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From Vietnamese plants to a biflavonoid that relieves inflammation by triggering the lipid mediator class switch to resolution

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Acta Pharmaceutica Sinica B 2021年第6期11卷 1629-1647页

作者： Tran Thi Van Anh Alilou Mostafa Zhigang Rao Simona Pace Stefan Schwaiger Christian Kretzer Veronika Temml Carsten Giesel Paul M.Jordan Rossella Bilancia Christina Weinigel Silke Rummler birgit waltenberger Tran Hung Antonietta Rossi Hermann Stuppner Oliver Werz Andreas Koeberle Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck(CMBI) University of InnsbruckInnsbruck 6020Austria Faculty of Pharmacy University of Medicine and Pharmacy at Ho Chi Minh City 700000Viet Nam Michael Popp Institute and Center for Molecular Biosciences Innsbruck(CMBI) University of InnsbruckInnsbruck 6020Austria Department of Pharmaceutical/Medicinal Chemistry Institute of PharmacyFriedrich Schiller University JenaJena 07743Germany Institute of Pharmacy Department of Pharmaceutical and Medicinal ChemistryParacelsus Medical University SalzburgSalzburgSalzburg 5020Austria Department of Pharmacy School of MedicineUniversity of Naples FedericoⅡNaples'80131Italy Institute of Transfusion Medicine University Hospital JenaJena 07747Germany

Chronic inflammation results from excessive pro-inflammatory signaling and the failure to resolve the inflammatory *** mediators orchestrate both the initiation and resolution of *** from pro-inflammatory to pro-resolving lipid mediator biosynthesis is considered as efficient strategy to relieve chronic inflammation,though drug candidates exhibiting such features are *** from a library of Vietnamese medical plant extracts,we identified isomers of the biflavanoid 8-methylsocotrin-4’-ol from Dracaena cambodiana,which limit inflammation by targeting 5-lipoxygenase and switching the lipid mediator profile from leukotrienes to specialized pro-resolving mediators(SPM).Elucidation of the absolute configurations of 8-methylsocotrin-4’-ol revealed the 2 S,γSisomer being most active,and molecular docking studies suggest that the compound binds to an allosteric site between the 5-lipoxygenase *** identified additional subordinate targets within lipid mediator biosynthesis,including microsomal prostaglandin E2 *** production is efficiently suppressed in activated human neutrophils,macrophages,and blood,while the induction of SPM biosynthesis is restricted to M2 *** shift from leukotrienes to SPM was also evident in mouse peritonitis in vivo and accompanied by a substantial decrease in immune cell *** summary,we disclose a promising drug candidate that combines potent 5-lipoxygenase inhibition with the favorable reprogramming of lipid mediator profiles.

关键词： Lipoxygenase Inflammation Resolution Natural product Lipidomics Lipid mediator

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Synthesis of iron（ll） complexes with asymmetric N2O2 coordinating Schiff base-like ligands and their spin crossover properties

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Frontiers of Chemical Science and Engineering 2018年第3期12卷 400-408页

作者： Wolfgang Bauer Tanja Ossiander birgit Weber Department of Chemistry University of Bayreuth 95440 Bayreuth Germany

The synthesis of new Schiff base-like ligands with asymmetric substituents pattern and their iron complexes with pyridine as axial ligand is described. Two of the ligands and one of the iron（II） complexes were characterized by single crystal X-ray structure analysis. One of the the iron（II） complexes shows spin crossover behavior while the others remain in the high spin state. The influence of the reduced symmetry of the ligand on the properties of the complexes is discussed.

关键词： iron Schiffbase-like ligands magnetism spin crossover X-ray structures

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Intracellular transport of hepatitis B virus

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World Journal of Gastroenterology 2007年第1期13卷 39-47页

作者： Michael Kann André Schmitz birgit Rabe CNRS-REGER(UMR 5097) Université Bor-deaux 2146 rue Léo SaignatF-33076 Bordeaux CedexFrance Institute of Medical Virology Fran-kfurter Str.107D-35392 GiessenGermany

For genome mulUplication hepadnaviruses use the transcriptional machinery of the cell that is found within the nucleus. Thus the viral genome has to be transported through the cytoplasm and nuclear pore. The intracytosolic translocation is facilitated by the viral capsid that surrounds the genome and that interacts with cellular microtubules. The subsequent passage through the nuclear pore complexes （NPC） is mediated by the nuclear transport receptors importin α andβ. Importin α binds to the C-terminus of the capsid protein that comprises a nuclear localization signal （NLS）. The exposure of the NLS is regulated and depends upon genome maturation and/or phosphorylation of the capsid protein. As for other karyophilic cargos using this pathway importin α interacts with importin β that facilitates docking of the import complex to the NPC and the passage through the pore. Being a unique strategy, the import of the viral capsid is incomplete in that it becomes arrested inside the nuclear basket, which is a cage-like structure on the karyoplasmic face of the NPC. Presumably only this compartment provides the factors that are required for capsid disassembly and genome release that is restricted to those capsids comprising a mature viral DNA genome.

关键词： Hepatitis B virus Capsid Intracellular transport Microtubules Nuclear pore Importin Nuclear localization signal Nuclear basket

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Product Variability of the ‘Cineole Cassette＇ Monoterpene Synthases of Related Nicotiana Species

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Molecular Plant 2011年第6期4卷 965-984页

作者： Anke Fahnrich Katrin Krause birgit Piechulla University of Rostock Institute for Biological Sciences Albert-Einstein-Str. 3 18059 Rostock Germany

Nicotiana species of the section Alatae characteristically emit the floral scent compounds of the ＇cineole cassette＇ comprising 1,8-cineole, limonene, myrcene, α-pinene, β-pinene, sabinene, and α-terpineol. We successfully isolated genes of Nicotiana alata and Nicotiana langsdorfii that encoded enzymes, which produced the characteristic monoter- penes of this ＇cineole cassette＇ with α-terpineol being most abundant in the volatile spectra. The amino acid sequences of both terpineol synthases were 99% identical. The enzymes cluster in a monophyletic branch together with the closely related cineole synthase of Nicotiana suaveolens and monoterpene synthase 1 of Solanum lycopersicum. The cyclization reactions （α-terpineol to 1,8-cineole） of the terpineol synthases of N. alata and N. langsdorfii were less efficient compared to the ＇cineole cassette＇ monoterpene synthases of Arabidopsis thaliana, N. suaveolens, Salvia fruticosa, Salvia officinalis, and Citrus unshiu. The terpineol synthases of IV. alata and N. langsdorfii were localized in pistils and in the adaxial and abaxial epidermis of the petals. The enzyme activities reached their maxima at the second day after anthesis when flowers were fully opened and the enzyme activity in N. alata was highest at the transition from day to night （diurnal rhythm）.

关键词： Nicotiana alata Nicotiana langsdorfii cineole cassette terpineol synthase multiproduct enzyme monoterpene synthase 1,8-cineole, α-terpineol.

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Osteoclast-like giant cell tumors of the pancreas and liver

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World Journal of Gastroenterology 2006年第48期12卷 7878-7883页

作者： Juergen Bauditz birgit Rudolph Wolfram Wermke Fourth Department of Medicine Charité University Hospital Berlin Ger-many Institute of Pathology Charité University Hospital Berlin Germany

Osteoclast-like giant cell tumors （OGCT） are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient＇s survival is currently more than 15 too, making him the longest survivor with an OGCT of the liver to date.

关键词： Osteoclast-like giant cell tumor Liver cancer Pancreatic cancer Contrast sonography

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IRF1 and BATF—transcription factors that set the epigenetic landscape for Tr1 cell differentiation?

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Cellular & Molecular Immunology 2017年第9期14卷 727-729页

作者： Katarina Stanko birgit Sawitzki Charité-Universitaetsmedizin Berlin Corporate Member of Freie Universitaet BerlinHumboldt-Universitaet zu Berlinand Berlin Institute of HealthInstitute of Medical ImmunologyAugustenburger Platz 113353 BerlinGermany

Type 1 regulatory T(Tr1)cells are Foxp3-negative regulatory CD4+T cells that develop outside of the thymus and mediate regulatory functions in large part by producing the immunosuppressive cytokine IL-10.

关键词： Foxp3 Tr1 landscape

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Do concentrations in eggs and liver tissue tell the same story of temporal trends of mercury in high Arctic seabirds?

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Journal of Environmental Sciences 2018年第6期30卷 65-72页

作者： Mark L.Mallory birgit M.Braune Biology Department Acadia University Environment and Climate Change Canada National Wildlife Research Centre Carleton University

Mercury（Hg） remains a key contaminant of concern in Arctic biota, and monitoring of Hg concentrations in seabird tissues will be an effective approach to track the effects of implementing the Minamata Convention. We examined trends in total Hg（THg） in liver and egg tissues of two Arctic seabirds, thick-billed murres（Uria lomvia） and northern fulmars（Fulmarus glacialis）, between 1976 and 2013 to assess whether both tissues showed similar patterns of Hg change. Hepatic THg was consistently higher than egg THg, and both species had similar egg THg concentrations, but fulmars had higher hepatic THg than *** THg concentrations showed more relative variation through time than *** suggest that egg THg better reflects exposure of birds to THg in local, Arctic prey,whereas liver THg may incorporate longer term, year-round THg exposure. Additional analysis of THg distribution in Arctic seabirds post-laying would help inform interpretation of long-term trends.

关键词： Canada Fulmarus glacialis Northern fulmar Thick-billed murre Uria lomvia

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The Monumentenwacht model for preventive conservation of built heritage:A case study of Monumentenwacht Vlaanderen in Belgium

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Frontiers of Architectural Research 2021年第1期10卷 92-107页

作者： Meiping Wu birgit van Laar Department of Architecture Built Environment and Construction EngineerinsPolytechnic University of MilanMilan20133Italy Key Laboratory of Urban and Architectural Heritage Conservation Southeast UniversityNanjing210096China

Monumentenwacht(Monument Watch)is an organization that specializes in the periodic inspection of built heritage to raise awareness among owners and caretakers of the importance of proper maintenance and preventive *** originated in the Netherlands in *** was later established in Belgium,Germany,the UK,Denmark,Hungary,Italy,Slovak,Spain,France,and Portugal in the form of similar organizations and projects with similar *** organization promotes the idea of,fprevention is better than cureM by offering periodic inspection,monitoring,and minor urgent repair and writing independent professional inspection reports as a reference for owners and users for further maintenance and conservation *** study explores the working mode of Monumentenwacht in Flanders,Belgium,including its historical development,organizational structure,inspection team configuration,professional inspection report,database,reporting system,and technical manuals.A brief analysis of other similar organizations and projects in various European countries is included to reveal efficient ways to promote this model while respecting different cultural,economic,social,legal,and political contexts.

关键词： Monum entenwacht Preventive conservation Maintenance Periodic inspection Built heritage

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Proteomic and metabolic prediction of response to therapy in gastric cancer

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World Journal of Gastroenterology 2014年第38期20卷 13648-13657页

作者： Michaela Aichler birgit Luber Florian Lordick Axel Walch Research Unit Analytical Pathology Institute of Pathology Helmholtz Zentrum MünchenInstitute of Pathology Technische Universit t MünchenUniversity Cancer Center Leipzig University of LeipzigResearch Unit Analytical Pathology Institute of Pathology Helmholtz Zentrum München German Research Centre for Environmental Health

Several new treatment options for gastric cancer have been introduced but the prognosis of patients diagnosed with gastric cancer is still poor. Disease prognosis could be improved for high-risk individuals by implementing earlier screenings. Because many patients are asymptomatic during the early stages of gastric cancer,the diagnosis is often delayed and patients present with unresectable locally advanced or metastatic disease. Cytotoxic treatment has been shown to prolong survival in general,but not all patients are responders. The application of targeted therapies and multimodal treatment has improved prognosis for those with advanced ***,these new therapeutic strategies do not uniformly benefit all *** whether patients will respond to specific therapies would be of particular value and would allow for stratifying patients for personalized treatment *** imaging by positron emission tomography was the first technique with the potential to predict the response of esophagogastric cancer to neoadjuvant *** and validating tissue-based biomarkers are ongoing *** this review,we discuss the status of several targeted therapies for gastric cancer,as well as proteomic and metabolic methods for investigating biomarkers for therapy response prediction in gastric cancer.

关键词： Gastric cancer Therapy Response prediction Positron emission tomography Matrix-assisted laser desorption-ionization

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Evolution of particle number size distribution in an urban atmosphere during episodes of heavy pollution and new particle formation

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Science China Earth Sciences 2011年第11期54卷 1772-1778页

作者： WU ZhiJun, HU Min YUE DingLi birgit WEHNER Alfred WIEDENSOHLER State Key Joint Laboratory of Environmental Simulation and Pollution Control College of Environmental Sciences and Engineering Peking University Beijing 100871 China Leibniz-lnstitutefor Tropospheric Research 04318 Leipzig Germany

This study discusses the evolution of particle number size distribution during episodes of heavy pollution and new particle formation in the urban atmosphere of Beijing to quantify the effects of dynamic processes (coagulation and condensation) on the particle number size *** a heavy-pollution event,an extremely low number concentration of 3-10 nm particles (on average 46 cm-3) was *** is because nucleation-mode particles were easily removed by strong coagulational scavenging of larger particles under this *** addition,a large condensation sink (on average 0.13 s-1) restrained nucleation,which is one of the major sources of nucleation-mode ***,during a new-particle formation event,the small condensation sink (0.01 s-1) of precursor facilitated *** the same time,preexisting particles had little ability to scavenge newly formed particles (around 1 nm) and allowed them to grow to a detectable size (larger than 3 nm currently).We suggest that the effects of dynamic processes (coagulation and condensation) on particle size distribution should be stressed under some extreme conditions of the relatively polluted urban atmosphere in addition to traffic and meteorological factors.

关键词： particle number size distribution new particle formation coagulation and condensation sinks

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