The brokering approach can be successfully used to overcome the crucial question of searching among enormous amount of data （raw and/or processed） produced and stored in different information systems. In this paper,...The brokering approach can be successfully used to overcome the crucial question of searching among enormous amount of data （raw and/or processed） produced and stored in different information systems. In this paper, authors describe the Data Management System the DMS （Data Management System） developed by INGV （Istituto Nazionale di Geofisica e Vulcanologia） to support the brokering system GEOSS （Global Earth Observation System of Systems） adopted for the ARCA （Arctic Present Climate Change and Past Extreme Events） project. This DMS includes heterogeneous data that contributes to the ARCA objective （www.arcaproject.it） focusing on multi-parametric and multi-disciplinary studies on the mechanism （s） behind the release of large volumes of cold and fresh water from melting of ice caps. The DMS is accessible directly at the www.arca.rm.ingv.it, or through the IADC （Italian Arctic Data Center） at http：//arcticnode.dta.cnr.it/iadc/gi-portal/index.jsp that interoperates with the GEOSS brokering system （http：//www.geoportal.org0 making easy and fast the search of specific data set and its URL.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As t...The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.展开更多
Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental...Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.展开更多
The 7 ka old Qixiangzhan lava flow(QXZ,Tianchi volcano)represents the last eruptive event before the 946 CE,caldera-forming‘Millennium’eruption(ME).Petrographic,whole rock,mineral composition,Sr-Nd isotopic data on ...The 7 ka old Qixiangzhan lava flow(QXZ,Tianchi volcano)represents the last eruptive event before the 946 CE,caldera-forming‘Millennium’eruption(ME).Petrographic,whole rock,mineral composition,Sr-Nd isotopic data on QXZ show that:(a)the lava consists of two components,constituted by comenditic obsidian fragments immersed in a continuous,aphanitic component;(b)both components have the same geochemical and isotopic variations of the ME magma.The QXZ and ME comendites result from fractional crystallization and crustal assimilation processes.The temperature of the QXZ magma was about 790℃ and the depth of the magma reservoir around 7 km,the same values as estimated for ME.QXZ had a viscosity of 10^(5.5)-10^(9) Pa s and a velocity of 3-10 km/yr.The emplacement time was 0.5-1.6yr and the flow rate 0.48-1.50 m^(3)/s.These values lie within the range estimated for other rhyolitic flows worldwide.The QXZ lava originated through a mixed explosive-effusive activity with the obsidian resulting from the ascent of undercooling,degassing and the fragmentation of magma along the conduit walls,whereas the aphanitic component testifies to the less undercooled and segregated flow at the center of the conduit.The QXZ lava demonstrates the extensive history of the ME magma chamber.展开更多
PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different patho...PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.展开更多
Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to...The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to reconstruct the architecture of the oceanic sector from which they derived.The collected data indicate that this oceanic crust consists of a mantle metaperidotites and metaophicalcites,both covered by massive or pillow metabasalts with or without a layer of ophiolite-bearing metabreccias.展开更多
BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHOD...BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.展开更多
All-inorganic perovskites based on cesium-lead-bromine(Cs-Pb-Br)have been a prominent research focus in optoelectronics in recent years.The optimisation and tunability of their macroscopic properties exploit the confo...All-inorganic perovskites based on cesium-lead-bromine(Cs-Pb-Br)have been a prominent research focus in optoelectronics in recent years.The optimisation and tunability of their macroscopic properties exploit the conformational flexibility,resulting in various crystal structures.Varying synthesis parameters can yield distinct crystal structures from Cs,Pb,and Br precursors,and manually exploring the relationship between these synthesis parameters and the resulting crystal structure is both labour-intensive and time-consuming.Machine learning(ML)can rapidly uncover insights and drive discoveries in chemical synthesis with the support of data,significantly reducing both the cost and development cycle of materials.Here,we gathered synthesis parameters from published literature(220 synthesis runs)and implemented eight distinct ML models,including eXtreme Gradient Boosting(XGB),Decision Tree(DT),Support Vector Machine(SVM),Random Forest(RF),Naïve Bayes(NB),Logistic Regression(LR),Gradient Boosting(GB),and K-Nearest(KN)to classify and predict Cs-Pb-Br crystal structures from given synthesis parameters.Validation accuracy,precision,F1 score,recall,and average area under the curve(AUC)are employed to evaluate these ML models.The XGB model exhibited the best performance,achieving a validation accuracy of 0.841.The trained XGB model was subsequently utilised to predict the structure from 10 experimental runs using a randomised set of parameters,achieving a testing accuracy of 0.8.The results indicate that the Cs/Pb molar ratio,reaction time,and the concentration of organic compounds(ligands)play crucial roles in synthesising various crystal structures of Cs-Pb-Br.This study demonstrates a significant decrease in effort required for experimental procedures and builds a foundational basis for predicting crystal structures from synthesis parameters.展开更多
Cenozoic trachytes are characteristic of some active volcanic fields in China.In particular,the origin and mechanisms of the evolution of trachytes from the Tianchi(Changbaishan)volcano(TV,China/North Korea)are poorly...Cenozoic trachytes are characteristic of some active volcanic fields in China.In particular,the origin and mechanisms of the evolution of trachytes from the Tianchi(Changbaishan)volcano(TV,China/North Korea)are poorly known.Here,we present new geochronological,geochemical and isotopic data on two trachytic suites outcropping on the northern and southern upper slopes of TV.Detailed zircon laser ablation-multicollector-inductively coupled plasma-mass spectrometry(LA-MC-ICP-MS)U-Pb dating,Rb-Sr isochron dating of plagioclase and hornblende,^(40)Ar/^(39)Ar chronology with mineral chemistry,whole-rock element and Sr-Nd-Pb isotope data are used to explore their origins and evolutionary mechanisms during the late Middle Pleistocene.Our data indicate that the trachytes mainly consist of sanidine,orthoclase and plagioclase,with minor albite,quartz and hornblende.They formed at 0.353-0.346 Ma(lava flow from the northern slope)and 0.383-0.311 Ma(lava flow from the southern slope),respectively.The TV trachytes are characterized by high K_(2)O/Na_(2)O and AR values,with low A/CNK and Mg~#values.They are enriched in rare earth elements(REEs;except Eu),depleted in Sr and Ba,crystallizing at 742-858℃.The TV trachytes have high(^(87)Sr/^(86)Sr)_i values(0.70776-0.71195),positiveε_(Nd)(t)values(0.61-2.93)and radiogenic^(206)Pb/^(204)Pb values(17.515-17.806).These values are similar to those of the Pleistocene and Holocene TV trachytes.Geochemical data indicate that they were formed by fractional crystallization from a basaltic melt and assimilated upper crust material.The trace element pattern of the studied trachytes is consistent with an evolution from basaltic melts representative of an enriched mantle source.The vent from which the trachytic magma was erupted probably collapsed inside the caldera during the TV'Millennium'eruption(ME)in 946 AD.The contemporaneous emission of basaltic and trachytic magma during the Middle-Late Pleistocene suggests the coexistence of fissural basaltic volcanism and central-type trachytic volcanism,the latter of which was associated with a magma chamber in the upper crust during the TV cone-construction stage.展开更多
Passive-roof duplexes accommodate shortening at the mountain front of many fold-and-thrust belts worldwide.These structures typically manifest at the surface by hinterland-verging backthrusts that decouple thin-skinne...Passive-roof duplexes accommodate shortening at the mountain front of many fold-and-thrust belts worldwide.These structures typically manifest at the surface by hinterland-verging backthrusts that decouple thin-skinned thrust sheets from underlying foreland-verging duplexes.Although the main fac-tors controlling the development of passive-roof duplexes have mostly been identified,some of their intrinsic characteristics are still poorly defined.These relate to their spatio-temporal relationships to thrust faults located further inland in orogens,and their ability to transport younger rocks over older ones.This study explores these issues in the Casentino-Romagna axial sector of the Northern Apennines,which expose regional forethrusts and backthrusts.Detailed field mapping and analysis of superposed tectonic structures were integrated with apatite fission-track dating for constraining the tim-ing of rock exhumation and correlated tectonic events.Collectively,the results have allowed us to inter-pret the evolution of the study area in terms of two main deformation stages.Specifically,a first,long phase(D_(1))progressed from NE-directed,in-sequence thrusting(∼18 to∼10-9 Ma)to late out-of-sequence thrusting(∼8-5 Ma).A successive deformation phase,that we refer to as D_(2)(∼4-2 Ma),con-sisted of backthrusts and associated folds that were ubiquitous and systematically overprinted onto the foreland-verging D_(1)structures.Such retrovergent structures identify a late deformation phase dom-inated by the development of passive-roof duplexes that propagated hinterlandward into the orogen up to beyond the primary watershed ridge.Orogen-scale processes controlled the evolution of forelandward D_(1)-phase thrusts,although late erosion could have played a major role by bringing the Apennine thrust wedge toward an undercritical state.The latter conditions could have contributed to keeping the out-of-sequence thrusts active,and eventually promoted the development of the D_(2)passive-roof duplexes.展开更多
Robust numerical tools are essential for enabling the use of hybrid rocket engines(HREs)in future space applications.In this context,Computational Fluid Dynamics(CFD)transient simulations can be employed to analyse an...Robust numerical tools are essential for enabling the use of hybrid rocket engines(HREs)in future space applications.In this context,Computational Fluid Dynamics(CFD)transient simulations can be employed to analyse and predict relevant fluid dynamics phenomena within the thrust chamber of small-scale HREs.This work applies such techniques to investigate two unexpected behaviours observed in a 10 N-class hydrogen peroxide-based hybrid thruster:an uneven regression rate during High-Density Polyethylene(HDPE)and Acrylonitrile Butadiene Styrene(ABS)fuel tests,and non-negligible axial consumption in the ABS test case.The present study seeks to identify their fluid-dynamic origins by analysing key aspects of the thruster’s internal ballistics.The impact of recirculation zones and mixing on regression rates is quantified,as is the effect of grain heating on performance.Although already known in the present scientific literature,these phenomena prove to become particularly relevant for small-scale engines.Furthermore,the study demonstrates how appropriate numerical tools can replicate experimental findings,helping to foresee and mitigate undesirable behaviours in the design phases of future HRE propulsion systems.CFD results match the final HDPE grain geometry,reproducing the uneven port diameters with a maximum error below 9%.For ABS,axial regression is accurately captured,confirming the model’s reliability.Furthermore,average regression rates differ by only 1.60%and 1.20%for HDPE and ABS,respectively,while mass consumption is reproduced within 1.70%for HDPE and 3.01%for ABS.Overall,the results of the work demonstrate the reliability of the numerical approach adopted.This enriches the analysis capabilities devoted to 10 N-class engines,provides an additional tool for simulating the internal ballistics of small-scale hybrid thrusters,and integrates the existing literature with new insights into their fluid dynamics.展开更多
Evidence is not homogeneous on indicators able to monitor and assess qualityperformance for organ donation. This may be related to differences in healthcareorganizations among countries but also to the scarcity of dat...Evidence is not homogeneous on indicators able to monitor and assess qualityperformance for organ donation. This may be related to differences in healthcareorganizations among countries but also to the scarcity of data on this topic so far.In the present review, we assessed available evidence on quality metrics in solidorgan procurement in the United States and in Europe by means of a PubMedsearch. Evidence was summarized according to countries, considering that thedonation and transplantation systems differ from country to country. In UnitedStates, the assessment of these indicators is periodically performed by the nationalnetwork for organ sharing to evaluate the performance of each Organ ProcurementOrganization (OPO). Quality metrics consider several factors, in primispopulation characteristics (i.e. race/ethnicity, age, socio-economic status). That iswhy the assessment of each OPO performance relies on several quality metrics,not only one single indicator. In Europe, quality improvement programs representa structural element of organ and transplant system in several countries, but fewpapers have to date addressed the results obtained by a quality improvementprogram based on indicators. In Poland, the use of quality indicators and improvementprocedures were associated with better results in those hospitals whichimplemented these programs in respect to hospitals who did not. In TuscanyRegion (Italy) the implementation of a monitoring and reporting approach basedon indicators by the Regional Transplant Center was associated with an increasedin transplant and donation activity (especially in cDCD donors). According toavailable evidence, the development of a method for quality assessment andquality improvement has been recognized as pivotal for donation and transplantauthorities to identify key interventions either at national and/or hospital levels.展开更多
The experiment addressed the effects of preharvest KH_(2)PO_(4)foliar spraying(20 mmol·L^(-1))on fruit quality and composition(including volatile organic compounds,VOCs)of cherry tomatoes(‘Caravaggio’,‘Sugarl...The experiment addressed the effects of preharvest KH_(2)PO_(4)foliar spraying(20 mmol·L^(-1))on fruit quality and composition(including volatile organic compounds,VOCs)of cherry tomatoes(‘Caravaggio’,‘Sugarland’and‘Top Stellina’)after 0(S0),7(S7)and 14 days(S14)of storage at 8.0°C.On the average of the 3 genotypes,the KH_(2)PO_(4)treatment improved fruit pressure firmness,total soluble solids(TSS),titratable acidity(TA),total phenols and carotenoids concentrations,along with the fruits'antioxidant capacity(by up to 17%for FRAP assay).Within the S7–S14 period,control fruits showed the highest reductions in TSS,TSS/TA ratio and total carotenoids(-17,-12 and-45,respectively),whereas treated fruits proved the strongest increase in DPPH(+12%).Sixteen out of 32 VOCs were promoted following KH_(2)PO_(4)application,including the aldehydes hexanal,(E)-2-hexenal and(Z)-3-hexenal and the apocarotenoids(E)-citral,(E)-β-ionone,geranylacetone and 6-methyl-5-hepten-2-one.Proceeding from S0 to S14,several VOCs decreased more strongly in control fruits,as for hexanal(-48%)and total aldehydes(-42%,whereas at S14 treated fruits had higher concentrations of linalool,geranylacetone and 6-methyl-5-hepten-2-one(1.06,52.50 and 79.27μg·kg^(-1),respectively).‘Caravaggio’demonstrated the strongest apocarotenoid reduction at S14,whereas‘Top Stellina’was more responsive to KH_(2)PO_(4)(mainly forβ-cyclocitral,geranylacetone and total terpenes/terpenoids),thus highlighting the central role of the genotype in responding to other experimental factors.Nonetheless,these results suggest that proper preharvest KH_(2)PO_(4)applications can preserve specific commercial,nutritional and quality traits of cold-stored cherry tomatoes.展开更多
Background Mitophagy is an essential cellular autophagic process which maintains mitochondrial homeostasis,but its role in high fat diet(HFD)-induced lipid accumulation is unclear in the yellow catfish.Thus,this study...Background Mitophagy is an essential cellular autophagic process which maintains mitochondrial homeostasis,but its role in high fat diet(HFD)-induced lipid accumulation is unclear in the yellow catfish.Thus,this study aimed to elucidate mechanism of mitochondria mediating HFD-induced hepatic fat accumulation.Results In the present study,yellow catfish were fed three diets with dietary fat at 6.31%(low fat;LFD,control),12.03%(middle fat;MFD)and 15.32%(high fat;HFD),respectively,for 8 weeks.High dietary fat addition raised hepatic lipid accumulation,and declined mRNA and protein levels of Parkin-dependent mitophagy,down-regulated the Parkin protein expression and the estrogen-related receptor alpha(Errα)ubiquitination,and induced Errαprotein levels;fatty acid(FA)incubation reduced Parkin-dependent mitophagy,inhibited Errαubiquitination and increased Errαprotein expression,and raised TG accumulation.Furthermore,yellow catfish hepatocytes were isolated and cultured.Nicotinamide mononucleotide,N-acetyl-L-cysteine,Parkin and errαsiRNA knockdown were used under FA incubation,respectively.Parkin downregulation mediated FA incubation-induced TG accumulation and mitoautophagic inhibition;Parkin ubiquitinated Errα,and K63 was an important ubiquitination site for deubiquitinating Parkin activity;Errαtargets fas,acca and pparγgenes,whose activation contributed to FA-induced lipogenesis and lipid accumulation.Thus,high fat diet(HFD)and FA incubation inhibited Parkin activity,suppressed mitophagy and activated Errαpathway,and induced hepatic lipogenic metabolism and lipotoxicity.Conclusions Overall,our study provided new targets against HFD-induced hepatic lipid accumulation and nonalcoholic fatty liver disease in the vertebrates.展开更多
文摘The brokering approach can be successfully used to overcome the crucial question of searching among enormous amount of data （raw and/or processed） produced and stored in different information systems. In this paper, authors describe the Data Management System the DMS （Data Management System） developed by INGV （Istituto Nazionale di Geofisica e Vulcanologia） to support the brokering system GEOSS （Global Earth Observation System of Systems） adopted for the ARCA （Arctic Present Climate Change and Past Extreme Events） project. This DMS includes heterogeneous data that contributes to the ARCA objective （www.arcaproject.it） focusing on multi-parametric and multi-disciplinary studies on the mechanism （s） behind the release of large volumes of cold and fresh water from melting of ice caps. The DMS is accessible directly at the www.arca.rm.ingv.it, or through the IADC （Italian Arctic Data Center） at http：//arcticnode.dta.cnr.it/iadc/gi-portal/index.jsp that interoperates with the GEOSS brokering system （http：//www.geoportal.org0 making easy and fast the search of specific data set and its URL.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
文摘The brain,with its trillions of neural connections,different cellular types,and molecular complexities,presents a formidable challenge for researchers aiming to comprehend the multifaceted nature of neural health.As traditional methods have provided valuable insights,emerging technologies offer unprecedented opportunities to delve deeper into the underpinnings of brain function.In the everevolving landscape of neuroscience,the quest to unravel the mysteries of the human brain is bound to take a leap forward thanks to new technological improvements and bold interpretative frameworks.
基金supported by funds from the Italian Ministry of Health,Ricerca Finalizzata,(Grant N.GR-2013-02355882 and GR-2021-12373946 to AL)5x1000 Project of the Istituto Superiore di Sanità(Project code:ISS5x1000_21-949432e8c9be to AL)the European Union–NextGeneration EU through the Italian Ministry of University and Research under PNRR-M4C2-I1.3 Project PE_00000019“HEAL ITALIA”to EA(CUP I83C22001830006)。
文摘Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult life.To maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.
基金funded by the National Natural Science Foundation of China(Grant Nos.41972313 and 41790453)the Engineering Research Center of Geothermal Resources Development Technology and Equipment,Ministry of Education,Jilin University。
文摘The 7 ka old Qixiangzhan lava flow(QXZ,Tianchi volcano)represents the last eruptive event before the 946 CE,caldera-forming‘Millennium’eruption(ME).Petrographic,whole rock,mineral composition,Sr-Nd isotopic data on QXZ show that:(a)the lava consists of two components,constituted by comenditic obsidian fragments immersed in a continuous,aphanitic component;(b)both components have the same geochemical and isotopic variations of the ME magma.The QXZ and ME comendites result from fractional crystallization and crustal assimilation processes.The temperature of the QXZ magma was about 790℃ and the depth of the magma reservoir around 7 km,the same values as estimated for ME.QXZ had a viscosity of 10^(5.5)-10^(9) Pa s and a velocity of 3-10 km/yr.The emplacement time was 0.5-1.6yr and the flow rate 0.48-1.50 m^(3)/s.These values lie within the range estimated for other rhyolitic flows worldwide.The QXZ lava originated through a mixed explosive-effusive activity with the obsidian resulting from the ascent of undercooling,degassing and the fragmentation of magma along the conduit walls,whereas the aphanitic component testifies to the less undercooled and segregated flow at the center of the conduit.The QXZ lava demonstrates the extensive history of the ME magma chamber.
基金supported by Telethon Italy award GGP15225(to RC and GM)Italian Ministry of Health award RF-2016-02362950(to RC and CZ)+1 种基金the CJD Foundation USA(to RC)the Associazione Italiana Encefalopatie da Prioni(AIEnP)(to RC).
文摘PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other mammals.PrPSccan adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective therapies.Since PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion diseases.In this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of action.We argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
基金supported by PRIN 2020 project(Resp.Michele Marroni)Claudia D’Oriano(INGV)Matteo Masotta and Danis Filimon(Earth Science Dept)are also thanked for analytical support in the laboratoriesThis work benefited from the PRA 2022 project handled by Francesca Meneghini.
文摘The Middle to Late Jurassic,high-pressure metamorphic ophiolites of Inzecca Unit are well exposed in the Noceta-Vezzani area of Alpine Corsica.These metaophiolites were studied by using a multidisciplinary approach to reconstruct the architecture of the oceanic sector from which they derived.The collected data indicate that this oceanic crust consists of a mantle metaperidotites and metaophicalcites,both covered by massive or pillow metabasalts with or without a layer of ophiolite-bearing metabreccias.
文摘BACKGROUND The CAR-OLT score predicts major adverse cardiovascular events 1 year after liver transplant(LT).AIM To test the hypothesis that the CAR-OLT score may help avoid cardiac stress tests in LT candidates.METHODS This retrospective single-center cohort study included all adult patients undergoing elective evaluation for first cadaveric donor orthotopic LT for liver cirrhosis with or without hepatocellular carcinoma at Fondazione Policlinico Universitario Agostino Gemelli Istituto di Ricerca e Cura a Carattere Scientifico in Rome,Italy.Cardiac contraindications for LT listing were defined after a center-specific cardiac workup,which included cardiac stress tests for most patients.The diagnostic accuracy of the CAR-OLT score was evaluated using the area under the receiver operating characteristic(AUROC)method.RESULTS A total of 342 LT candidates were evaluated between 2015 and 2019,with a moderate cardiovascular risk profile(37%diabetes,34%hypertension,22%obesity).Of these,80(23%)candidates underwent coronary angiography.Twenty-one(6%)candidates were given cardiac contraindications to LT listing,48%of which were due to coronary artery disease.The CAR-OLT score predicted cardiac contraindications to LT listing with an AUROC of 0.81.The optimal cut-off for sensitivity was a CAR-OLT score≤23,which showed a 99%negative predictive value for cardiac contraindications to LT listing.A total of 84(25%)LT candidates with a CAR-OLT score≤23 underwent 87 non-invasive cardiac tests and 13 coronary angiographies pre-listing,with estimated costs of approximately 48000€.The estimated savings per patient was€574.70 for the Italian National Health System.CONCLUSION A CAR-OLT score≤23 can identify LT candidates who can be safely listed without the need for cardiac stress tests,providing time and cost savings.These findings require external validation.
基金the Italian Space Agency(Agenzia Spaziale Italiana,ASI)in the framework of the Research Day“Giornate della Ricerca Spaziale”initiative through the contract ASI N.2023-4-U.0.
文摘All-inorganic perovskites based on cesium-lead-bromine(Cs-Pb-Br)have been a prominent research focus in optoelectronics in recent years.The optimisation and tunability of their macroscopic properties exploit the conformational flexibility,resulting in various crystal structures.Varying synthesis parameters can yield distinct crystal structures from Cs,Pb,and Br precursors,and manually exploring the relationship between these synthesis parameters and the resulting crystal structure is both labour-intensive and time-consuming.Machine learning(ML)can rapidly uncover insights and drive discoveries in chemical synthesis with the support of data,significantly reducing both the cost and development cycle of materials.Here,we gathered synthesis parameters from published literature(220 synthesis runs)and implemented eight distinct ML models,including eXtreme Gradient Boosting(XGB),Decision Tree(DT),Support Vector Machine(SVM),Random Forest(RF),Naïve Bayes(NB),Logistic Regression(LR),Gradient Boosting(GB),and K-Nearest(KN)to classify and predict Cs-Pb-Br crystal structures from given synthesis parameters.Validation accuracy,precision,F1 score,recall,and average area under the curve(AUC)are employed to evaluate these ML models.The XGB model exhibited the best performance,achieving a validation accuracy of 0.841.The trained XGB model was subsequently utilised to predict the structure from 10 experimental runs using a randomised set of parameters,achieving a testing accuracy of 0.8.The results indicate that the Cs/Pb molar ratio,reaction time,and the concentration of organic compounds(ligands)play crucial roles in synthesising various crystal structures of Cs-Pb-Br.This study demonstrates a significant decrease in effort required for experimental procedures and builds a foundational basis for predicting crystal structures from synthesis parameters.
基金financially supported by the project of the National Observation and Research Station of the Institute of Geology,China Earthquake Administration(Grant No.NORSCBS22-06)the Youth Science and Technology Development Project of the Jilin Earthquake Agency(Grant No.JZQ-202402)+1 种基金the Earthquake Science and Technology Spark Project(Grant No.XH23013B)the China Scholarship Council(Grant No.202104190014)。
文摘Cenozoic trachytes are characteristic of some active volcanic fields in China.In particular,the origin and mechanisms of the evolution of trachytes from the Tianchi(Changbaishan)volcano(TV,China/North Korea)are poorly known.Here,we present new geochronological,geochemical and isotopic data on two trachytic suites outcropping on the northern and southern upper slopes of TV.Detailed zircon laser ablation-multicollector-inductively coupled plasma-mass spectrometry(LA-MC-ICP-MS)U-Pb dating,Rb-Sr isochron dating of plagioclase and hornblende,^(40)Ar/^(39)Ar chronology with mineral chemistry,whole-rock element and Sr-Nd-Pb isotope data are used to explore their origins and evolutionary mechanisms during the late Middle Pleistocene.Our data indicate that the trachytes mainly consist of sanidine,orthoclase and plagioclase,with minor albite,quartz and hornblende.They formed at 0.353-0.346 Ma(lava flow from the northern slope)and 0.383-0.311 Ma(lava flow from the southern slope),respectively.The TV trachytes are characterized by high K_(2)O/Na_(2)O and AR values,with low A/CNK and Mg~#values.They are enriched in rare earth elements(REEs;except Eu),depleted in Sr and Ba,crystallizing at 742-858℃.The TV trachytes have high(^(87)Sr/^(86)Sr)_i values(0.70776-0.71195),positiveε_(Nd)(t)values(0.61-2.93)and radiogenic^(206)Pb/^(204)Pb values(17.515-17.806).These values are similar to those of the Pleistocene and Holocene TV trachytes.Geochemical data indicate that they were formed by fractional crystallization from a basaltic melt and assimilated upper crust material.The trace element pattern of the studied trachytes is consistent with an evolution from basaltic melts representative of an enriched mantle source.The vent from which the trachytic magma was erupted probably collapsed inside the caldera during the TV'Millennium'eruption(ME)in 946 AD.The contemporaneous emission of basaltic and trachytic magma during the Middle-Late Pleistocene suggests the coexistence of fissural basaltic volcanism and central-type trachytic volcanism,the latter of which was associated with a magma chamber in the upper crust during the TV cone-construction stage.
文摘Passive-roof duplexes accommodate shortening at the mountain front of many fold-and-thrust belts worldwide.These structures typically manifest at the surface by hinterland-verging backthrusts that decouple thin-skinned thrust sheets from underlying foreland-verging duplexes.Although the main fac-tors controlling the development of passive-roof duplexes have mostly been identified,some of their intrinsic characteristics are still poorly defined.These relate to their spatio-temporal relationships to thrust faults located further inland in orogens,and their ability to transport younger rocks over older ones.This study explores these issues in the Casentino-Romagna axial sector of the Northern Apennines,which expose regional forethrusts and backthrusts.Detailed field mapping and analysis of superposed tectonic structures were integrated with apatite fission-track dating for constraining the tim-ing of rock exhumation and correlated tectonic events.Collectively,the results have allowed us to inter-pret the evolution of the study area in terms of two main deformation stages.Specifically,a first,long phase(D_(1))progressed from NE-directed,in-sequence thrusting(∼18 to∼10-9 Ma)to late out-of-sequence thrusting(∼8-5 Ma).A successive deformation phase,that we refer to as D_(2)(∼4-2 Ma),con-sisted of backthrusts and associated folds that were ubiquitous and systematically overprinted onto the foreland-verging D_(1)structures.Such retrovergent structures identify a late deformation phase dom-inated by the development of passive-roof duplexes that propagated hinterlandward into the orogen up to beyond the primary watershed ridge.Orogen-scale processes controlled the evolution of forelandward D_(1)-phase thrusts,although late erosion could have played a major role by bringing the Apennine thrust wedge toward an undercritical state.The latter conditions could have contributed to keeping the out-of-sequence thrusts active,and eventually promoted the development of the D_(2)passive-roof duplexes.
文摘Robust numerical tools are essential for enabling the use of hybrid rocket engines(HREs)in future space applications.In this context,Computational Fluid Dynamics(CFD)transient simulations can be employed to analyse and predict relevant fluid dynamics phenomena within the thrust chamber of small-scale HREs.This work applies such techniques to investigate two unexpected behaviours observed in a 10 N-class hydrogen peroxide-based hybrid thruster:an uneven regression rate during High-Density Polyethylene(HDPE)and Acrylonitrile Butadiene Styrene(ABS)fuel tests,and non-negligible axial consumption in the ABS test case.The present study seeks to identify their fluid-dynamic origins by analysing key aspects of the thruster’s internal ballistics.The impact of recirculation zones and mixing on regression rates is quantified,as is the effect of grain heating on performance.Although already known in the present scientific literature,these phenomena prove to become particularly relevant for small-scale engines.Furthermore,the study demonstrates how appropriate numerical tools can replicate experimental findings,helping to foresee and mitigate undesirable behaviours in the design phases of future HRE propulsion systems.CFD results match the final HDPE grain geometry,reproducing the uneven port diameters with a maximum error below 9%.For ABS,axial regression is accurately captured,confirming the model’s reliability.Furthermore,average regression rates differ by only 1.60%and 1.20%for HDPE and ABS,respectively,while mass consumption is reproduced within 1.70%for HDPE and 3.01%for ABS.Overall,the results of the work demonstrate the reliability of the numerical approach adopted.This enriches the analysis capabilities devoted to 10 N-class engines,provides an additional tool for simulating the internal ballistics of small-scale hybrid thrusters,and integrates the existing literature with new insights into their fluid dynamics.
文摘Evidence is not homogeneous on indicators able to monitor and assess qualityperformance for organ donation. This may be related to differences in healthcareorganizations among countries but also to the scarcity of data on this topic so far.In the present review, we assessed available evidence on quality metrics in solidorgan procurement in the United States and in Europe by means of a PubMedsearch. Evidence was summarized according to countries, considering that thedonation and transplantation systems differ from country to country. In UnitedStates, the assessment of these indicators is periodically performed by the nationalnetwork for organ sharing to evaluate the performance of each Organ ProcurementOrganization (OPO). Quality metrics consider several factors, in primispopulation characteristics (i.e. race/ethnicity, age, socio-economic status). That iswhy the assessment of each OPO performance relies on several quality metrics,not only one single indicator. In Europe, quality improvement programs representa structural element of organ and transplant system in several countries, but fewpapers have to date addressed the results obtained by a quality improvementprogram based on indicators. In Poland, the use of quality indicators and improvementprocedures were associated with better results in those hospitals whichimplemented these programs in respect to hospitals who did not. In TuscanyRegion (Italy) the implementation of a monitoring and reporting approach basedon indicators by the Regional Transplant Center was associated with an increasedin transplant and donation activity (especially in cDCD donors). According toavailable evidence, the development of a method for quality assessment andquality improvement has been recognized as pivotal for donation and transplantauthorities to identify key interventions either at national and/or hospital levels.
基金funded by the National Recovery and Resilience Plan(NRRP),Mission 4 Component 2 Investment 1.3—Call for proposals No.341 of 15 March 2022 of Italian Ministry of University and Research funded by the European Union—NextGenerationEU,Award Number:Project code PE00000003Concession Decree No.1550 of 11 October 2022 adopted by the Italian Ministry of University and Research,CUP E63C22002060006+1 种基金Project title“ON Foods—Research and innovation network on food and nutrition Sustainability,Safety and Security—Working ON Foodsfunded by the Italian Ministry of University and Research(MUR)under the project“Conservabilità,qualitàe sicurezza dei prodotti ortofrutticoli ad alto contenuto di servizio-ARS01_00640–POFACS”(Grant Nos.D.D.1211/2020 and 1104/2021).
文摘The experiment addressed the effects of preharvest KH_(2)PO_(4)foliar spraying(20 mmol·L^(-1))on fruit quality and composition(including volatile organic compounds,VOCs)of cherry tomatoes(‘Caravaggio’,‘Sugarland’and‘Top Stellina’)after 0(S0),7(S7)and 14 days(S14)of storage at 8.0°C.On the average of the 3 genotypes,the KH_(2)PO_(4)treatment improved fruit pressure firmness,total soluble solids(TSS),titratable acidity(TA),total phenols and carotenoids concentrations,along with the fruits'antioxidant capacity(by up to 17%for FRAP assay).Within the S7–S14 period,control fruits showed the highest reductions in TSS,TSS/TA ratio and total carotenoids(-17,-12 and-45,respectively),whereas treated fruits proved the strongest increase in DPPH(+12%).Sixteen out of 32 VOCs were promoted following KH_(2)PO_(4)application,including the aldehydes hexanal,(E)-2-hexenal and(Z)-3-hexenal and the apocarotenoids(E)-citral,(E)-β-ionone,geranylacetone and 6-methyl-5-hepten-2-one.Proceeding from S0 to S14,several VOCs decreased more strongly in control fruits,as for hexanal(-48%)and total aldehydes(-42%,whereas at S14 treated fruits had higher concentrations of linalool,geranylacetone and 6-methyl-5-hepten-2-one(1.06,52.50 and 79.27μg·kg^(-1),respectively).‘Caravaggio’demonstrated the strongest apocarotenoid reduction at S14,whereas‘Top Stellina’was more responsive to KH_(2)PO_(4)(mainly forβ-cyclocitral,geranylacetone and total terpenes/terpenoids),thus highlighting the central role of the genotype in responding to other experimental factors.Nonetheless,these results suggest that proper preharvest KH_(2)PO_(4)applications can preserve specific commercial,nutritional and quality traits of cold-stored cherry tomatoes.
基金funded by National Key R&D Program of China(2024YFD2402000)。
文摘Background Mitophagy is an essential cellular autophagic process which maintains mitochondrial homeostasis,but its role in high fat diet(HFD)-induced lipid accumulation is unclear in the yellow catfish.Thus,this study aimed to elucidate mechanism of mitochondria mediating HFD-induced hepatic fat accumulation.Results In the present study,yellow catfish were fed three diets with dietary fat at 6.31%(low fat;LFD,control),12.03%(middle fat;MFD)and 15.32%(high fat;HFD),respectively,for 8 weeks.High dietary fat addition raised hepatic lipid accumulation,and declined mRNA and protein levels of Parkin-dependent mitophagy,down-regulated the Parkin protein expression and the estrogen-related receptor alpha(Errα)ubiquitination,and induced Errαprotein levels;fatty acid(FA)incubation reduced Parkin-dependent mitophagy,inhibited Errαubiquitination and increased Errαprotein expression,and raised TG accumulation.Furthermore,yellow catfish hepatocytes were isolated and cultured.Nicotinamide mononucleotide,N-acetyl-L-cysteine,Parkin and errαsiRNA knockdown were used under FA incubation,respectively.Parkin downregulation mediated FA incubation-induced TG accumulation and mitoautophagic inhibition;Parkin ubiquitinated Errα,and K63 was an important ubiquitination site for deubiquitinating Parkin activity;Errαtargets fas,acca and pparγgenes,whose activation contributed to FA-induced lipogenesis and lipid accumulation.Thus,high fat diet(HFD)and FA incubation inhibited Parkin activity,suppressed mitophagy and activated Errαpathway,and induced hepatic lipogenic metabolism and lipotoxicity.Conclusions Overall,our study provided new targets against HFD-induced hepatic lipid accumulation and nonalcoholic fatty liver disease in the vertebrates.
