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Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson Fariba Roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu Donald F.Becker Jonathan L.Robinson Jens Nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of Biochemistry and Redox Biology Center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in ***-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell ***,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion *** addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human *** combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid ***,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer *** identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was *** work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

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Electroactivity of the magnetotactic bacteria Magnetospirillum magneticum AMB-1 and Magnetospirillum gryphiswaldense MSR-1

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 103-110页

作者： Mathias Fessler Qingxian Su Marlene Mark Jensen Yifeng Zhang Department of Environmental and Resource Engineering Technical University of DenmarkCopenhagenDK-2800Denmark

Magnetotactic bacteria reside in sediments and stratified water *** are named after their ability to synthesize internal magnetic particles that allow them to align and swim along the Earth’s magnetic field ***,we show that two magnetotactic species,Magnetospirillum magneticum strain AMB-1 and Magnetospirillum gryphiswaldense strain MSR-1,are *** *** and *** were able to generate current in microbial fuel cells with maximum power densities of 27 and 11μW/m^(2),*** the presence of the electron shuttle resazurin both species were able to reduce the crystalline iron oxide hematite(Fe_(2)O_(3)).In addition,*** could reduce poorly crystalline iron oxide(FeOOH).Our study adds *** and *** to the growing list of known electroactive bacteria,and implies that electroactivity might be common for bacteria within the Magnetospirillum genus.

关键词： Magnetotactic bacteria Magnetospirillum magneticum Magnetospirillum gryphiswaldense Extracellular electron transfer Microbial fuel cells

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Risk Assessment for Hybrid AC/DC Systems Based on Transient Energy Function

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CSEE Journal of Power and Energy Systems 2024年第4期10卷 1654-1663页

作者： Peng Sun Yun Teng Mingli Zhang Zhe Chen Shenyang University of Technology Shenyang 110870China Liaoning Electric Power Co.Ltd.Economic Research Institute Shenyang 110000China Department of Energy Technology Aalborg UniversityAalborgDK DK 9220

In order to accurately assess the risk of the hybrid AC/DC network under fault,a risk assessment method for the hybrid AC/DC system based on the transient energy function is ***,based on the energy transfer relationship of the hybrid AC/DC power system,the transient energy function model of the hybrid AC/DC system is *** on the operating data of the power grid,the energy function is used as an efficiency variable,and the efficiency variable is integrated into the prior risk probability calculation of nodes in the network,and a Bayesian network-based risk assessment model of hybrid AC/DC system is *** the dynamic update model of network cascading failures,the clique tree propagation algorithm is used to dynamically calculate the posterior risk probability of the node to realize the dynamic assessment of the network ***,the improved IEEE-39 node hybrid AC/DC system is used as an example for *** results show that the proposed model can not only effectively evaluate the overall safety of the network,but also has feasibility in predicting faults,which can provide a theoretical basis for the stability control of the hybrid AC/DC system.

关键词： Cascading failure energy function hybrid AC-DC system risk assessment

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Transcriptional reprogramming during human osteoclast differentiation identifies regulators of osteoclast activity

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Bone Research 2024年第1期12卷 180-198页

作者： Morten S.Hansen Kaja Madsen Maria Price Kent Søe Yasunori Omata Mario M.Zaiss Caroline M.Gorvin Morten Frost Alexander Rauch Molecular Endocrinology Laboratory(KMEB) Department of EndocrinologyOdense University HospitalDK-5000 Odense CDenmark Department of Clinical Research Faculty of Health SciencesUniversity of Southern DenmarkDK-5000 Odense CDenmark Clinical Cell Biology Pathology Research UnitDepartment of Clinical ResearchUniversity of Southern DenmarkDK-5000 Odense CDenmark Institute of Metabolism and Systems Research(IMSR)and Centre for Diabetes Endocrinology and Metabolism(CEDAM)University of BirminghamBirmingham B152TTUK Centre for Membrane Proteins and Receptors(COMPARE) Universities of Birmingham and NottinghamBirmingham B152TTUK Department of Molecular Medicine University of Southern DenmarkDK-5000 Odense CDenmark Department of Orthopedic Surgery Faculty of MedicineThe University of TokyoTokyo 113-8655Japan Department of Internal Medicine 3 Rheumatology and ImmunologyFriedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenD-91054 ErlangenGermany Deutsches Zentrum Immuntherapie(DZI) Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum ErlangenD-91054 ErlangenGermany Steno Diabetes Center Odense Odense University HospitalDK-5000 Odense CDenmark

Enhanced osteoclastogenesis and osteoclast activity contribute to the development of osteoporosis,which is characterized by increased bone resorption and inadequate bone *** novel antiosteoporotic therapeutics are needed,understanding the genetic regulation of human osteoclastogenesis could help identify potential treatment *** study aimed to provide an overview of transcriptional reprogramming during human osteoclast *** were differentiated from CD14+monocytes from eight female *** sequencing during differentiation revealed 8980 differentially expressed genes grouped into eight temporal patterns conserved across *** patterns revealed distinct molecular functions associated with postmenopausal osteoporosis susceptibility genes based on RNA from iliac crest biopsies and bone mineral density *** analyses revealed mutual dependencies between temporal expression patterns and provided insight into subtype-specific transcriptional *** donor-specific expression patterns revealed genes at the monocyte stage,such as filamin B(FLNB)and oxidized low-density lipoprotein receptor 1(OLR1,encoding LOX-1),that are predictive of the resorptive activity of mature *** expression of differentially expressed G-protein coupled receptors was strong during osteoclast differentiation,and these receptors are associated with bone mineral density SNPs,suggesting that they play a pivotal role in osteoclast differentiation and *** regulatory effects of three differentially expressed G-protein coupled receptors were exemplified by in vitro pharmacological modulation of complement 5 A receptor 1(C5AR1),somatostatin receptor 2(SSTR2),and free fatty acid receptor 4(FFAR4/GPR120).Activating C5AR1 enhanced osteoclast formation,while activating SSTR2 decreased the resorptive activity of mature osteoclasts,and activating FFAR4 decreased both the number and resorptive activity of mature *** conclus

关键词： osteoclast programming identif

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Magnetic Co-doped 1D/2D structuredγ-Fe_(2)O_(3)/MoS_(2) effectively activated peroxymonosulfate for efficient abatement of bisphenol A via both radical and non-radical pathways

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 143-159页

作者： Junge Xu Dong Wang Die Hu Ziwei Zhang Junhong Chen Yingmu Wang Yifeng Zhang College of Civil Engineering Fuzhou UniversityFuzhou 350116China China Nuclear Power Engineering Co. Ltd.Shenzhen 518120China Department of Environmental&Resource Engineering Technical University of DenmarkLyngby DK-2800Denmark

Iron-based catalysts have been widely used to treat refractory organic pollutants in *** this paper,magnetic Co-γ-Fe_(2)O_(3)was synthesized by a facile tartaric acid-assisted hydrothermal method,and Co-γ-Fe_(2)O_(3)/MoS_(2) nanocomposite catalyst was obtained via in situ growth of MoS_(2) nanosheets on Co-γ-Fe_(2)O_(3)*** nanocomposite catalysts were used to decompose bisphenol A(BPA)by activating peroxymonosulfate(PMS).It was shown that only 0.15 g/L catalyst and 0.5 mmol/L PMS degraded 10 mg/L of BPA(99.3%within 10 min)in the pH range of 3–*** was activated due to redox cycling among the pairs Co(III)/Co(II),Fe(III)/Fe(II),and Mo(VI)/Mo(IV).Quenching experiments and electron paramagnetic resonance spectroscopy demonstrated that both radical and non-radical pathways were involved in BPA degradation,in which active radical sulfate radical and non-radical singlet oxygen were the main reactive oxygen *** intermediates were identified by liquid chromatography-coupled mass spectrometry,and three possible BPA degradation pathways were *** toxicity of several degradation intermediates was lower,and Co-γ-Fe_(2)O_(3)/MoS_(2) exhibited excellent reusability and could be magnetically recovered.

关键词： Magnetic Co-γ-Fe_(2)O_(3) /MoS_(2) Hydrothermal method Bisphenol A Degradation pathways Toxicity analysis

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Revolutionizing solid-state single-photon sources with multifunctional metalenses

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Light(Science & Applications) 2024年第1期13卷 8-9页

作者： Fei Ding Centre for Nano Optics University of Southern DenmarkCampusvej 55Odense MDK-5230Denmark

Ultrathin multifunctional metalenses are demonstrated to control the multiple degrees of freedom of a single-photon source in hexagonal boron nitride.

关键词： hexagonal boron state

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Metabolic and hepatic effects of liraglutide,obeticholic acid and elafibranor in diet-induced obese mouse models of biopsy-confirmed nonalcoholic steatohepatitis

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World Journal of Gastroenterology 2018年第2期24卷 179-194页

作者： Kirstine S Tolbol Maria NB Kristiansen Henrik H Hansen Sanne S Veidal Kristoffer TG Rigbolt Matthew P Gillum Jacob Jelsing Niels Vrang Michael Feigh Gubra Aps Horsholm DK-2970Denmark Department of Biomedical Sciences Faculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Section for Metabolic Imaging and Liver Metabolism The Novo Nordisk Foundation Center for Basic Metabolic ResearchFaculty of Health SciencesUniversity of CopenhagenCopenhagen DK-2200Denmark Department of Chemistry Faculty of ScienceUniversity of CopenhagenCopenhagen DK-2200Denmark

AIM To evaluate the pharmacodynamics of compounds in clinical development for nonalcoholic steatohepatitis(NASH) in obese mouse models of *** Male wild-type C57 BL/6 J mice(DIO-NASH) and Lep^(ob/ob)(ob/ob-NASH) mice were fed a diet high in trans-fat(40%), fructose(20%) and cholesterol(2%) for 30 and 21 wk, respectively. Prior to treatment, all mice underwent liver biopsy for confirmation and stratification of liver steatosis and fibrosis, using the nonalcoholic fatty liver disease activity score(NAS) and fibrosis staging system. The mice were kept on the diet and received vehicle, liraglutide(0.2 mg/kg, SC, BID), obeticholic acid(OCA, 30 mg/kg PO, QD), or elafibranor(30 mg/kg PO, QD) for eight weeks. Within-subject comparisons were performed on changes in steatosis, inflammation, ballooning degeneration, and fibrosis scores. In addition, compound effects were evaluated by quantitative liver histology, including percent fractional area of liver fat, galectin-3, and collagen 1 *** Liraglutide and elafibranor, but not OCA, reduced body weight in both models. Liraglutide improved steatosis scores in DIO-NASH mice only. Elafibranor and OCA reduced histopathological scores of hepatic steatosis and inflammation in both models, but only elafibranor reduced fibrosis severity. Liraglutide and OCA reduced total liver fat, collagen 1 a1, and galectin-3 content, driven by significant reductions in liver weight. The individual drug effects on NASH histological endpoints were supported by global gene expression(RNA sequencing) and liver lipid *** DIO-NASH and ob/ob-NASH mouse models show distinct treatment effects of liraglutide, OCA, and elafibranor, being in general agreement with corresponding findings in clinical trials for NASH. The present data therefore further supports the clinical translatability and utility of DIO-NASH and ob/ob-NASH mouse models of NASH for probing the therapeutic efficacy of compounds in preclinical d

关键词： Nonalcoholic steatohepatitis Disease models Pathology Fibrosis Liver biopsy Transcriptomics Pharmacodynamics Glucagon-like peptide-1 receptor Peroxisome proliferator-activated receptor Farnesoid X receptor

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A new vaccination strategy to trigger specific CD4 T-cell response in chronic viral infection

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Cellular & Molecular Immunology 2018年第9期15卷 868-869页

作者： Allan Randrup Thomsen Department of Immunology and Microbiology University of CopenhagenPanum InstituteCopenhagen DK-2200Denmark

Persistent viral infections such as HIV and hepatitis C virus pose a severe health risk to the human population,which so far cannot be addressed by efficient prophylactic *** treatment is expensive and often associated with significant adverse *** vaccination could therefore represent an important addition to current treatment ***,vaccination of chronically infected hosts has mostly fallen short of *** important reason for this is that during the development of a chronic infection,normal memory T cells do not develop.1 Instead,some specificities of virusspecific T cells are eliminated while others develop into a dysfunctional cell type termed exhausted cells.

关键词： vaccination infection treatment

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ADAM12 is a costimulatory molecule that determines Th1 cell fate and mediates tissue inflammation

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Cellular & Molecular Immunology 2021年第8期18卷 1904-1919页

作者： Yawei Liu Robert Bockermann Mahdieh Hadi Iman Safari Belinda Carrion Marie Kveiborg Shohreh Issazadeh-Navikas Neuroinflammation Unit Biotech Research&Innovation Centre(BRIC)Faculty of Health and Medical SciencesUniversity of CopenhagenOle Maaløes Vej 5DK-2200Copenhagen NDenmark BRIC Faculty of Health and Medical SciencesUniversity of CopenhagenOle Maaløes Vej 5DK-2200Copenhagen NDenmark

A disintegrin and metalloproteinase(ADAM)12 was previously found to be expressed in T cells in the inflamed ***,the function of ADAM12 in T-cell responses in general and in tissue inflammation has not been ***,we studied the role of ADAM12 in T-cell responses,fate determination on activation,and its functions in T cells to mediate tissue *** identified ADAM12 as a costimulatory molecule that is expressed on naive T cells and downregulated on ***12 mimics CD28 costimulatory signaling to activate and induce the proliferation of T-helper 1(Th1)*** ADAM12 Fab antibodies trigger T-cell activation by amplifying TCR signaling to stimulate T-bet-mediated IFNγ*** of genomic ADAM12 and its knockdown in T cells diminished T-bet and IFNγproduction in Th1 cells,whereas other T cells,including Th17 cells,were ***12 had similar functions in vivo on myelin antigen(MOG_(35-55))-induced T-cell *** found that genetic loss of ADAM12 profoundly alleviated Th1-mediated neuroinflammation and thus disease severity in experimental autoimmune encephalomyelitis,a model of multiple *** profiling of MOG_(35-55)-specific ADAM12^(−/−)T cells revealed differentially expressed genes that are important for T-cell activation,proliferation,and costimulatory signaling and Th1 pathogenicity,consistent with their inability to cause T-cell-mediated skin inflammation in a model of adoptive delayed-type *** conclude that ADAM12 is a T-cell costimulatory molecule that contributes to the pathogenesis of tissue inflammation and a potential target for the treatment of Th1-mediated diseases.

关键词： T cells T-bet Th17 EAE DTH GM-CSF

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Electronic regulation to achieve efficient anaerobic digestion of organic fraction of municipal solid waste(OFMSW):strategies,challenges and potential solutions

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 159-165页

作者： Yongdong Chen Hong Wang Parisa Ghofrani-Isfahani Li Gu Xiaoguang Liu Xiaohu Dai State Key Laboratory of Pollution Control and Resources Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China Shanghai Institute of Pollution Control and Ecological Security Tongji UniversityShanghai 200092China Department of Chemical and Biochemical Engineering Technical University of DenmarkKgs Lyngby DK-2800Denmark College of Environment and Ecology Chongqing UniversityChongqing 400045China

Anaerobic digestion(AD)of organic fraction of municipal solid waste(OFMSW)is prone to system breakdown under high organic loading rates(OLRs)condition,which subsequently reduces the efficiency of digestion process and results in substantial economic *** this perspective paper,the substances metabolisms,electrons flow,as well as microbial interaction mechanisms within AD process are comprehensively discussed,and the underlying bottleneck that causes inefficient methane production is identified,which is“electrons surplus”.Systems encountering severe electron surplus are at risk of process failure,making it crucial to proactively prevent this phenomenon through appropriate *** this basis,the present perspective proposes three potential electronic regulation strategies to prevent electrons surplus,namely,electron shunt,accelerating electron transfer and regulating methanogenic metabolism pathway,and presents specific methodologies for each ***,the potential solutions to challenges that may occur during the electronic regulation process are also presented in this *** perspective aims to provide innovative approaches to achieve the efficient and stable operation of OFMSW anaerobic digestion,especially under high OLRs condition.

关键词： Anaerobic digestion Electrons surplus Electronic regulation Electrons shunt Electron transfer Methanogenic metabolism pathway

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