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Aberrant DNA repair as a potential contributor for the clonal evolution in subsets of anaplastic thyroid carcinomas arising through dedifferentiation: implications for future therapeutic algorithms?

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Cancer Drug Resistance 2020年第4期3卷 992-1000页

作者： Carl Christofer Juhlin Department of Oncology-Pathology Karolinska InstitutetStockholm SE-17176Sweden Department of Pathology and cytology Karolinska University HospitalStockholm SE-17176Sweden

Well-differentiated thyroid carcinoma(WDTC,including papillary thyroid carcinoma and follicular thyroid carcinoma)are fairly slow-growing tumors with an overall low mortality due to the efficacy of combinatory surgery and postoperative radioiodine *** of WDTCs may dedifferentiate into poorly differentiated thyroid carcinoma(PDTC)and anaplastic thyroid carcinoma(ATC),of which especially the latter has an exceptionally poor patient *** underlying genetics responsible for this tumor progression is only partly understood,and is complicated by the fact that subgroups of ATCs are thought to arise de novo without a demonstrable,pre-existing *** so,recent advances using next generation sequencing(NGS)techniques have identified a genetic link between WDTCs and ATCs,suggesting a step-wise accumulation of mutations driving the loss of differentiation for most *** this Commentary,recent findings from an NGS study on synchronous FTC,PDTC,and ATC tumor components from the same patient are *** using whole-genome data,clonality analyses identified a chief ancestral clone carrying mutations in TP53-associated signaling networks regulating genes involved in DNA repair,with sub-clones in each tumor component that were identified also in the less differentiated,neighboring ***,mutational signatures suggested a general mismatch repair(MMR)deficiency along with microsatellite *** findings support the chained progression model of dedifferentiation in thyroid cancer,and pinpoint a central role for defective DNA *** effective treatment modalities for ATCs are urgently needed,studies regarding therapeutic agents specifically targeting defective MMR in dedifferentiated thyroid carcinoma could be pursued.

关键词： DNA repair mismatch repair P53 thyroid carcinoma dedifferentiation anaplastic thyroid carcinoma clone treatment

Corrosion Resistance of High Performance Weathering Steel for Bridge Building Applications

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Journal of Iron and Steel Research International 2012年第6期19卷 59-63页

作者： CHEN Ai-hua XU Jian-qiu LI Ran LI Hua-long Institute of Research of Iron and Steel Shasteel GroupZhangjiagang 215625JiangsuChina chief Engineering Office Shasteel GroupZhangjiagang 215625JiangsuChina

The mechanical properties, corrosion resistance and microstructures of high performance steel （HPS） was investigated by tensile testing machine, Charpy V-Notch （CVN） testing machine, cyclic immersion corrosion tester, XRD, optical microscopy （OM）, scanning electron microscopy （SEM）, and electron probe micro-analyzer （EPMA）. The results showed that significant differences existed in the tensile strength, yield strength and impact toughness between HPS and PCS. After 72 h cyclic immersion accelerated corrosion test, the inner rust layer on HPS was com- posed of a-FeOOH phase and denser than that on PCS that was a mixture of a-FeOOH and Fe3 04. The rust formed on HPS provides better protection and HPS has lower corrosion rates than PCS. Copper and chromium in HPS en- rich in the rust layer and enhance the compactness of the rust layer. Based on the results of the accelerated corrosion tests and rust layer analysis, the roles of Cu and Cr against corrosion are discussed, providing HPS with chemical specification which has been industrially successful to produce weathering steel for bridge structure.

关键词： HPS corrosion resistancel microstructure mechanical property

Development of Genetic Engineering Tools for p75ngfr Methylation and Expression Modulation

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Journal of Biosciences and Medicines 2020年第11期8卷 197-207页

作者： D. A. Lanshakov E. V. Sukhareva Postgenomic Neurobiology Laboratory Institute of Cytology and Genetics SB RAS Novosibirsk Russia Functional Neurogenomics Laboratory Institute of Cytology and Genetics SB RAS Novosibirsk Russia

Neurotrophic factors, as well as their receptors are key players in the formation and development of the central nervous system. Like the sculptor’s incisor, they form the neural networks and circuits of the future organism. The neurotrophic growth factor receptor p75ngfr interacts with sortilin, serves as a receptor for proform of neurotrophic factors and exhibits a proapoptotic effect in developing neurons—dorsal root ganglia neurons and brainstem norepinephrine neurons. p75ngfr is highly expressed in Locus Coeruleus norepinephrine neurons. Therefore, an important task for developing further methods of CNS gene therapy is the development of tools and molecular methods for suppressing p75ngfr expression in norepinephrine neurons. For this purpose, we’ve developed improved dCas9 vectors with Suntag system to suppress gene expression and enhance methylation of CpG islands. We used 10 times repetitive GCN peptide that were fused to dCas9. Single chain antibody against GCN peptide was fused to KRAB repressor or Dnmt3a catalytic domain. Expression specificity was achieved by using a promoter consisting of 8 repeated phox2a/2b binding sites. In this work, we’ve tested a set of guide RNAs targeting p75ngfr cpg island in the promoter. Usage of Suntag system led us to the conclusion that topological orientation and length of the final complex could influence on p75ngfr antisense transcript expression, and that sequence was established in the rat P3 brainstem.

关键词： dCas9 Suntag System CRISPRi Dnmt3a p75ngfr

Journal of Geriatric Cardiology comes to press with a new look

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Journal of Geriatric Cardiology 2004年第2期1卷 69-70,76页

作者： Shiwen WANG MD,MCAE Editor-in-chief Professor and Director of the Institute of Geriatric Cardiology Beijing,China Editor-in-chief Professor and Director of the Institute of Geriatric Cardiology Beijing China

On behalf of all the editors and editorial board members, I would like to announce that the inaugural issue of the Journal of Geriatric Cardiology ( JGC ) was published after over two years of preparation, and the JGC will be continuously published. The JGC was born in accordance with the tough challenge of higher prevalence of cardiac diseases and/or complicated with other organ diseases in the elderly accompanied by the rapid growing number of the aged.

关键词： Journal of Geriatric Cardiology comes to press with a new look

Integrative Zoology enters a new stage of growth

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Integrative Zoology 2009年第2期4卷 161-161页

作者： Zhibin ZHANG John S.BUCKERIDGE Editor-in-chief Integrative Zoology Honorary Editor-in-chief Integrative Zoology

We are pleased to announce that Integrative Zoology(INZ)was recently accepted for inclusion in Zoological Record and ISI Web of *** development marks a turning point for INZ and will have a positive effect on the jour... 详细信息

关键词： journal turning effect

Biological Consequences of Global Change:past and future

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Integrative Zoology 2013年第2期8卷 123-123页

作者： Zhibin ZHANG Editor-in-chief

Zoology encompasses an increasing amount of research on the question of global change,including the biodiversity losses,pest outbreaks,disease transmission,biological invasions and many other *** is the third issue of Integrative Zoology,with papers focusing specifically on these topics,with collaboration from members of the Biological Consequences of Global Change(BCGC)program.

关键词： biodiversity sequences Global

Nontoxic virus nanofibers improve the detection sensitivity for the anti-p53 antibody, a biomarker in cancer patients

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Nano Research 2015年第11期8卷 3562-3570页

作者： Pengtao Pan Yicun Wang Ye Zhu Xiang Gao Zhigang Ju Penghe Qiu Li Wang Chuanbin Mao Institute of Genetics and cytology School of Life Sciences Northeast Normal University 5268 Renmin Street Changchun 130024 China Department of Chemistry and Biochemistry Stephenson Life Sciences Research Center University of Oklahoma Norman Oklahoma 73019 USA

The presence of anti-p53 antibody in serum is a biomarker for cancer. However, its high sensitivity detection is still an issue in cancer diagnosis. To tackle this challenge, we used fd phage, a human-safe bacteria-specific virus nanofiber that can be mass-produced by infecting host bacteria in an error-free manner, and genetically engineered it to display a peptide capable of recognizing and capturing anti-p53 antibody on its side wall. We employed the resultant phage nanofibers as a capture probe to develop a modified version of the enzyme- linked immunosorbent assay （ELISA） method, termed phage-ELISA. We compared it to the traditional ELISA method for the detection of anti-p53 antibody, p53-ELISA, which uses recombinant wild-type p53 protein to capture anti-p53 antibody. We applied phage-ELISA to detect anti-p53 antibody in an experimental group of 316 patients with various types of malignant tumors. We found that a detection rate of 17.7% （56 positive cases） was achieved by phage-ELISA, which was comparable to the detection rate of 20.6% for p53-ELISA （65 positive cases）. However, when both phage and p53 were combined to form antibody-capturing probes for phage/p53-ELISA, a detection rate of 30.4% （96 positive cases） was achieved. Our work showed that owing to the combined capture of the anti-p53 antibody by both phage nanofibers and p53, the phage/p53-ELISA achieved the highest diagnostic accuracy and detection efficiency for the anti-p53 antibody in patients with various types of cancers. Our work suggests that a combination of nanofibers and antigens, both of which capture antibody, could lead to increased detection sensitivity, which is useful for applications in the life sciences, clinical medicine, and environmental sciences.

关键词： phage virus protein nanofibers cancer diagnosis

HJ-1A And HJ-1B Small Satellite Constellation For Environment And Disaster Monitoring

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Aerospace China 2009年第2期10卷 2-7页

作者： Bai Zhaoguang chief designer and chief Commander of HJ-1A and HJ-1B satellite

HJ-1A and HJ-1B small satellites were launched atop a LM- 2C/SMA on September 6,2008 from Taiyuan Satellite Launch Center. The satellites began to transmit

关键词：小卫星星座环境保护中国航天科技集团公司灾害监测太原卫星发射中心 A型卫星传送运行评估

Pathogenesis and managenent of pain in chronic pancreatitis

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World Journal of Gastroenterology 2000年第4期6卷 490-496页

作者： C. S. Pitchumoni Professor of Medicine/Community and Preventive Medicine New York Medical College Director of Medicine and Chief of GastroenterologyOur Lady of Mercy Medical CenterBronxNew York 10466

INTRODUCTIONOf the three cardinal manifestations of chronic pancreatitis-pain,diabetes mellitus and steatorrhea,it is pain thatbrings the patient to the physician and is the most difficultto *** intractabale pain that... 详细信息

关键词： pancreatitis/therapy pain/therapy pain intractable/therapy lithotripsy alcoholics anonymous parenteral nutrition total antioxidants analgesics enzyme inhibitors somatostatin sphincterotomy endoscopic