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Immunological mechanisms and therapeutic targets of fatty liver diseases

Cellular & Molecular Immunology 2021年第1期18卷 73-91页

作者： Hua Wang Wajahat Mehal laura E.Nagy Yaron Rotman Department of Oncology the First Affiliated Hospital of Anhui Medical UniversityHefeiAnhuiChina InfIammation and Immune Mediated Diseases Laboratory of Anhui Province HefeiAnhuiChina West Haven VA Medical Center West Haven CT and Yale University School of MedicineNew HavenCTUSA Department of Inflammation and Immunity Cleveland ClinicClevelandOHUSA Department of Gastroenterology and Hepatology Center for Liver Disease ResearchCleveland ClinicClevelandOHUSA Department of Molecular Medicine Case Western Reserve UniversityClevelandOHUSA Liver and Energy Metabolism Section Liver Diseases BranchNational Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA

Alcoholic liver disease(ALD)and nonalcoholic fatty liver disease(NAFLD)are the two major types of chronic liver disease *** processes play key roles in the pathogeneses of fatty liver diseases,and continuous inflammation promotes the progression of alcoholic steatohepatitis(ASH)and nonalcoholic steatohepatitis(NASH).Although both ALD and NAFLD are closely related to inflammation,their respective developmental mechanisms differ to some ***,we review the roles of multiple immunological mechanisms and therapeutic targets related to the inflammation associated with fatty liver diseases and the differences in the progression of ASH and *** cell types in the liver,including macrophages,neutrophils,other immune cell types and hepatocytes,are involved in fatty liver disease *** addition,microRNAs(miRNAs),extracellular vesicles(EVs),and complement also contribute to the inflammatory process,as does intertissue crosstalk between the liver and the intestine,adipose tissue,and the nervous *** point out that inflammation also plays important roles in promoting liver repair and controlling bacterial *** the complex regulatory process of disrupted homeostasis during the development of fatty liver diseases may lead to the development of improved targeted therapeutic intervention strategies.

关键词： ALD NAFLD inflammation cytokine target immune

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Dieback of managed spruce stands in western Germany promotes beetle diversity

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Journal of Forestry Research 2024年第3期35卷 55-71页

作者： Eva Plath Chantal Trauth Jan Gerhards laura Griebel Klaus Fischer Department Biology Institute of Integrated Natural SciencesKoblenz-Landau University56070 KoblenzGermany

Biodiversity loss is a significant problem at a global scale and may be amplified by climate *** recent years,coniferous forests have had substantial die-back across Europe due to drought and subsequent bark-beetle *** many studies on the consequences of disturbance and subsequent management have focused on natural stands,management implications for managed spruce stands are not well understood,even though such stands are widespread throughout *** this study,beetle taxonomy,conservation value,and community com-position are compared among spruce plantations and four post-disturbance management approaches:standing dead-wood,lying deadwood,clear cuts,and long-term *** and community composition differed significantly among management categories,while different beetle fami-lies responded *** spruce stands harbored the lowest beetle diversity while the highest taxonomic diver-sity and conservation value was on clear cuts and stands with lying or standing *** proportion of forest specialists was highest in successional *** summary,different forest management categories harbored distinct beetle communities at the family-,species-,and ecological guild ***,post-disturbance management should consider the landscape scale and include different management *** enhances landscape heterogeneity and thus overall biodiversity but could also mitigate negative impacts of natural disturbances on ecosystem services.

关键词： Bark-beetle outbreak Forest dieback Spruce Deadwood Nature conservation Beetle biodiversity-Coleoptera Coniferous forests

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Virtual drug design： Skpl-Skp2 inhibition targets cancer stem cells

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Asian Journal of Andrology 2013年第6期15卷 717-718页

作者： laura E Pascal Zhou Wang Department of Urology University of Pittsburgh School of Medicine Pittsburgh PA 15232 USA University of Pittsburgh Cancer Institute University of Pittsburgh School of Medicine Pittsburgh PA 15232 USA Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine Pittsburgh PA 15232 USA

The dysregulation of pathways regulat-ing cellular function is a frequent hall-mark of cancer and the development of specific pathway inhibitors that alter tumor growth and progression are the focus of multiple recent studies. E3 ubiquitin ligases are a large group of diverse protein enzymes that specifically target proteins for dear- ance, and their importance to normal cel-lular function is illustrated in the many diseases associated with their loss of func- tion or inappropriate targeting. S-phase kinase-associated protein 2 （Skp2） is an F box protein that plays critical roles in cell-cycle progression, senescence, metabolism, and acts as an Skpl-Cullin-l-F box （SCF） ubiquitin ligase substrate recognition fac-tor. Overexpression of Skp2 is associated with poor prognosis and metastasis in many cancers and is a well validated drug target. In a recent report, Chart et al. have iden-tified an Skp2 inhibitor that selectively impairs Skp2 E3 ligase activity using an integrated virtual high-throughput drug screening and experimental validation approach. This Skp2 inhibitor restricts cancer stemness and potentiates sensitivity to chemotherapeutic agents in multiple ani-mal tumor models. These findings identify a new novel small molecule that targets the Skp2 and reduces tumor growth by attenu-ating aerobic glycolysis and inducing cel-lular senescence.

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Phenotyping Key Fruit Quality Traits in Olive Using RGB Images and Back Propagation Neural Networks

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Plant Phenomics 2023年第3期5卷 484-500页

作者： Giuseppe Montanaro Angelo Petrozza laura Rustioni Francesco Cellini Vitale Nuzzo Università degli Studi della Basilicata 85100 PotenzaItaly ALSIA Agenzia Lucana Sviluppo Innovazione in AgricolturaMetapontum Agrobios Research Center75010 MetapontoItaly Department of Biological and Environmental Sciences and Technologies University of SalentoLecceItaly

To predict oil and phenol concentrations in olive fruit,the combination of back propagation neural networks(BPNNs)and contact-less plant phenotyping techniques was employed to retrieve RGB image-based digital proxies of oil and phenol *** of cultivars(×3)differing in ripening time were sampled(~10-day interval,×2 years),pictured and analyzed for phenol and oil *** to this,fruit samples were pictured and images were segmented to extract the red(R),green(G),and blue(B)mean pixel values that were rearranged in 35 RGB-based colorimetric *** BPNNs were designed using as input variables(a)the original 35 RGB indexes,(b)the scores of principal components after a principal component analysis(PCA)pre-processing of those indexes,and(c)a reduced number(28)of the RGB indexes achieved after a sparse *** results show that the predictions reached the highest mean R^(2) values ranging from 0.87 to 0.95(oil)and from 0.81 to 0.90(phenols)across the *** addition to the R^(2),other performance metrics were calculated(root mean squared error and mean absolute error)and combined into a general performance indicator(GPI).The resulting rank of the GPI suggests that a BPNN with a specific topology might be designed for cultivars grouped according to their ripening *** present study documented that an RGB-based image phenotyping can effectively predict key quality traits in olive fruit supporting the developing olive sector within a digital agriculture domain.

关键词： Image image supporting

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Do different measures of maternal fitness affect estimation of natural selection on floral traits? A lesson from Linum pubescens (Linaceae)

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Journal of Plant Ecology 2017年第2期10卷 406-413页

作者： laura Bigio Merav Lebel Yuval Sapir The Botanical Garden Department of Molecular Biology and Ecology of PlantsTel Aviv UniversityRamat AvivTel Aviv 69978Israel Earth Science Institute The Hebrew University of JerusalemGivat RamJerusalem 91904Israel Nature-Parks Authority Science DivisionAm-Veolamo 2Jerusalem 95463Israel

Aims Floral traits in animal-pollinated plants are proposed to be selected by the behavior of pollinators,which create differential ***,fitness estimation is not trivial and there is no agreed or universal measure of *** plants,fitness can be measured in various ways,including the number of fruits or seeds,probability of survival,or growth *** Because each fitness measure can be associated with different pol-linator behavior,estimating pollinator-mediated selection on floral traits can differ among various fitness *** used the annual Mediterranean plant,Linum pubescens,as a model to assess the relative role of various fitness measures in estimating pollinator-mediated selection on floral *** compared four maternal fit-ness measures and estimated their relative advantage in assessing natural selection on floral traits of *** identify whether each trait is under pollinator-mediated selection,we used media-tional *** Findings We found that each floral trait was under natural selection assessed by a different fitness *** color combination of floral tube throat and stamen color was under selection when using seed mass as a fitness measure,and floral diameter was under positive direc-tional selection when the number of seeds or number of fruits was used as a fitness *** on floral color was not mediated by pollinators’visitation rates,while flower diameter showed par-tial pollinator-mediated *** conclude that using several fitness measures gives an insight into the mechanisms underlying phenotypic selection on a floral trait,and facilitates the understand-ing of pollinator-mediated selection.

关键词： fitness flower size fruit-set Linum pubescens natural selection pollinator-mediated selection pollinator visitation rate seed-set seed mass

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Two paths for stabilization of ERG in prostate carcinogenesis： TMPRSS2-ERG fusions and speckle-type pox virus and zinc finger protein mutations

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Asian Journal of Andrology 2016年第4期18卷 594-595页

作者： laura E Pascal Zhou Wang Department of Urology University of Pittsburgh Cancer Institute Department of Pharmacology and Chemical Biology Department of Pathology University of Pittsburgh School of Medicine Pittsburgh PA 15232 USA.

Speckle-type POZ （pox virus and zinc finger protein） protein （SPOP） is anE3 ubiquitin ligase adaptor protein that specifically promotes the ubiquitination and proteasome degradation of proteins. SPOP mutations are frequent in prostate cancer, and in a previous study, An et al. demonstrated that SPOP induced the degradation of the androgen receptor （AR） suggesting that SPOP is important in maintaining prostate homeostasis. In this current highlighted report, An and colleagues showed that ERG, which has been implicated as an oncoprotein in prostate cancer.

关键词： @@

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Comparative Analysis of Reaction to Fire and Flammability of Hemp Shives Insulation Boards with Incorporated Microencapsulated Phase Change Materials

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Journal of Renewable Materials 2024年第3期12卷 603-613页

作者： Inga Zotova Edgars Kirilovs laura Ziemele Institute of Architecture and Design Riga Technical UniversityRigaLV-1048Latvia Forest and Wood Products Research and Development Institute JelgavaLV-3001Latvia

Nowadays buildings contain innovative materials,materials from local resources,production surpluses and rapidly renewable natural *** Change Materials(PCM)are one such group of novel materials which reduce building energy *** the wider availability of microencapsulated PCM,there is an opportunity to develop a new type of insulating materials,combinate PCM with traditional insulation materials for latent heat energy *** materials are typically flammable and are located on the interior wall finishing yet there has been no detailed assessment of their fire *** this research work prototypes of low-density insulating boards for indoor spaces from hemp shives using carbamide resin binder and cold pressing were ***-scale cone calorimeter tests were conducted to evaluate fire risk,with a focus on assessing material flammability properties and the influence of PCM on the *** this research,the amount of smoke,heat release rate,effective heat of combustion,specific extinction coefficient,mass loss,carbon dioxide yield,specific loss factor,ignition time of hemp straws samples and samples of hemp straws with 10%and without PCM admixture were *** is a risk of flammability for PCM and their fire reaction has not been evaluated when incorporating PCM into interior wall finishing *** obtained results can be used by designers to balance the potential energy savings of using PCM with a more complete understanding and predictability of the associated fire risk when using the proposed *** also allows for appropriate risk mitigation strategies.

关键词： Encapsuled phase change material renewable resources reaction to fire flammability

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Ethylene-Propene Copolymerization with C1-symmetric ansa-Fluorenyl-zirconocene Catalysts: Effects of Catalyst Structure and Comonomer on Molar Mass

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Chinese Journal of Polymer Science 2020年第3期38卷 220-230,I0005页

作者： Simona Losio laura Boggioni Massimiliano Cornelio Abbas Razavi Incoronata Tritto CNR–Istituto di Scienze e Tecnologie Chimiche"G.Natta"(CNR-SCITEC) via Alfonso Corti 12-20133 MilanoItaly Total Petrochemicals Research Zone Industrielle CB-7181 FeluyBelgium

Ethylene-propene copolymers have been synthesized by three C1-symmetric metallocene molecules(1,2,and 3),having tert-butyl substituents on the Cp moiety,on the fluorenyl moiety,or on both moieties,and methylaluminoxane(MAO)at different polymerization temperatures and monomer *** were investigated by 13 C-NMR,1 H-NMR,and SEC analyses.A relationship was found between[EEE]/[E]ratios and copolymer molar masses in each series:the higher the[EEE]/[E]ratio,the lower the copolymer molar *** parity of[EEE]/[E]ratio,copolymer molar mass follows the order 1>>3>*** end group analysis reveals that copolymers mainly terminate when propene is the last inserted unit,confirming that it is the greater facility of Mt-P-E-poly(E-co-P)to terminate that influences the copolymer molar *** the catalysts considered,catalyst 1,which gives syndiospecific polypropene,gives greater activities,comonomer incorporation,and molar *** 3,which gives isospecific polypropene,in copolymerization performs better than 2,having the same bridge,with respect to activities,ethylene content,and molar *** good performance of this catalyst arises from the not necessity of polymer chain to back skip when ethylene is the last inserted unit.

关键词： Ethylene-propene Metallocene catalysts Copolymers Microstructure Molar masses

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Extracellular vesicles in liver disease and beyond

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World Journal of Gastroenterology 2018年第40期24卷 4519-4526页

作者： laura Morán Francisco Javier Cubero Department of Immunology Ophthalmology and ORLComplutense University School of MedicineMadrid 28040Spain 12 de Octubre Health Research Institute(imas12) Madrid 28041Spain

Extracellular vesicles(EVs) are membrane-derived vesicles which can be released by different cell types, including hepatocytes, hepatic stellate cells and immune cells in normal and pathological conditions. EVs carry lipids, proteins, coding and non-coding RNAs and mitochondrial DNA causing modifications on the recipient cells. These vesicles are considered potential biomarkers and therapeutic agents for human diagnostic and prognostic due to their function as intercellular mediators of cell-cell communication within the liver and between other organs. However, the development and optimization of methods for EVs isolation is required to characterize their biological functions as well as their potential as a treatment option in the clinic. Nevertheless, many questions remain unanswered related to the function of EVs under physiological and pathological conditions. In the current editorial, the results obtained in different studies that investigated the role of intrahepatic EVs during liver diseases, including drug-induced liver injury, non-alcoholic fatty liver, nonalcoholic steatohepatitis, alcoholic liver disease and hepatocellular carcinoma and extrahepatic EVs in remote organs during pathological events such as pulmonary disease, cardiovascular diseases, neurodegenerative disorders e.g., Alzheimer's disease, Parkinson's disease and multiple sclerosis as well as in immunopathological processes, are discussed. Although much light needs to be shed on the mechanisms of EVs, these membranederived vesicles represent both a novel promising diagnostic, and a therapeutic tool for clinical use that we emphasize in the current editorial.

关键词： Extracellular vesicles microRNA Hepatocytes Drug-induced liver injury Alcoholic liver disease Nonalcoholic fatty liver disease Non-alcoholic steatohepatitis Hepatocellular carcinoma

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Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

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Horticulture Research 2016年第1期3卷 198-207页

作者： laura Dougherty Yuandi Zhu Kenong Xu Horticulture Section School of Integrative Plant ScienceCornell UniversityNew York State Agricultural Experiment StationGenevaNY 14456USA Department of Pomology China Agricultural UniversityBeijing 100193China

Phytohormone ethylene largely determines apple fruit shelf life and *** studies demonstrated that MdACS1 and MdACS3a,which encode 1-aminocyclopropane-1-carboxylic acid synthases(ACS),are crucial in apple fruit ethylene ***1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening,while MdACS3a has been regarded a main regulator for ethylene production transition from system 1(during fruit development)to system 2(during fruit ripening).However,MdACS3a was also shown to have limited roles in initiating the ripening process *** better assess their roles,fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled *** was accomplished using an existing marker(ACS1)for MdACS1 and two markers(CAPS866 and CAPS870)developed here to specifically detect the two null alleles(ACS3a-G289V and Mdacs3a)of *** total,952 Malus accessions were allelotyped with the three *** major findings included:The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable;allele MdACS1–2 was significantly associated with low ethylene and slow softening;under the same background of the MdACS1 allelotypes,null allele Mdacs3a(not ACS3a-G289V)could confer a significant delay of ethylene peak;alleles MdACS1–2 and Mdacs3a(excluding ACS3a-G289V)were highly enriched in *** and *** when compared with those in *** findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a.

关键词： effect softening finding

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