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Sequence-activated chemiluminescence probes: programmable illumination for high-contrast in vivo sensing and imaging

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Science China Chemistry 2025年第1期68卷 26-34页

作者： Yutao Zhang Juan Li Wei-Hong Zhu Zhiqian Guo Shanghai Key laboratory of Functional Materials Chemistry Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology State Key laboratory of Bioreactor Engineering Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell MetabolismEast China University of Science & Technology

Sequence-activated chemiluminescence(CL) technique offers a unique approach to detecting specific biomolecules or cellular events with high sensitivity and spatial resolution. The fundamental principle behind sequence-activated CL probes involves tailoring highly-controllable CL signals in response to specific sequences or events of interest, thus enabling high-contrast signals under complex physiological conditions. This sequential activation could be triggered by enzymes, reactive oxygen species(ROS), biothiols or changes in the microenvironment. These unique sequence-activated CL probes bestow several advantages, including minimal background, deep-tissue penetration, and the ability of non-invasive or minimally invasive detection. The sequence-activated CL techniques represent a significant advancement in molecular imaging and diagnostics. In this mini-review, we focus on the latest developments in sequential CL probes, addressing the technical challenges and discussing the future trajectory by harnessing CL signaling and molecular recognition.

关键词： chemiluminescnece sequence-activation in-vivo bioimaging cyclic peroxide

Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

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Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe laboratory of cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing Key laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State Key laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for Cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Nuclear Factor-κB signaling Pathway Constitutively Activated in Esophageal Squamous cell Carcinoma cell Lines and Inhibition of Growth of cells by Small Interfering RNA

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Acta Biochimica et Biophysica Sinica 2006年第5期38卷 318-326页

作者： Fang TIAN Wei-Dong ZANG Wei-Hong HOU Hong-Tao LIU Le-Xun XUE laboratory for cell Biology,Medical College,Zhengzhou University,Zhengzhou 450052,China laboratory for cell Biology Medical College Zhengzhou UniversityZhengzhou 450052 China

Although constitutive nuclear factor(NF)-kB activation has been reported in many humantumors,the role of the NF-kB pathway in esophageal squamous cell carcinoma(ESCC)has not been *** this study,NF-kB pathway in two ESCC cell lines was investigated using immunocytochemistry,Westernblot and reverse transciiption-polymerase chain *** activation of NF-kB DNA binding was determinedby electrophoretic mobility-shift *** interference was used to specifically inhibit the expression *** of cells Was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide *** results showed that p50,p65,IkBα,p-IkBα and IkB kinase β were expressed and mainly localized in *** transcription-polymerase chain reaction results showed the constitutive expressions ofp50,p65 and IkBα mRNA in the two ESCC cell ***,the nuclear extracts revealed that p50and p65 translocated to the nucleus had DNA-binding ***,small interfering RNA of p65 decreasedthe expression of p65,and the viability of ceils transfected with p65 small interfering RNA was significantlysuppressed at the same concentration of 5-fluorouracil(Psignaling pathway in the ESCC *** interference targeting at p65 increased the sensitivity of the ESCC cell lines to 5-fluorouracil,suggesting that NF-kB might be a good target for cancer treatment.

关键词： NF-κB RNA interference esophageal squamous cell carcinoma IκBα IκBα kinase

Conserved and differentiated functions of CIK receptor kinases in modulating stem cell signaling in Arabidopsis

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Molecular Plant 2021年第7期14卷 1119-1134页

作者： Yafen Zhu Chong Hu Yanwei Cui Li Zeng Sunjingnan Li Mingsong Zhu Fanhui Meng Shuting Huang Li Long Jing Yi Jia Li Xiaoping Gou Ministry of Education Key laboratory of cell Activities and Stress Adaptations School of Life SciencesLanzhou UniversityLanzhou 730000China

The shoot apical meristem(SAM)and root apical meristem(RAM)act as pools of stem cells that give rise to aboveground and underground tissues and organs in higher plants,*** CLAVATA3(CLV3)-WUSCHEL(WUS)negative-feedback loop acts as a core pathway controlling SAM homeostasis,while CLV3/EMBRYO SURROUNDING REGION(ESR)40(CLE40)and WUSCHEL-RELATED HOMEOBOX5(WOX5),homologs of CLV3 and WUS,direct columella stem cell ***,CLV3 INSENSITIVE KINASES(CIKs)have been shown to be essential for maintaining SAM homeostasis,whereas whether they regulate the distal root meristem remains to be ***,we report that CIKs are indispensable for transducing the CLE40 signal to maintain homeostasis of the distal root *** found that the cik mutant roots displayed disrupted quiescent center and delayed columella stem cell(CSC)*** assays demonstrated that CIKs interact with ARABIDOPSIS CRINKLY4(ACR4)in a ligand-independent manner and can be phosphorylated by ACR4 in *** addition,the phosphorylation of CIKs can be rapidly induced by CLE40,which partially depends on *** CIKs act as conserved and redundant regulators in the SAM and RAM,our results demonstrated that they exhibit differentiated functions in these meristems.

关键词： ACR4 CIKs CLE40 stem cells distal root meristem phosphorylation

Angelica sinensis polysaccharides ameliorate 5-flourouracil-induced bone marrow stromal cell proliferation inhibition via regulating Wnt/β-catenin signaling

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BIOcell 2021年第4期45卷 1045-1058页

作者： HANXIANZHI XIAO RONGJIA QI ZILING WANG MINGHE XIAO YUE XIANG YAPING WANG LU WANG laboratory of Stem cell and Tissue Engineering Department of Histology and EmbryologyChongqing Medical UniversityChongqing40012China

Chemotherapy may cause cellular oxidative stress to bone *** damage of bone marrow hematopoietic microenvironment is closely related to chronic myelosuppression after chemotherapeutic *** sinensis polysaccharides(ASP)are major effective ingredients of traditional Chinese medicine Angelica with multi-target anti-oxidative stress *** the current study,we investigated the protective roles and mechanisms of ASP on chemotherapy-induced bone marrow stromal cell(BMSC)*** human bone marrow stromal cell line HS-5 cells were divided into control group,5-FU group,5-FU+ASP group,and 5-FU+LiCl group to investigate the mechanism of ASP to alleviate 5-FU-induced BMSC proliferation *** results showed that 5-FU inhibits the growth of HS-5 cells in a time and dose-dependent manner;however,ASP partially counteracted the 5-FU-induced decrease in cell viability,whereas Wnt signaling inhibitor Dkk1 antagonized the effect of ASP on HS-5 *** reversed the decrease in total cytoplasmicβ-catenin,p-GSK-3β,and CyclinD1 following 5-FU treatment and modulated nuclear expression ofβ-catenin,Lef-1,and C-myc ***,ASP also enhanced the antioxidant capacity of cells and reduced 5-FU-induced oxidative stress,attenuated FoxO1 expression,thus weakened its downstream apoptosis-related proteins and G0/G1 checkpoint-associated p27^(Kip1) expression to alleviate 5-FU-induced apoptosis and to promote cell cycle *** the results above suggest that the protective role of ASP in 5-FU-treated BMSCs proliferation for the chemotherapy may be related to its activating Wnt/β-catenin signaling and keeping homeostasis betweenβ-catenin and FoxO1 under oxidative *** study provides a potential therapeutic strategy for alleviating chemotherapeutic damage on BMSCs.

关键词： Angelica sinensis polysaccharides 5-Fluorouracil Wnt/β-catenin signaling pathway Oxidative stress cell proliferation FoxO1

Copper homeostasis and neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International Research laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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Differential function analysis: identifying structure and activation variations in dysregulated pathways

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Science China(Information Sciences) 2017年第1期60卷 116-131页

作者： Chuanchao ZHANG Juan LIU Qianqian SHI Tao ZENG Luonan CHEN State Key laboratory of Software Engineering School of Computer Wuhan University Key laboratory of Systems Biology Innovation Center for Cell Signaling Network Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences

Complex diseases are generally caused by the dysregulation of biological functions rather than individual molecules. Hence, a major challenge of the systematical study on complex diseases is how to capture the differentially regulated biological functions, e.g., pathways. The traditional differential expression analysis(DEA) usually considers the changed expression values of genes rather than functions. Meanwhile, the conventional function-based analysis(e.g., PEA: pathway enrichment analysis) mainly considers the varying activation of functions but disregards the structure change of genetic elements of functions. To achieve precision medicine against complex diseases, it is necessary to distinguish both the changes of functions and their elements from heterogeneous dysregulated pathways during the disease development and progression. In this work, in contrast to the traditional DEA, we developed a new computational framework, namely differential function analysis(DFA), to identify the changes of element-structure and expression-activation of biological functions, based on comparative non-negative matrix factorization(cN MF). To validate the effectiveness of our method, we tested DFA on various datasets, which shows that DFA is able to effectively recover the differential element-structure and differential activation-score of pre-set functional groups. In particular, the analysis of DFA on human gastric cancer dataset, not only capture the changed network-structure of pathways associated with gastric cancer, but also detect the differential activations of these pathways(i.e., significantly discriminating normal samples and disease samples), which is more effective than the state-of-the-art methods, such as GSVA and Pathifier. Totally,DFA is a general framework to capture the systematical changes of genes, networks and functions of complex diseases, which not only provides the new insight on the simultaneous alterations of pathway genes and pathway activations, but a

关键词： complex disease biological function non-negative matrix factorization network structure function activation

Regulation of AMP-activated protein kinase by natural and synthetic activators

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Acta Pharmaceutica Sinica B 2016年第1期6卷 1-19页

作者： David Grahame Hardie Division of cell signaling & Immunology College of Life SciencesUniversity of Dundee

The AMP-activated protein kinase(AMPK)is a sensor of cellular energy status that is almost universally expressed in eukaryotic *** it appears to have evolved in single-celled eukaryotes to regulate energy balance in a cell-autonomous manner,during the evolution of multicellular animals its role has become adapted so that it also regulates energy balance at the whole body level,by responding to hormones that act primarily on the *** monitors energy balance at the cellular level by sensing the ratios of AMP/ATP and ADP/ATP,and recent structural analyses of the AMPK heterotrimer that have provided insight into the complex mechanisms for these effects will be *** the central importance of energy balance in diseases that are major causes of morbidity or death in humans,such as type 2 diabetes,cancer and inflammatory disorders,there has been a major drive to develop pharmacological activators of *** such activators have been described,and the various mechanisms by which these activate AMPK will be discussed.A particularly large class of AMPK activators are natural products of plants derived from traditional herbal *** the mechanism by which most of these activate AMPK has not yet been addressed,I will argue that many of them may be defensive compounds produced by plants to deter infection by pathogens or grazing by insects or herbivores,and that many of them will turn out to be inhibitors of mitochondrial function.

关键词： AMP-activated protein kinase Energy balance AMP AMPK activator Mitochondrial function Regulatory mechanism

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cell signaling leads the way

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Journal of Integrative Plant Biology 2018年第9期60卷 743-744页

作者： Jia Li Ministry of Education Key laboratory of cell Activities and Stress Adaptations School of Life SciencesLanzhou UniversityLanzhou 730000China

cells in plants, like in animals, constantly communicate with one another to coordinate their cellular activities in response to surrounding environmental conditions. Higher plants are multicellular organisms. A plant is originated from a single fertilized egg, which eventually develops into an intact individual with all necessary tissues and organs. cell-to-cell communication is therefore especially critical throughout its life span, from embryo development, to tissue and organ formation, and finally to flowering and senescence, in addition.

关键词： Li cell signaling leads the way

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