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Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma

World Journal of Gastroenterology 2022年第29期28卷 3917-3933页

作者： Juliane Malik Martin Klammer Vinzent Rolny Henry Lik-Yuen Chan Teerha Piratvisuth Tawesak Tanwandee Satawat Thongsawat Wattana Sukeepaisarnjaroen Juan Ignacio Esteban marta bes Bruno Kohler Magdalena Swiatek-de Lange Diagnostics GmbH Penzberg 82377Germany Faculty of Medicine The Chinese University of Hong KongHong Kong 999077China NKC Institute of Gastroenterology and Hepatology Songklanagarind HospitalHat Yai 90112Thailand Division of Gastroenterology Faculty of MedicineSiriraj HospitalMahidol UniversityBangkok 10700Thailand Department of Internal Medicine Maharaj Nakorn Chiang Mai HospitalChiang Mai UniversityChiang Mai 50200Thailand Faculty of Medicine Srinagarind HospitalKhon Kaen UniversityKhon Kaen 40000Thailand Liver Unit Vall d’Hebron University HospitalBarcelona 08035Spain Transfusion Safety Laboratory Banc de Sang i TeixitsBarcelona 08005Spain Department of Medical Oncology National Center for Tumor DiseasesUniversity Hospital HeidelbergHeidelberg 69120Germany Liver Cancer Center Heidelberg University Hospital HeidelbergHeidelberg 69120Germany

BACKGROUND Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein(AFP), protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs(miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including *** To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein *** Our prospective, multicenter, case-control study recruited 660 participants(354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR(n = 60) and next-generation sequencing(n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs(including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-Ⅱ via real-time quantitative PCR in training(n = 200) and validation cohorts(n = 300).RESULTS We identified 26 miRNAs that differentiated chronic liver disease controls from(early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p(miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423could significantly distinguish(Q < 0.05) between the HCC and chronic liver disease control grou

关键词： Carcinoma Hepatocellular MicroRNAs Biomarkers Alpha-fetoprotein Protein induced by vitamin K absence-Ⅱ Diagnosis

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ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1068-1076页

作者： Luisa Roade Mar Riveiro-Barciela Adriana Palom Francisco Rodríguez-Frías marta bes Ariadna Rando María Teresa Salcedo Rosario Casillas Elena Vargas-Accarino David Tabernero Silvia Sauleda Rafael Esteban María Buti Liver Unit Internal Medicine DepartmentHospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Universitat Autònoma de Barcelona(UAB) Department of MedicineBarcelonaSpain Universitat Au-tònoma de Barcelona(UAB) Department of Biochemistry and Molecular BiologyBarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadridSpain Liver Pathology Lab Biochemistry and Microbiology Departments(Clinical Laboratories)Hospital Universitari Vall d’HebronVall d’Hebron Barcelona Hospital CampusBarcelonaSpain Vall d’Hebron Institut de Recerca(VHIR) Liver Diseases GroupBarcelonaSpain Transfusion Safety Laboratory Banc de Sang i TeixitsServei Catalàde la SalutBarcelonaSpain De-partment of Pathology Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelonaSpain

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their *** aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their ***-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative ***,analytical,and virological data were collected,and a liver biopsy was performed if *** were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap ***:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray ***-nine(25.9%)individuals re-quired a liver *** HBV DNA hazard ratio(HR)6.0,p<0.001),HBV core-related antigen(HBcrAg)(HR 6.5,p<0.001),and elastography(HR 4.6,p<0.001)were inde-pendently associated with the IC *** ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUROC)of 0.925(95%CI:0.880-0.970,p<0.001)for identification of *** AUROC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/*** ACE score of<1 had a positive predictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.

关键词： Hepatitis B virus Inactive carrier Liver stiffness HBV DNA Quan-titative HBsAg Core-related antigen.

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Superplasticity of a friction stir processed overaged WE54 magnesium alloy

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Journal of Magnesium and Alloys 2022年第11期10卷 3156-3166页

作者： Oscar A.Ruano marta Alvarez-Leal Alberto Orozco-Caballero Fernando Carreño Physical Metallurgy Department CENIM-CSICAv.Gregorio del Amo 828040 MadridSpain Department of R&D and programmes Technology Centre of Metal-Mechanical and Transport(CETEMET).Avda.1°de Mayos/n.LinaresJaén2370Spain Department of Mechanical Engineering Chemistry and Industrial DesignPolytechnic University of MadridRonda de Valencia 328012MadridSpain

The coarse-grained WE54 magnesium alloy was heat treated in order to have minimum hardness minimizing the effects of precipitates and solid solution. Friction stir processing(FSP) was applied in severe conditions to obtain fine, equiaxed and highly misoriented grains, with grain sizes even less than 1 μm. The high severity of processing demonstrated to have a strong impact in the microstructure. Consequently,the processed materials exhibited excellent superplasticity at the high strain rate 10^(-2)s^(-1), and temperatures between 300 and 400 ℃. The maximum tensile superplastic elongation of 756% was achieved at 400 ℃ thanks to the operation of grain boundary sliding mechanism(GBS). besides the new data obtained through tensile testing, the paper deals with a transcendental question regarding the large differences in strain rate values at a given stress in the superplastic regime at maximum elongation compared to other magnesium-based alloys. With this is mind, 19 magnesium alloys from 22 different investigations were analyzed to give some light to this behavior that never was treated before. It is proposed that this behavior has to be attributed to the accommodation process, necessary for GBS to occur, which is hindered by reinforcing solutes.

关键词： WE54 magnesium alloy Friction stir processing Processing severity Superplasticity Grain boundary sliding Solutes

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Isotopic niche provides an insight into the ecology of a symbiont during its geographic expansion

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Current Zoology 2022年第2期68卷 185-197页

作者： Enrique GONZALEZ-ORTEGON marta PEREZ-MIGUEL Jose I.NAVAS Pilar DRAKE Jose A.CUESTA Instituto de Ciencias Marinas de Andalucia(ICMAN-CSIC) Campus Universitario Rio San PedroAvda.Republica Saharaui211519CadizPuerto RealSpain Unidad Asociada Crecimiento Azul CSIC-IFAPA El Puerto de Santa Maria SpainSpain Instituto de Investigacion y Formacion Agraria y Pesquera IFAPA-Centro Agua del PinoCtra.EI Rompido-Punta Umbriakm 3.821459 EI RompidoHuelvaSpain

The study of the recent colonization of a symbiont and its interaction with host communities in new locations is an opportunity to understand how they *** use of isotopic ratios in trophic ecology can provide measurements of a species'isotopic niche,as well as knowledge about how the isotopic niches between symbiont and host species *** isotope measurements were used to assess the sources of carbon assimilated by the host species(the bivalves Mytilus galloprovincialis and Scrobicularia plana)and their associated symbiont pea crab Afropinnotheres monodi,which occurs within these bivalves'mantle *** mixing model estimates suggest that all of them assimilate carbon from similar sources,particularly from pseudofaeces and particulate organic matter in this symbiotic system based on filter *** symbiotic species occupy comparable trophic levels and its association seems to be commensal or parasitic depending on the duration of such *** pea crab *** reflects a sex-specific diet,where males are more generalist than the soft females because the latter's habitat is restricted to the host *** high isotopic overlap between soft females and *** may reflect a good commensal relationship with the host.

关键词： bivalves commensal kleptoparasitism parasitism stable isotope trophic position

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Effects of dielectric stoichiometry on the photoluminescence properties of encapsulated WSe2 monolayers

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Nano Research 2018年第3期11卷 1399-1414页

作者： Javier Martfn-Sanchez Antonio Mariscal marta De Luca Aitana Tarazaga Martin-Luengo Georg Gramse Alma Halilovic Rosalia Serna Alberta Bonanni Ilaria Zardo Rinaldo Trotta Armando Rastelli Institute of Semiconductor and Solid State Physics Johannes Kepler University Linz Altenbergerstrasse 69 A-4040 Linz Austria Laser Processing Group Instituto de Optica CSIC C/Serrano 121 28006 Madrid Spain Department of Physics University of Basel Klingelbergstrasse 82 4056 Basel Switzerland Institute for Biophysics Johannes Kepler University Linz Gruberstrasse 40 A-4020 Linz Austria

Two-dimensional transition metal dichalcogenide semiconductors have emerged as promising candidates for optoelectronic devices with unprecedented properties and ultra-compact footprints. However, the high sensitivity of atomically thin materials to the surrounding dielectric media imposes severe limitations on their practical applicability. Hence, to enable the effective integration of these materials in devices, the development of reliable encapsulation procedures that preserve their physical properties is required. Here, the excitonic photoluminescence （at room temperature and 10 K） is assessed on mechanically exfoliated WSe2 monolayer flakes encapsulated with SiOx and AlxOy layers by means of chemical and physical deposition techniques. Conformal coating on untreated and non- functionalized flakes is successfully achieved by all the techniques examined, with the exception of atomic layer deposition, for which a cluster-like oxide coating is formed. No significant compositional or strain state changes in the flakes are detected upon encapsulation, independently of the technique adopted. Remarkably, our results show that the optical emission of the flakes is strongly influenced by the stoichiometry quality of the encapsulating oxide. When the encapsulation is carried out with slightly sub-stoichiometric oxides, two remarkable phenomena are observed. First, dominant trion （charged exciton） photoluminescence is detected at room temperature, revealing a clear electrical doping of the monolayers. Second, a strong decrease in the optical emission of the monolayers is observed, and attributed to non-radiative recombination processes and/or carrier transfer from the flake to the oxide. Power- and temperature-dependent photoluminescence measurements further confirm that stoichiometric oxides obtained by physical deposition lead to a successful encapsulation, opening a promising route for the development of integrated two-dimensional devices.

关键词： two dimensional (2D)materials dielectric encapsulation transition metaldichalcogenides semiconductors photoluminescence WSe2

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SUPPRESSOR OF VARIEGATION4, a New var2 Suppressor Locus, Encodes a Pioneer Protein that Is Required for Chloroplast Biogenesis

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Molecular Plant 2011年第2期4卷 229-240页

作者： Fei Yu ung-Soon Park Xiayan Liu Andrew Foudree Aigen Fu marta Powikrowska Anastassia Khrouchtchova Poul Erik Jensen Jillian N. Kriger Gordon RI Gray Steven R. Rodermel College of Life Sciences Northwest A&F University Yangling Shaanxi 712100 People's Republic of China Department of Plant and Microbial Biology University of California Berkeley Berkeley CA 94720 USA Department of Genetics Development and Cell Biology iowa State University 253 Bessey Hall Ames IA 50011 USA Department of Plant Biology and Biotechnology Faculty of Life Sciences University of Copenhagen Thorvaldsensvej 40 DK-1871 Frederiksberg C Denmark Department of Plant Sciences University of Saskatchewan Saskatoon Saskatchewan S7N 5A8 Canada

VAR2 is an integral thylakoid membrane protein and a member of the versatile FtsH class of metalloproteases in prokaryotes and eukaryotes. Recessive mutations in the VAR2 locus give rise to variegated plants （var2） that contain white sectors with abnormal plastids and green sectors with normal-appearing chloroplasts. In a continuing effort to isolate second-site suppressors of var2 variegation, we characterize in this report ems2505, a suppressor strain that has a virescent phenotype due to a missense mutation in At4g28590, the gene for a pioneer protein. We designated this gene SVR4 （for SUPPRESSOR OF VARIEGATION4） and the mutant allele in ems2505 as svr4-1. We demonstrate that SVR4 is located in chloroplasts and that svr4-1 single mutants are normal with respect to chloroplast anatomy and thylakoid membrane protein accumulation. However, they are modestly impaired in several aspects of photochemistry and have enhanced non-photochemical quenching （NPQ） capacity. A T-DNA insertion allele of SVR4, svr4-2, is seedling-lethal due to an early blockage of chloroplast development. We conclude that SVR4 is essential for chloroplast biogenesis, and hypothesize that SVR4 mediates some aspect of thylakoid structure or function that controls NPQ. We propose that in the suppressor strain, photoinhibitory pressure caused by a lack of VAR2 is ameliorated early in chloroplast development by enhanced NPQ capacity caused by reduced SVR4 activity. This would result in an increase in the number of chloroplasts that are able to surmount a threshold necessary to avoid photo-damage and thereby develop into functional chloroplasts.

关键词： Arabidopsis chloroplast biogenesis non-photochemical quenching (NPQ) photo-damage suppressor strain variegation

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Robust transcriptional indicators of immune cell death revealed by spatiotemporal transcriptome analyses

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Molecular Plant 2022年第6期15卷 1059-1075页

作者： Jose Salguero-Linares Irene Serrano Nerea Ruiz-Solani marta Salas-Gómez Ujjal Jyoti Phukan Victor Manuel González MartíBernardo-Faura Marc Valls David Rengel Nuria S.Coll Centre for Research in Agricultural Genomics(CRAG) CSIC-IRTA-UAB-UBCampus UABBellaterra08193 BarcelonaSpain LIPM Universitéde ToulouseINRACNRS84195 Castanet-TolosanFrance INRAE GeT-PlaGeGenotoul31326 Castanet-TolosanFrance Department of Genetics Universitat de Barcelona08028 BarcelonaSpain Consejo Superior de Investigaciones Científicas(CSIC) BarcelonaSpain Department of Plant Molecular Biology and Physiology.Albrechtvon Haller Institute for Plant Sciences niversity of GottingenJulia-Lermontowa-Weg3.37077 GottingenGrmany Institut de Phammacologie et de Biologie Structurale IPBS Universite deToulouse CNRSUPSBP 64182205 route de Nartxonne310077 Toulouse Cedex 04France

Recognition of a pathogen by the plant immune system often triggers a form of regulated cell death traditionally known as the hypersensitive response(HR).This type of cell death occurs precisely at the site of pathogen recognition,and it is restricted to a few *** research has shed light on how plant immune receptors are mechanistically ***,two central key questions remain largely unresolved:how does cell death zonation take place,and what are the mechanisms that underpin this phenomenon?Consequently,bona fide transcriptional indicators of HR are lacking,which prevents deeper insight into its mechanisms before cell death becomes macroscopic and precludes early or live *** this study,to identify the transcriptional indicators of HR we used the paradigmatic Arabidopsis thaliana–Pseudomonas syringae pathosystem and performed a spatiotemporally resolved gene expression analysis that compared infected cells that will undergo HR upon pathogen recognition with bystander cells that will stay alive and activate *** data revealed unique and time-dependent differences in the repertoire of differentially expressed genes,expression profiles,and biological processes derived from tissue undergoing HR and that of its ***,we generated a pipeline based on concatenated pairwise comparisons between time,zone,and treatment that enabled us to define 13 robust transcriptional HR *** these genes,the promoter of an uncharacterized AAA-ATPase was used to obtain a fluorescent reporter transgenic line that displays a strong spatiotemporally resolved signal specifically in cells that will later undergo pathogen-triggered cell *** valuable set of genes can be used to define cells that are destined to die upon infection with HR-triggering bacteria,opening new avenues for specific and/or high-throughput techniques to study HR processes at a single-cell level.

关键词： Arabidopsis thaliana cell death indicator effector-triggered immunity hypersensitive response pattern-triggered immunity plant immunity Pseudomonas syringae

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