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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

Utilizing a metal-forging inspired chain combing strategy to enhance properties and expand applications of Nylon 66 plastic via heat inducing

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Nano Research 2024年第3期17卷 2164-2171页

作者： Junyu Yang Jiangwei Zhang Nan Wang Guangyuan Zhou division of Energy Materials Daglian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Innovation Center of Energy Material and Chemistry College of Chemistry and Chemical EngineeringInner Mongolia UniversityHohhot 010021China

The mechanical properties of engineering plastics can be enhanced through effective surface mechanical treatment(SMT),which can be applied to various types of engineering plastics,eliminating the limitations of conventional polymer processing and could potentially extend their applications and improve their performance and reliability as structural-functional *** by metal forging,this work proposes a simple and effective SMT strategy to enhance the mechanical properties of polyamide 66(PA66).Tensile tests have shown that SMTed PA66 samples exhibit significant improvements in both Young’s modulus and ultimate tensile strength(UTS),with a 2104 MPa Young’s modulus,almost double that of the pristine samples,and a 35.56%increase in UTS,reaching 183 ***,the modulus within the localized SMTed surface layer could reach up to 14 GPa,which is approximately 14 times higher than that of the pristine *** Vickers hardness within the localized SMTed surface layer can be doubled,reaching 10.72 Hv,and the crystallinity can increase by approximately 20%compared to the untreated ***,force field molecular dynamics(FFMD)simulations were conducted to investigate the ternary relationship between the SMT method,PA66’s molecular structure,and its *** combination of MD simulations and versatile structural characterizations provides evidence that the SMT method’s mechanism,under heat induction,results in a chain-combing procedure that changes the polymer’s molecular morphology microscopically and enhances its mechanical properties macroscopically.

关键词： Nylon 66 mechanical properties hardness crystallinity structural characterizations molecular dynamics simulation

New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei Ye Cong Duan Jiaxin Han Jinrong Chen Ning Sun Yuan Li Tifei Yuan Daihui Peng division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

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Food Science and Human Wellness 2024年第1期13卷 146-153页

作者： Baifeng Fu Di Wu Shuzhen Cheng Xianbing Xu Ling Zhang Lishu Wang Heshanm REl-Seedi Hanxiong Liu Ming Du School of Food Science and Technology Dalian Polytechnic UniversityDalian 116034China Collaborative Innovation Center of Seafood Deep Processing Dalian Polytechnic UniversityDalian 116034China National Engineering Research Center of Seafood Dalian Polytechnic UniversityDalian 116034China division of Hematology and Oncology Department of MedicineMedical College of WisconsinMilwaukee 53226USA division of Pharmacognosy Department of Medicinal ChemistryBiomedical CentreUppsala UniversityUppsala SE-75123Sweden

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami *** this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their *** threshold of the three peptides ranged from 0.38 to 0.55 mg/m *** with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces ***,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami *** with two Glu residues at the terminus had stronger umami,especially at the *** results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

关键词： Oyster umami peptides iUmami-SCM Taste characterization molecular docking

Overlap in oncogenic and pro-inflammatory pathways associated with areca nut and nicotine exposure

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Cancer Pathogenesis and Therapy 2024年第3期2卷 187-194页

作者： Krati Garg Anuj Kumar Vidisha Kizhakkethil Pramod Kumar Shalini Singh Department of Biochemical Engineering and Biotechnology Indian Institute of Technology(IIT)DelhiDelhi 110016India division of molecular Biology ICMR-National Institute of Cancer Prevention and Research(ICMR-NICPR)Indian Council of Medical ResearchNoidaUttar Pradesh 201301India Department of Biotechnology Vellore Institute of Technology(VIT)VelloreTamil Nadu 632024India ICMR-National Institute of Cancer Prevention&Research(ICMR-NICPR) Indian Council of Medical ResearchNoidaUttar Pradesh 201301India

Background:Betel nut/areca nut/Areca catechu is one of the most commonly used psychoactive substance,and is also a major preventable cause of *** other psychoactive substances,such as nicotine,the mechanisms underlying addiction to areca nuts and related oncogenesis remain *** reports suggest a possible overlap in the mechanisms of action of nicotine and areca nuts in the human ***,this study aimed to investigate the interactome of human proteins associated with areca nut exposure and the intricate similarities and differences in the effects of the two psychoactive substances on ***:A list of proteins associated with areca nut use was obtained from the available literature using terms from Medical Subject Headings(MeSH).Protein-protein interaction(PPI)networks and functional enrichment were *** results obtained for both psychoactive substances were ***:Given the limited number of common proteins(36/226,16%)in the two sets,a substantial overlap(612/1176 nodes,52%)was observed in the PPI networks,as well as in Gene *** nuts mainly affect signaling pathways through three hub proteins(alpha serine/threonine-protein kinase,tumor protein 53,and interleukin-6),which are common to both psychoactive substances,as well as two unique hub proteins(epidermal growth factor receptor and master regulator of cell cycle entry and proliferative metabolism).Areca nut-related proteins are associated with unique pathways,such as extracellular matrix organization,lipid storage,and metabolism,which are not found in nicotine-associated ***:Areca nuts affect regulatory mechanisms,leading to systemic toxicity and *** nuts also affect unique pathways that can be studied as potential markers of exposure,as well as targets for anticancer therapeutic agents.

关键词： Cancer Areca nut Nicotine Interactome Cell signaling

Functional characterization,structural basis,and protein engineering of a rare flavonoid 2′-O-glycosyltransferase from Scutellaria baicalensis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3746-3759页

作者： Zilong Wang Xueqing Du Guo Ye Haotian Wang Yizhan Liu Chenrui Liu Fudong Li HansÅgren Yang Zhou Junhao Li Chao He De-An Guo Min Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Anhui Key Laboratory of Modern Biomanufacturing and School of Life Sciences Anhui UniversityHefei 230601China National Science Center for Physical Sciences at Microscale division of molecular&Cell Biophysics and School of Life Sciences University of Science and Technology of ChinaHefei 230026China Department of Physics and Astronomy Uppsala UniversityUppsala SE-75120Sweden School of Pharmacy Jinan UniversityGuangzhou 510632China Shanghai Research Center for Modernization of Traditional Chinese Medicine Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China

Glycosylation is an important post-modification reaction in plant secondary metabolism,and contributes to structural diversity of bioactive natural *** plants,glycosylation is usually catalyzed by *** 2′-O-glycosides are rare ***,no UGTs have been reported,thus far,to specifically catalyze 2′-O-glycosylation of *** this work,UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2′-*** could preferentially transfer a glycosyl moiety to 2′-hydroxy of at least nine flavonoids to yield six new *** of the 2′-O-glycosides showed noticeable inhibitory activities against cyclooxygenase *** crystal structure of UGT71AP2(2.15Å)was solved,and mechanisms of its regio-selectivity was interpreted by pKa calculations,molecular docking,MD simulation,MM/GBSA binding free energy,QM/MM,and hydrogen‒deuterium exchange mass spectrometry *** structure-guided rational design,we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity(the ratio of 7-O-glycosylation byproducts decreased from 48%to 4%)and catalytic efficiency of 2′-O-glycosylation(kcat/Km,0.23 L/(s·μmol),12-fold higher than the native).Moreover,UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity,and is a dual function *** work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design.

关键词： Glycosyltransferase Regio-selectivity Crystal structure De-glycosylation Catalytic mechanisms

Disease clearance in ulcerative colitis:A new therapeutic target for the future

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World Journal of Gastroenterology 2024年第13期30卷 1801-1809页

作者： Syed Adeel Hassan Neeraj Kapur Fahad Sheikh Anam Fahad Somia Jamal division of Digestive Disease and Nutrition University of KentuckyLexingtonKY 40536United States Department of Pathology and Laboratory Medicine Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNY 10461United States division of Primary Care Essen HealthcareNew YorkNY 10457United States Department of Internal Medicine Karachi Medical and Dental CollegeKarachi 74700SindhPakistan

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and *** has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic ***,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal *** the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic *** recommendations lack consideration of histological *** simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully *** has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

关键词： Inflammatory bowel disease Ulcerative colitis Clinical remission Endoscopic remission Histological remission Mucosal healing Disease clearance

San Antonio witnesses Chinese urological achievements:The World Chinese Urological Society achievement and Rising Star Awards at the 16th annual meeting

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UroPrecision 2024年第2期2卷 65-72页

作者： Guiting Lin Run Wang Tom F.Lue Knuppe molecular Urology Laboratory Department of UrologySchool of MedicineUniversity of CaliforniaSan FranciscoCaliforniaUSA Department of Urology Uniersity of Texas MD Anderson Cancer CenterHoustonTexasUSA division of Urology Department of SurgeryUniversity of Texas McGovern Medical SchoolHoustonTexasUSA

San Antonio,May 3,2024—The 16th Annual meeting of the World Chinese Urological Society(WCUS)was successfully held in San Antonio,drawing together experts and scholars from around the globe in the field of Chinese *** conference served as a platform for academic exchange,as well as an occasion for medical professionals of Chinese descent to learn from,inspire,and motivate one *** events are crucial for advancing research and clinical practice in Chinese urology worldwide,and the success of this conference signals a bright and progressive future for the field.

关键词： World exchange witness

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