANTEC) Beijing Jiaotong UniversityBeijing 100044China

Battery pack capacity estimation under real-world operating conditions is important for battery performance optimization and health management,contributing to the reliability and longevity of batterypowered systems.However,complex operating conditions,coupling cell-to-cell inconsistency,and limited labeled data pose great challenges to accurate and robust battery pack capacity estimation.To address these issues,this paper proposes a hierarchical data-driven framework aimed at enhancing the training of machine learning models with fewer labeled data.Unlike traditional data-driven methods that lack interpretability,the hierarchical data-driven framework unveils the“mechanism”of the black box inside the data-driven framework by splitting the final estimation target into cell-level and pack-level intermediate targets.A generalized feature matrix is devised without requiring all cell voltages,significantly reducing the computational cost and memory resources.The generated intermediate target labels and the corresponding features are hierarchically employed to enhance the training of two machine learning models,effectively alleviating the difficulty of learning the relationship from all features due to fewer labeled data and addressing the dilemma of requiring extensive labeled data for accurate estimation.Using only 10%of degradation data,the proposed framework outperforms the state-of-the-art battery pack capacity estimation methods,achieving mean absolute percentage errors of 0.608%,0.601%,and 1.128%for three battery packs whose degradation load profiles represent real-world operating conditions.Its high accuracy,adaptability,and robustness indicate the potential in different application scenarios,which is promising for reducing laborious and expensive aging experiments at the pack level and facilitating the development of battery technology.

关键词： Lithium-ion battery pack Capacity estimation Label generation Multi-machine learning model Real-world operating

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TBK1:a new target for overcoming cancer immunotherapy resistance

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Science China(Life Sciences) 2024年第1期67卷 217-218页

作者： Jizhong Guan Long Zhang Fangfang Zhou Institutes of Biology and Medical Science Soochow UniversitySuzhou 215123China MOE Laboratory of Biosystems Homeostasis and Protection and Innovation center for cell Signaling network Life Sciences InstituteZhejiang UniversityHangzhou 310058China

In a recent study published in Nature,Sun et al.(2023)discovered that targeting TANK-binding kinase 1(TBK1)can successfully overcome resistance to immune checkpoint blockade(ICB)treatment and the study revealed its potential mechanism.The authors provided evidence that the disruption of TBK1 signal enhances the blockade of programmed cell death protein-1(PD-1)and promotes anti-tumor immunity in the tumor microenvironment(TME).Tumor cells rely on Janus kinase(JAK)and signal transducer as well as activator of transcription(STAT)signals to elicit an immune response by perceiving tumor necrosis factorα(TNF-α)and interferon-γ(IFN-γ),resulting in receptor-interacting protein kinase(RIPK)-caspase-mediated cell death in tumor cells(Figure 1).

关键词： TBK1 immunity

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Physical Layer Encryption of OFDM-PON Based on Quantum Noise Stream Cipher with Polar Code

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China Communications 2024年第3期21卷 174-188页

作者： Xu Yinbo Gao Mingyi Zhu Huaqing Chen Bowen Xiang Lian Shen Gangxiang Jiangsu Engineering research center of Novel Optical Fiber Technology and Communication network Suzhou Key Laboratory of Advanced Optical Communication Network Technologythe School of Electronic and Information EngineeringSoochow UniversityNo.1 Shizi StreetSuzhou 215006China

Orthogonal frequency division multiplexing passive optical network(OFDM-PON) has superior anti-dispersion property to operate in the C-band of fiber for increased optical power budget. However,the downlink broadcast exposes the physical layer vulnerable to the threat of illegal eavesdropping. Quantum noise stream cipher(QNSC) is a classic physical layer encryption method and well compatible with the OFDM-PON. Meanwhile, it is indispensable to exploit forward error correction(FEC) to control errors in data transmission. However, when QNSC and FEC are jointly coded, the redundant information becomes heavier and thus the code rate of the transmitted signal will be largely reduced. In this work, we propose a physical layer encryption scheme based on polar-code-assisted QNSC. In order to improve the code rate and security of the transmitted signal, we exploit chaotic sequences to yield the redundant bits and utilize the redundant information of the polar code to generate the higher-order encrypted signal in the QNSC scheme with the operation of the interleaver.We experimentally demonstrate the encrypted 16/64-QAM, 16/256-QAM, 16/1024-QAM, 16/4096-QAM QNSC signals transmitted over 30-km standard single mode fiber. For the transmitted 16/4096-QAM QNSC signal, compared with the conventional QNSC method, the proposed method increases the code rate from 0.1 to 0.32 with enhanced security.

关键词： physical layer encryption polar code quantum noise stream cipher

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Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou 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 Tianjin Institutes of Health Science Tianjin 301600China CAMS center for Stem cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage biases.It is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental stage.In this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic lineages.We discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM cells.Mechanistically,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its enhancer.Inhibition of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell differentiation.In conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

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Immune rebalancing at the maternal-fetal interface of maternal SARS-CoV-2 infection during early pregnancy

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Protein & cell 2024年第6期15卷 460-473页

作者： Chenxiang Xi Zihui Yan Dandan Bai Yalin Zhang Beiying Wang Xiaoxiao Han Li Wu Xiaohui Shi Zhiyi Hu Ming Tang Zhongqu Su Yingdong Liu Binya Liu Jiqing Yin Hong Wang Xiaocui Li Yanping Zhang Shaorong Gao Wenqiang Liu Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalShanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Jiaxing Maternity and Child Health Care Hospital Jiaxing 314050China

The current coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus(SARS-CoV-2)remains a threat to pregnant women.However,the impact of early pregnancy SARS-CoV-2 infection on the maternal-fetal interface remains poorly understood.Here,we present a comprehensive analysis of single-cell transcriptomics and metabolomics in placental samples infected with SARS-CoV-2 during early pregnancy.Compared to control placentas,SARS-CoV-2 infection elicited immune responses at the maternal-fetal interface and induced metabolic alterations in amino acid and phospholipid profiles during the initial weeks post-infection.However,subsequent immune cell activation and heightened immune tolerance in trophoblast cells established a novel dynamic equilibrium that mitigated the impact on the maternal-fetal interface.Notably,the immune response and metabolic alterations at the maternal-fetal interface exhibited a gradual decline during the second trimester.Our study underscores the adaptive immune tolerance mechanisms and establishment of immunological balance during the first two trimesters following maternal SARS-CoV-2 infection.

关键词： fetal alterations pregnancy

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Foundation models in molecular biology

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Biophysics Reports 2024年第3期10卷 135-151页

作者： Yunda Si Jiawei Zou Yicheng Gao Guohui Chuai Qi Liu Luonan Chen Key Laboratory of Systems Health Science of Zhejiang Province School of Life Science Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai Institute of Biochemistry and cell Biology Center for Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Translational Medical center for Stem cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Frontier Science Center for Stem Cell Research Bioinformatics Department School of Life Sciences and Technology Tongji University Shanghai research Institute for Intelligent Autonomous Systems

Determining correlations between molecules at various levels is an important topic in molecular biology. Large language models have demonstrated a remarkable ability to capture correlations from large amounts of data in the field of natural language processing as well as image generation, and correlations captured from data using large language models can also be applicable to solving a wide range of specific tasks, hence large language models are also referred to as foundation models. The massive amount of data that exists in the field of molecular biology provides an excellent basis for the development of foundation models, and the recent emergence of foundation models in the field of molecular biology has really pushed the entire field forward. We summarize the foundation models developed based on RNA sequence data, DNA sequence data, protein sequence data, single-cell transcriptome data, and spatial transcriptome data respectively, and further discuss the research directions for the development of foundation models in molecular biology.

关键词： Foundation models Molecular biology Transcriptome

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PEG400-mediated nanocarriers improve the delivery and therapeutic efficiency of mRNA tumor vaccines

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Chinese Chemical Letters 2024年第5期35卷 314-319页

作者： Wen Xiao Fazhan Wang Yangzhuo Gu Xi He Na Fan Qian Zheng Shugang Qin Zhongshan He Yuquan Wei Xiangrong Song Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Medical research center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450000China

Dendritic cell(DC)-targeted delivery of mRNA is a prominent method to boost the efficacy of mRNA tumor vaccines.The targeting ligands are often modified on nanocarriers by polyethylene glycol(PEG)linker in mRNA delivery systems.Whether the PEG linker length influences the targeting delivery efficiency of mRNA nanocarrier in vivo remains unclear.Here,we designed and constructed DC-targeted mRNA delivery systems modified by mannose via different PEG linker lengths(100/400/1000/2000)(MPn-LPX).The top candidate MP_(400)-LPX(the linker was PEG400)showed the optimal mRNA expression and antigen presentation owing to the highly efficient uptake by DCs.Furthermore,MP_(400)-LPX could better inhibited tumor growth and extended survival in the E.G7-OVA lymphoma and TC-1 cervical tumor mouse model.Collectively,these results demonstrated that PEG400 was the optimal linker for the PEGylated DC-targeted mRNA vaccines.Our findings provided a new platform for the rational design of targeted mRNA nanovaccines with shorter-length PEG.

关键词： Cancer immunotherapy mRNA vaccines DC-targeted delivery PEGylated liposomes cellular uptake

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Simplified liver imaging reporting and data system for the diagnosis of hepatocellular carcinoma on gadoxetic acid-enhanced magnetic resonance imaging

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2439-2448页

作者： Rong Lyu Wei-Juan Hu Di Wang Jiao Wang Yu-Bing Ye Ke-Feng Jia Department of Radiology Tianjin Third Central HospitalTianjin Key Laboratory of Extracorporeal Life Support for Critical DiseasesArtificial Cell Engineering Technology Research CenterTianjin 300170China

BACKGROUND The liver imaging reporting and data system(LI-RADS)diagnostic table has 15 cells and is too complex.The diagnostic performance of LI-RADS for hepatocellular carcinoma(HCC)is not satisfactory on gadoxetic acid-enhanced magnetic resonance imaging(EOB-MRI).AIM To evaluate the ability of the simplified LI-RADS(sLI-RADS)to diagnose HCC on EOB-MRI.METHODS A total of 331 patients with 356 hepatic observations were retrospectively analysed.The diagnostic performance of sLI-RADS A-D using a single threshold was evaluated and compared with LI-RADS v2018 to determine the optimal sLIRADS.The algorithms of sLI-RADS A-D are as follows:The single threshold for sLI-RADS A and B was 10 mm,that is,classified observations≥10mm using an algorithm of 10-19 mm observations(sLI-RADS A)and≥20 mm observations(sLI-RADS B)in the diagnosis table of LI-RADS v2018,respectively,while the classification algorithm remained unchanged for observationssingle threshold for sLI-RADS C and D was 20 mm,that is,forsingle threshold of 20 mm),because its sensitivity was greater than that of LI-RADS v2018(89.8%vs 87.0%,P=0.031),and its specificity was not lower(89.4%vs 90.1%,P>0.999).With HBP hypointensity as an MF,the sensitivity of F-sLI-RADS was greater than that of LI-RADS v2018(93.0%vs 87.0%,P<0.001)and sLI-RADS D(93.0%vs 89.8%,P=0.016),without a lower specificity(86.5%vs 90.1%,P=0.062;86.5%vs 89.4%,P=0.125).Compared with that of LI-RADS v2018,the time to classify lesions according to FsLI-RADS was shorter(51±

关键词： Hepatocellular carcinoma Magnetic resonance imaging Liver Diagnosis Contrast agent

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Degeneration Directory:a multi-omics web resource for degenerative diseases

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Protein & cell 2024年第5期15卷 385-392页

作者： Haoteng Yan Changfa Lu Chenyang Lan Si Wang Weiqi Zhang Zan He Jinghao Hu Jiaqi Ai Guang-Hui Liu Shuai Ma Yuanchun Zhou Jing Qu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation center for Human Brain Protection and National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Computer network Information center Chinese Academy of SciencesBeijing 100190China The Fifth People’s Hospital of Chongqing Chongqing 400062China Aging Biomarker Consortium Beijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Beijing Institute for Stem cell and Regenerative Medicine Beijing 100101China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Background of database.Organ degeneration refers to the gradual decline in organ function and structure deterioration that occurs during aging,which represents the greatest risk factor for various degenerative diseases,including cardiovascular diseases,neurodegenerative diseases,and osteoarthritis,etc.(Aging Biomarker et al.,2023;Becker et al.,2018;Cai et al.,2022).

关键词： Directory web Becker

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