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Antidiabetic profiling of veramycins,polyketides accessible by biosynthesis,chemical synthesis and precursor-directed modification

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Organic Chemistry Frontiers 2022年第6期9卷 1604-1615页

作者： Denis Dardić Nils Böhringer Alberto Plaza Florian Zubeil Juliane Pohl svenja Sommer Leo Padva Jonathan Becker Maria A.Patras Mona-Katharina Bill Michael Kurz Luigi Toti sven w.görgens Sören M.M.Schuler AndréBillion Oliver Schwengers Paulus wohlfart Alexander goesmann Norbert Tennagels Andreas Vilcinskas Peter E.Hammann Till F.Schäberle Armin Bauer Fraunhofer Institute for Molecular Biology and Applied Ecology(IME) Branch for Bioresources35392 GießenGermany Justus-Liebig-University gießen 35392 GießenGermany Sanofi-Aventis Deutschland gmbH R&D Integrated Drug Discovery65926 Frankfurt am MainGermany Sanofi-Aventis Deutschland gmbH R&D German Hub65926 Frankfurt am MainGermany german Center of Infection Research(DZIF) Partner Site Gießen-Marburg-Langen35392 GießenGermany

Seven new polyketides,termed veramycins,were isolated from a Streptomyces *** the Sanofi microbial strain collection along with their known congeners NFAT-133 and *** A,anα-pyrone congener of TM-123 and NFAT-133 showed an increased baseline deoxy-glucose uptake in the absence of insulin in a modified L6 rat skeletal muscle cell line(L6 gLUT4 AS160-like cells).In addition,both compounds slightly increased the sensitivity to insulin in this cell *** syntheses of NFAT-133,TM-123 and veramycin A were accomplished starting from a central building block,which bears the three contiguous stereogenic centers of this polyketide *** approach enables an efficient,selective and flexible access to all possible isomers of the stereotriad for further exploration of this series as a potential anti-diabetic lead structure as exemplified by the synthesis of an NFAT-133 ***,the corresponding biosynthetic gene cluster(BgC)was identified by genome sequencing and gene *** on feeding experiments,a biosynthetic pathway was proposed,which enabled access to new veramycin A analogs by precursor-directed biosynthesis.

关键词： synthesis directed isomers

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The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

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Two-photon emission from a superlattice-based superconducting light-emitting structure

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Light(Science & Applications) 2024年第7期13卷 1331-1340页

作者： Shlomi Bouscher Dmitry Panna Ronen Jacovi Fauzia Jabeen Christian Schneider sven Höfling Alex Hayat Department of Electrical Engineering TechnionHaifa 32000Israel. Technische Physik Universität WürzburgAm HublandD-97074 WürzburgGermany. Institute of Physics Carl von Ossietzky Universität OldenburgD-26111 OldenburgGermany

Superconductor-semiconductor hybrid devices can bridge the gap between solid-state-based and photonics-based quantum systems,enabling new hybrid computing schemes,offering increased scalability and *** example for a hybrid device is the superconducting light-emitting diode(SLED).SLEDs have been theoretically shown to emit polarization-entangled photon pairs by utilizing radiative recombination of Cooper ***,the twophoton nature of the emission has not been shown experimentally *** demonstrate two-photon emission in a gaAs/AlgaAs *** electroluminescence spectra reveal unique two-photon superconducting features below the critical temperature(Tc),while temperature-dependent photon-pair correlation experiments(g(2)(τ,T))demonstrate temperature-dependent time coincidences below Tc between photons emitted from the *** results pave the way for compact and efficient superconducting quantum light sources and open new directions in light-matter interaction studies.

关键词： photon quantum utilizing

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Photoionisation detection of a single Er3+ ion with sub-100-ns time resolution

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National Science Review 2024年第4期11卷 38-45页

作者： Yangbo Zhang wenda Fan Jiliang Yang Hao guan Qi Zhang Xi Qin Changkui Duan gabriele g.de Boo Brett C.Johnson Jeffrey C.Mc Callum Matthew J.Sellars sven Rogge Chunming Yin Jiangfeng Du CAS Key Laboratory of Microscale Magnetic Resonance and School of Physical Sciences University of Science and Technology of China CAS Center for Excellence in Quantum Information and Quantum Physics University of Science and Technology of China Hefei National Laboratory University of Science and Technology of China Centre of Excellence for Quantum Computation and Communication Technology School of Physics University of New South Wales Centre of Excellence for Quantum Computation and Communication Technology School of Engineering RMIT University Centre of Excellence for Quantum Computation and Communication Technology School of Physics University of Melbourne Centre of Excellence for Quantum Computation and Communication Technology Research School of Physics and Engineering Australian National University

Efficient detection of single optical centres in solids is essential for quantum information processing, sensing and single-photon generation *** this work,we use radio-frequency（RF） reflectometry to electrically detect the photoionisation induced by a single Er3+ion in *** high bandwidth and sensitivity of the RF reflectometry provide sub-100-ns time resolution for the photoionisation *** this technique,the optically excited state lifetime of a single Er3+ion in a Si nano-transistor is measured for the first time to be 0.49±0.04μ*** results demonstrate an efficient approach for detecting a charge state change induced by Er excitation and *** approach could be used for fast readout of other single optical centres in solids and is attractive for large-scale integrated optical quantum systems thanks to the multi-channel RF reflectometry demonstrated with frequency multiplexing techniques.

关键词： single optical centres erbium ions RF reflectometry photoionisation detection

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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

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Cancer Communications 2024年第1期44卷 101-126页

作者： Monika Raab Izabela Kostova Samuel Peña-Llopis Daniela Fietz Monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich sven Becker Mourad Sanhaji Klaus Strebhardt Department of gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany german Cancer Consortium(DKTK) EssenGermany german Cancer Research Center(DKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany german Cancer Consortium(DKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HgSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(wT)p53-mRNA to HgSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,wT p53 was exogenously expressed in HgSOC cell lines using a mammalian vector ***,IVT wT p53 mRNA was delivered into different HgSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HgSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HgSOC model systems using newly designed IVT mRNA-based *** introduction of wT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HgSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and DNA *** p53 function concurrently reduces chromosomal instability within the HgSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HgSOC metastatic intraperitoneal mouse model HgSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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罗马共和国晚期埃涅阿斯币(RRC 458/1)新解

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古代文明（中英文） 2024年第2期18卷 3-14,M0003页

作者：张红霞顾斯文东北师范大学历史文化学院吉林长春130024 东北师范大学世界古典文明史研究所吉林长春130024

学界主流认为埃涅阿斯币(RRC 458/1)制造于公元前47至前46年的北非,但论据较为薄弱。实际上,相关窖藏仅与恺撒从高卢南进意大利,继而远征非洲行军路线的前段重合,可以推测该币造于起兵地高卢,而非目的地北非。根据图像学分析,埃涅阿斯... 详细信息

学界主流认为埃涅阿斯币(RRC 458/1)制造于公元前47至前46年的北非,但论据较为薄弱。实际上,相关窖藏仅与恺撒从高卢南进意大利,继而远征非洲行军路线的前段重合,可以推测该币造于起兵地高卢,而非目的地北非。根据图像学分析,埃涅阿斯币的纹样以置换图像符号的方式暗示恺撒和维纳斯的联系,藉以提升个人威望,显然属于恺撒与庞培正面对抗前舆论战的手法,而非他掌控罗马政权后的公开宣传。这无疑佐证了埃涅阿斯币制作的较早系年——公元前49年前后。埃涅阿斯币及相关钱币的图像学研究,揭示出罗马由共和向帝制过渡期间政治认同由国家认同向家族认同、个人权威认同的转变,为理解当时的政治史提供了直观却微妙的视角。

关键词：埃涅阿斯币内战恺撒庞培正统性

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“全球TOP100汽车零部件供应商”榜单发布,电气化、智能化成为主要增长引擎

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汽车制造业 2024年第4期 4-7页

作者：龚淑娟 sven Prawitz 《汽车制造业》编辑部德国Automobil Industrie

德国弗戈传播集团Automobil Industrie杂志与德国Berylls战略咨询公司联合发布的全球汽车零部件供应商的前100名企业榜单来了!今年最亮眼的是新能源汽车电池的5家上榜企业,业务增长均超过两位数,最高增长率达到了62.8%。

关键词：战略咨询上榜企业增长引擎新能源汽车汽车零部件供应商传播集团电气化智能化

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中国上泥盆统阳朔阶牙形类生物地层研究

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地层学杂志 2024年第1期48卷 57-76页

作者：常君滢韩淑朋覃斌贤郭文 sven Hartenfels 宋俊俊梁昆殷保安郄文昆中国科学院大学北京100049 中国科学院南京地质古生物研究所现代古生物学和地层学国家重点实验室江苏南京210008 广西区域地质调查研究院广西桂林541003 桂林旅游学院旅游管理学院广西桂林541006 Institute of geology and Mineralogy University of CologneZulpicher Str.49a50674KolnGermany 中国科学院大学南京学院江苏南京211135

阳朔阶最早由殷保安于2008年提出,命名源自桂林市阳朔县,用以指代上泥盆统锡矿山阶与邵东阶之间的一个地方阶,大致相当于国际年代地层单位法门阶上部。阳朔阶底界以牙形类Palmatolepis rugosa trachytera的首次出现为定义,顶界则以有孔... 详细信息

阳朔阶最早由殷保安于2008年提出,命名源自桂林市阳朔县,用以指代上泥盆统锡矿山阶与邵东阶之间的一个地方阶,大致相当于国际年代地层单位法门阶上部。阳朔阶底界以牙形类Palmatolepis rugosa trachytera的首次出现为定义,顶界则以有孔虫Eoendothyra regularis的首现为标志。阳朔阶典型剖面为广西桂林市铁山剖面,自下而上包括“五指山组”和融县组,形成于孤立碳酸盐岩台地边缘,以浅水相的内碎屑、鲕粒泥粒灰岩、粒泥灰岩和颗粒灰岩为特征,局部夹有少量黑色钙质泥岩。在桂林铁山剖面和邻近的小龙门剖面中共采集牙形样品149件,其中94件样品产丰富的牙形类分子,该牙形动物群以Palmatolepis、Neopolygnathus、Polygnathus、Pseudopolygnathus、Bispathodus、Icriodus、Rhodalepis、Mehlina和Branmehla属分子为特征,自下而上可识别出6个牙形类生物带,包括*** marginifera带、*** trachytera带、*** postera带、*** expansa带、***带和*** ultimus带,为环古特提斯洋地区法门阶地层对比提供了高精度的生物地层格架。基于详细的牙形类生物地层和沉积相分析,在铁山剖面*** trachytera带上部和*** expansa带顶部浅水相碳酸盐岩序列中识别出两次黑色富有机质沉积事件,对应于相对海平面快速上升和海洋贫氧,可能是法门期全球性Annulata和Dasberg事件在华南边缘海区的沉积响应。

关键词：泥盆系生物地层桂林牙形类 Annulata事件 Dasberg事件

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ROMAN LAw: OPENINg THE SYSTEM

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Journal of Ancient Civilizations 2018年第2期33卷 267-282,284页

作者： sven günther IHAC NENU Changchun

Throughout the 20th century, Roman Law was mainly an enigma for historians and classical philologists alike. Its position in the Faculties of Law as Legal History and a systematic, and sometimes even synchronic, perspective of many researchers on legal sources together with self-referential tendencies made it appear a closed system, even though the nestor of Altertumswissenschaften, Theodor Mommsen had once encompassed the trias history, law and philology, albeit with his own taxonomy and connected with his liberal ideas that can be frequently found in his Romische geschichte and Romisches Staatsrecht.

关键词： ROMAN LAw OPENINg THE SYSTEM classical philologists

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NARRATINg CHECKS AND BALANCES?THE SETUP OF FINANCERELATED ADMINISTRATIVE DOCUMENTS AND INSTITUTIONS IN 5TH AND 4TH CENTURY BC ATHENS

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Journal of Ancient Civilizations 2019年第2期34卷 211-227,328页

作者： sven günther IHAC NENUChangchun

The setup and narratives of finance-related administrative documents and powers tell the story and fate of the Athenian *** the one hand,one can see the permanently repeated and impressive statement of stability that did not only astonish contemporaries,especially critics of the democratic *** was mirrored in the frequent publication of financial *** were more representative in various aspects than informative in the sense of a real transparent ***,the many offices mentioned both in the literary and epigraphic documents reflect the constant mistrust in,and restriction of,the accumulation of power in the democratic *** the other hand,these formalities and standardized formulas do clearly not carry the whole story,and are superseded in the course of the 4th century by informal powerconglomerations.

关键词： SETUP finance statement

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