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Heat Shock Factor A1s are required for phytochrome-interacting factor 4-mediated thermomorphogenesis in Arabidopsis

Journal of Integrative Plant Biology 2024年第1期66卷 20-35页

作者： Bingjie Li Shimeng Jiang Liang Gao Wenhui Wang Haozheng Luo Yining Dong Zhihua Gao Shuzhi Zheng Xinye Liu Wenqiang Tang Key laboratory of Molecular and cellular Biology of Ministry of Education Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell SignalingHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China School of Information Technology Hebei University of Economics and BusinessShijiazhuang 050061China

Thermomorphogenesis and the heat shock(HS)response are distinct thermal responses in plants that are regulated by PHYTOCHROME-INTERACTING FACTOR 4(PIF4)and HEAT SHOCK FACTOR A1s(HSFA1s),*** is known about whether these responses are interconnected and whether they are activated by similar *** analysis of transcriptome dynamics in response to warm temperature(28℃)treatment revealed that 30 min of exposure activated the expression of a subset of HSFA1 target genes in Arabidopsis ***,a loss-of-function HSFA1 quadruple mutant(hsfa1-cq)was insensitive to warm temperature-induced hypocotyl *** hsfa1-cq plants grown at 28℃,the protein and transcript levels of PIF4 were greatly reduced,and the circadian rhythm of many thermomorphogenesis-related genes(including PIF4)was ***,the nuclear localization of HSFA1s and the binding of HSFA1d to the PIF4 promoter increased following warm temperature exposure,whereas PIF4 overexpression in hsfa1-cq partially rescued the altered warm temperature-induced hypocotyl growth of the *** together,these results suggest that HSFA1s are required for PIF4 accumulation at a warm temperature,and they establish a central role for HSFA1s in regulating both thermomorphogenesis and HS responses in Arabidopsis.

关键词： HSFA1 PIF4 thermomorphogenesis

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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 *** 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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AtVQ25 promotes salicylic acid-related leaf senescence by fine-tuning the self-repression of AtWRKY53

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Journal of Integrative Plant Biology 2024年第6期66卷 1126-1147页

作者： Qi Tan Mingming Zhao Jingwei Gao Ke Li Mengwei Zhang Yunjia Li Zeting Liu Yujia Song Xiaoyue Lu Zhengge Zhu Rongcheng Lin Pengcheng Yin Chunjiang Zhou Geng Wang Ministry of Education Key laboratory of Molecular and cellular Biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental AdaptationHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China College of Chemical Engineering Shijiazhuang UniversityShijiazhuang 050035China Institute of Botany Chinese Academy of SciencesBeijing 100093China

Most mechanistic details of chronologically ordered regulation of leaf senescence are *** networks centered on AtWRKY53 are crucial for orchestrating and integrating various senescence-related ***,AtWRKY53binds to its own promoter and represses transcription of AtWRKY53,but the biological significance and mechanism underlying this selfrepression remain *** this study,we identified the VQ motif-containing protein AtVQ25as a cooperator of *** expression level of AtVQ25 peaked at mature stage and was specifically repressed after the onset of leaf ***25-overexpressing plants and atvq25 mutants displayed precocious and delayed leaf senescence,***,we identified AtWRKY53 as an interacting partner of *** determined that interaction between AtVQ25 and AtWRKY53 prevented AtWRKY53from binding to W-box elements on the AtWRKY53promoter and thus counteracted the selfrepression of *** addition,our RNA-sequencing data revealed that the AtVQ25-AtWRKY53 module is related to the salicylic acid(SA)*** leaf senescence and SA-induced leaf senescence in AtVQ25-overexpressing lines were inhibited by an SA pathway mutant,atsid2,and Nah G transgenic plants;AtVQ25-overexpressing/atwrky53 plants were also insensitive to SA-induced leaf ***,we demonstrated that AtVQ25 directly attenuates the self-repression of AtWRKY53 during the onset of leaf senescence,which is substantially helpful for understanding the timing of leaf senescence onset modulated by AtWRKY53.

关键词： AtWRKY53 leaf senescence salicylic acid transcriptional regulation VQ motif-containing proteins

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Generation and characterization of nanobodies targeting GPCR

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Biophysics Reports 2024年第1期10卷 22-30页

作者： Shenglan Zhang Zhiran Fan Jianfeng Liu Bioland laboratory (Guangzhou Regenerative Medicine and Health Guangdong laboratory) cellular signaling laboratory International Research Center for Sensory Biology and Technology of MOST Key Laboratory of Molecular Biophysics of MOE College of Life Science and Technology Huazhong University of Science and Technology

G protein-coupled receptors(GPCRs) are a large family of cell membrane proteins that are important targets for drug discovery. Nanobodies, also known as VHH(variable domains of heavy chain-only antibodies, HcAbs) antibodies, are small antibody fragments derived from camelids that have gained significant attention as potential therapeutics for targeting GPCRs due to their advantages over conventional antibodies. However, there are challenges in developing nanobodies targeting GPCRs, among which epitope accessibility is the most significant because the cell membrane partially shields the GPCR surface. We developed a universal protocol for making nanobodies targeting GPCRs using the cell membrane extract of GPCR-overexpressing HEK293 cells as the llama/alpaca immunization antigen. We constructed an immune VHH library and identified nanobodies by phage display bio-panning. The monoclonal nanobodies were recombinantly expressed in Escherichia coli(E. coli) and purified to characterize their binding potency.

关键词： Nanobody Single domain antibody Heavy chain-only antibody GPCR G protein-coupled receptor

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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem cell Research Tongji UniversityShanghai 200092China Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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TabHLH27 orchestrates root growth and drought tolerance to enhance water use efficiency in wheat

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Journal of Integrative Plant Biology 2024年第7期66卷 1295-1312页

作者： Dongzhi Wang Xiuxiu Zhang Yuan Cao Aamana Batool Yongxin Xu Yunzhou Qiao Yongpeng Li Hao Wang Xuelei Lin Xiaomin Bie Xiansheng Zhang Ruilian Jing Baodi Dong Yiping Tong Wan Teng Xigang Liu Jun Xiao Key laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050022China Key laboratory of Crop Biology College of Life SciencesShandong Agricultural UniversityTai'an 271018China State Key laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Ministry of Education Key laboratory of Molecular and cellular Biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental AdaptationHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China Centre of Excellence for Plant and Microbial Science(CEPAMS) JIC‐CASBeijing 100101China

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid *** water scarcity,plants activate drought response signaling,yet the delicate balance between drought tolerance and development remains *** genome-wide association studies and transcriptome profiling,we identified a wheat atypical basic helix-loop-helix(b HLH)transcription factor(TF),Tab HLH27-A1,as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in *** HLH27-A1/B1/D1 knockout reduced wheat drought tolerance,yield,and water use efficiency(WUE).Tab HLH27-A1 exhibited rapid induction with polyethylene glycol(PEG)treatment,gradually declining over *** activated stress response genes such as Ta CBL8-B1 and Ta CPI2-A1 while inhibiting root growth genes like Ta SH15-B1 and Ta WRKY70-B1 under short-term PEG *** distinct transcriptional regulation of Tab HLH27-A1 involved diverse interacting factors such as Ta ABI3-D1 and Tab *** variations of Tab HLH27-A1influence its transcriptional responses to drought stress,with Tab HLH27-A1^(Hap-II)associated with stronger drought tolerance,larger root system,more spikelets,and higher WUE in ***,the excellent Tab HLH27-A1^(Hap-II)was selected during the breeding process in China,and introgression of Tab HLH27-A1^(Hap-II)allele improved drought tolerance and grain yield,especially under water-limited *** study highlights Tab HLH27-A1's role in balancing root growth and drought tolerance,providing a genetic manipulation locus for enhancing WUE in wheat.

关键词： drought tolerance GWAS root growth wheat WUE

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T cell receptor signaling and cell immunotherapy

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National Science Open 2024年第4期3卷 156-171页

作者： Linsong Zhang Xinyi Xu Xiaoshan Shi Chenqi Xu Key laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State Key laboratory of Molecular Biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China

As the major sensor of adaptive immune system,T cell receptor(TCR)can recognize diverse antigens and initiate specific immune responses against invading pathogens and cancer *** the mechanisms of TCR signaling has led to the development of engineered T cell therapies,which have extensive applications in the treatment of diseases such as cancer,infection and ***,we review the current understanding of antigen-induced TCR signaling and discuss its applications in T cell therapies.

关键词： T cell receptor-CD3 complex signaling T cell therapy

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Lipidomic remodeling during mammalian preimplantation embryonic development

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Life Metabolism 2024年第2期3卷 3-5页

作者： Qingran Kong Shaorong Gao Zhejiang Provincial Key laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhouZhejiang 325035China Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

The dynamic changes in lipids during early embryonic development in mammals have not yet been comprehensively investi*** a recent paper published in Nature cell Biology,Zhang et *** the dynamic lipid landscapes during preimplantation embryonic development in mice and *** highlight the crucial role of lipid unsaturation in regulating embryogenesis.

关键词： Lipid al. lipids

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Novel PIKfyve/Tubulin Dual-target Inhibitor as a Promising Therapeutic Strategy for B-cell Acute Lymphoblastic Leukemia

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Current Medical Science 2024年第2期44卷 298-308页

作者： Zhen LU Qian LAI Zhi-feng LI Meng-ya ZHONG Yue-long JIANG Li-ying FENG Jie ZHA Jing-wei YAO Yin LI Xian-ming DENG Bing XU Department of Hematology The First Affiliated Hospital of Xiamen University and Institute of HematologySchool of MedicineXiamen UniversityXiamen361005China Key laboratory of Xiamen for Diagnosis and Treatment of Hematological Malignancy Xiamen361005China Department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China State Key laboratory of cellular Stress Biology Innovation Center for Cell Signaling NetworkSchool of Life SciencesXiamen UniversityXiamen361003China

Objective:In B-cell acute lymphoblastic leukemia(B-ALL),current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50%of cases,underscoring the urgent need for new therapeutic regimens for this patient *** present study aimed to determine whether HZX-02-059,a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase(PIKfyve)and tubulin,is lethal to B-ALL cells and is a potential therapeutic for B-ALL ***:cell proliferation,vacuolization,apoptosis,cell cycle,and in-vivo tumor growth were *** addition,Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in ***:HZX-02-059 was found to inhibit cell proliferation,induce vacuolization,promote apoptosis,block the cell cycle,and reduce in-vivo tumor *** of the p53 pathway and suppression of the phosphoinositide 3-kinase(PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these ***:Overall,these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.

关键词： B-cell acute lymphoblastic leukemia dual-target inhibitor NF-kB c-Myc PI3K/AKT p53

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Hesperidin ameliorates H_(2)O_(2)-induced bovine mammary epithelial cell oxidative stress via the Nrf2 signaling pathway

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1737-1750页

作者： Qi Huang Jiashuo Liu Can Peng Xuefeng Han Zhiliang Tan CAS Key laboratory for Agro‑Ecological Processes in Subtropical Region National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125HunanChina State Key laboratory of Animal Nutrition and Feeding Institute of Animal SciencesChinese Academy of Agricultural SciencesBeijing 100193China

Background Hesperidin is a citrus flavonoid with anti-inflammatory and antioxidant potential. However, its protective effects on bovine mammary epithelial cells(b MECs) exposed to oxidative stress have not been *** In this study, we investigated the effects of hesperidin on H_(2)O_(2)-induced oxidative stress in b MECs and the underlying molecular mechanism. We found that hesperidin attenuated H_(2)O_(2)-induced cell damage by reducing reactive oxygen species(ROS) and malondialdehyde(MDA) levels, increasing catalase(CAT) activity, and improving cell proliferation and mitochondrial membrane potential. Moreover, hesperidin activated the Keap1/Nrf2/ARE signaling pathway by inducing the nuclear translocation of Nrf2 and the expression of its downstream genes NQO1 and HO-1, which are antioxidant enzymes involved in ROS scavenging and cellular redox balance. The protective effects of hesperidin were blocked by the Nrf2 inhibitor ML385, indicating that they were Nrf2 *** Our results suggest that hesperidin could protect b MECs from oxidative stress injury by activating the Nrf2 signaling pathway, suggesting that hesperidin as a natural antioxidant has positive potential as a feed additive or plant drug to promote the health benefits of bovine mammary.

关键词： Bovine mammary epithelial cell Hesperidin Nrf2 signaling pathway Oxidative stress

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