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A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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Bio-Design and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos P.J.Dijkstra c.Mota J.Bauer H.Ferreira Rui L.Reis N.Neves S.camarero-Espinosa M.B.Baker L.Moroni Department of complex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Research Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal IcVS/3B’s-PT Government Associate Laboratory 4806-909 Braga/GuimarãesPortugal POLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PcL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PcL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PcL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMScs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-a

关键词： Additive manufacturing Blending Surface functionalization Surface density click chemistry Human

Lithium bis(trifluoromethanesulfonyl)imide blended in polyurethane acrylate photocurable solid polymer electrolytes for lithium-ion batteries

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Journal of Energy chemistry 2021年第11期30卷 485-496,I0011页

作者： cristian Mendes-Felipe J.c.Barbosa R.Gonsalves D.Miranda c.M.costa J.L.Vilas-Vilela S.Lanceros-Mendez BcMaterials Basque Center for MaterialsApplications and NanostructuresUPV/EHU Science Park48940 LeioaSpain Macromolecular chemistry Group(LABQUIMAc) Department of Physical ChemistryFaculty of Science and TechnologyUniversity of the Basque Country(UPV/EHU)Barrio Sarriena s/nE-48940 LeioaSpain center of Physics University of MinhoCampus of Gualtar4710-057 BragaPortugal center of chemistry University of MinhoCampus of Gualtar4710-057 BragaPortugal Ai–School of Technology IPCABarcelosPortugal Ikerbasque Basque Foundation for Science48009 BilbaoSpain

The increased demand of electronic devices promotes the development of advanced and more efficient energy storage devices, such as batteries. Lithium-ion batteries (LIBs) are the most studied battery systems due to their high performance. Among the different battery components, the separator allows the control of lithium ion diffusion between the electrodes. To overcome some drawbacks of liquid electrolytes, including safety and environmental issues, solid polymer electrolytes (SPEs) are being developed. In this work, a UV photocurable polyurethane acrylate (PUA) resin has been blended with lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) up to 30 wt% LiTFSI content to reach a maximum ionic conductivity of 0.0032 mS/cm at room temperature and 0.09 mS/cm at 100 ℃. Those values allowed applying the developed materials as photocurable SPE in Swagelok type Li/c-LiFePO_(4) half-cells, reaching a battery discharge capacity value of 139 mAh.g^(−1) at c/30 rate. Those results, together with the theoretical studies of the discharge capacity at different c-rates and temperatures for batteries with LiTFSI/PUA SPE demonstrate the suitability of the developed photocurable SPE for LIB applications.

关键词： Solid polymer electrolytes Photocuring Polyurethane acrylate LiTFSI Li-ion batteries

高效液相色谱法测定小叶黑柴胡中槲皮素与异鼠李素的含量

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中国药房 2007年第9期18卷 693-695页

作者：周伟蔡光明黄鹤慧何桂霞刘鄂湖朱海升熊含晖解放军302医院全军中药研究所北京市100039 湖南中医药大学药学院长沙市410007

目的:建立以高效液相色谱法测定小叶黑柴胡茎叶中槲皮素、异鼠李素含量的方法。方法:色谱柱为Kromasilc18(250mm×4.6mm,5μm),流动相为甲醇-0.4%磷酸溶液(55∶45),流速为1.0mL.min-1,检测波长为256nm。结果:槲皮素的线性范围为0.08～0... 详细信息

目的:建立以高效液相色谱法测定小叶黑柴胡茎叶中槲皮素、异鼠李素含量的方法。方法:色谱柱为Kromasilc18(250mm×4.6mm,5μm),流动相为甲醇-0.4%磷酸溶液(55∶45),流速为1.0mL.min-1,检测波长为256nm。结果:槲皮素的线性范围为0.08～0.40μg(r=0.9996),平均回收率为101.02%(RSD=1.53%);异鼠李素的线性范围为0.06～0.30μg(r=0.9992),平均回收率为101.26%(RSD=2.95%)。结论:本法操作简便、准确、重现性好,可用于小叶黑柴胡药材的质量控制。

关键词：高效液相色谱法小叶黑柴胡槲皮素异鼠李素含量测定

Simple statistical models for relating river discharge with precipitation and air temperature——case study of River Vouga （Portugal）

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Frontiers of Earth Science 2017年第2期11卷 203-213页

作者： T. STOIcHEV J. ESPINHA MARQUES c.M. ALMEIDA A. DE DIEGO M.c.P. BASTO R. MOURA V.M. VAScONcELOS Interdiscplinary center of Marine and Environmental Research (cI1MAR/cIMAR) University of Porto 4450-208 Matosinhos Portugal Institute of Earth Sciences (IcT) and Department of Geosciences Environment and Land Planning Faculty of Sciences University of Porto 4169-007 Porto Portugal Department of Analytical chemistry Faculty of Science and Technology University of the Basque Country UPV/EHU 48080 Bilbao Basque Country Spain cIIMAR/cIMAR and Faculty of Sciences University of Porto 4169-007 Porto Portugal

Simple statistical models were developed to relate available meteorological data with daily river discharge （RD） for rivers not influenced by melting of ice and snow. In a case study of the Vouga River （Portugal）, the RD could be determined by a linear combination of the recent （PR） and non-recent （PNR） atmospheric precipitation history. It was found that a simple linear model including only PR and PnR cannot account for low RD. The model was improved by including non-linear terms of precipitation that accounted for the water loss. Additional improvement of the models was possible by including average monthly air temperature （7）. The best model was robust when up to 60% of the original data were randomly removed. The advantage is the simplicity of the models, which take into account only PR, PNR and T. These models can provide a useful tool for RD estimation from current meteorological data.

关键词： multiple regression atmospheric precipitation river discharge runoff Aveiro Lagoon

高效液相色谱法测定青海小叶黑柴胡茎叶中芦丁的含量

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解放军药学学报 2006年第6期22卷 439-440页

作者：黄鹤慧蔡光明金光洙刘鄂湖周伟熊晗晖中国人民解放军第302医院中药研究所北京100039 延边大学医学院吉林延吉133000 不详

目的采用高效液相色谱测定青海小叶黑柴胡茎叶提取物中芦丁的含量。方法色谱柱为Kromasil c18柱（250mm×4．6mm．5μm），以乙腈-水（18：82）为流动相，流速1．0ml／min，检测波长260nm。结果芦丁的线性范围0.200～2.00μg，r=0．999... 详细信息

目的采用高效液相色谱测定青海小叶黑柴胡茎叶提取物中芦丁的含量。方法色谱柱为Kromasil c18柱（250mm×4．6mm．5μm），以乙腈-水（18：82）为流动相，流速1．0ml／min，检测波长260nm。结果芦丁的线性范围0.200～2.00μg，r=0．9999，平均回收率99．69％，RSD为2．06％。结论该方法简便、快速、准确，适用于小叶黑柴胡茎叶的含量测定。

关键词：芦丁小叶黑柴胡 HPLc

Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation

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World Journal of Gastroenterology 2020年第34期26卷 5101-5117页

作者： David Fernández-Ramos Fernando Lopitz-Otsoa Laura Delacruz-Villar Jon Bilbao Martina Pagano Laura Mosca Maider Bizkarguenaga Marina Serrano-Macia Mikel Azkargorta Marta Iruarrizaga-Lejarreta Jesús Sot Darya Tsvirkun Sebastiaan Martijn van Liempd Felix M Goni cristina Alonso María Luz Martínez-chantar Felix Elortza Liat Hayardeny Shelly c Lu JoséM Mato Precision Medicine and Metabolism Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160BizkaiaSpain cIBERehd-centro de Investigación Biomédica en Red de enfermedades hepáticas y digestivas Madrid 28029Spain Department of Precision Medicine University of Campania"Luigi Vanvitelli"Naples 80138Italy Liver Disease Laboratory Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Proteomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain OWL Metabolomics Derio 48160Spain Instituto Biofisika(UPV/ehu CSIC)Leioa 48940SpainDepartamento de Bioquímica y Biología MolecularUniversidad del País VascoLeioa 48940Spain Pre-clinical and chemistry Manufacturing and ControlsGalmed PharmaceuticalsTel Aviv 6578317Israel Metabolomics Platform Centro de Investigación Cooperativa en Biociencias(CIC bioGUNE)Derio 48160Spain Division of Digestive and Liver Diseases Cedars-Sinai Medical CenterLos AngelesCA 90048United States

BAcKGROUND Arachidyl amido cholanoic acid(Aramchol)is a potent downregulator of hepatic stearoyl-coA desaturase 1(ScD1)protein expression that reduces liver triglycerides and fibrosis in animal models of steatohepatitis.In a phase IIb clinical trial in patients with nonalcoholic steatohepatitis(NASH),52 wk of treatment with Aramchol reduced blood levels of glycated hemoglobin A1c,an indicator of glycemic control.AIM To assess lipid and glucose metabolism in mouse hepatocytes and in a NASH mouse model[induced with a 0.1%methionine and choline deficient diet(0.1McD)]after treatment with Aramchol.METHODS Isolated primary mouse hepatocytes were incubated with 20μmol/L Aramchol or vehicle for 48 h.Subsequently,analyses were performed including Western blot,proteomics by mass spectrometry,and fluxomic analysis with 13c-uniformly labeled glucose.For the in vivo part of the study,male c57BL/6J mice were randomly fed a control or 0.1McD for 4 wk and received 1 or 5 mg/kg/d Aramchol or vehicle by intragastric gavage for the last 2 wk.Liver metabolomics were assessed using ultra-high-performance liquid chromatography-time of flight-MS for the determination of glucose metabolism-related metabolites.RESULTS combination of proteomics and Western blot analyses showed increased AMPK activity while the activity of nutrient sensor mTORc1 was decreased by Aramchol in hepatocytes.This translated into changes in the content of their downstream targets including proteins involved in fatty acid(FA)synthesis and oxidation[PAccα/β(S79),ScD1,cPT1A/B,HADHA,and HADHB],oxidative phosphorylation(NDUFA9,NDUFB11,NDUFS1,NDUFV1,ETFDH,and UQcRc2),tricarboxylic acid(TcA)cycle(MDH2,SUcLA2,and SUcLG2),and ribosome(P-p70S6K[T389]and P-S6[S235/S236]).Flux experiments with 13cuniformely labeled glucose showed that TcA cycle cataplerosis was reduced by Aramchol in hepatocytes,as indicated by the increase in the number of rounds that malate remained in the TcA cycle.Finally,liver metabolomic analysis showed that glucose homeostasis was improved by Aramcho

关键词： Nonalcoholic fatty liver disease Steatohepatitis Methionine and choline deficient diet Tricarboxylic acid cycle Hemoglobin A1c Stearoyl-coA desaturase 1

Parkin and <i>LRRK2</i>/Dardarin Mutations in Early Onset Parkinson’s Disease in the Basque country (Spain)

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Journal of Behavioral and Brain Science 2015年第3期5卷 101-108页

作者： J. F. Martí Massó J. Ruiz-Martínez c. Paisán-Ruiz A. Gorostidi A. Bergareche A. Lopez de Munain A. Alzualde J. Pérez-Tur Servicio Neurologia Hospital Donostia San Sebastián Spain center for Biomedical Research in Neurodegenerative Diseases Network (cIBERNED) Spain Neurosciences Area Biodonostia Institute San Sebastián Spain Department of Neuroscience University of Basque Country UPV-EHU San Sebastián Spain Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai New York USA Molecular Genetics Unit Instituto de Biomedicina de Valencia-CSIC Valencia Spain

We have performed a complete screening of the Parkin gene (PRKN2) and looked for p.Gly2019Ser (G2019S) and p.Arg1441Gly (R1441G) LRRK2/dardarin gene mutations in twenty seven patients with Parkinson’s disease (PD) with an age at onset younger than 50 years (EOPD), living in Gipuzkoa (Basque country, Spain). Thirteen of them (48%) were PRKN2 mutation carriers. The c.255-256DelA mutation was the most frequent, followed by a deletion involving exons 3 and 4. A deletion involving exons 3 and 12 of the PRKN2 gene and R1441G LRRK2 mutation was found together in one PD patient. Four out of fourteen PRKN2 negative patients carried the p.G2019S mutation. Both PRKN2 mutation carriers and non-carriers presented frequently with family history (10 PRKN2 mutation carriers and 8 PRKN2 non-carriers);in fact, five patients without a known gene mutation had a first degree relative affected, suggesting another monogenic disease. PRKN2 carriers presented with a younger age at onset (36.7 vs. 41.7) and more benign disease progression. Indeed, those PD patients younger than forty who initially presented with unilateral tremor became shortly bilateral. Relatively, symmetric parkinsonism and slow disease progression carried more frequently PRKN2 mutations than patients with unilateral akinetic rigid parkinsonism and age at onset later than 40 years. As expected in a recessive disease, PRKN2 patients present more often with affected siblings and unaffected patients. The G2019S LRRK2 mutation, less prevalent than R1441G in our area, may be also a frequent cause of PD in EOPD (4 patients).

关键词： Parkin Early Onset Parkinsonism Parkinson’s Disease LRRK2 Dardarin

Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

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Acta Pharmaceutica Sinica B 2019年第2期9卷 443-454页

作者： Bing cui Patrick A. Eyers Leonard L. Dobens Nguan Soon Tan Peter D. Mace Wolfgang A. Link Endre Kiss-Toth Karen Keeshan Takuro Nakamura Warren S. Pear Yodit Feseha Jessica Johnston Arkatiz carracedo Marcel Scheideler Zabran llyas Robert c. Bauer Jorge D. Erusalimsky Dominika Grzesik Juan Salamanca-Viloria Xiaoxi Lv Yishi Jin Ke Li Guillermo Velasco Shuang Shang Jose M. Lizcano Xiaowei Zhang Jichao Zhou Jiaojiao Yu Fang Hua Feng Wang Shanshan Liu Jinmei Yu Zhuowei Hu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Department of Biochemistry Institute of Integrative Biology University of Liverpool Division of Molecular Biology and Biochemistry School of Biological Sciences University of Missouri-Kansas City School of Biological Sciences Nanyang Technological University Lee Kong chian School of Medicine Nanyang Technological University Institute of Molecular and cell Biology KK Women's and children Hospital Biochemistry Department School of Biomedical Sciences University of Otago centre for Biomedical Research (cBMR) University of Algarve Campus de Gambelas Department of Biomedical Sciences and Medicine University of Algarve Algarve Biomedical center (ABc) University of Algarve Campus de Gambelas Department of Infection Immunity and Cardiovascular Disease University of Sheffield Paul O'Gorman Leukaemia Research centre Institute of Cancer Sciences University of Glasgow Division of carcinogenesis The Cancer Institute Japanese Foundation for Cancer Research Department of Pathology and Laboratory Medicine Abramson Family Cancer Research Institute Perelman School of Medicine at the University of Pennsylvania centre de Recherche en Transplantation et Immunologie (ou cRTI) Inserm Université de Nantes Nantes France Institut de Transplantation Urologie Néphrologie (ou ITUN) cIc bioGUNE cIBERONc Ikerbasque Basque Foundation for Science Biochemistry and Molecular Biology Department University of the Basque Country (UPV/EHU) Institute for Diabetes and cancer IDc Helmholtz Center Munich Joint Heidelberg-IDc Translational Diabetes Program University Hospital Heidelberg Molecular Metabolic control Medical Faculty Technical University Munich German center for Diabetes Research (DZD) Division of cardiology Department of Medicine Columbia University Irving Medical Center School of Sport and Health Sciences Cardiff Metropolitan Universit

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, china, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

关键词： Tribbles Immunology Metabolism cell biology Kinase inhibitor Tumorigenesis Metastasis TRIB1 TRIB2 TRIB3 Pseudokinase Inflammation Atomic structure Protein quality control Ubiqutin

Reflecting laser-driven shocks in diamond in the megabar pressure range

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High Power Laser Science and Engineering 2021年第1期9卷 29-41页

作者： K.Jakubowska D.Mancelli R.Benocci J.Trela I.Errea A.S.Martynenko P.Neumayer O.Rosmej B.Borm A.Molineri c.Verona D.cannatà A.Aliverdiev H.E.Roman D.Batani IPPLM Institute of Plasma Physics and Laser Microfusion WarsawPoland cNRS CEACELIAUniversite de BordeauxTalenceFrance Donostia International Physics center(DIPc) Donostia-San SebastianBasque CountrySpain Department of Earth and Environmental Sciences University of Milano-BicoccaMilanoItaly Fisika Aplikatua 1 Saila Ingeniaritza EskolaUniversity of the Basque Country(UPV/EHU)Basque CountrySpain&Centro de Física de Materiales(CSIC-UPV/EHU)Donostia/San SebastianBasque CountrySpain Department of Plasma Physics National Research Nuclear University MEPh IMoscowRussia Joint Institute for High Temperature RAS MoscowRussia GSI Helmholtzzentrum für Schwerionenforschung GmbH DarmstadtGermany Dipartimento di Ingegneria Industriale Universitàdegli studi di Roma“Tor Vergata”RomaItaly Institute for Microelectronics and Microsystems-cNR RomaItaly IGRRE-Joint Institute for High Temperatures RAS MakhachkalaRussia Department of Physics“G.Occhialini” University of Milano-BicoccaMilanoItaly

In this work we present experimental results on the behavior of diamond at megabar pressure. The experiment was performed using the PHELIX facility at GSI in Germany to launch a planar shock into solid multi-layered diamond samples. The target design allows shock velocity in diamond and in two metal layers to be measured as well as the free surface velocity after shock breakout. As diagnostics, we used two velocity interferometry systems for any reflector(VISARs). Our measurements show that for the pressures obtained in diamond(between 3 and 9 Mbar),the propagation of the shock induces a reflecting state of the material. Finally, the experimental results are compared with hydrodynamical simulations in which we used different equations of state, showing compatibility with dedicated SESAME tables for diamond.

关键词： carbon dynamic compression equation of state shock wave VISAR