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signal transduction and Targeted Therapy 2024年第8期9卷 3163-3164页

作者： Marina Kolesnichenko Claus Scheidereit Department of Hepatology and Gastroenterology Charite-Universitatsmedizin BerlinBerlinGermany Laboratory for signal transduction in Tumor Cells Max Delbruck Center for Molecular Medicine in the Helmholtz Association(MDC)BerlinGermany

In a landmark study recently published in Nature,Petropoulous et *** that synthetic lethality of poly(ADP-ribose)polymerase(PARP)inhibitors in cells with defective homologous recombination repair(HR)results predominantly from transcription replication conflicts(TRC)and not,as previously proposed,from PARP trapping on DNA(Fig.1).The article unveils a new mechanism behind synthetic lethality of PARP inhibitors with relevance for cancer therapy.

关键词： al. PARP mechanism

Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National center for Liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation Laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China Laboratory of signaling Regulation and Targeting Therapy of Liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis Liver diseases SOX9

Genome-wide CRISPR screening reveals key genes and pathways associated with 20-hydroxyecdysone signal transduction in the silkworm(Bombyx mori)

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Insect Science 2024年第1期31卷 47-58页

作者： Hao Sun Jingya Chen Ruolin Wang Dan Liu Na Zhang Tong Zhang Ling Jia Sanyuan Ma Qingyou Xia State Key Laboratory of Silkworm Genome Biology Southwest UniversityChongqingChina biological Science Research center Southwest UniversityChongqingChina

Metamorphosis is a complex developmental process involving multiple pathways and a large number of genes that are regulated by juvenile hormone(JH)and 20-hydroxyecdysone(20E).Despite important progress in understanding various aspects of silkworm biology,the hormone signaling pathway in the silkworm remains poorly ***-wide screening using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)-based libraries has recently emerged as a novel method for analyzing genome function,enabling further research into essential genes,drug targets,and virus-host ***,we constructed a genome-wide CRISPR/Cas9-based library of the silkworm(Bombyx mori)and successfully revealed the genes involved in biotic or abiotic stress factor *** this study,we used our silkworm CRISPR library and large-scale genome-wide screening to analyze the key genes in the silkworm 20E signaling pathway and their mechanisms of *** annotation showed that 20E regulates key proteins in processes that mainly occur in the cytoplasm and *** enrichment analysis showed that 20E can activate phosphorylation and may affect innate immunity,interfere with intracellular nutrition and energy metabolism,and eventually cause cell *** screening results were experimentally validated by generating cells with knockout alleles of the relevant genes,which had increased tolerance to *** findings provide a panoramic overview of signaling in response to 20E in the silkworm,underscoring the utility of genome-wide CRISPR mutant libraries in deciphering hormone signaling pathways and the mechanisms that regulate metamorphosis in insects.

关键词： CRISPR/Cas9 CRISPR library screening ecdysone 20E signal transduction silkworm whole genome editing

Cancer stem cell-immune cell crosstalk in the tumor microenvironment for liver cancer progression

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Frontiers of Medicine 2024年第3期18卷 430-445页

作者： Yue Ma Hongwei Lv Fuxue Xing Wei Xiang Zixin Wu Qiyu Feng Hongyang Wang Wen Yang Cancer Research center First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei230027China National center for Liver Cancer Naval Medical University(Second Military Medical University)Shanghai201805China International Co-operation Laboratory on signal transduction Eastern Hepatobiliary Surgery HospitalNaval Medical University(Second Military Medical University)Shanghai200438China Shanghai Key Laboratory of Hepato-biliary Tumor Biology Shanghai200438China Key Laboratory of signaling Regulation and Targeting Therapy of Liver Cancer Ministry of EducationShanghai200438China

Crosstalk between cancer cells and the immune microenvironment is determinant for liver cancer progression.A tumor subpopulation called liver cancer stem cells(CSCs)significantly accounts for the initiation,metastasis,therapeutic resistance,and recurrence of liver *** evidence demonstrates that the interaction between liver CSCs and immune cells plays a crucial role in shaping an immunosuppressive microenvironment and determining immunotherapy *** review sheds light on the bidirectional crosstalk between liver CSCs and immune cells for liver cancer progression,as well as the underlying molecular mechanisms after presenting an overview of liver CSCs characteristic and their ***,we discuss the potential application of liver CSCs-targeted immunotherapy for liver cancer treatment.

关键词： liver cancer cancer stem cell immune cell immunotherapy

A phase separation-fortified bi-specific adaptor for conditional tumor killing

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Science China(Life Sciences) 2024年第7期67卷 1385-1397页

作者： Yuyan Liu Yuting Zhu Weifan Xu Pilong Li State Key Laboratory of Membrane Biology Frontier Research Center for Biological StructureTsinghua University-Peking University Joint Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China

A common approach in therapeutic protein development involves employing synthetic ligands with multivalency,enabling sophisticated control of signal *** the emerging concept of liquid-liquid phase separation(LLPS)and its ability to organize cell surface receptors into functional compartments,we herein have designed modular ligands with phase-separation modalities to engineer programmable interreceptor communications and precise control of signal pathways,thus inducing the rapid,potent,and specific apoptosis of tumor *** their simplicity,these“triggers”,named phase-separated Tumor Killers(hereafter referred to as psTK),are sufficient to yield interreceptor clustering of death receptors(represented by DR5)and tumor-associated receptors,with notable features:LLPSmediated robust high-order organization,well-choreographed conditional activation,and broad-spectrum capacity to potently induce apoptosis in tumor *** development of novel therapeutic proteins with phase-separation modalities showcases the power of spatially reorganizing signal *** approach facilitates the diversification of cell fate and holds promising potential for targeted therapies against challenging tumors.

关键词： phase separation therapeutic proteins receptor-ligand interactions DR5 tumor apoptosis

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Toward predictable universal genetic circuit design

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Quantitative Biology 2024年第2期12卷 225-229页

作者： Yuanli Gao Baojun Wang College of Chemical and biological Engineering Zhejiang UniversityHangzhouChina ZJU-Hangzhou Global Scientific and Technological Innovation center Zhejiang UniversityHangzhouChina School of biological Sciences University of EdinburghEdinburghUK

In thepast 2decades,synthetic biologists have applied systematic engineering principles to genetic circuit design to devise biological systems with bespoke behaviors,such as Boolean logic gates,signal filters,oscillators,state machines,perceptrons,and genetic controllers[1,2].Following a bottom-up strategy,the genetic circuits are designed by assembling a set of well-characterized biological components,or genetic parts[3],and optimized through the iterative Design-Build-Test-Learn(DBTL)cycles.

关键词： circuit predictability genetic circuit design host independent part characterization portability

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Biophysical cues involved in the stem cell niche for stemness maintenance

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Medicine in Novel Technology and Devices 2024年第2期22卷 80-89页

作者： Chiyu Li Lisha Zheng Yubo Fan Key Laboratory of Biomechanics and Mechanobiology(Beihang University) Ministry of EducationBeijing Advanced Innovation Center for Biomedical EngineeringSchool of Biological Science and Medical EngineeringBeihang UniversityBeijing100083China

The characteristics of stem cells are self-renewal ability and differentiation *** properties are defined as stemness,offering them application in tissue repair and regeneration based on stem cells with great ***,stem cells undergo functional deterioration and gradually lose stemness with long-term *** evidence implies that the regulation of stemness is primarily orchestrated by the niche,which comprises the connection between stem cells and niche cells,extracellular matrix(ECM)proteins,and secreted ***,physical signals are being acknowledged as paramount regulators of cellular behavior,governing stem cell stemness,tissue development,and *** review outlines current approaches for stemness maintenance and the important biophysical cues involved in the stem *** first encompass the latest discoveries regarding the sources and transduction pathways of these biophysical ***,the specific biophysical factors for regulating stemness have been ***,we summarize existing challenges and prospect future research in this field.

关键词： Stemness Stem cell Biophysical Niche

Effect of Zn2+ ions on ryanodine binding to sarcoplasmic reticulum of striated muscles in the presence of pyrithione

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Acta Pharmacologica Sinica 2004年第12期25卷 81-85页

作者： Hong XIE, Ke-ying CHEN, Pei-hong ZHU2 Unit of Cell signal transduction, Key Laboratory of Neuroscience, Shanghai Institutes for biologicalSciences, Chinese Academy ofSciences, Shanghai200031, China Unit of Cell signal transduction Key Laboratory of Neuroscience Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China

AIM: To explore whether the differential effects of Zn2+ on ryanodine binding to the sarcoplasmic reticulum (SR) of skeletal and cardiac muscles resulted from different permeability of the SR to Zn2+. METHODS: [3H]ryanodine binding assays were performed to examine the effect of Zn2+ on ryanodine binding to the SR in the presence of pyrithione sodium (PyNa), a specific Zn2+ ionophore. RESULTS: As a control, PyNa up to 50 μmol/L did not induce any effect on ryanodine binding to the SR of cardiac muscle. But PyNa 1-100 μmol/L increased ryanodine binding in skeletal muscle with maximum binding (222.2 %±20.9 % of the control) and inhibited ryanodine binding to 50 % of the control at about 500 μmol/L. In the presence of PyNa 10 and 50 μmol/L the dose-dependence of the effect of Zn2+ in cardiac muscle was still monophasic and not changed by PyNa, while the biphasic effect of Zn2+ in skeletal muscle became monophasic. CONCLUSION: Different permeability of the SR to Zn2+ may account for the differential effects of Zn2+on ryanodine binding in skeletal and cardiac muscles. PyNa is not a strictly specific Zn2+ ionophore.

关键词： zinc ion pyrithione radioligand binding ryanodine receptor skeletal muscle myocardium

HCCDB v2.0:Decompose Expression Variations by Single-cell RNA-seq and Spatial Transcriptomics in HCC

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 131-142页

作者： Ziming Jiang Yanhong Wu Yuxin Miao Kaige Deng Fan Yang Shuhuan Xu Yupeng Wang Renke You Lei Zhang Yuhan Fan Wenbo Guo Qiuyu Lian Lei Chen Xuegong Zhang Yongchang Zheng Jin Gu Eight-Year Program of Clinical Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100006China MOE Key Laboratory of Bioinformatics BNRIST Bioinformatics DivisionInstitute for Precision Medicine&Department of AutomationTsinghua UniversityBeijing 100084China Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Fuzhou Institute for Data Technology Fuzhou 350207China University of Michigan-Shanghai Jiao Tong University Joint Institute Shanghai Jiao Tong UniversityShanghai 200240China Department of Automation Shanghai Jiao Tong UniversityShanghai 200240China International Cooperation Laboratory on signal transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438China National center for Liver Cancer Shanghai 201805China

Large-scale transcriptomic data are crucial for understanding the molecular features of hepatocellular carcinoma(HCC).Integrated 15 transcriptomic datasets of HCC clinical samples,the first version of HCC database(HCCDB v1.0)was released in *** the meta-analysis of differentially expressed genes and prognosis-related genes across multiple datasets,it provides a systematic view of the altered biological processes and the inter-patient heterogeneities of HCC with high reproducibility and *** four years having passed,the database now needs integration of recently published ***,the latest single-cell and spatial transcriptomics have provided a great opportunity to decipher complex gene expression variations at the cellular level with spatial ***,we present HCCDB v2.0,an updated version that combines bulk,single-cell,and spatial transcriptomic data of HCC clinical *** dramatically expands the bulk sample size by adding 1656 new samples from 11 datasets to the existing 3917 samples,thereby enhancing the reliability of transcriptomic meta-analysis.A total of 182,832 cells and 69,352 spatial spots are added to the single-cell and spatial transcriptomics sections,respectively.A novel single-cell level and 2-dimension(sc-2D)metric is proposed as well to summarize cell type-specific and dysregulated gene expression *** are all graphically visualized in our online portal,allowing users to easily retrieve data through a user-friendly interface and navigate between different *** extensive clinical phenotypes and transcriptomic data in the database,we show two applications for identifying prognosis-associated cells and tumor *** v2.0 is available at http://***/database/hccdb2.

关键词： Hepatocellular carcinoma Database Integrative analysis Single-cell RNA sequencing Spatial transcriptomics

Accurate expression of neck motion signal by piezoelectric sensor data analysis

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Chinese Chemical Letters 2024年第9期35卷 250-256页

作者： Neng Shi Haonan Jia Jixiang Zhang Pengyu Lu Chenglong Cai Yixin Zhang Liqiang Zhang Nongyue He Weiran Zhu Yan Cai Zhangqi Feng Ting Wang State Key Laboratory of Digital Medical Engineering National Demonstration Center for Experimental Biomedical Engineering EducationSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China SceneRay Co. Ltd.Suzhou 215123China School of Chemistry and Chemical Engineering Nanjing University of Science and TechnologyNanjing 210094China

The development of high-precision sensors using flexible piezoelectric materials has the advantages of high sensitivity,high stability,good durability,and *** main problem with sensing equipment is low sensitivity,which is due to the mismatch between materials and analysis methods,resulting in the inability to effectively eliminate *** address this issue,we developed the denoising analysis method to motion signals captured by a flexible piezoelectric sensor fabricated from poly(l-lactic acid)(PLLA)and polydimethylsiloxane(PDMS)*** results demonstrate that this improved denoising method effectively removes noise components from neck muscle motion signals,thus obtaining high-quality,low-noise motion signal *** decomposition and reconstruction is a signal processing technique that involves decomposing a signal into different scales and frequency components using wavelets and then selectively reconstructing the signal to emphasize specific features or eliminate *** study employed the sym8 wavelet basis for wavelet decomposition and *** the denoised signals,a high degree of stability and periodic peaks are distinctly manifested,while amplitude and frequency differences among different types of movements also become noticeably *** a result of this study,we are enabled to accurately analyze subtle variations in neck muscle motion signals,such as nodding,shaking the head,neck lateral flexion,and neck *** temporal and frequency domain analysis of denoised motion signals,differentiation among various motion states can be ***,this improved analytical approach holds broad application prospects across various types of piezoelectric sensors,such as healthcare monitoring,sports biomechanics.

关键词： Piezoelectric transducer Wavelet decomposition Muscle motion signal signal analysis Noise component Healthcare monitoring

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