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Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2804-2818页

作者： Fenglian He Zhongen wu Chenglong Liu Yuanyuan Zhu Yan zhou Enming Tian Rina Rosin-Arbesfeld Dehua yang Ming-Wei Wang Di Zhu Department of Pharmacology Minhang Hospitaland Key Laboratory of Smart Drug DeliveryShanghai Engineering Research Center of Immune TherapySchool of PharmacyFudan UniversityShanghai 201203China The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai 201203China Department of Microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources SanyaChina Department of Chemistry School of ScienceThe University of TokyoTokyoJapan Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education School of PharmacyHainan Medical UniversityHaikouChina Shandong Academy of Pharmaceutical Science JinanChina

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor *** B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against ***,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely ***,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into *** inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell ***,targeting BCL9/BCL9L promoted antigen presentation in *** is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 ***,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 ***,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor *** BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

关键词： immunity Targeting markedly

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A biocompatible Horner-Wadsworth-Emmons(HWE)reaction triggered by a bioorthogonal proximity-induced platform

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Chinese Chemical Letters 2024年第8期35卷 217-220页

作者： Yayue Wang Haojie yang Jie Li Qiao Kong Siming zhou Hongbao Sun Lili Pan Qiyong Gong Ping Feng Haoxing wu Department of Radiology and Huaxi MR Research Center(HMRRC) Functional and Molecular Imaging Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan UniversityChengdu 610041China Department of Nuclear Medicine Laboratory of Clinical Nuclear MedicineWest China HospitalSichuan UniversityChengdu 610041China Reseacrch Unit of Psychoradiology Chinese Academy of Medical SciencesChengdu 610041China Department of Pharmacy West China HospitalSichuan UniversityChengdu 610041China Clinical Trial Center and National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs West China HospitalSichuan UniversityChengdu 610041China

Here,we present a novel bioorthogonal platform that enables precise positioning of attached moieties in close proximity,thereby facilitating the discovery and optimization of biocompatible *** this platform,we achieve a Horner-Wadsworth-Emmons(HWE)reaction under physiological conditions,generating a fluorophore in situ with a yield of up to 93%.This proximity platform should facilitate the discovery of various types of biocompatible reactions,making it a versatile tool for biomedical applica-tions.

关键词： Biocompatible reactions Horner-Wadsworth-Emmons reaction Bioorthogonal reactions Tetrazines Proximity effects

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Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2362-2379页

作者： Yi zhou Shuang wu Fan-Jie Qu Department of Oncology Affiliated Dalian Third People’s Hospital of Dalian Medical UniversityDalian 116033Liaoning ProvinceChina

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and ***,colorectal ranks third in incidence,but second in *** than half of the patients are in advanced stages at *** options are complex because of the heterogeneity of the patient population,including different molecular *** have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,*** recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor B-type RAF mutation Kirsten rat sarcoma viral oncogene wild type Kirsten rat sarcoma viral oncogene G12C mutation Human epidermal growth factor receptor 2 overexpression/amplification

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BoMyrosinase plays an essential role in sulforaphane accumulation in response to selenite treatment in broccoli

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Horticultural Plant Journal 2024年第2期10卷 488-502页

作者： Qiuyun wu Qi wu Yuxiao Tian Chunyan zhou Shuxiang Mao Junwei Wang Ke Huang College of Horticulture Hunan Agricultural UniversityChangshaHunan 410128China Engineering Research Center for Horticultural Crop Germplasm Creation and New Variety Breeding Ministry of EducationChangshaHunan 410128China Key Laboratory for Vegetable Biology of Hunan Province ChangshaHunan 410128China Key Laboratory for Evaluation and Utilization of Gene Resources of Horticultural Crops Ministry of Agriculture and Rural Affairs of ChinaChangshaHunan 410128China

Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase(MY) is a key gene responsible for the catalysis of sulforaphane formation, but the molecular mechanisms through which MY regulates sulforaphane biosynthesis in plants remains largely unknown. Here, we discovered that the change of sulforaphane content in broccoli sprouts caused by exogenous selenite treatments is positively related to BoMY expression. BoMY overexpression in the Arabidopsis thaliana tgg1 mutants could dramatically increase myrosinase activity and sulforaphane content in the rosette leaves of 35S::BoMY/tgg1 and rescue its ***, an obvious increase of myrosinase activity and sulforaphane content was displayed in transgenic BoMY-overexpressed broccoli *** addition, a 2 033 bp promoter fragment of BoMY was isolated. Yeast one-hybrid(Y1H) library screening experiment uncovered that one bHLH transcription factor, BoFAMA, could directly bind to BoMY promoter to activate its expression, which was further evidenced by Y1H assay and dual-luciferase reporter assay. BoFAMA is a selenite-responsive transcription factor that is highly expressed in broccoli leaves;its protein is solely localized to nucleus. Additionally, genetic evidence suggested that the knockdown of FAMA gene in Arabidopsis thaliana could significantly decrease sulforaphane yield by inhibiting the expression of myrosinase genes. Interestingly, exogenous selenite supply could partially restore the low level of sulforaphane content in transgenic Arabidopsis FAMA-silencing plants. Our findings uncover a novel function of FAMAMY module in the regulation of selenite-mediated sulforaphane synthesis and provide a new insights into the molecular mechanism by which selenite regulates the accumulation of sulforaphane in plants.

关键词： Brassica oleracea var.italica Myrosinase BoMY Sulforaphane Selenite treatment

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Experimental quantum state compression from two identical qubits to a qutrit

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Science China(Physics,Mechanics & Astronomy) 2024年第7期67卷 1-5页

作者： Qiao Xu Lin-Xiang zhou Tian-Feng Feng Shang-Feng Qiu Si-wu Li wu-Ji Zhang Hui Luo Xiao-Qi zhou State Key Laboratory of Optoelectronic Materials and Technologies and School of Physics Sun Yat-sen UniversityGuangzhou 510000China Hefei National Laboratory Hefei 230088China

In the realm of modern information technology,data compression technology occupies a pivotal *** advancements in quantum information technology,the need to compress large-scale qubits ensembles has become urgent,aiming to reduce the demand on quantum storage ***,existing quantum state compression schemes generally face a limitation:the particles before and after compression must reside in the same dimensional *** specific scenarios,compressing qubits into particles of higher dimensions not only enhances the efficiency of quantum state compression but also further reduces the usage of quantum storage *** we experimentally demonstrated a quantum state compression between particles of different dimensions,successfully compressing two qubits into a single *** average fidelity of the resulting qutrit with the ideal quantum state is *** study may have potential applications in future quantum information,such as increasing quantum communication bandwidth and reducing storage resource consumption in quantum computing.

关键词： quantum state compression quantum information technology optics

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Selenocysteine methyltransferase SMT catalyzed the synthesis of Se-methylselenocysteine to regulate the accumulation of glucosinolates and sulforaphane in broccoli

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Horticultural Plant Journal 2024年第5期10卷 1151-1164页

作者： Qi wu Junwei Wang Yuxiao Tian Chunyan zhou Shuxiang Mao Qiuyun wu Ke Huang College of Horticulture Hunan Agricultural UniversityChangshaHunan 410128China Engineering Research Center for Horticultural Crop Germplasm Creation and New Variety Breeding Ministry of EducationChangshaHunan 410128China Key Laboratory for Vegetable Biology of Hunan Province ChangshaHunan 410128China

Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound *** studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates(GSLs)and sulforaphane,but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain *** this study,we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs *** assays revealed that BoSMT is involved in SeMSC biosynthesis in *** importantly,the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines,suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane *** evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC *** with the mock(water)treatment,selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane *** with the mock treatment,exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression,suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane *** findings provided novel insights into selenium-mediated GSLs and sulforaphane *** genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.

关键词： Selenocysteine methyltransferase Transgenic broccoli Se-methylselenocysteine Glucosinolate sulforaphane Selenium

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World’s first implementation of close-fit pipe jacking of twin tunnels for construction of subway station--Innovation in equipment and construction technology

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Frontiers of Engineering Management 2024年第2期11卷 369-376页

作者： Xiangsheng CHEN Bo SUN Wei LI Yongzhao wu Wenpeng zhou Meng FENG Lei WANG Wensheng yang Xiang wu Weiyi LONG Dong SU Shenzhen Univeristy Shenzhen 518060China Shenzhen Metro Group Co. Ltd.Shenzhen 518031China Shenzhen Municipal Design&Research Co. Ltd.Shenzhen 518000China Sinohydro Bureau 11 Co. Ltd.Zhengzhou 450001China China Railway Engineering Equipment Group Co. LTD.Zhengzhou 450000China Shenzhen University Shenzhen 518060China

1 Project overview The Shasan station of Phase II of Shenzhen’s urban rail transit Line 12 is situated in Bao’an District,*** comprises a two-level underground island platform station,measuring 212 m in length,and 22.6 m in width,with an overburden thickness of about 7.0 ***.1 illustrates the presence of a large underground reinforced concrete stormwater culvert,measuring 11.5 m by 3.6 m,traversing the station’s center.

关键词： Subway station close-fit pipe jacking of twin tunnels modular rectangular pipe jacking machine Structural Transformation equipment construction

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Reduction of pulmonary inflammatory response by erythropoietin n a rat model of endotoxaemia

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Chinese Medical Journal 2009年第7期122卷 834-838页

作者： SHANG You JIANG Yuan-xu XU San-peng wu Yan wu zhou-yang YUAN Shi-ying YAO Shang-long Department of Anesthesiology and Intensive Care Medicine Union Hospital Tongji Medical CollegeHuazhong Vniversiiy of Science and Technology Wuhan Hubei430022 China Department of Neurology Union Hospital Tongji Medical CollegeHuazhong Vniversiiy of Science and Technology Wuhan Hubei430022 China Department of Pathology Tongji Hospital Tongji Medical CollegeHuazhong University of Science and Technology Wuhan Hubei430030 China

Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20）（P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35）（P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-

关键词： endotoxaemia acute lung injury erythropoietin

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Black-box membership inference attacks based on shadow model

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The Journal of China Universities of Posts and Telecommunications 2024年第4期31卷 1-16页

作者： Han Zhen zhou Wen'an Han Xiaoxuan wu Jie School of Computer Science Beijing University of Posts and TelecommunicationsBeijing 100876China

Membership inference attacks on machine learning models have drawn significant *** current research primarily utilizes shadow modeling techniques,which require knowledge of the target model and training data,practical scenarios involve black-box access to the target model with no available *** training data further complicate the implementation of these *** this paper,we experimentally compare common data enhancement schemes and propose a data synthesis framework based on the variational autoencoder generative adversarial network(VAE-GAN)to extend the training data for shadow ***,this paper proposes a shadow model training algorithm based on adversarial training to improve the shadow model's ability to mimic the predicted behavior of the target model when the target model's information is *** conducting attack experiments on different models under the black-box access setting,this paper verifies the effectiveness of the VAE-GAN-based data synthesis framework for improving the accuracy of membership inference ***,we verify that the shadow model,trained by using the adversarial training approach,effectively improves the degree of mimicking the predicted behavior of the target *** with existing research methods,the method proposed in this paper achieves a 2%improvement in attack accuracy and delivers better attack performance.

关键词： machine learning membership inference attack shadow model black-box model

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Supporting-electrolyte-free electrochemical[2+2+1]annulation of benzo[d]isothiazole 1,1-dioxides,N-arylglycines and paraformaldehyde

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Chinese Chemical Letters 2024年第6期35卷 327-330页

作者： Hai-yang Song Jun Jiang Yu-Hang Song Min-Hang zhou Chao wu Xiang Chen Wei-Min He School of Chemistry and Chemical Engineering University of South ChinaHengyang 421001China

The H-bond promoted electrochemical[2+2+1]annulation of benzo[d]isothiazole 1,1-dioxides,Narylglycines and paraformaldehyde for the synthesis of various benzo[d]imidazo[1,5-b]isothiazole 5,5-dioxide derivatives under ... 详细信息

关键词： H-bond N-Arylglycines Paraformaldehyde Organic electro-synthesis Electrolyte-free

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