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Defining and tracing subtypes of patient-derived xenograft models in pancreatic ductal adenocarcinoma

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Cancer Communications 2024年第8期44卷 915-920页

作者： Sangyeop Hyun Youngmin Han Jae Yun Moon Young-Ah Suh Won-Gun Yun Wooil Kwon Jong-Eun Lee Daeun Kim Ja-Lok Ku Jin-Young Jang Daechan Park Department of molecular Science and Technology Ajou UniversitySuwonRepublic of Korea Department of Surgery and Cancer research Institute Seoul National University College of MedicineSeoulRepublic of Korea molecular Science and Technology research center Ajou UniversitySuwonRepublic of Korea DNA Link Inc. SeoulRepublic of Korea Korean Cell Line Bank Laboratory of Cell BiologyCancer Research InstituteSeoul National University College of MedicineSeoulRepublic of Korea

Patient-derived xenograft(PDX)models have been used to explore therapeutic opportunities for pancreatic ductal adenocarcinoma(PDAC)[1].Although original tumor characteristics are altered by cancer-stromal interactions... 详细信息

关键词： adenocarcinoma ductal xenograft

The evolution of cancer genomic medicine in Japan and the role of the National Cancer center Japan

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Cancer biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Self-assembled amphiphilic NIR-Ⅱ emissive nano-micelles for imaging-guided photothermal therapy of colorectal cancer

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Science China Chemistry 2024年第8期67卷 2767-2774页

作者： Axin He Fangfang Xia Da Han Qinglai Yang Weihong Tan Institute of molecular Medicine(IMM) Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China center for molecular Imaging Probe Hunan Province Key Laboratory of Cancer Cellular and Molecular PathologyCancer Research InstituteHengyang Medical SchoolUniversity of South ChinaHengyang 421001China The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer Hospital Hangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhou 310022China molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China

Colorectal cancer(CRC) is one of the major causes of cancer-related mortality worldwide. Most near-infrared(NIR) agents used in clinical CRC treatment are at NIR-I(700–900 nm) window, which has limitations on deep tissue, and fluorescent probes in the second NIR(1,000–1,700 nm) allow high-resolution bioimaging with deep tissue penetration. However, existing NIR-II fluorophores used in clinical are still rare. Herein, based on shielding-donor-acceptor-donor-shielding(S-D-A-D-S) scaffold, we developed an organic small-molecule fluorophore IR-BTGP with NIR-II emission for imaging-guided photothermal therapy(PTT) in CRC mice model. Amphiphilic IR-BTGP can be self-assembled into spherical nano-micelles, which presents reliable water solubility and photothermal conversion efficiency(30.2%). In vitro experiments indicate that cancer cells treated with IRBTGP were significantly killed upon 808 nm light irradiation. Furthermore, in vivo NIR-II fluorescence imaging confirms that IR-BTGP accumulates in the tumor region. Remarkably, a significant tumor inhibition rate(78.5%) was observed in tumorbearing mice when treated with IR-BTGP plus 808 nm irradiation. Therefore, this work shows that IR-BTGP holds great promise as an NIR-II fluorescence imaging-guided PTT platform for CRC in the future.

关键词： photothermal therapy(PTT) second near-infrared(NIR-Ⅱ)imaging organic molecule

Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration research 2024年第2期19卷 405-406页

作者： Fabio Coppedè Department of Translational research and of New Surgical and Medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

Mitigating growth-stress tradeoffs via elevated TOR signaling in rice

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molecular Plant 2024年第2期17卷 240-257页

作者： Wei Li Jiaqi Liu Zeqi Li Ruiqiang Ye Wenzhen Chen Yuqing Huang Yue Yuan Yi Zhang Huayi Hu Peng Zheng Zhongming Fang Zeng Tao Shiyong Song Ronghui Pan Jian Zhang Jumim Tu Jen Sheen Hao Du State Key Laboratory of Rice biology College of Agriculture and BiotechnologyZhejiang UniversityYu-Hang-Tang Road No.866Hangzhou 310058China ZJU-Hangzhou Global Scientific and Technological Innovation center Zhejiang UniversityHangzhou 311215China Hainan Institute of Zhejiang University Sanya 572025China National Key Laboratory of Plant molecular Genetics CASCenter for Excellence in Molecular Plant SciencesShanghai lnstitute of Plant Physiology and EcologyChineseAcademy of SciencesShanghai 200032China Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region(Ministry of Education) College of Agricultural SciencesGuizhouUniversityGuiyang 550025China State Key Laboratory of Rice biology and Breeding China National Rice Research InstituteHangzhou 311400China Department of molecular biology and center for Computational and Integrative biology Massachusetts General Hospitaland Department of GeneticsHarvard Medical SchoolBostonMA02114USA

Rice production accounts for approximately half of the freshwater resources utilized in agriculture,result-ing in greenhouse gas emissions such as methane(CH4)from flooded paddy *** address this chal-lenge,environmentally friendly and cost-effective water-saving techniques have become widely adopted in rice ***,the implementation of water-saving treatments(WsTs)in paddy-field rice has been associated with a substantial yield loss of up to 50%as well as a reduction in nitrogen use efficiency(NUE).In this study,we discovered that the target of rapamycin(TOR)signaling pathway is compromised in rice under *** profiling-coupled transcriptome sequencing(polysome-seq)analysis unveiled a substantial reduction in global translation in response to WST associated with the downregulation of TOR ***,biochemical,and genetic analyses revealed new insights into the impact of the positive TOR-S6K-RPS6 and negative TOR-MAF1 modules on translation repression under ***,ammonium exhibited a greater ability to alleviate growth constraints under WsT by enhancing TOR signaling,which simultaneously promoted uptake and utilization of ammonium and nitrogen *** further demonstrated that TOR modulates the ammonium transporter AMT1;1 as well as the amino acid permease APP1 and dipeptide transporter NPF7.3 at the translational level through the 5'untranslated ***,these findings reveal that enhancing TOR signaling could mitigate rice yield penalty due to WST by regulating the processes involved in protein synthesis and *** study will contribute to the breeding of new rice varieties with increased water and fertilizer utilization efficiency.

关键词： target of rapamycin TOR water-saving rice low-carbon agriculture drought nitrogen use efficiency NUE

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

Central cell:the key to determine persistent pollen tube attraction or termination

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Science China(Life Sciences) 2024年第9期67卷 2030-2032页

作者： Jiang-Guo Meng Shi-Zhen Li Hong-Ju Li center for Developmental biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation Integrative Science Center of Germplasm Creation Western China(Chongqing)Science CitySchool of Life SciencesSouthwest UniversityChongqing400715 China Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China center for molecular Agrobiology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China

Most eukaryotic species depend on sexual reproduction,characterized by fertilization,to produce a new *** process requires the transfer of sperm(male gamete),containing half of the genetic information,from the male to the egg cell(female gamete),which holds half of the maternal genome,within the female reproductive *** strategies have been evolved to ensure fertilization success in plants.

关键词： organs termination holds

Nphos:Database and Predictor of Protein N-phosphorylation

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Genomics, Proteomics & Bioinformatics 2024年第3期22卷 139-151页

作者： Ming-Xiao Zhao Ruo-Fan Ding Qiang Chen Junhua Meng Fulai Li Songsen Fu Biling Huang Yan Liu Zhi-Liang Ji Yufen Zhao Institute of Drug Discovery Technology Ningbo UniversityNingbo 315211China Department of Chemical biology Key Laboratory for Chemical Biology of Fujian ProvinceCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China State Key Laboratory of Cellular Stress biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Zhejiang Key Laboratory of Pathophysiology Department of Biochemistry and Molecular BiologyHealth Science CenterNingbo UniversityNingbo 315211China BGI Genomics BGI-ShenzhenShenzhen 518083China Key Laboratory of Bioorganic Phosphorus Chemistry&Chemical biology Department of ChemistryTsinghua UniversityBeijing 100084China

Protein N-phosphorylation is widely present in nature and participates in various biological ***,current knowledge on N-phosphorylation is extremely limited compared to that on *** this study,we collected 11,710 experimentally verified N-phosphosites of 7344 proteins from 39 species and subsequently constructed the database Nphos to share up-to-date information on protein *** these substantial data,we characterized the sequential and structural features of protein ***,after comparing hundreds of learning models,we chose and optimized gradient boosting decision tree(GBDT)models to predict three types of human N-phosphorylation,achieving mean area under the receiver operating characteristic curve(AUC)values of 90.56%,91.24%,and 92.01%for pHis,pLys,and pArg,***,we discovered 488,825 distinct N-phosphosites in the human *** models were also deployed in Nphos for interactive N-phosphosite *** summary,this work provides new insights and points for both flexible and focused investigations of *** will also facilitate a deeper and more systematic understanding of protein N-phosphorylation modification by providing a data and technical *** is freely available at http://***/Nphos/and http://***/Nphos/.

关键词： N-phosphorylation Post-translational modification Machine learning Database Benchmark dataset

A new oxidative pathway of nitric oxide production from oximes in plants

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molecular Plant 2024年第1期17卷 178-198页

作者： Pedro Lopez-Gomez Javier Buezo Marina Urra Alfonso Cornejo Raquel Esteban Jorge Fernandez de los Reyes Estibaliz Urarte Estefania Rodriguez-Dobreva Alejandro Chamizo-Ampudia Alejandro Eguaras Sebastian Wolf Daniel Marino Victor Martinez-Merino Jose F.Moran Institute for Multidisciplinary research in Applied biology(IMAB) Department of SciencesPublic University of Navarre(UPNA)Avda.de Pamplona 12331192 MutilvaSpain Institute for Advanced Materials and Mathematics(INAMAT2) Department of SciencesPublic University of Navarre(UPNA)Campus de Arosadia31006 PamplonaSpain Department of Plant biology and Ecology University of the Basque Country(UPV/EHU)Sarriena s/nApdo.64448080 BilbaoSpain center for Plant molecular biology(ZMBP) University of TubingenGeschwister-Scholl-Platz72074 TubingenGermany Institute of Natural Resources and Agrobiology of Salamanca(IRNASA) Department of Plant-Microorganism InteractionsSpanish National Research Council(CSIC)Cordel de Merinas40-5237008SalamancaSpain Department of biochemistry Area of Molecular BiologyVeterinary FacultyUniversity of LeonCampus de Vegazanas/n.24071 LeonSpain

Nitric oxide(NO)is an essential reactive oxygen species and a signal molecule in *** several studies have proposed the occurrence of oxidative NO production,only reductive routes for NO production,such as the nitrate(NO_(3)^(-))-upper-reductase pathway,have been evidenced to date in land ***,plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3−,evidencing the existence of a metabolic pathway for oxidative production of *** hypothesized that oximes,such as indole-3-acetaldoxime(IAOx),a precursor to indole-3-acetic acid,are intermediate oxidation products in NO *** detected the production of NO from IAOx and other oximes catalyzed by peroxidase(POD)enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and *** stimulated the reaction,while superoxide dismutase inhibited ***,mouse NO synthase can also use IAOx to produce NO at a lower rate than *** provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory *** showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO,while in vivo supplementation of IAOx and other oximes increased the number of lateral roots,as shown for NO donors,and a more than 10-fold increase in IAOx dehydratase ***,we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants,while prx33-34 mutant plants,defective in POD33-34,had reduced *** data show that the release of NO by IAOx,as well as its auxinic effect,explain the superroot ***,our study reveals that plants produce NO utilizing diverse molecules such as oximes,POD,and flavins,which are widely distributed in the plant kingdom,thus introducing a long-awaited oxidative pathway to NO production in plants.T

关键词： ammonium oxidation auxin nitric oxide oxime peroxidase root phenotype