Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularit...Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.展开更多
The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and sta...The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.展开更多
The incidence of primary liver cancers,and particularly hepatocellular carcinoma(HCC),is increasing throughout the world.The vast majority of HCCs develop on cirrhotic livers(CLs)(CL HCC)or livers chronically infected...The incidence of primary liver cancers,and particularly hepatocellular carcinoma(HCC),is increasing throughout the world.The vast majority of HCCs develop on cirrhotic livers(CLs)(CL HCC)or livers chronically infected by hepatotropic viruses,mainly hepatitis B virus(HBV)and hepatitis C virus(HCV)(1).As HCC occurring on non-HBV non-HCV non-CL(NCL)HCC occurs much less frequently,its management is less established than for CL HCC.Consequently,many clinicians might confuse the prognosis and management of NCL HCC with the one of CL HCC.It is however demonstrated that NCL HCCs behave differently than CL HCCs.Their prognostic factors and sensibility to systemic therapy are different,added to the fact that NCLs can undergo major resections allowing curative surgical management or even systemic therapies that are not even possible in CL HCCs due to the failing function of the CL.The established criteria for liver transplantation of CL HCCs,including the famous Milan criteria,have no role in NCL HCC management(2-4).The Barcelona Clinic Liver Cancer(BCLC)strategy for prognosis prediction and treatment recommendation also concerns only CL HCCs;and should not be used for NCL HCCs(5).展开更多
Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis(OA), and osteomodulin(OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the scleroti...Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis(OA), and osteomodulin(OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.展开更多
Coastal zones, with their significant geodiversity, are vital areas for geotourism. Effective management is crucial to harness the geological interest of these sites as geotourism resources while ensuring their conser...Coastal zones, with their significant geodiversity, are vital areas for geotourism. Effective management is crucial to harness the geological interest of these sites as geotourism resources while ensuring their conservation. ManabíProvince is one of the most representative regions along the Ecuadorian coast due to its beaches and coastal cliffs, offering a wealth of tourist attractions and cultural elements. This study aims to evaluate the geosite potential of six cliffs in ManabíProvince through quantitative and qualitative analyses to propose geotourism promotion strategies. The methodology involves (i) inventory and characterisation of the cliffs, (ii) assessment of the sites by the Spanish Inventory of Places of Geological Interest method (IELIG), and (iii) qualitative evaluation through focus group discussions and Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. The results reveal that all six sites boast diverse geological assets, including geomorphological, stratigraphic, sedimentological, and tectonic elements. They are characterised by “high ”scientific, didactic, and tourist interest, while also being sus- ceptible to degradation due to natural and anthropic threats. The SWOT analysis demonstrates that the valuable geological and geomorphological heritage of potential geosites provides an opportunity to foster geotourism and boost the province’s economy, incorporating geoconservation and geoeducation strategies. This study proposes a georoute called “Ruta Acantilados del Sol ”, a 245 km journey encompassing all six sites, incorporating diverse tourist and cultural activities. Our research lays the foundation for fostering geotourism along the Manabícoast and strengthening the connection between nature, heritage, and the welfare of residents within a global resilience plan.展开更多
The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and d...The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of IBD, long term safety of biologics, immunosuppressors （IS） cessation and some preliminary studies on biologics cessation may help us to discuss this topic. The decision to stop a biological treatment is currently based on a compromise between the benefits and risks associated with the prolongation of this treatment. IBD, more particularly CD, are characterized by the development of complications and the need for recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these patients potentially in need of biological treatments, it is probable that, as it has been demonstrated for IS, the longer a stable remission has be achieved under treatment, the lower the risk of relapse is alter treatment cessation. Further prospective studies should now aim at disclosing patient characteristics associated with a low risk of relapse to imple- ment this strategy.展开更多
While therapeutic strategies able to change the natural history of the disease are developing,it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic s...While therapeutic strategies able to change the natural history of the disease are developing,it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic strategies.Clinical predictors have probably been the most broadly studied.In both Crohn's disease(CD) and ulcerative colitis(UC),age at diagnosis,disease location and smoking habit are currently the strongest predictors of disease course.A younger age at onset is associated with more aggressive disease both in CD and UC.Disease location in CD is associated with different types of complications:surgery and recurrence in upper gastrointestinal and proximal small bowel disease;and surgery in distal small bowel disease and peri-anal lesions in rectal disease.In UC,extensive colitis is clearly been associated with more severe disease.Finally,active smoking globally increases disease severity in CD but decreases it in UC.Besides these important factors,others may predispose to some specific disease evolution and complications,and are also reviewed in the present paper.展开更多
The exploitation of industrial strains of chickens in the Sahelian climate of Niger is characterized by a decline in performance and significant costs associated with their maintenance. In contrast, local chickens are...The exploitation of industrial strains of chickens in the Sahelian climate of Niger is characterized by a decline in performance and significant costs associated with their maintenance. In contrast, local chickens are well adapted to these environmental conditions but with poor production performance. Genetic selection of these local chickens could improve their productivity. The first step is to determine if the genetic parameters of their growth are high enough to ensure a successful selection strategy. To do so, weekly weights of 69 parents and 119 offspring were followed for 20 weeks. The heritability and genetic correlations of these weights were estimated through the Bayesian approach using the MCMCglmm package on R software. At hatching, weights ranged from 23 to 25 g. At 20 weeks, these weights ranged from 1031 to 1052 g for females and 1308 to 1445 g for males. Heritabilities for hatch weights at 4, 8, 12, 16, and 20 weeks of age were estimated to be 0.56, 0.31, 0.52, 0.53, 0.52 and 0.48 respectively and all genetic correlations were positive. In particular, weight at 8 weeks of age showed both good heritability (h<sup>2</sup> = 0.52) and strong, positive genetic correlations with weights at older ages. These results indicate that genetic selection to improve weight at 8 weeks of age would be a good strategy to improve the overall growth performance of these chickens.展开更多
Some cities worldwide have oil wells directly affecting the management of the territory.For example,La Libertad and Salinas districts contain 467 oil wells in urban areas representing a major land-use planning challen...Some cities worldwide have oil wells directly affecting the management of the territory.For example,La Libertad and Salinas districts contain 467 oil wells in urban areas representing a major land-use planning challenge.The objective is to apply the CLUE-S land use model in coastal cities with oil wells(Salinas-La Libertad),using geographic information systems considering environmental and security characteristics for territorial development.The stages of the study are:i)classification and categorisation of oil wells;ii)application of the GIS-CLUE-S method and visualisation of land use dynamics;iii)use the SWOT-TOWS matrix,for the analysis of the situation and the main factors affecting the territory.The results indicate high vulnerability in many urban sectors and those close to the coastline.Furthermore,the CLUE-S analysis shows that the population growth in the urban sector is close to oil well areas,making it a complex pole of human-industry interaction that impacts the management of the territory.This study synthesises three technical aspects:some oil wells do not comply with municipal ordinance regulations;identification of vulnerable zones due to environmental and security factors,which recommends a territorial reordering policy;as well as an education plan for the application of territorial ordering policies,with awareness and sustainability projections.展开更多
In this paper, we propose a new spatial-multiplexing(SM) scheme employing an orthogonal precoder over Rayleigh-fading channels for an erasure event in single frequency networks(SFN). To optimize the precoder, the aver...In this paper, we propose a new spatial-multiplexing(SM) scheme employing an orthogonal precoder over Rayleigh-fading channels for an erasure event in single frequency networks(SFN). To optimize the precoder, the average bit error rate(BER) is evaluated and minimized through a mathematical analysis. Compared to an ordinary SM, the proposed scheme guarantees identical BER performance under non-erasure fading channels and achieves a greatly improved performance under erasure fading channels, especially for a higher erasure-ratio and SNR values. This improvement is mainly due to the increase in the diversity gain incurred by the optimized precoder over the erasure event. We also compare the performance of the proposed SM to that of the conventional constellation-rotation(CR) scheme applied to the single antenna SFN systems. The results of a computer simulation show that the performance of the new scheme is more effective than that of a conventional CR across all simulation cases.展开更多
The uniparental inheritance and conserved structure of the chloroplast genome among many angiosperms makes it suitable for constructing gene lineages and inferring population histories based on these relationships. Ho...The uniparental inheritance and conserved structure of the chloroplast genome among many angiosperms makes it suitable for constructing gene lineages and inferring population histories based on these relationships. However, the analysis of a single chloroplast region to solve population issues has not yielded the desired amount of variability due to the low mutation rate. Therefore, it is necessary to screen and carefully analyze chloroplast intergenic or intronic regions to select the most appropriate for studying the genetic variability in the chloroplast genome of a particular taxon. In this context, the aim of this work was to characterize 8 regions in Calophyllum brasiliense using 11 selected primer pairs and to evaluate their usefulness for phylogeographic analysis. Intergenic spacers petA-psbJ, petG-trnP and rp132-trnL and the trnL intron demonstrated potentially informative sites. The combination of these 4 regions will allow the analysis of genetic population structure and the integration of historical aspects to inform strategies for conserving C. brasiliense, especially for highly impacted populations and those at risk of local extinction.展开更多
Arecent study published in Nature Immunology by Sheedy et al.1 indicates that uptake of modified low-den- sity lipoprotein （LDL） by the scavenger receptor CD36 primes and activates the NLRP3 inflammasome, providing ...Arecent study published in Nature Immunology by Sheedy et al.1 indicates that uptake of modified low-den- sity lipoprotein （LDL） by the scavenger receptor CD36 primes and activates the NLRP3 inflammasome, providing an early pathogenic pathway that links cho- lesterol accumulation to the chronic inflammatory process of atherosclero- sis.1 Atherosclerosis arises from chronic vascular inflammation elicited by lipids.展开更多
The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal lan...The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac-targeted Ch IP-Seq and RNA-Seq in fetal(prenatal days 74–75) and adult(postnatal days 132–150) tissues(brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bama Xiang and European highly selected Large White pigs of both sexes. We identified 101,290 H3K27ac peaks, marking 18,521promoters and 82,769 enhancers, including peaks that were active across all tissues and developmental stages(which could indicate safe harbor locus for exogenous gene insertion) and tissue-and developmental stage-specific peaks(which regulate gene pathways matching tissue-and developmental stage-specific physiological functions). We found that H3K27ac and DNA methylation in the promoter region of the XIST gene may be involved in X chromosome inactivation and demonstrated the utility of the present resource for revealing the regulatory patterns of known causal genes and prioritizing candidate causal variants for complex traits in pigs. In addition, we identified an average of 1,124 super-enhancers per sample and found that they were more likely to show tissue-specific activity than ordinary peaks. We have developed a web browser to improve the accessibility of the results(http://segtp.jxau.edu.cn/pencode/?genome=sus Scr11).展开更多
In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells(MSC) isolation. So far, bone marrow(BM) has been presented as the main source of MSC despite the invasive isolation pro-cedur...In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells(MSC) isolation. So far, bone marrow(BM) has been presented as the main source of MSC despite the invasive isolation pro-cedure related to this source. During the last years, the umbilical cord(UC) matrix was cited in different studies as a reliable source from which long term ex vivo prolif-erating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an inter-esting question emerged: Are cells isolated from cord matrix(UC-MSC) different from other MSCs? In this re-view, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue.展开更多
Convection-permitting modeling allows us to understand mechanisms that influence rainfall in specific regions.However,microphysics parameterization(MP) and planetary boundary layer(PBL) schemes remain an important sou...Convection-permitting modeling allows us to understand mechanisms that influence rainfall in specific regions.However,microphysics parameterization(MP) and planetary boundary layer(PBL) schemes remain an important source of uncertainty,affecting rainfall intensity,occurrence,duration,and propagation.Here,we study the sensitivity of rainfall to three MP [Weather Research and Forecasting(WRF) Single-Moment 6-class(WSM6),Thompson,and Morrison] and two PBL [the Yonsei University(YSU) and Mellor–Yamada Nakanishi Niino(MYNN)] schemes with a convection-permitting resolution(4 km) over northwestern South America(NWSA).Simulations were performed by using the WRF model and the results were evaluated against soundings,rain gauges,and satellite data,considering the spatio-temporal variability of rainfall over diverse regions prone to deep convection in NWSA.MP and PBL schemes largely influenced simulated rainfall,with better results for the less computationally expensive WSM6 MP and YSU PBL schemes.Regarding rain gauges and satellite estimates,simulations with Morrison MP overestimated rainfall,especially westward of the Andes,whereas the MYNN PBL underestimated precipitation in the Amazon–Savannas flatlands.We found that the uncertainty in the rainfall representation is highly dependent on the region,with a higher influence of MP in the Colombian Pacific and PBL in the Amazon–Savannas flatlands.When analyzing rainfall-related processes,the selection of both MP and PBL parameterizations exerted a large influence on the simulated lower tropospheric moisture flux and moisture convergence.PBL schemes significantly influenced the downward shortwave radiation,with MYNN simulating a greater amount of low clouds,which decreased the radiation income.Furthermore,latent heat fluxes were greater for YSU,favoring moist convection and rainfall.MP schemes had a marked impact on vertical velocity.Specifically,Morrison MP showed stronger convection and higher precipitation rates,which is associated with a greater latent heat release d展开更多
Hypnosis is a modified state of consciousness which showed its benefits to decrease different symptoms,mainly pain.During the last decade,this technique has also been proposed to adults with cancer to improve other sy...Hypnosis is a modified state of consciousness which showed its benefits to decrease different symptoms,mainly pain.During the last decade,this technique has also been proposed to adults with cancer to improve other symptoms,such as emotional distress,fatigue,or sleep difficulties.In pediatric oncology,hypnosis is also used to decrease disease-,treatment-,and procedure-related pain and anxiety.The learning of self-hypnosis and self-care techniques also improves the well-being of adults or children with cancer,their parents,and their siblings.Through several clinical cases,we will illustrate how hypnosis and self-care techniques have been implemented in the pediatric haemato-oncology department of the CHC MontLégia(Liège,Belgium)and will describe their benefits.展开更多
The rivalry between Iran and Israel has intensified over the past decades.Iran has continuously expanded its involvement across the region,which has led to a‘balance of terror’between the two countries.Various incid...The rivalry between Iran and Israel has intensified over the past decades.Iran has continuously expanded its involvement across the region,which has led to a‘balance of terror’between the two countries.Various incidents of confrontation have occurred between the two countries in the Red Sea and East of Africa since 2010s.The Iranian regime,has been expanding its strategic depth into various regions,including Africa.Different Iranian administra-tions have adopted distinct policies in their term,that are influ-enced by various factors.The relations between Iran and East African countries have been transactional and facilitated by Iran’s effort to provide various forms of financial and military assistance in exchange for friendly diplomatic relations and ability to influ-ence African leaders’attitude towards the West and its allies,par-ticularly Israel.This paper reviews the history of involvement of the two countries in these regions,and analyses how policies of con-frontation in both countries have changed and developed over the different historical periods.The paper will have a particular focus on post-2005,because there is compelling evidence indicating a substantial expansion of Iran’s engagement in these regions.展开更多
We previously reported 18FPRGD2 uptake by the coxofemoral lining,intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging.However,the molecular mechanism by which the PRGD2 tracer interacts with j...We previously reported 18FPRGD2 uptake by the coxofemoral lining,intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging.However,the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains unclear.As PRGD2 ligands are expected to belong to the RGD-specific integrin family,the purpose of this study was(i)to determine which integrin complexes display the highest affinity for PRGD2-based ligands,(ii)to analyze integrin expression in relevant tissues,and(iii)to test integrin regulation in chondrocytes using OA-related stimuli to increase the levels of fibrosis and ossification markers.To this end,the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with 125I-echistatin.In situ analyses were performed in human normal vs.OA cartilage and spinal osteophytes.Osteophytes were characterized by(immuno-)histological staining.Integrin subunit expression was tested in chondrocytes undergoing dedifferentiation,osteogenic differentiation,and inflammatory stimulation.The integrinsαVβ5,αVβ3,andαVβ6 presented the highest affinity for PRGD2-based ligands.In situ,the expression of these integrins was significantly increased in OA compared to normal cartilage.Within osteophytes,the mean integrin expression score was significantly higher in blood vessels,fibrous areas,and cells from the bone lining than in osteocytes and cartilaginous zones.In vitro,the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation(except forβ6),fibrosis,and osteogenic differentiation as well as under inflammatory stimuli.In conclusion,anatomical zones(such as OA cartilage,intervertebral discs,and facet joint osteophytes)previously reported to show PRGD2 ligand uptake in vivo expressed increased levels ofαVβ5,αVβ3,andβ6 integrins,whose subunits are modulated in vitro by OA-associated conditions that increase fibrosis,inflammation,and osteogenic differentiation.These results suggest that the increa展开更多
基金supported by NYUAD Faculty Research Funds(AD060)Tamkeen under the NYU Abu Dhabi Research Institute Award to the NYUAD Center for Genomics and Systems Biology(7371210 CGSB9)。
文摘Macroalgae are multicellular,aquatic autotrophs that play vital roles in global climate maintenance and have diverse applications in biotechnology and eco-engineering,which are directly linked to their multicellularity phenotypes.However,their genomic diversity and the evolutionary mechanisms underlying multicellularity in these organisms remain uncharacterized.In this study,we sequenced 110 macroalgal genomes from diverse climates and phyla,and identified key genomic features that distinguish them from their microalgal relatives.Genes for cell adhesion,extracellular matrix formation,cell polarity,transport,and cell differentiation distinguish macroalgae from microalgae across all three major phyla,constituting conserved and unique gene sets supporting multicellular processes.Adhesome genes show phylum-and climate-specific expansions that may facilitate niche adaptation.Collectively,our study reveals genetic determinants of convergent and divergent evolutionary trajectories that have shaped morphological diversity in macroalgae and provides genome-wide frameworks to understand photosynthetic multicellular evolution in aquatic environments.
基金This study was supported by grants from the National Natural Science Foundation of China(No.31800763 to Y.Z.)Special Grant from Postdoctoral Science Foundation of China(No.2020T130791 to Y.Z.)the National Key Research and Development Plan of China(No.2016YFA0502202 to L.Y).
文摘The efficient induction and long-term persistence of pathogen-specific memory CD8 T cells are pivotal to rapidly curb the reinfection.Recent studies indicated that long-noncoding RNAs expression is highly cell-and stage-specific during T cell development and differentiation,suggesting their potential roles in T cell programs.However,the key lncRNAs playing crucial roles in memory CD8 T cell establishment remain to be clarified.Through CD8 T cell subsets profiling of lncRNAs,this study found a key lncRNA-Snhgl with the conserved naivehl-effectorlo-memoryh,expression pattern in CD8 T cells of both mice and human,that can promote memory formation while impeding effector CD8 in acute viral infection.Further,Snhgl was found interacting with the conserved vesicle trafficking protein Vps13D to promote IL-7Ra membrane location specifically.With the deep mechanism probing,the results show Snhgl-Vps13D regulated IL-7 signaling with its dual effects in memory CD8 generation,which not just because of the sustaining role of STAT5-BCL-2 axis for memory survival,but more through the STAT3-TCF1-Blimp1 axis for transcriptional launch program of memory differentiation.Moreover,we performed further study with finding a similar high-low-high expression pattern of human SNHG1A/PS13D/IL7R/TCF7 in CD8 T cell subsets from PBMC samples of the convalescent COVID-19 patients.The central role of Snhgl-Vps13D-IL-7R-TCF1 axis in memory CD8 establishment makes it a potential target for improving the vaccination effects to control the ongoing pandemic.
文摘The incidence of primary liver cancers,and particularly hepatocellular carcinoma(HCC),is increasing throughout the world.The vast majority of HCCs develop on cirrhotic livers(CLs)(CL HCC)or livers chronically infected by hepatotropic viruses,mainly hepatitis B virus(HBV)and hepatitis C virus(HCV)(1).As HCC occurring on non-HBV non-HCV non-CL(NCL)HCC occurs much less frequently,its management is less established than for CL HCC.Consequently,many clinicians might confuse the prognosis and management of NCL HCC with the one of CL HCC.It is however demonstrated that NCL HCCs behave differently than CL HCCs.Their prognostic factors and sensibility to systemic therapy are different,added to the fact that NCLs can undergo major resections allowing curative surgical management or even systemic therapies that are not even possible in CL HCCs due to the failing function of the CL.The established criteria for liver transplantation of CL HCCs,including the famous Milan criteria,have no role in NCL HCC management(2-4).The Barcelona Clinic Liver Cancer(BCLC)strategy for prognosis prediction and treatment recommendation also concerns only CL HCCs;and should not be used for NCL HCCs(5).
基金funded by the F.R.S.-FNRS for the “EOS: The Excellence of Science-Join-t-against-Osteoarthritis”, grant number 30480119by a research grant from the Osteoarthritis Foundation and by the University of Liege (Fonds Léon Fredericq and Fonds Speciaux à la Recherche)funded by Versus Arthritis senior fellowship 21937。
文摘Abnormal subchondral bone remodeling leading to sclerosis is a main feature of osteoarthritis(OA), and osteomodulin(OMD), a proteoglycan involved in extracellular matrix mineralization, is associated with the sclerotic phenotype. However, the functions of OMD remain poorly understood, specifically in vivo. We used Omd knockout and overexpressing male mice and mutant zebrafish to study its roles in bone and cartilage metabolism and in the development of OA. The expression of Omd is deeply correlated with bone and cartilage microarchitectures affecting the bone volume and the onset of subchondral bone sclerosis and spontaneous cartilage lesions. Mechanistically, OMD binds to RANKL and inhibits osteoclastogenesis, thus controlling the balance of bone remodeling. In conclusion, OMD is a key factor in subchondral bone sclerosis associated with OA. It participates in bone and cartilage homeostasis by acting on the regulation of osteoclastogenesis. Targeting OMD may be a promising new and personalized approach for OA.
基金ESPOL Polytechnic University research project:“Register of geological and mining heritage and its incidence in the defence and preservation of geodiversity in Ecuador”with institu-tional code CIPAT-01-2018.
文摘Coastal zones, with their significant geodiversity, are vital areas for geotourism. Effective management is crucial to harness the geological interest of these sites as geotourism resources while ensuring their conservation. ManabíProvince is one of the most representative regions along the Ecuadorian coast due to its beaches and coastal cliffs, offering a wealth of tourist attractions and cultural elements. This study aims to evaluate the geosite potential of six cliffs in ManabíProvince through quantitative and qualitative analyses to propose geotourism promotion strategies. The methodology involves (i) inventory and characterisation of the cliffs, (ii) assessment of the sites by the Spanish Inventory of Places of Geological Interest method (IELIG), and (iii) qualitative evaluation through focus group discussions and Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. The results reveal that all six sites boast diverse geological assets, including geomorphological, stratigraphic, sedimentological, and tectonic elements. They are characterised by “high ”scientific, didactic, and tourist interest, while also being sus- ceptible to degradation due to natural and anthropic threats. The SWOT analysis demonstrates that the valuable geological and geomorphological heritage of potential geosites provides an opportunity to foster geotourism and boost the province’s economy, incorporating geoconservation and geoeducation strategies. This study proposes a georoute called “Ruta Acantilados del Sol ”, a 245 km journey encompassing all six sites, incorporating diverse tourist and cultural activities. Our research lays the foundation for fostering geotourism along the Manabícoast and strengthening the connection between nature, heritage, and the welfare of residents within a global resilience plan.
文摘The optimal duration of biological treatment, particularly anti-TNF, in inflammatory bowel disease （IBD） is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of IBD, long term safety of biologics, immunosuppressors （IS） cessation and some preliminary studies on biologics cessation may help us to discuss this topic. The decision to stop a biological treatment is currently based on a compromise between the benefits and risks associated with the prolongation of this treatment. IBD, more particularly CD, are characterized by the development of complications and the need for recurrent hospitalizations and surgeries in approximately 2/3 of cases. In these patients potentially in need of biological treatments, it is probable that, as it has been demonstrated for IS, the longer a stable remission has be achieved under treatment, the lower the risk of relapse is alter treatment cessation. Further prospective studies should now aim at disclosing patient characteristics associated with a low risk of relapse to imple- ment this strategy.
文摘While therapeutic strategies able to change the natural history of the disease are developing,it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic strategies.Clinical predictors have probably been the most broadly studied.In both Crohn's disease(CD) and ulcerative colitis(UC),age at diagnosis,disease location and smoking habit are currently the strongest predictors of disease course.A younger age at onset is associated with more aggressive disease both in CD and UC.Disease location in CD is associated with different types of complications:surgery and recurrence in upper gastrointestinal and proximal small bowel disease;and surgery in distal small bowel disease and peri-anal lesions in rectal disease.In UC,extensive colitis is clearly been associated with more severe disease.Finally,active smoking globally increases disease severity in CD but decreases it in UC.Besides these important factors,others may predispose to some specific disease evolution and complications,and are also reviewed in the present paper.
文摘The exploitation of industrial strains of chickens in the Sahelian climate of Niger is characterized by a decline in performance and significant costs associated with their maintenance. In contrast, local chickens are well adapted to these environmental conditions but with poor production performance. Genetic selection of these local chickens could improve their productivity. The first step is to determine if the genetic parameters of their growth are high enough to ensure a successful selection strategy. To do so, weekly weights of 69 parents and 119 offspring were followed for 20 weeks. The heritability and genetic correlations of these weights were estimated through the Bayesian approach using the MCMCglmm package on R software. At hatching, weights ranged from 23 to 25 g. At 20 weeks, these weights ranged from 1031 to 1052 g for females and 1308 to 1445 g for males. Heritabilities for hatch weights at 4, 8, 12, 16, and 20 weeks of age were estimated to be 0.56, 0.31, 0.52, 0.53, 0.52 and 0.48 respectively and all genetic correlations were positive. In particular, weight at 8 weeks of age showed both good heritability (h<sup>2</sup> = 0.52) and strong, positive genetic correlations with weights at older ages. These results indicate that genetic selection to improve weight at 8 weeks of age would be a good strategy to improve the overall growth performance of these chickens.
文摘Some cities worldwide have oil wells directly affecting the management of the territory.For example,La Libertad and Salinas districts contain 467 oil wells in urban areas representing a major land-use planning challenge.The objective is to apply the CLUE-S land use model in coastal cities with oil wells(Salinas-La Libertad),using geographic information systems considering environmental and security characteristics for territorial development.The stages of the study are:i)classification and categorisation of oil wells;ii)application of the GIS-CLUE-S method and visualisation of land use dynamics;iii)use the SWOT-TOWS matrix,for the analysis of the situation and the main factors affecting the territory.The results indicate high vulnerability in many urban sectors and those close to the coastline.Furthermore,the CLUE-S analysis shows that the population growth in the urban sector is close to oil well areas,making it a complex pole of human-industry interaction that impacts the management of the territory.This study synthesises three technical aspects:some oil wells do not comply with municipal ordinance regulations;identification of vulnerable zones due to environmental and security factors,which recommends a territorial reordering policy;as well as an education plan for the application of territorial ordering policies,with awareness and sustainability projections.
文摘In this paper, we propose a new spatial-multiplexing(SM) scheme employing an orthogonal precoder over Rayleigh-fading channels for an erasure event in single frequency networks(SFN). To optimize the precoder, the average bit error rate(BER) is evaluated and minimized through a mathematical analysis. Compared to an ordinary SM, the proposed scheme guarantees identical BER performance under non-erasure fading channels and achieves a greatly improved performance under erasure fading channels, especially for a higher erasure-ratio and SNR values. This improvement is mainly due to the increase in the diversity gain incurred by the optimized precoder over the erasure event. We also compare the performance of the proposed SM to that of the conventional constellation-rotation(CR) scheme applied to the single antenna SFN systems. The results of a computer simulation show that the performance of the new scheme is more effective than that of a conventional CR across all simulation cases.
基金partially supported by Consejo de Investigación y Desarrollo Tecnológico(CIDET Project 16Q409 to C.F.A.)Fondo para la Investigación Científica y Tecnológica Project(PICTO UNaM 2011 No.122 to C.F.A)
文摘The uniparental inheritance and conserved structure of the chloroplast genome among many angiosperms makes it suitable for constructing gene lineages and inferring population histories based on these relationships. However, the analysis of a single chloroplast region to solve population issues has not yielded the desired amount of variability due to the low mutation rate. Therefore, it is necessary to screen and carefully analyze chloroplast intergenic or intronic regions to select the most appropriate for studying the genetic variability in the chloroplast genome of a particular taxon. In this context, the aim of this work was to characterize 8 regions in Calophyllum brasiliense using 11 selected primer pairs and to evaluate their usefulness for phylogeographic analysis. Intergenic spacers petA-psbJ, petG-trnP and rp132-trnL and the trnL intron demonstrated potentially informative sites. The combination of these 4 regions will allow the analysis of genetic population structure and the integration of historical aspects to inform strategies for conserving C. brasiliense, especially for highly impacted populations and those at risk of local extinction.
文摘Arecent study published in Nature Immunology by Sheedy et al.1 indicates that uptake of modified low-den- sity lipoprotein （LDL） by the scavenger receptor CD36 primes and activates the NLRP3 inflammasome, providing an early pathogenic pathway that links cho- lesterol accumulation to the chronic inflammatory process of atherosclero- sis.1 Atherosclerosis arises from chronic vascular inflammation elicited by lipids.
基金supported by the National Natural Science Foundation of China (31790413, 31760657)。
文摘The limited knowledge of genomic noncoding and regulatory regions has restricted our ability to decipher the genetic mechanisms underlying complex traits in pigs. In this study, we characterized the spatiotemporal landscape of putative enhancers and promoters and their target genes by combining H3K27ac-targeted Ch IP-Seq and RNA-Seq in fetal(prenatal days 74–75) and adult(postnatal days 132–150) tissues(brain, liver, heart, muscle and small intestine) sampled from Asian aboriginal Bama Xiang and European highly selected Large White pigs of both sexes. We identified 101,290 H3K27ac peaks, marking 18,521promoters and 82,769 enhancers, including peaks that were active across all tissues and developmental stages(which could indicate safe harbor locus for exogenous gene insertion) and tissue-and developmental stage-specific peaks(which regulate gene pathways matching tissue-and developmental stage-specific physiological functions). We found that H3K27ac and DNA methylation in the promoter region of the XIST gene may be involved in X chromosome inactivation and demonstrated the utility of the present resource for revealing the regulatory patterns of known causal genes and prioritizing candidate causal variants for complex traits in pigs. In addition, we identified an average of 1,124 super-enhancers per sample and found that they were more likely to show tissue-specific activity than ordinary peaks. We have developed a web browser to improve the accessibility of the results(http://segtp.jxau.edu.cn/pencode/?genome=sus Scr11).
文摘In cell therapy protocols, many tissues were proposed as a source of mesenchymal stem cells(MSC) isolation. So far, bone marrow(BM) has been presented as the main source of MSC despite the invasive isolation pro-cedure related to this source. During the last years, the umbilical cord(UC) matrix was cited in different studies as a reliable source from which long term ex vivo prolif-erating fibroblasts were isolated but with contradictory data about their immunophenotype, gene expression profile, and differentiation potential. Hence, an inter-esting question emerged: Are cells isolated from cord matrix(UC-MSC) different from other MSCs? In this re-view, we will summarize different studies that isolated and characterized UC-MSC. Considering BM-MSC as gold standard, we will discuss if UC-MSC fulfill different criteria that define MSC, and what remain to be done in this issue.
基金Supported by the Patrimonio Autónomo Fondo Nacional de Financiamiento para la Ciencia,la Tecnología y la Innovación,Fondo Francisco Joséde Caldas from the Colombian Ministry of Science,Technology,and Innovation (MINCIENCIAS,1115-852-70955)Open Access funding provided by Colombia Consortium。
文摘Convection-permitting modeling allows us to understand mechanisms that influence rainfall in specific regions.However,microphysics parameterization(MP) and planetary boundary layer(PBL) schemes remain an important source of uncertainty,affecting rainfall intensity,occurrence,duration,and propagation.Here,we study the sensitivity of rainfall to three MP [Weather Research and Forecasting(WRF) Single-Moment 6-class(WSM6),Thompson,and Morrison] and two PBL [the Yonsei University(YSU) and Mellor–Yamada Nakanishi Niino(MYNN)] schemes with a convection-permitting resolution(4 km) over northwestern South America(NWSA).Simulations were performed by using the WRF model and the results were evaluated against soundings,rain gauges,and satellite data,considering the spatio-temporal variability of rainfall over diverse regions prone to deep convection in NWSA.MP and PBL schemes largely influenced simulated rainfall,with better results for the less computationally expensive WSM6 MP and YSU PBL schemes.Regarding rain gauges and satellite estimates,simulations with Morrison MP overestimated rainfall,especially westward of the Andes,whereas the MYNN PBL underestimated precipitation in the Amazon–Savannas flatlands.We found that the uncertainty in the rainfall representation is highly dependent on the region,with a higher influence of MP in the Colombian Pacific and PBL in the Amazon–Savannas flatlands.When analyzing rainfall-related processes,the selection of both MP and PBL parameterizations exerted a large influence on the simulated lower tropospheric moisture flux and moisture convergence.PBL schemes significantly influenced the downward shortwave radiation,with MYNN simulating a greater amount of low clouds,which decreased the radiation income.Furthermore,latent heat fluxes were greater for YSU,favoring moist convection and rainfall.MP schemes had a marked impact on vertical velocity.Specifically,Morrison MP showed stronger convection and higher precipitation rates,which is associated with a greater latent heat release d
文摘Hypnosis is a modified state of consciousness which showed its benefits to decrease different symptoms,mainly pain.During the last decade,this technique has also been proposed to adults with cancer to improve other symptoms,such as emotional distress,fatigue,or sleep difficulties.In pediatric oncology,hypnosis is also used to decrease disease-,treatment-,and procedure-related pain and anxiety.The learning of self-hypnosis and self-care techniques also improves the well-being of adults or children with cancer,their parents,and their siblings.Through several clinical cases,we will illustrate how hypnosis and self-care techniques have been implemented in the pediatric haemato-oncology department of the CHC MontLégia(Liège,Belgium)and will describe their benefits.
基金supported by the German Research Foundation(DFG,463159331)H2020 Marie Sklodowska‐Curie Actions,Grant/Award Number:101025388.
文摘The rivalry between Iran and Israel has intensified over the past decades.Iran has continuously expanded its involvement across the region,which has led to a‘balance of terror’between the two countries.Various incidents of confrontation have occurred between the two countries in the Red Sea and East of Africa since 2010s.The Iranian regime,has been expanding its strategic depth into various regions,including Africa.Different Iranian administra-tions have adopted distinct policies in their term,that are influ-enced by various factors.The relations between Iran and East African countries have been transactional and facilitated by Iran’s effort to provide various forms of financial and military assistance in exchange for friendly diplomatic relations and ability to influ-ence African leaders’attitude towards the West and its allies,par-ticularly Israel.This paper reviews the history of involvement of the two countries in these regions,and analyses how policies of con-frontation in both countries have changed and developed over the different historical periods.The paper will have a particular focus on post-2005,because there is compelling evidence indicating a substantial expansion of Iran’s engagement in these regions.
基金This study was supported by the“Fond d’Investissement pour la Recherche Scientifique”(FIRS),CHU de Liège,Belgium.
文摘We previously reported 18FPRGD2 uptake by the coxofemoral lining,intervertebral discs and facet joint osteophytes in OA using PET/SCAN imaging.However,the molecular mechanism by which the PRGD2 tracer interacts with joint tissues and osteophytes in OA remains unclear.As PRGD2 ligands are expected to belong to the RGD-specific integrin family,the purpose of this study was(i)to determine which integrin complexes display the highest affinity for PRGD2-based ligands,(ii)to analyze integrin expression in relevant tissues,and(iii)to test integrin regulation in chondrocytes using OA-related stimuli to increase the levels of fibrosis and ossification markers.To this end,the affinity of PRGD2-based ligands for five heterodimeric integrins was measured by competition with 125I-echistatin.In situ analyses were performed in human normal vs.OA cartilage and spinal osteophytes.Osteophytes were characterized by(immuno-)histological staining.Integrin subunit expression was tested in chondrocytes undergoing dedifferentiation,osteogenic differentiation,and inflammatory stimulation.The integrinsαVβ5,αVβ3,andαVβ6 presented the highest affinity for PRGD2-based ligands.In situ,the expression of these integrins was significantly increased in OA compared to normal cartilage.Within osteophytes,the mean integrin expression score was significantly higher in blood vessels,fibrous areas,and cells from the bone lining than in osteocytes and cartilaginous zones.In vitro,the levels of integrin subunits were significantly increased during chondrocyte dedifferentiation(except forβ6),fibrosis,and osteogenic differentiation as well as under inflammatory stimuli.In conclusion,anatomical zones(such as OA cartilage,intervertebral discs,and facet joint osteophytes)previously reported to show PRGD2 ligand uptake in vivo expressed increased levels ofαVβ5,αVβ3,andβ6 integrins,whose subunits are modulated in vitro by OA-associated conditions that increase fibrosis,inflammation,and osteogenic differentiation.These results suggest that the increa
