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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

Aagab is required for zebrafish larval development by regulating neural activity

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Journal of Genetics and Genomics 2024年第6期51卷 630-641页

作者： Shihui Ding Tursunjan Aziz Anming Meng Shunji Jia State Key laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Guangzhou laboratory GuangzhouGuangdong 510320China State Key laboratory of Molecular Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Clathrin-mediated endocytosis has been implicated in various physiological processes,including nutrient uptake,signal transduction,synaptic vesicle recycling,maintenance of cell polarity,and antigen *** prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis,the physiological function of α-and γ-adaptin binding protein(aagab)remains *** this study,we investigate the biological function of aagab during zebrafish *** establish a loss-of-function mutant of aagab in zebrafish,revealing impaired swimming and early larval *** the high expression level of aagab in the brain,we probe into its physiological role in the nervous *** mutants display subdued calcium responses and local field potential in the optic tectal neurons,aligning with reduced neurotransmitter release(e.g.,norepinephrine)in the tectal neuropil of aagab *** aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release,calcium responses,swimming ability,and ***,our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells,pointing towards a probable link to defective clathrin-mediated synaptic vesicle *** conclusion,our study underscores the significance of Aagab in neurobiology and suggests its potential impacts on neurological disorders.

关键词： Aagab Endocytosis Neural activity Synaptic transmitter release Zebrafish

Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

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cellular & Molecular Immunology 2024年第1期21卷 91-94页

作者： Shengduo Pei Jonas Sjölund Yueyun Pan Kristian Pietras Mikael C.I.Karlsson Department of Microbiology Tumor and Cell BiologyKarolinska InstitutetStockholmSweden Division of Translational Cancer Research Department of Laboratory MedicineLund University Cancer CentreLund UniversityLundSweden

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid ***,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor *** iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

关键词： killer CD1d Cancer

COVID-19 vaccines and beyond

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cellular & Molecular Immunology 2024年第3期21卷 207-209页

作者： Yiyuan Liu Danying Li Jiahuai Han State Key laboratory of cellular Stress biology Innovation Center for Cell BiologySchool of Life SciencesXiamen UniversityXiamenFujianChina laboratory Animal Center Xiamen UniversityXiamenFujianChina Research Unit of cellular Stress of CAMS Cancer Research Center of Xiamen UniversityXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenFujianChina

Hundreds of vaccines have been developed worldwide for Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the cause of Coronavirus disease 2019(COVID-19),since the beginning of the *** vaccines have saved innumerable lives and contributed to partial control of the COVID-19 *** of the vaccines approved for clinical use exhibit satisfactory initial protection rates against corresponding ***,vaccine protection declines over time,with almost all vaccines falling below 50%protection after 6 months[1].In the case of natural infections,protection lasts longer,but the incidence of reinfection is also quite high.

关键词： vaccines acute beyond

Development of functional dye with redshifted absorption based on Knoevenagel condensation at 1-site in phenyl[b]-fused BODIPY

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Chinese Chemical Letters 2024年第6期35卷 349-352页

作者： Tianze Wang Junyi Ren Dongxiang Zhang Huan Wang Jianjun Du Xin-Dong Jiang Guiling Wang Liaoning&Shenyang Key laboratory of Functional Dye and Pigment Shenyang University of Chemical TechnologyShenyang 110142China Department of cell biology China Medical UniversityShenyang 110122China State Key laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China

Integrating ring-fused modification withπ-conjugated extension is an effective approach for designing,synthesizing,and application for novel borondipyrromethene(BODIPY)*** this work,based on phenyl[b]-fused BODIPY,we made reasonable modification of the methyl group at 1-site to generate dye *** possessed near-infrared region(NIR)absorption and emission properties,and the intramolecular charge transfer(ICT)resulted in low ***,heat energy is evidently released in the presence of light,which can be exploited for intracellular photothermal therapy via the cell apoptosis process,reducing the inflammatory side-effects induced by *** research provides a crucial foundation for the novel molecule via BODIPY multi-directional alteration and its potential application in anti-tumor phototherapy.

关键词： NIR dyes [b]-Fused BODIPY Knoevenagel condensation Photothermal therapy cell apoptosis

Genome-wide identifcation of the histone acetyltransferase gene family in Citrus clementina and its potential roles in citrate metabolism

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Food Quality and Safety 2024年第1期8卷 201-211页

作者： Xiahui Lin Yanna Shi Shengchao Liu Xincheng Liu Minglei Zhang Bo Zhang Shaojia Li Kunsong Chen College of Agriculture and Biotechnology Zhejiang UniversityZijingang CampusHangzhouChina Zhejiang Provincial Key laboratory of Horticultural Plant integrative biology Zhejiang UniversityZijingang CampusHangzhouChina The State Agriculture Ministry laboratory of Horticultural Plant Growth Development and Quality ImprovementZhejiang UniversityZijingang CampusHangzhouChina Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhenChina Institute of Horticulture Jiangxi Academy of Agricultural SciencesNanchangChina

Histone acetyltransferase(HAT)catalyzes histone acetylation and is involved in plant growth and development and stress ***,37 CitHAT genes were identifed in Citrus *** physicochemical properties,chromosomal location,gene structure,conserved domain and motif,and cis-acting elements were *** were classifed into four subfamilies based on protein sequence homology,which was strongly supported by gene structure,conserved domain,and motif *** cis-acting elements in gene promoter regions were predicted to be associated with the regulation of plant growth,stress resistance,and response to *** and transcriptomic analyses of citrus callus with mock treatment and HAT inhibitor treatment revealed that increased citric acid content in inhibitor treatment may be attributed to differential expression of CitPEPCK2 and CitGS2,which may be due to the hypo-acetylation of histone *** expression patterns of CitHATs in citrus fruit development stages showed that CitHAG11 and CitHAG28 exhibited a negative correlation with citric acid *** study associates the potential function of histone acetyltransferases in citrate metabolism and extends the molecular mechanism of citrate metabolism in fruits.

关键词： Citrus histone acetyltransferases citric acid citrate metabolism histone acetylation.

The ubiquitin codes in cellular stress responses

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Protein & cell 2024年第3期15卷 157-190页

作者： Xiangpeng Sheng Zhixiong Xia Hanting Yang Ronggui Hu Key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key laboratory of Molecular biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China State Key laboratory of Animal Disease Control Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China Department of Neurology State Key Laboratory of Medical NeurobiologyInstitute for Translational Brain ResearchMOE Frontiers Center for Brain ScienceZhongshan HospitalFudan UniversityShanghai 200032China

Ubiquitination/ubiquitylation,one of the most fundamental post-translational modifications,regulates almost every critical cellular process in *** evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses,from exogenous factors to cellular reactions,causing a dazzling variety of functional *** forms of ubiquitin sig-nals generated by ubiquitylation events in specific milieus,known as ubiquitin codes,constitute an intrinsic part of myriad cellular stress *** ubiquitination events,leading to proteolytic turnover of the substrates or just switch in functionality,initiate,regulate,or supervise multiple cellular stress-associated responses,supporting adaptation,homeostasis recovery,and survival of the stressed *** this review,we attempted to summarize the crucial roles of ubiquitination in response to different environmental and intracellular stresses,while discussing how stresses modulate the ubiquitin *** review also updates the most recent advances in understanding ubiquitination machinery as well as different stress responses and discusses some important questions that may warrant future investigation.

关键词： ubiquitin E3 ligase environmental stresses intercellular stresses stress response homeostasis

MAD2L2 overexpression attenuates the effects of TNF-α-induced migration and invasion capabilities in colorectal cancer cells

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BIOcell 2024年第9期48卷 1311-1322页

作者： HAOTONG SUN HEYING WANG YANJIE HAO XIN LI JUN LING HUAN WANG FEIMIAO WANG FANG XU School of Basic Medicine Medical Genetics and Cell BiologyNingxia Medical UniversityYinchuan750004China Key laboratory of Reproduction and Genetics Ningxia Medical UniversityYinchuan750004China

Background:Colorectal cancer is a major global health concern,exacerbated by tumor necrosis factor-alpha(TNF-α)and its role in inflammation,with the effects of Mitotic Arrest Deficient 2 Like 2(MAD2L2)in this context still ***:The colorectal carcinoma cell lines HCT116 and SW620 were exposed to TNF-αfor a period of 24 h to instigate an inflammatory *** assessments were conducted to measure the expression of inflammatory cytokines,the activity within the p38 mitogen-activated protein kinase(p38 MAPK)and Phosphoinositide 3-Kinase/AKT Serine/Threonine Kinase pathway(PI3K/AKT)signaling *** sequencing and subsequent integrative analysis with the Cancer Genome Atlas(TCGA)program database revealed a significant downregulation of the key factor *** of MAD2L2 expression was facilitated via lentiviral vector-mediated *** influence of this overexpression on TNF-α-prompted inflammation,intracellular signaling pathways,and the migratory and invasive behaviors of the colorectal cancer cells was then ***:TNF-αtreatment significantly increased the expression of Interleukin-1 beta(IL-1β)and Interleukin-6(IL-6),activated the MAPK p38 and PI3K/AKT signaling pathways,and enhanced cell migration and invasion.A decrease in MAD2L2 expression was observed following TNF-α***,overexpression of MAD2L2 reversed the effects of TNF-α,reducing IL-1βand IL-6 levels,attenuating PI3K/AKT pathway activation,and inhibiting cell migration and ***:Overexpression of MAD2L2 attenuates the pro-inflammatory effects of TNF-α,suggesting that MAD2L2 plays a protective role against TNF-α-induced migration and invasion of colorectal carcinoma ***,MAD2L2 holds potential as a therapeutic target in the treatment of colorectal cancer.

关键词： Colorectal cancer TNF-α MAD2L2 Migration Invasion

Low-density lipoprotein receptor-related protein 2(LRP2)is required for lipid export in the midgut of the migratory locust,Locusta migratoria

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Journal of integrative Agriculture 2024年第5期23卷 1618-1633页

作者： Yiyan Zhao Weimin Liu Xiaoming Zhao Zhitao Yu Hongfang Guo Yang Yang Hans Merzendorfer Kun Yan Zhu Jianzhen Zhang Research Institute of Applied biology Shanxi Key Laboratory of Nucleic Acid BiopesticidesShanxi UniversityTaiyuan 030006China College of Life Science Shanxi UniversityTaiyuan 030006China Interfaculty Institute of cell biology University of TubingenTubingen 72076Germany Institute of biology University of SiegenSiegen 57076Germany Department of Entomology Kansas State UniversityManhattanKS 66506USA

Low-density lipoprotein receptor-related protein 2(LRP2)is a multifunctional endocytic receptor expressed in epithelial *** mammals,it acts as an endocytic receptor that mediates the cellular uptake of cholesterol-containing apolipoproteins to maintain lipid ***,little is known about the role of LRP2 in lipid homeostasis in *** the present study,we investigated the function of LRP2 in the migratory locust Locusta migratoria(LmLRP2).The mRNA of LmLRP2 is widely distributed in various tissues,including integument,wing pads,foregut,midgut,hindgut,Malpighian tubules and fat body,and the amounts of LmLRP2 transcripts decreased gradually in the early stages and then increased in the late stages before ecdysis during the nymphal developmental *** immunohistochemistry revealed that the LmLRP2 protein is mainly located in cellular membranes of the midgut and *** RNAi to silence LmLRP2 caused molting defects in nymphs(more than 60%),and the neutral lipid was found to accumulate in the midgut and surface of the integument,but not in the fat body,of dsLmLRP2-treated *** results of a lipidomics analysis showed that the main components of lipids(diglyceride and triglyceride)were significantly increased in the midgut,but decreased in the fat body and ***,the content of total triglyceride was significantly increased in the midgut,but markedly decreased in the fat body and hemolymph in dsLmLRP2-injected *** results indicate that LmLRP2 is located in the cellular membranes of midgut cells,and is required for lipid export from the midgut to the hemolymphand fat body in locusts.

关键词： Locusta migratoria low-density lipoprotein receptor-related protein 2 midgut lipids transport RNAi