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Multitarget Thiol-Activated Tetrapyridyl Gold(Ⅲ)Complexes for Hypoxic Cancer Therapy

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CCS Chemistry 2024年第3期6卷 783-797页

作者： Xue-Quan Zhou Selda Abyar Imma Carbo-Bague Lan Wang Sebastian Türck Maxime ASiegler Uttara Basu ingo Ott Rongfang Liu Adriaan PIJzerman Sylvestre Bonnet Institute of Biopharmaceutical and Health Engineering Tsinghua Shenzhen International Graduate School(SIGS)Tsinghua UniversityShenzhen 518055 Leiden Institute of Chemistry Leiden University2333 CC Leiden Department of Chemistry Simon Fraser UniversityBurnabyBritish Columbia V5A 1S6 Institute of Medicinal and Pharmaceutical Chemistry Technische Universität Braunschweig38106 Braunschweig Department of Chemistry Johns Hopkins UniversityBaltimoreMaryland 21218 Division of Drug Discovery&Safety Leiden Academic Centre for Drug ResearchLeiden University2333 CC Leiden

Gold complexes have emerged as promising anticancer metallodrugs due to their efficient thioredoxin reductase(TrxR)inhibition,which disturbs the redox balance of cancer cells.However,in this model,the role of the ligand(s)coordinated to gold is often overlooked.In this work,we present a series of tetrapyridyl Au(Ⅲ)complexes that exhibit thiol-induced release of a Au(Ⅰ)ion and a tetrapyridyl ligand.The formation of a free Au(Ⅰ)center is responsible for the expected TrxR inhibition.Additionally,the released ligand,which was visible in cells due to its intense blue fluorescence,showed excellent binding properties to the hERG potassium channel.Moreover,these ligands ended up in the lysosomes,resulting in significant lysosome damage.Altogether,the Au(Ⅲ)complexes presented in this work showed broad-spectrum anticancer properties,both in hypoxic 2D monolayers and 3D tumor spheroids.We suggest that the interaction of the released Au(Ⅰ)center and the tetrapyridyl ligand with two different protein targets may combine into prodrugs that overcome hypoxia-induced drug deactivation.

关键词： anticancer Au(Ⅲ)complexes enzyme inhibtion potassium channel affinity lysosome damage cell imaging prodrug

Gallai-Ramsey Number for the Union of Stars

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Acta Mathematica Sinica,English Series 2022年第8期38卷 1317-1332页

作者： Ya Ping MAO Zhao WANG Colton MAGNANT ingo SCHIERMEYER School of Mathematics and Statistics Qinghai Normal UniversityXining 810008P.R.China College of Science China Jiliang UniversityHangzhou 310018P.R.China Department of Mathematics Clayton State UniversityMorrowGA30260USA Technische Universit?t Bergakademie Freiberg Institut für Diskrete Mathematik und Algebra09596 FreibergGermany

Given a graph G and a positive integer k,define the Gallai–Ramsey number to be the minimum number of vertices n such that any k-edge coloring of Kn contains either a rainbow(all different colored)triangle or a monochromatic copy of G.In this paper,we obtain exact values of the Gallai–Ramsey numbers for the union of two stars in many cases and bounds in other cases.This work represents the first class of disconnected graphs to be considered as the desired monochromatic subgraph.

关键词： Ramsey theory Gallai-Ramsey number union of stars

Tempering of exhausted T cells to comprehend their adaptive response for suitable clinical translation

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Cellular & Molecular Immunology 2023年第12期20卷 1401-1402页

作者： Amit Sharma ingo G.H.Schmidt-Wolf Department of Integrated Oncology Center for Integrated Oncology(CIO)BonnUniversity Hospital BonnBonnGermany

Although cancer immunotherapy has taken center stage,exhaustion of T cells is undeniably one of the major problems preventing it from being fully successful[1].Certainly,reversal of T-cell exhaustion or dysfunction is of great importance for developing new strategies and restoring immune function.Nevertheless,counterarguments about the adverse effect of reversing T-cell exhaustion(leading to overactivation of T cells and cytotoxicity)and even their irreversible properties have been quite common in scientific debates.With more to be discovered about the reasons for T-cell failure,a better understanding of the molecular factors/determinants[2,3]that shape/remodel“heterogeneous”dysfunctional T cells in cancer makes clear sense.Indeed,two recent publications in Nature immunology have described the intriguing perspective of T-cell exhaustion[4,5].Of interest,Vignali et al.focused on the hypoxia-driven CD39-dependent suppressor function of exhausted T cells,whereas Saadey et al.emphasized restoring the epigenetic balance of TGFβ1/BMP signaling in exhausted T cells to unlock responsiveness to immune checkpoint blockade therapy.

关键词： irreversible exhaustion publications

Male mate choice in livebearing fishes： an overview

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Current Zoology 2018年第3期64卷 393-403页

作者： ingo SCHLUPP Department of Biology University of Oklahoma 730 Van Vleet Oval Norman OK 73019 USA

Although the majority of studies on mate choice focus on female mate choice, there is growing recognition of the role of male mate choice too. Male mate choice is tightly linked to 2 other phenomena: female competition for males and ornamentation in females. In the current article, I review the existing literature on this in a group of fishes, Poeciliidae. In this group, male mate choice appears to be based on differences in female quality, especially female size, which is a proxy for fecundity. Some males also have to choose between heterospecific and conspecific females in the unusual mating system of the Amazon molly. In this case, they typically show a preference for conspecific females. Whereas male mate choice is relatively well documented for this family, female ornamentation and female competition are not.

关键词：配偶选择钓鱼交配系统女性亚马逊竞争装饰男性

Comparison of drug abuse in Germany and China

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Acta Pharmacologica Sinica 2007年第10期28卷 1505-1518页

作者： ingo Ilja MICHELS Office of the Federal Drug Commissioner Federal Ministry of HealthBerlin 10117Germany

Drug abuse has a long,but also different history in Germany and China.TheOpium War largely influenced the history of China in 19th century;however,China was once recognized as a drug-free nation for 3 decades from the 1950s tothe 1980s.Drug abuse has spread quickly since re-emerging as a national problemin China in the late 1980s.The number of registered drug abusers increased from70 000 in 1990 to more than 1 million by the end of 2005.In past decades,illicit drugtrafficking and production have swept most provinces in China,and drug abusehas caused many problems for both abusers and the community.One major drug-related problem is the spread of HIV,which has caused major social and economicdamage in China.Germany,the largest developed European country,also facesthe drug and addiction problem.Germany has about 150 000 heroin addicts,forwhom HIV/AIDS has become a serious threat since the mid 1980s.To control thedrug problem,the German Government adopted the"Action Plan on Drugs andAddiction"in 2003;the China Central Government approved a similar regulationin the antidrug campaign in 2005.Germany has experience in reducing drug-re-lated harm.The methadone maintenance treatment (MMT) program has run formore than 20 years and the public has become more tolerant of addicts.In 2003,China began the MMT program for controlling the spread of HIV/AIDS.It isnecessary for China to learn from developed countries to acquire success in itsantidrug campaign.In this review,we will go over the differences and similaritiesin drug abuse between Germany and China.The differences are related to history,population and economics,drug policy context,drug laws,HIV/hepatitis C virusinfection,the MMT program and so on.These 2 nations have drug abuse prob-lems with different histories and currently use different approaches to handleillicit drug marketing and use.The legal penalties for illicit drug offences reflectthe social differences of these 2 nations with respect to the seriousness of particu-lar types of crimes.The characteristics of th

关键词： drug abuse methadone maintenance treatment heroin HIV/AIDS harm reduction comparison Germany China

Optimized Three-Dimensional Cardiovascular Magnetic Resonance Whole Heart Imaging Utilizing Non-Selective Excitation and Compressed Sensing in Children and Adults with Congenital Heart Disease

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Congenital Heart Disease 2023年第3期18卷 279-294页

作者： ingo Paetsch Roman Gebauer Christian Paech Frank-Thomas Riede Sabrina Oebel Andreas Bollmann Christian Stehning Jouke Smink ingo Daehnert Cosima Jahnke Department of Electrophysiology Heart Center Leipzig at University of LeipzigLeipzigGermany Department of Pediatric Cardiology Heart Center Leipzig at University of LeipzigLeipzigGermany Philips Research Laboratories HamburgGermany Philips Medical Systems BestThe Netherlands

Background:In congenital heart disease(CHD)patients,detailed three-dimensional anatomy depiction plays a pivotal role for diagnosis and therapeutical decision making.Hence,the present study investigated the applicability of an advanced cardiovascular magnetic resonance(CMR)whole heart imaging approach utilizing nonselective excitation and compressed sensing for anatomical assessment and interventional guidance of CHD patients in comparison to conventional dynamic CMR angiography.Methods:86 consecutive pediatric patients and adults with congenital heart disease(age,1 to 74 years;mean,35 years)underwent CMR imaging including a freebreathing,ECG-triggered 3D nonselective SSFP whole heart acquisition using compressed SENSE(nsWHcs).Anatomical assessability and signal intensity ratio(SIR)measurements were compared with conventional dynamic 3D-/4D-MR angiography.Results:The most frequent diagnoses were partial anomalous pulmonary venous drainage(17/86,20%),transposition of the great arteries(15/86,17%),tetralogy of Fallot(12/86,14%),and a single ventricle(7/86,8%).Image quality of nsWHcs was rated as excellent/good in 98%of patients.nsWHcs resulted in a reliable depiction of all large thoracic vessels(anatomic assessability,99%–100%)and the proximal segments of coronary arteries and coronary sinus(>90%).nsWHcs achieved a homogenously distributed SIR in all cardiac cavities and thoracic vessels without a significant difference between pulmonary and systemic circulation(10.9±3.5 and 10.6±3.4;p=0.15),while 3D angiography showed significantly increased SIR for targeted vs.non-targeted circulation(PA-angiography,15.2±8.1 vs.5.8±3.6,p<0.001;PV-angiography,7.0±3.9 vs.17.3±6.8,p<0.001).Conclusions:The proposed nsWHcs imaging approach provided a consistently high image quality and a homogeneous signal intensity distribution within the pulmonary and systemic circulation in pediatric patients and adults with a wide spectrum of congenital heart diseases.nsWHcs enabled detailed anatomical assessment and three-dimensional reconstruct

关键词： Cardiovascular magnetic resonance imaging congenital heart disease whole heart imaging nonselective SSFP compressed SENSE MR angiography

Microstructure analyses and phase-field simulation of partially divorced eutectic solidification in hypoeutectic Mg-Al Alloys

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Journal of Magnesium and Alloys 2022年第6期10卷 1672-1679页

作者： Joo-Hee Kang Jiwon Park Kyung Song Chang-Seok Oh Oleg Shchyglo ingo Steinbach Korea Institute of Materials Science Changwon 51508Republic of Korea Interdisciplinary Centre for Advanced Materials Simulation Ruhr-University Bochum44801 BochumGermany

In this study the partially divorced eutectic microstructure ofα-Mg andβ-Mg17Al12was investigated by electron backscatter diffraction,transmission electron microscopy,and phase-field modeling in hypoeutectic Mg-Al alloys.The orientation relationships between the individual eutecticαgrains,eutecticβphase,and primaryαgrains were investigated.While the amount of eutectic morphology is primarily determined by the Al content,the in-depth microstructure analyses and the phase-field simulation suggest non-interactive nucleation and growth of eutecticαphase in theβphase grown on the interdendritic primaryαdendrites.Also,phase-field simulations showed a preferred nucleation sequence where theβphase nucleates first and subsequently triggers the nucleation of eutecticαphase at the movingβphase solidification front,which supports the microstructural analysis results.

关键词： Mg-Al alloy Partially divorced eutectic Solidification Electron backscatter diffraction Phase-Field modeling

Identification and mapping of Rpi-blb4 in diploid wild potato species Solanum bulbocastanum

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The Crop Journal 2023年第6期11卷 1828-1835页

作者： Jie Li Amanpreet Kaur Brian Harrower Miles Armstrong Daolong Dou Xiaodan Wang ingo Hein Department of Plant Pathology and MOA Key Lab of Pest Monitoring and Green Management College of Plant ProtectionChina Agricultural UniversityBeijing 100193China The James Hutton Institute InvergowrieDundee DD25DAUK University of Dundee Dundee DD14HNUK Crop Research Centre TeagascOakParkCarlow R93 XE12Ireland College of Plant Protection Academy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095JiangsuChina

More than 170 years after causing the potato famine in Ireland,late blight is still considered one of the most devastating crop diseases.Commercial potato breeding efforts depend on natural sources of resistance to protect crops from the rapidly evolving late blight pathogen,Phytophthora infestans.We have identified and mapped a novel broad-spectrum disease resistance gene effective against P.infestans from the wild,diploid potato species Solanum bulbocastanum.Diagnostic resistance gene enrichment sequencing(dRenSeq)was used to confirm the uniqueness of the identified resistance.RenSeq and GenSeq-based mapping of the resistance,referred to as Rpi-blb4,alongside recombinant screening,positioned the locus responsible for the resistance to potato chromosome 5.The interval spans approximately 2.3 Mb and corresponds to the DM reference genome positions of 11.25 and 13.56 Mb.

关键词： Renseq Disease resistance Late blight Solanum bulbocastanum

Tracking the phase transformation and microstructural evolution of Sn anode using operando synchrotron X-ray energy-dispersive diffraction and X-ray tomography

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Journal of Energy Chemistry 2023年第1期76卷 429-437,I0011页

作者： Kang Dong Fu Sun Andre Hilger Paul H.Kamm Markus Osenberg Francisco Garcia-Moreno ingo Manke Institute of Applied Materials Helmholtz-Zentrum Berlin fur Materialien und EnergieHahn-Meitner-Platz 1Berlin 14109Germany Institute of Materials Science and Technology Technische Universitat BerlinHardenbergstraβe 36Berlin 10623Germany Qingdao Institute of BioEnergy and Bioprocess Technology Chinese Academy of Sciences189 Songling RoadQingdao 266101ShandongChina

Tin(Sn)holds great promise as an anode material for next-generation lithium(Li)ion batteries but suffers from massive volume change and poor cycling performance.To clarify the dynamic chemical and microstructural evolution of Sn anode during lithiation and delithiation,synchrotron X-ray energydispersive diffraction and X-ray tomography are simultaneously employed during Li/Sn cell operation.The intermediate Li-Sn alloy phases during de/lithiation are identified,and their dynamic phase transformation is unraveled which is further correlated with the volume variation of the Sn at particle-and electrode-level.Moreover,we find that the Sn particle expansion/shrinkage induced particle displacement is anisotropic:the displacement perpendicular to the electrode surface(z-axis)is more pronounced compared to the directions(x-and y-axis)along the electrode surface.This anisotropic particle displacement leads to an anisotropic volume variation at the electrode level and eventually generates a net electrode expansion towards the separator after cycling,which could be one of the root causes of mechanical detachment and delamination of electrodes during long-term operation.The unraveled chemical evolution of Li-Sn and deep insights into the microstructural evolution of Sn anode provided here could guide future design and engineering of Sn and other alloy anodes for high energy density Li-and Na-ion batteries.

关键词： Sn anode Li-Sn phase transformation X-ray tomography Operando X-ray diffraction Anisotropic displacement Digital volume correlation(DVC)