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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

Heterobimetallic[NiCo]integration in a hydrogenase mimic for boosting light-driven hydrogen evolution in CaTiO_(3)

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Nano research 2024年第8期17卷 6888-6894页

作者： Kang Li Juanji Hong Ningning Song Zhanjun Guo Minmin Liang experimental center of Advanced Materials School of Materials Science&EngineeringBeijing Institute of TechnologyBeijing 10081China

Light-drive hydrogen production using titanium-based perovskite is one sustainable way to reduce current reliance on fossil fuels,but its wide applications are still limited by high electron−hole recombination and sluggish surface ***,the developments for low-cost and highly efficient co-catalysts remain *** by natural[NiFe]-hydrogenase active center structure,a hydrogenase-mimic,NiCo_(2)S_(4) nanozyme was synthesized,and subsequently decorated onto the CaTiO_(3) to catalyze the hydrogen evolution reaction(HER).Among the following test,CaTiO_(3)with a 15%loading of NiCo_(2)S_(4) nanozyme exhibited the highest HER rate of 307.76μmol·g^(–1)·h^(–1),which is 60 times higher than that of the CaTiO_(3) *** results reveal that NiCo_(2)S_(4) not only significantly increased the charge separation efficiency of the photogenerated carriers,but also substantively lowered the HER activation *** studies show that NiCo_(2)S_(4) readily splits H_(2)O by forming the Ni(OH)-Co intermediate and only Ni in the bimetallic center alters the oxidation state during the HER process in a manner analogous to the[NiFe]-*** contrast to the often-expensive synthetic catalysts that rely on rare elements such as ruthenium and platinum,this study shows a promising way to develop the nature-inspired cocatalysts to enhance the photocatalysts’HER performance.

关键词： hydrogen evolution reaction hydrogenase-mimic nanozyme photocatalyst water-splitting

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou Li-Juan Luo Cui-Jin Wang Nan Shen Hao Li Ji-Wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency *** Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome *** analyzed the patients’convulsions and treatment with antiepileptic *** patients were followed up at different time periods after ketogenic diet *** Six patients with SLC2A1 mutations were included in this *** patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their *** were then treated with a ketogenic diet for at least four *** analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet *** patients were seizure-free within a month of receiving the diet *** patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this *** antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment *** severe adverse events occurred during the *** Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 ***,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

TIMP-1 Promotes Expression of MCP-1 and Macrophage Migration by Inducing Fli-1 in experimental Liver Fibrosis

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 634-645页

作者： Xiaoli Huang Xiaofan Wang Yanhong Wang Shuangjun Shen Wei Chen Tianhui Liu Ping Wang Xu Fan Lin Liu Jidong Jia Min Cong Liver research center Beijing Friendship HospitalCapital Medical UniversityBeijingChina Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical research center of Digestive Disease BeijingChina Dongying People’s Hospital DongyingShandongChina experimental and Translational research center Beijing Friendship HospitalCapital Medical UniversityBeijingChina

Background and Aims:Tissue inhibitor of metalloproteinase-1(TIMP-1)plays a role in the excessive generation of extracellular matrix in liver *** study aimed to explore the pathways through which TIMP-1 controls monocyte chemoattractant protein-1(MCP-1)expression and promotes hepatic macrophage ***:Liver fibrosis was triggered through carbon tetrachloride,and an adenoassociated virus containing small interfering RNA targeting TIMP-1(siRNA-TIMP-1)was administered to both rats and *** assessed the extent of fibrosis and macrophage *** molecular mechanisms regulating macrophage recruitment by TIMP-1 were investigated through transwell migration assays,luciferase reporter assays,the use of pharmacological modulators,and an analysis of extracellular vesicles(EVs).Results:siRNA-TIMP-1 alleviated carbon tetrachloride-induced liver fibrosis,reducing macrophage migration and MCP-1 ***-culturing macrophages with hepatic stellate cells(HSCs)post-TIMP-1 downregulation inhibited macrophage *** siRNATIMP-1-treated HSCs,microRNA-145(miRNA-145)expression increased,while the expression of Friend leukemia virus integration-1(Fli-1)and MCP-1 was *** of Fli-1 led to decreased MCP-1 expression,whereas Fli-1 overexpression increased MCP-1 expression within *** with miRNA-145 mimics reduced the expression of both Fli-1 and MCP-1,while miRNA-145 inhibitors elevated the expression of both Fli-1 and MCP-1 in ***-145 bound directly to the 3'-UTR of Fli-1,and mi RNA-145-EN-riched EVs secreted by HSCs after TIMP-1 downregulation influenced macrophage ***:TIMP-1 induces Fli-1 expression through miRNA-145,subsequently increasing MCP-1 expression and macrophage ***-145-enriched EVs from HSCs can transmit biological information and magnify the function of TIMP-1.

关键词： TIMP-1 Fli-1 MCP-1 miRNA-145 Liver fibrosis Extracellular vesicles

Skeletal muscle as a molecular and cellular biomarker of disease progression in amyotrophic lateral sclerosis:a narrative review

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Neural Regeneration research 2024年第4期19卷 747-753页

作者： Peter H.King Department of Neurology and center for Neurodegeneration and experimental Therapeutics The University of Alabama at BirminghamBirminghamALUSA Birmingham Veterans Affairs Medical center BirminghamALUSA

Amyotrophic lateral sclerosis is a fatal multisystemic neurodegenerative disease with motor neurons being a primary *** progressive weakness is a hallmark feature of amyotrophic lateral sclerosis,there is considerable heterogeneity,including clinical presentation,progression,and the underlying triggers for disease *** on longitudinal studies with families harboring amyotrophic lateral sclerosis-associated gene mutations,it has become apparent that overt disease is preceded by a prodromal phase,possibly in years,where compensatory mechanisms delay symptom *** 85-90%of amyotrophic lateral sclerosis is sporadic,there is a strong need for identifying biomarkers that can detect this prodromal phase as motor neurons have limited capacity for *** Food and Drug Administration-approved therapies work by slowing the degenerative process and are most effective early in the *** muscle,including the neuromuscular junction,manifests abnormalities at the earliest stages of the disease,before motor neuron loss,making it a promising source for identifying biomarkers of the prodromal *** accessibility of muscle through biopsy provides a lens into the distal motor system at earlier stages and in real *** advent of“omics”technology has led to the identification of numerous dysregulated molecules in amyotrophic lateral sclerosis muscle,ranging from coding and non-coding RNAs to proteins and *** technology has opened the door for identifying biomarkers of disease activity and providing insight into disease mechanisms.A major challenge is correlating the myriad of dysregulated molecules with clinical or histological progression and understanding their relevance to presymptomatic phases of *** are two major goals of this *** first is to summarize some of the biomarkers identified in human amyotrophic lateral sclerosis muscle that have a clinicopathological correlation with disease activi

关键词： amyotrophic lateral sclerosis biomarkers clinicopathological correlation disease progression muscle biomarkers neurogenic atrophy neuromuscular junction non-coding RNAs presymptomatic stages skeletal muscle SOD1G93A mouse model

Synthesis of boron nitride nanorod and its performance as a metalfree catalyst for oxidative desulfurization of diesel fuel

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Chinese Journal of Chemical Engineering 2024年第4期68卷 120-132页

作者： Tanaz Ghanadi Gholamreza Moradi Alimorad Rashidi Catalyst research center Faculty of Chemical and Petroleum EngineeringRazi UniversityKermanshahIran Nanotechnology research center Research Institute of Petroleum Industry(RIPI)TehranIran

In order to reduce the sulfur compounds in diesel fuel,boron nitride(BN)has been used as a novel metal-free catalyst in the present *** nanocatalyst was synthesized via template-free approach followed by heating treatment at 900℃ in nitrogen atmosphere that the characteristics of the sample were identified by the X-ray diffraction,Fourier-transform infrared spectroscopy,Raman spectroscopy,field emission scanning electron microscopy,transmission electron microscopy,atomic force microscopy,and N2 adsorption-desorption *** results of structural and morphological analysis represented that BN has been successfully *** efficacy of the main operating parameters on the process was studied by using response surface methodology based on the Box-Behnken design *** prepared catalyst showed high efficiency in oxidative desulfurization of diesel fuel with initial sulfur content of 8040 mg·kg^(-1)*** statistical analysis,a significant quadratic model was obtained to predict the sulfur removal as a function of efficient *** maximum efficiency of 72.4%was achieved under optimized conditions at oxidant/sulfur molar ratio of 10.2,temperature of 71℃,reaction time of 113 min,and catalyst dosage of 0.36 ***,the reusability of the BN was studied,and the result showed little reduction in activity of the catalyst after 10 times ***,a plausible mechanism was proposed for oxidation of sulfur compounds on the surface of the *** present study shows that BN materials can be selected as promising metal-free catalysts for desulfurization process.

关键词： Desulfurization Boron nitride(BN)nanostructure experimental design BoxeBehnken

4-Hydroxy-2-Oxoglutaric Acid,A KeyMetabolite Involved in Trypsin-Regulation of Arginine Metabolism in Hylocereus undatus during Storage

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Phyton-International Journal of experimental Botany 2024年第5期93卷 885-900页

作者： Bairu Li Jingyu Jia Hemin Wang Jiaju Sun Enyan Chen Xin Li College of Food and Bioengineering Henan University of Science and TechnologyLuoyang471023China Henan Engineering research center of Food Microbiology Luoyang471023China National Demonstration center for experimental Food Processing and Safety Education Luoyang471000China

Trypsin,a novel superoxide scavenger,significantly enhances the storage quality of Hylocereus undatus(***).To elucidate the preservation mechanism of trypsin on ***,a widely targeted metabolomic analysis,and transcriptomics analysis were ***,a total of 453 metabolites were identified,with organic acids and their derivatives constituting the largest proportion(25%).Amino acids and their metabolites,prominent among organic acids,were further *** them,73 metabolites were associated with amino acids,and 37 exhibited significant *** most enriched Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway was arginine biosynthesis(map00220),with polyamine metabolites showing the most pronounced differences,particularly spermine(FC=1.7594).Compared with the control group,4-hydroxy-2-oxoglutaric acid was significantly upregulated(FC=2.117)in the process of spermine ***,the results of Gene Ontology(GO)and KEGG enrichment analysis of the *** transcriptome profile revealed that trypsin treatment led to 187 differentially expressed genes associated with *** GO and KEGG analyses exhibited significant enrichment in the spermine biosynthetic process(GO:0006597)(map:00220)within the arginine biosynthesis ***,most enzymes and metabolites within the spermine biosynthesis pathway in *** were *** results of the PPI network highlighted that ADC,SPDS,and SAMDC,among others,were pivotal proteins involved in trypsin-regulated arginine metabolism and spermine *** study revealed that trypsin could significantly delay postharvest senescence of *** at room *** effect might be attributed to trypsin triggering the synthesis of 4-hydroxy-2-oxoglutaric acid in the fruit peel,thereby promoting the biosynthesis of spermine and other polyamines.

关键词： Trypsin arginine transcriptomics widely targeted metabolomics

EuSHT Acts as a Hub Gene Involved in the Biosynthesis of 6-Hydroxyluteolin and Quercetin Induced by Salt Stress in Eucommia ulmoides

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Phyton-International Journal of experimental Botany 2024年第8期93卷 2095-2113页

作者： Fuxin Li Enyan Chen Xinxin Chen Jingyu Jia Hemin Wang Jie Zhang Jianrui Sun Xin Li College of Food and Bioengineering Henan University of Science and TechnologyLuoyang471023China Henan Engineering research center of Food Microbiology Luoyang471023China National Demonstration center for experimental Food Processing and Safety Education Luoyang471000China

Salt stress inhibits plant growth and affects the biosynthesis of its secondary *** are natural compounds that possess many important biological activities,playing a significant role in the medicinal activity of Eucommia ulmoides(***).To investigate the mechanism by which salt stress affects the biosynthesis of flavonoids in ***,a comprehensive analysis of metabolomics and transcriptomics was *** results indicated that salt stress led to the wilting and darkening of *** leaves,accompanied by a decrease in chlorophyll levels,and significantly induced malondialdehyde(MDA)and relative electrical *** salt stress,most metabolites in the flavonoid biosynthesis pathway of *** were upregulated,indicating that flavonoid biosynthesis is likely the main induced pathway under salt *** them,secondary metabolites such as 6-Hydroxyluteolin and Quercetin are likely key metabolites induced by salt *** correlation analysis of transcriptomics and metabolomics revealed that EuSHT is a hub gene induced by salt stress,promoting the production of flavonoids such as *** co-expression network showed a strong positive correlation between EuSHT and the biosynthesis of 6-Hydroxyluteolin and Quercetin,while it exhibited a negative correlation with Catechin *** branches leading to Luteolin and Dihydroquercetin are likely the main pathways for flavonoid compound biosynthesis in the plant stress response during salt *** results of this study provided a preliminary mechanism of secondary metabolites such as flavonoids in the medicinal plant *** induced by salt stress and provided new theoretical support for discussing the mechanism of plant stress *** also provided useful information for subsequent exploration of resistance genes in ***.

关键词： Eucommia ulmoides ﬂavonoid salt stress transcriptomics widely targeted metabolomics

Hydrogen production from hydrolysis of NaBH_(4) solution over Co-Fe-B@g-C_(3)N_(4)/NF thin film catalyst

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Rare Metals 2024年第6期43卷 2648-2659页

作者： Yan Wang Jia-Xin Ma Jian Ren Di Zhang Feng-Yan Xu Ke Zhang Zhong-Qiu Cao Qiu-Ju Sun Guo-De Li Shi-Wei Wu Hong-Hui Chen College of Chemistry and Chemical Engineering Shenyang Normal UniversityShenyang 110034China experimental center Shenyang Normal UniversityShenyang 110034China Hunan Shande Energy Storage New Materials research Institute Limited Company Changde 415000China

In this study,the double loaded Co-Fe-B@g-C_(3)N_(4)/NF(NF:Ni foam)thin film catalysts were prepared for the first time via chemical deposition method at room *** optimizing the reducing agent concentration to 0.9 mol·L^(-1),the as-obtained Co-Fe-B@g-C_(3)N_(4)/NF exhibited the twisted ribbon structure with more distinct three-dimensional hierarchy and the smaller particle size,showing the good catalytic property for the hydrolysis of NaBH_(4)*** H_(2)generation rate of Co-Fe-B@g-C_(3)N_(4)/NF and binary Co-B@g-C_(3)N_(4)/NF under visible light irradiation surpassed the value under natural *** apparent activation energy of Co-Fe-B@g-C_(3)N_(4)/NF(45.0 kJ·mol^(-1))under visible light irradiation was obviously reduced when compared with the natural condition(48.4 kJ·mol^(-1))and binary Co-B@g-C_(3)N_(4)/NF(60.6 kJ·mol^(-1))under visible light ***,the catalytic performance of the optimized Co-Fe-B@g-C_(3)N_(4)/NF thin film catalyst was superior to most of the reported non-noble metal and even noble metal ***,it illustrated that the catalytic H_(2)production performance of Co-Fe-B@g-C_(3)N_(4)/NF thin film was distinctly improved after the introduction of light and multicomponent recombination.

关键词： Sodium borohydride Co-Fe-B@g-C_(3)N_(4)/NF catalyst Chemical deposition Hydrogen production