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Elimination of undifferentiated cancer cells by pluripotent stem cell inhibitors

Journal of Molecular Cell Biology 2014年第3期8卷 267-269页

作者： Uri Ben-David1,2 Alva Biran2 Paola Scaffidi3,4,5 Christel Herold-Mende6 Markus Boehringer7 eran meshorer2 Nissim Benvenisty1,2 Stem Cell Unit Silberman Institute of Life Sciences The Hebrew University Jerusalem 91904 Israel Department of Genetics Silberman Institute of Life Sciences The Hebrew University Jerusalem 91904 Israel National Cancer Institute NIH Bethesda MD 20892 USA UCL Cancer Institute University College London London WC1E 6BT UK Cancer Research UK London Research Institute London WC2A 3LY UK Division of Neurosurgical Research Department of Neurosurgery University of Heidelberg Heidelberg Germany F. Hoffmann-La Roche AG Basel 4070 Switzerland

Dear Editor, According to the cancer stem cell （CSC） hypothesis, cancer ceils are organized in a hierarchical manner （Reya et al, 2001）. Indeed, the differentiation state of cancer cells has been linked to their proliferative potential, drug response, and ability to metastasize （Clevers, 2011）. Targeting self- renewing, undifferentiated cancer ceils could therefore be of importance for the success of cancer therapies. A classical case of a tumor composed of undifferenti- ated and differentiated cells is the tumor induced by pluripotent stem cells （PSCs）（Ben-David and Benvenisty, 2011）. We have recently identified several small mole- cules termed pluripotent-specific inhibitors （PluriSIns） that selectively target undif- ferentiated tumorigenic PSCs （Ben-David et aL, 2013）. Several of these compounds, including PluriSIn#1, inhibit the activity of stearoyl-coA desaturase （SCD1）（Ben- David et al, 2013）. SCD1 is an endoplasmic reticulum （ER）-membrane protein that plays a key role in the biosynthesis of the mono-unsaturated fatty acid oleate. This novel metabolic vulnerability is in line with the unique metabolome described in PSCs （Panopoulos et al, 2012）.

关键词： THERAPY

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Intraspecific scaling and early life history determine the cost of free-flight in a large beetle(Batocera rufomaculata)

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Insect Science 2024年第2期31卷 524-532页

作者： Tomer Urcai eran Levin eran Gefen Gal Ribak Faculty of Life Sciences School of ZoologyTel Aviv UniversityTel AvivIsrael Steinhardt Museum of Natural History Israel National Center for Biodiversity StudiesTel AvivIsrael Department of Biology University of Haifa-OranimKiryat TivonIsrael

The scaling of the energetic cost of locomotion with body mass is well documented at the interspecific ***,methodological restrictions limit our understanding of the scaling of flight metabolic rate(MR)in free-flying *** is particularly true at the intraspecific level,where variation in body mass and flight energetics may have direct consequences for the fitness of an *** applied a 13C stable isotope method to investigate the scaling of MR with body mass during free-flight in the beetle Batocera *** species exhibits large intraspecific variation in adult body mass as a consequence of the environmental conditions during larval *** show that the flight-MR scales with body mass to the power of 0.57,with smaller conspecifics possessing up to 2.3 fold higher mass-specific flight MR than larger *** the scaling exponent of free-flight MR was found to be like that determined for tethered-flight,the energy expenditure during free-flight was more than 2.7 fold higher than for *** metabolic cost of flight should therefore be studied under free-flight conditions,a requirement now enabled by the 13C technique described herein for insect flight.

关键词： allometry body mass Coleoptera free-flight insect flight stable carbon isotope tethered-flight

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Global epigenetic changes during somatic cell reprogramming to iPS cells

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分子细胞生物学报:英文版 2011年第6期3卷 341-350页

作者： Anna Mattout Alva Biran eran meshorer Department of Genetics Institute of Life SciencesThe Hebrew University of JerusalemJerusalem 91904Israel

Embryonic stem cells(ESCs)exhibit unique chromatin features,including a permissive transcriptional program and an open,decondensed chromatin *** pluripotent stem cells(iPSCs),which are very similar to ESCs,hold great promise for therapy and basic ***,the mechanisms by which reprogramming occurs and the chromatin organization that underlies the reprogramming process are largely *** we characterize and compare the epigenetic landscapes of partially and fully reprogrammed iPSCs to mouse embryonic fibroblasts(MEFs)and ESCs,which serves as a standard for *** immuno-fluorescence and biochemical fractionations,we analyzed the levels and distribution of a battery of histone modifications(H3ac,H4ac,H4K5ac,H3K9ac,H3K27ac,H3K4me3,H3K36me2,H3K9me3,H3K27me3,and gH2AX),as well as HP1a and lamin *** find that fully reprogrammed iPSCs are epigenetically identical to ESCs,and that partially reprogrammed iPSCs are closer to ***,combining both time-course reprogramming experiments and data from the partially reprogrammed iPSCs,we find that heterochromatin reorganization precedes Nanog expression and active histone ***,these data delineate the global epigenetic state of iPSCs in conjunction with their pluripotent state,and demonstrate that heterochromatin precedes euchromatin in reorganization during reprogramming.

关键词： chromatin pluripotency reprogramming iPSCs ESCs histone modifications epigenetics

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Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

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Journal of Geriatric Cardiology 2024年第2期21卷 135-152页

作者： The Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon(2^(nd)Edition) Jun-Bo GE Yun-Dai CHEN 不详 Zhongshan Hospital Fudan University Chinese PLA General Hospital

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary *** more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

关键词： balloon drugs dealing

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Progress of Lyman-alpha-based beam emission spectroscopy(Ly BES)diagnostic on the HL-2A tokamak

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Plasma Science and Technology 2024年第3期26卷 118-125页

作者：周艺轩余羿许敏柯锐聂林徐皓赵光义刘灏袁子豪肖晨雨李继全肖池阶 the HL-2A Team Southwestern Institute of Physics Chengdu 610041People's Republic of China Sino-French Institute of Nuclear Engineering and Technology Sun Yat-sen UniversityZhuhai 519082People's Republic of China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871People's Republic of China

An edge Lyman-alpha-based beam emission spectroscopy(LyBES)diagnostic,using a heating NBI(neutral beam injection)system,is currently under development on the HL-2A *** 20-channel edge LyBES,which is intended to measure the density fluctuation in plasma edge(from R=1960 mm to R=2026 mm)with an improved spatial resolution of 3.3 mm,is a complement to the existing conventional beam emission spectroscopy(BES)*** this article,we introduce the progress of LyBES diagnostic,including the collection optics,the monochromator,and the detector *** reflectance of the collection mirrors is measured to be~82%at 122 nm,and the aberration geometrical radius of the collection optics is tested to be~150μm in the aimed *** linear dispersion of the LyBES monochromator is designed to be~0.09 nm mm^(-1).The bandwidth of the detector system with the 5×10^(7)V A^(-1)preamplifier gain is measured to be~280 kHz,and the peak-to-peak noise of the detector system is tested to be~16 *** finalized design,components development and testing of the LyBES diagnostic have been completed at present,and an overall performance of the LyBES diagnostic is to be confirmed in the next HL-2A campaign.

关键词： density fluctuation Ly BES BES vacuum ultraviolet

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Chromatin in embryonic stem cell neuronal diiferentiation

Chromatin in embryonic stem cell neuronal diiferentiation

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第十五届国际药理学大会

作者： eran meshorer National Cancer Institute National Institutes of Health Bethesda MD 20892 USA

＜正＞ Embryonic stem （ES） cells, derived from the inner cell mass of the blastocyst. are unique in their ability to both self-renew and to differentiate into the three germ layers. Here we show global changes in nuclear architecture and chromatin structure during ES cell neuronal differentiation. A hyperdynamic pool of chromatin proteins is loosely bound in ES cells and become tightly associated with chromatin in neuronal progenitor cells （NPCs）. The levels of activity-associated histone marks, such as acetylated histones H3 and H4. are reduced during neuronal differentiation, while H3-triMeK9 is increased. Moreover, genomic tiling arrays, uridine incorporation assays and RT-PCR experiments revealed higher global transcriptional activity in ES cells compared with ES-derived NPCs and neurons. Taken together, these results suggest that chromatin is a fundamental regulator of neuronal commitment and that gene silencing by chromatin condensation and heterochromatin formation promotes neuronal differentiation.

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The tri-band high spectral resolution spectrometer with gratings in tandem for the charge-exchange recombination spectroscopy diagnostic system on HL-2A tokamak

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Plasma Science and Technology 2024年第6期26卷 103-110页

作者：刘亮余德良马倩何小斐 Maarten DE BOCK Manfred von HELLERMANN Michael WALSH 陈文锦何小雪魏彦玲张能李栋魏会领 the HL-2A Team Southwestern Institute of Physics Chengdu 610041People’s Republic of China College of Physics and Optoelectronic Technology Baoji University of Arts and SciencesBaoji 721000People’s Republic of China ITER Organization Route de Vinon-sur-VerdonCS 90046St.Paul Lez Durance Cedex 13067France Fusion Spectroscopy Markgraf-Albrecht Str.14Berlin 10711Germany

Charge-exchange(CX) recombination spectroscopy is a powerful tool monitoring ion temperature and plasma rotation with good temporal and spatial resolutions. A compact, new design for a high-throughput, tri-band high spectral resolution spectrometer has been developed for the charge-exchange recombination spectroscopy measurement on the HL-2A tokamak. The simultaneous measurements of He II(468.57 nm), C VI(529.1 nm), and Dα(656.1 nm accompanied by beam emission spectra) with an acquisition frequency up to 400 Hz are achieved by vertically binning the spectrum from each fiber in experiments. Initial results indicate that the system can provide radial profiles of not only ion temperature and rotation velocity,but also concentration of carbon. For the case of helium, the measurements for the ion temperature and rotation velocity are straightforward but the apparent concentration associated with the observed CX intensity is obviously too high. Modeling of the active He II CX feature including plume contributions needs to be carried out to extract the true helium *** spectrometer could become a prototype for the ITER charge-exchange recombination spectroscopy diagnostic and the pilot experiments, as presented here, demonstrate the possibility of impurity concentrations measurements based on the combined measurement of local beam emission and charge-exchange recombination spectroscopy spectra.

关键词： CXRS ion temperature plasma rotation impurity concentration

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Circumventing the phonon bottleneck by multiphonon-mediated hot exciton cooling at the nanoscale

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npj Computational Materials 2023年第1期9卷 845-852页

作者： Dipti Jasrasaria eran Rabani Department of Chemistry University of CaliforniaBerkeleyCA 94720USA Materials Sciences Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA The Sackler Center for Computational Molecular and Materials Science Tel Aviv UniversityTel Aviv 69978Israel Present address:Department of Chemistry Columbia UniversityNew YorkNY 10027USA

Nonradiative processes govern efficiencies of semiconductor nanocrystal(NC)-based devices.A central process is hot exciton cooling,or the nonradiative relaxation of a highly excited electron/hole pair to form a band-edge *** to quantum confinement effects,the timescale and mechanism of cooling are not well understood.A mismatch between electronic energy gaps and phonon frequencies has led to the hypothesis of a phonon bottleneck and extremely slow cooling,while enhanced electron-hole interactions have suggested ultrafast *** measurements of the cooling timescale range six orders of ***,we develop an atomistic approach to describe phonon-mediated exciton dynamics and simulate cooling in NCs of experimentally relevant *** find that cooling occurs on~30 fs timescales in CdSe NCs,in agreement with the most recent measurements,and that the phonon bottleneck is circumvented through a cascade of multiphonon-mediated relaxation ***,we identify NC handles for tuning the cooling timescale.

关键词： phonon relaxation excited

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钠-葡萄糖共转运蛋白2抑制剂联合胰岛素治疗2型糖尿病中国专家共识(2023版)

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中华糖尿病杂志 2024年第1期16卷 9-19页

作者：《钠-葡萄糖共转运蛋白2抑制剂联合胰岛素治疗2型糖尿病中国专家共识》编写委员会郭立新洪天配田勍张丽娜不详北京医院内分泌科国家老年医学中心北京100730 北京大学第三医院内分泌科北京100191 北京大学第三医院

口服降糖药(OAD)联合胰岛素治疗是2型糖尿病(T2DM)患者血糖控制达标的重要方法之一。新型OAD钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)在有效降糖的同时还可发挥心肾保护作用。近年来,SGLT2i在T2DM患者中广泛使用,如何将这一类新型OAD与胰岛... 详细信息

口服降糖药(OAD)联合胰岛素治疗是2型糖尿病(T2DM)患者血糖控制达标的重要方法之一。新型OAD钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)在有效降糖的同时还可发挥心肾保护作用。近年来,SGLT2i在T2DM患者中广泛使用,如何将这一类新型OAD与胰岛素安全、有效地联合应用,成为T2DM临床管理中需要关注的问题。本共识针对SGLT2i联合胰岛素的使用原则、患者人群选择、联合用药启动流程、治疗优势、联合治疗的安全性和注意事项等问题方面进行证据梳理,并结合我国的临床实际用药经验,提出13条推荐意见。旨在指导广大临床医师规范、合理用药,从而改善我国T2DM患者的临床结局。

关键词：糖尿病 2型钠-葡萄糖共转运蛋白2抑制剂胰岛素口服降糖药

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Neuromuscular junction mitochondrial enrichment: a “double-edged sword” underlying the selective motor neuron vulnerability in amyotrophic lateral sclerosis

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Neural Regeneration Research 2021年第1期16卷 115-116页

作者： Topaz Altman eran Perlson Department of Physiology and Pharmacology Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael Sagol School of Neuroscience Tel-Aviv UniversityTel-AvivIsrael

Motor neurons are highly polarized cells,with long axons that extend to more than 1 m in the adult *** axons further arborize into a specialized synaptic compartment,the motor unit,containing up to 2000 neuromuscular junctions(NMJs).While the size of other neuronal synapses can be up to 1μm,the NMJ is much larger and can reach 10–30μm(Jones et al.,2017).The vast size of the motor unit requires motor neurons to evolutionally adapt and supply this distal portion with a sufficient amount of ATP,as well as to replenish the axonal protein pool in order to maintain their synapses.

关键词： specialized maintain sword

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