The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various...The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.展开更多
Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most preva...Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most prevalent forms of post-translational modification,playing a crucial role in biological complexity.With more than ten monosaccharides identified within mammalian brain cells and more than 1×1012 possible combinations,the heterogeneity of glycosylation is extensive(Conroy et al.,2021).The diversity of glycans and the complexity of their structures allow for a wide range of protein functions.N-glycans are one of the most abundant forms of glycans and are involved in various cellular functions.N-glycans can be added to proteins at specific sequons,Asn-X-Ser/Thr,and are classified into three main types in mature glycoproteins:high mannose,complex,and hybrid.High mannose N-glycans consist of 5-9 mannose residues linked to a chitobiose core and undergo processing into complex or hybrid forms in the Golgi apparatus(Varki et al.,2017).Complex N-glycans are more diverse and contain various branched structures such as antennae with fucose,galactose,and sialic acid residues.Hybrid N-glycans contain one or more complex branches in conjunction with an oligomannose branch(Fisher and Ungar,2016).Understanding the specific functions of these different types of N-glycans in protein regulation,folding,and function is an active area of research in the life sciences,including glycobiology.展开更多
Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and on...Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.展开更多
BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC ...BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.展开更多
Metal halide perovskites have emerged as promising light-emitting materials for next-generation displays owing to their remarkable material characteristics including broad color tunability,pure color emission with rem...Metal halide perovskites have emerged as promising light-emitting materials for next-generation displays owing to their remarkable material characteristics including broad color tunability,pure color emission with remarkably narrow bandwidths,high quantum yield,and solution processability.Despite recent advances have pushed the luminance efficiency of monochromic perovskite light-emitting diodes(PeLEDs)to their theoretical limits,their current fabrication using the spincoating process poses limitations for fabrication of full-color displays.To integrate PeLEDs into full-color display panels,it is crucial to pattern red–green–blue(RGB)perovskite pixels,while mitigating issues such as cross-contamination and reductions in luminous efficiency.Herein,we present state-of-the-art patterning technologies for the development of full-color PeLEDs.First,we highlight recent advances in the development of efficient PeLEDs.Second,we discuss various patterning techniques of MPHs(i.e.,photolithography,inkjet printing,electron beam lithography and laserassisted lithography,electrohydrodynamic jet printing,thermal evaporation,and transfer printing)for fabrication of RGB pixelated displays.These patterning techniques can be classified into two distinct approaches:in situ crystallization patterning using perovskite precursors and patterning of colloidal perovskite nanocrystals.This review highlights advancements and limitations in patterning techniques for PeLEDs,paving the way for integrating PeLEDs into full-color panels.展开更多
Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adul...Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.展开更多
Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of...Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.展开更多
Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).S...Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.展开更多
Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upreg...Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.展开更多
Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Holl...Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.展开更多
Effective landscape-scale fuel management strategies are essential for reducing wildfire risk in Mediterranean fire-prone areas.In this study,the minimum travel time(MTT)fire-spread algorithm as implemented in FlamMap...Effective landscape-scale fuel management strategies are essential for reducing wildfire risk in Mediterranean fire-prone areas.In this study,the minimum travel time(MTT)fire-spread algorithm as implemented in FlamMap was applied to assess the potential of alternative fuel treatments for lowering wildfire losses in a 5,740-ha study area in eastern Sardinia,Italy.Twenty-seven wildfires at 10-m resolution were simulated considering three wind speeds(15,18,and 21 km h-1)to compare fuel treatments:no treatment(NT),irrigated agroforestry areas with shrub clearing(T1),prescribed fire in eucalyptus stands(T2),and irrigated grasslands(T3).The simulations replicated a recent large wildfire that occurred in the study area(Orrìwildfire,2019)and considered the weather and fuel moisture conditions associated with this event.The average wildfire exposure outputs(burned area,probability of burning,conditional flame length,potential crown fire occurrence,and surfaces withflame lengths above 2.5 m)decreased after fuel treatments,compared to no treatment.T1 was the most effective strategy in mitigating wildfire hazards and provided the most significant performance for several wildfire exposure indicators.Treating only 0.5%of the study area(~30 ha)resulted in a decrease in all wildfire exposure metrics to~10%within the study area.In addition,the total surface characterized by high flame length(average>2.5 m)was the lowest in the T1 treatment.This study can help land and fire managers optimize fuel treatment opportunities and wildfire risk mitigation strategies in Mediterranean areas.展开更多
Herein, a stable and efficient CoS_(2)-ReS_(2) electrocatalyst is successfully constructed by using the different molar ratios of CoS_(2) on ReS_(2). The size and morphology of the catalysts are significantly changed ...Herein, a stable and efficient CoS_(2)-ReS_(2) electrocatalyst is successfully constructed by using the different molar ratios of CoS_(2) on ReS_(2). The size and morphology of the catalysts are significantly changed after the CoS_(2) is grown on ReS_(2), providing regulation of the catalytic activity of ReS_(2). Particularly, the optimized CoS_(2)-ReS_(2) shows superior electrocatalytic properties with a low voltage of 1.48 V at 20 mA cm^(-2) for overall water splitting in 1.0 M KOH, which is smaller than the noble metal-based catalysts(1.77 V at 20 mA cm^(-2)). The XPS, XAS, and theoretical data confirm that the interfacial regulation of ReS_(2) by CoS_(2) can provide rich edge catalytic sites, which greatly optimizes the catalytic kinetics and drop the energy barrier for oxygen/hydrogen evolution reactions. Our results demonstrated that interfacial engineering is an efficient route for fabricating high-performance water splitting electrocatalysts.展开更多
Van der Waals(VDW)heterojunctions in a 2D/2D contact provide the highest area for the separation and transfer of charge carriers.In this work,a top-down strategy with a gas erosion process was employed to fabricate a ...Van der Waals(VDW)heterojunctions in a 2D/2D contact provide the highest area for the separation and transfer of charge carriers.In this work,a top-down strategy with a gas erosion process was employed to fabricate a 2D/2D carbon nitride VDW heterojunction in carbon nitride(g-C_(3)N_(4))with carbon-rich carbon nitride.The created 2D semiconducting channel in the VDW structure exhibits enhanced electric field exposure and radiation absorption,which facilitates the separation of the charge carriers and their mobility.Consequently,compared with bulk g-C_(3)N_(4)and its nanosheets,the photocatalytic performance of the fabricated carbon nitride VDW heterojunction in the water splitting reaction to hydrogen is improved by 8.6 and 3.3 times,respectively,while maintaining satisfactory photo-stability.Mechanistically,the finite element method(FEM)was employed to evaluate and clarify the contributions of the formation of VDW heterojunction to enhanced photocatalysis,in agreement quantitatively with experimental ones.This study provides a new and effective strategy for the modification and more insights to performance improvement on polymeric semiconductors in photocatalysis and energy conversion.展开更多
基金supported by the Spanish“Plan Nacional de Investigación Científica,Desarrollo e Innovación Tecnológica,Ministerio de Economía y Competitividad(Instituto de Salud CarlosⅢ)”,Grant FIS PI20-0318 co-financed by“Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”Grant P18-RT-5059“Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020),Consejería de Transformación Económica,Industria,Conocimiento y Universidades,Junta de Andalucía,Espana”(all to VC)Grant PPJIA202219“Ayudas del plan propio UGR 2022,Plan propio de investigación y transferencia,Universidad de Granada,Espana”(to JCA andóDGG)。
文摘The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.
基金supported by the Institute for Basic Science(IBS-R001-D2-2022-A03).
文摘Glycosylation is a process that involves the addition of sugar moieties or glycans to different types of molecules,including proteins,lipids,and nucleic acids.Among these,protein glycosylation is one of the most prevalent forms of post-translational modification,playing a crucial role in biological complexity.With more than ten monosaccharides identified within mammalian brain cells and more than 1×1012 possible combinations,the heterogeneity of glycosylation is extensive(Conroy et al.,2021).The diversity of glycans and the complexity of their structures allow for a wide range of protein functions.N-glycans are one of the most abundant forms of glycans and are involved in various cellular functions.N-glycans can be added to proteins at specific sequons,Asn-X-Ser/Thr,and are classified into three main types in mature glycoproteins:high mannose,complex,and hybrid.High mannose N-glycans consist of 5-9 mannose residues linked to a chitobiose core and undergo processing into complex or hybrid forms in the Golgi apparatus(Varki et al.,2017).Complex N-glycans are more diverse and contain various branched structures such as antennae with fucose,galactose,and sialic acid residues.Hybrid N-glycans contain one or more complex branches in conjunction with an oligomannose branch(Fisher and Ungar,2016).Understanding the specific functions of these different types of N-glycans in protein regulation,folding,and function is an active area of research in the life sciences,including glycobiology.
基金funded by the Ramón Areces Foundation.IEC is supported by the Spanish Ministry of Science and Innovation(RYC2019-027287-I)the Spanish Ministry of Economy and Competitiveness(RTI2018-095284-J-100)+1 种基金supported by a grant from ANID/BECAS Chile(Grant No.72180543)through a Margarita Salas grant from the Spanish Ministry Universities。
文摘Background:One of the pathological hallmarks distinguishing Alzheimer’s disease from other dementias is the accumulation of amyloid beta(Aβ).Higher physical activity is associated with decreased dementia risk,and one potential path could be through Aβlevels modulation.We aimed to explore the relationship between physical activity and Aβin middle-aged and older adults.Methods:A systematic search of PubMed,Web of Science,PsycINFO,Cochrane Central Register of Controlled Trials,and SPORTDiscus was performed from inception to April 28,2022.Studies were eligible if they included physical activity and Aβdata in adults aged 45 years or older.Multi-level metaanalyses of intervention and observational studies were performed to examine the role of physical activity in modulating Aβlevels.Results:In total,37 articles were included(8 randomized controlled trials,3 non-randomized controlled trials,4 prospective longitudinal studies,and 22 cross-sectional studies).The overall effect size of physical activity interventions on changes in blood Aβwas medium(pooled standardized mean difference=-0.69,95%confidence interval(95%CI):-1.41 to 0.03;I^(2)=74.6%).However,these results were not statistically significant,and there were not enough studies to explore the effects of physical activity on cerebrospinal fluid(CSF)and brain Aβ.Data from observational studies were examined based on measurements of Aβin the brain using positron emission tomography scans,CSF,and blood.Higher physical activity was positively associated with Aβonly in the CSF(Estimate r=0.12;95%CI:0.05-0.18;I^(2)=38.00%).Conclusion:Physical activity might moderately reduce blood Aβin middle-aged and older adults.However,results were only near statistical significance and might be interpreted with caution given the methodological limitations observed in some of the included studies.In observational studies,higher levels of physical activity were positively associated with Aβonly in CSF.Therefore,further research is needed to understand the modulating role of physical activity in the brain,CSF,and blood Aβ,as well as its implication for cognitive health.
文摘BACKGROUND Metastatic pancreatic ductal adenocarcinoma(PDAC)is a lethal malignancy with dispiriting survival data.Immunotherapy is a promising approach to many cancer types,but achieves poor outcomes in advanced PDAC due to its immunosuppressive tumor microenvironment.We describe a case of metastatic PDAC effectively treated with pembrolizumab.CASE SUMMARY We report the case of a 67-year-old woman with unresectable locally advanced PDAC,treated with gemcitabine plus nab-paclitaxel followed by radiotherapy plus capecitabine.At nine months,pancreatic tumor progression was observed at the level of the hepatic hilum with the appearance of a new pulmonary nodule suggestive of a second primary,confirmed by left lung biopsy.Systemic immunotherapy was then initiated with pembrolizumab,an immune checkpoint inhibitor targeting programmed cell death protein-1 that covers the two tumor types.The patient showed a complete metabolic response that was maintained throughout the treatment.The patient continues to be disease-free at 5.6 years since the start of immunotherapy.CONCLUSION These results suggest that the administration of pembrolizumab after chemoradiotherapy has a beneficial effect in patients with metastatic PDAC.To our knowledge,this is the first reported case of a patient with metastatic PDAC and metastatic lung cancer showing such a long-lasting complete response after pembrolizumab treatment without curative surgery.Further studies are required to determine biomarkers that identify PDAC patients most likely to benefit from this immunotherapy.
基金the National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(Grant No.2021R1C1C1007997).
文摘Metal halide perovskites have emerged as promising light-emitting materials for next-generation displays owing to their remarkable material characteristics including broad color tunability,pure color emission with remarkably narrow bandwidths,high quantum yield,and solution processability.Despite recent advances have pushed the luminance efficiency of monochromic perovskite light-emitting diodes(PeLEDs)to their theoretical limits,their current fabrication using the spincoating process poses limitations for fabrication of full-color displays.To integrate PeLEDs into full-color display panels,it is crucial to pattern red–green–blue(RGB)perovskite pixels,while mitigating issues such as cross-contamination and reductions in luminous efficiency.Herein,we present state-of-the-art patterning technologies for the development of full-color PeLEDs.First,we highlight recent advances in the development of efficient PeLEDs.Second,we discuss various patterning techniques of MPHs(i.e.,photolithography,inkjet printing,electron beam lithography and laserassisted lithography,electrohydrodynamic jet printing,thermal evaporation,and transfer printing)for fabrication of RGB pixelated displays.These patterning techniques can be classified into two distinct approaches:in situ crystallization patterning using perovskite precursors and patterning of colloidal perovskite nanocrystals.This review highlights advancements and limitations in patterning techniques for PeLEDs,paving the way for integrating PeLEDs into full-color panels.
基金funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud CarlosⅢ(PI13/01393)by the Retos de la Sociedad program(DEP2016-79512-R)+7 种基金European Regional Development Funds(ERDF)the Spanish Ministry of Education(FPU13/04365 and FPU19/01609)the Fundación Iberoamericana de Nutrición(FINUT)the Redes Temáticas de Investigación Cooperativa RETIC(Red SAMID RD16/0022)the Astra Zeneca Health Care Foundationthe University of Granada Plan Propio de Investigación 2016-Excellence actions:Unit of Excellence on Exercise and Health(UCEES)-and Plan Propio de Investigación 2018-the Programa Contratos-Puente and Contratos Perfeccionamiento de Doctoresthe Junta de Andalucía,Consejería de Conocimiento,Investigacióny Universidades(ERDF,ref.SOMM17/6107/UGR)the Fundación Alfonso Martín Escudero(grant awarded to GSD)。
文摘Purpose:The present work examines the associations of dietary habits,sedentarism,physical activity(PA)levels and sleep habits,with thyroid function in young euthyroid adults.Methods:A total of 105 young euthyroid adults participated in this cross-sectional study.Thyroid function was determined in fasting conditions(>6 h).Dietary habits were measured by a food frequency questionnaire and three non-consecutive 24 h recalls,and different dietary intake and patterns were then estimated.The time spent in sedentary,PA levels and sleep habits were objectively measured using a wrist-worn accelerometer.Results:Energy and carbohydrate intake were positively associated with thyroid stimulating hormone(TSH)(β=0.222;R^(2)=0.102;P=0.022 andβ=0.425;R^(2)=0.129;P=0.007,respectively)whereas fat intake was negatively associated with TSH(β=-0.428;R^(2)=0.137;P=0.004).Energy intake was also positively associated with free triiodothyronine(β=0.277;R^(2)=0.137;P=0.004).Further,adherence to the Mediterranean diet was negatively related to TSH and free thyroxine(FT4)(β=-0.221;R^(2)=0.113;P=0.020 andβ=-0.268;R^(2)=0.071;P=0.007,respectively).Vigorous-intensity and overall PA were negatively associated with FT4(β=-0.227;R^(2)=0.052;P=0.022 andβ=-0.204;R^(2)=0.042;P=0.041,respectively).In contrast,no associations were found between sleep parameters and thyroid function.Conclusions:Lifestyle factors such as dietary intake and PA levels seems to be related to thyroid function even in young euthyroid adults.
基金support by the Spanish Ministry of Science and Innovation(Ref:PID2020-117302RA-I00)La Caixa Foundation(Ref:LCF/BQ/PR19/11700007)+3 种基金the University of Granada Plan Propio de Investigación 2021-Excellence actions:Unit of Excellence on Exercise,Nutrition,and Health(UCEENS)and by CIBEROBN,Centro de Investigación Biomédica en Red(CB22/3/00058)Instituto de Salud Carlos III,Ministerio de Ciencia e Innovación and Unión Europea-European Regional Development FundAMP was also recipient of a predoctoral fellowship(FPU20/05530)by the Spanish Ministry of Education,Culture and SportEUG was supported by the Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea-NextGenerationEU.
文摘Background Pediatric cancer survivors are at increased risk of muscle weakness and low areal bone mineral density(aBMD).However,the prevalence of muscle strength deficits is not well documented,and the associations of muscle strength with aBMD are unknown in this population.Therefore,this study aimed to investigate the prevalence of upper-and lower-body muscle strength deficits and to examine the associations of upper-and lower-body muscle strength with age-,sex,and race-specific aBMD Z-scores at the total body,total hip,femoral neck,and lumbar spine.Methods This cross-sectional study included 116 pediatric cancer survivors(12.1±3.3 years old,mean±SD;42.2%female).Upper-and lower-body muscle strength were assessed by handgrip and standing long jump test,respectively.Dual‑energy X‑ray absorptiometry was used to measure aBMD(g/cm2).Associations between muscle strength and aBMD were evaluated in multivariable linear regression models.Logistic regression was used to evaluate the contribution of muscle strength(1-decile lower)to the odds of having low aBMD(Z-score≤1.0).All analyses were adjusted for time from treatment completion,radiotherapy exposure,and body mass index.Results More than one-half of survivors were within the 2 lowest deciles for upper-(56.9%)and lower-body muscle strength(60.0%)in comparison to age-and sex-specific reference values.Muscle strength deficits were associated with lower aBMD Z-scores at all sites(B=0.133–0.258,p=0.001–0.032).Each 1-decile lower in upper-body muscle strength was associated with 30%–95%higher odds of having low aBMD Z-scores at all sites.Each 1-decile lower in lower-body muscle strength was associated with 35%–70%higher odds of having low aBMD Z-scores at total body,total hip,and femoral neck.Conclusion Muscle strength deficits are prevalent in young pediatric cancer survivors,and such deficits are associated with lower aBMD Z-scores at all sites.These results suggest that interventions designed to improve muscle strength in this vulnerable population may have the added benefit of improving aBMD.
文摘Autoimmune pancreatitis(AIP),a chronic inflammation caused by the immune system attacking the pancreas,usually presents imaging and clinical features that overlap with those of pancreatic ductal adenocarcinoma(PDAC).Serum biomarkers,substances that quantitatively change in sera during disease development,are a promising non-invasive tool with high utility for differentiating between these diseases.In this way,the presence of AIP is currently suspected when serum concentrations of immunoglobulin G4(IgG4)antibody are elevated.However,this approach has some drawbacks.Notably,IgG4 antibody concentrations are also elevated in sera from some patients with PDAC.This review focuses on the most recent and relevant serum biomarkers proposed to differentiate between AIP and PDAC,evaluating the usefulness of immunoglobulins,autoantibodies,chemokines,and cytokines.The proposed serum biomarkers have proven useful,although most studies had a small sample size,did not examine their presence in patients with PDAC,or did not test them in humans.In addition,current evidence suggests that a single serum biomarker is unlikely to accurately differentiate these diseases and that a set of biomarkers will be needed to achieve adequate specificity and sensitivity,either alone or in combination with clinical data and/or radiological images.
基金financed by the Spanish"Plan Nacional de Investigación Cientifica,Desorrollo e Innovación Tecnológica,Ministerio de Economíay Competitividod(Instituto de Solud CarlosⅢ)",grant Nos:FIS PI17-0393,FIS PI20-0318co-financed by the"Fondo Europeo de Desorrollo Regional ERDF-FEDER European Union",grant No.P18-RT-5059+2 种基金by"Plan Andaluz de Investigación,Desarrollo e Innovación(PAIDI 2020)Consejerio de Transformoción Económico,Industria,Conocimiento y Universidades,Junta de Andolucío,Espa?a",and grant No.A-CTS-498-UGR18by"Programa Operotivo FEDER Andalucía 2014-2020,Universidod de Granada,Junta de Andalucía,Espa?a",ca-funded by ERDF-FEDER,the European Union(all to VC)。
文摘Growth-associated protein 43 plays a key role in neurite outgrowth through cytoskeleton remodeling.We have previously demonstrated that structural damage of peripheral nerves induces growth-associated protein 43 upregulation to promote growth cone formation.Conversely,the limited regenerative capacity of the central nervous system due to an inhibitory environment prevents major changes in neurite outgrowth and should be presumably associated with low levels of growth-associated protein 43 expression.However,central alterations due to peripheral nerve damage have never been assessed using the growthassociated protein 43 marker.In this study,we used the tubulization technique to repair 1 cm-long nerve gaps in the rat nerve injury/repair model and detected growth-associated protein 43 expression in the peripheral and central nervous systems.First,histological analysis of the regeneration process confirmed an active regeneration process of the nerve gaps through the conduit from 10 days onwards.The growth-associated protein 43 expression profile varied across regions and follow-up times,from a localized expression to an abundant and consistent expression throughout the regeneration tissue,confirming the presence of an active nerve regeneration process.Second,spinal cord changes were also histologically assessed,and no apparent changes in the structural and cellular organization were observed using routine staining methods.Surprisingly,remarkable differences and local changes appeared in growth-associated protein 43 expression at the spinal cord level,in particular at 20 days post-repair and beyond.Growth-associated protein 43 protein was first localized in the gracile fasciculus and was homogeneously distributed in the left posterior cord.These findings differed from the growth-associated protein 43 pattern observed in the healthy control,which did not express growth-associated protein 43 at these levels.Our results revealed a differential expression in growth-associated protein 43 protein not only in the regenerating nerve tissue but also in the spinal cord after peripheral nerve transection.These findings open the possibility of using this marker to monitor changes in the central nervous system after peripheral nerve injury.
基金funded by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos Ⅲ),grants Nos. FIS PI14-1343, FIS PI17-0393, and FIS PI20-0318 co-financed by the “Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”grant No. P18-RT-5059 by “Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020),Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España”grant No. A-CTS-498-UGR18 by “Programa Operativo FEDER Andalucía 2014–2020, Universidad de Granada, Junta de Andalucía, España”, co-funded by ERDF-FEDER, the European Union (all to VC)
文摘Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair;however,results are still not comparable with the current gold standard technique“autografts”.Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair.Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance.In this study,we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model.Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks.Nevertheless,the molecular assessment in the early regeneration phase(7,14,and 28 days)has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones.Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1,a growth factor that plays an important role in Schwann cell transdifferentiation.The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2,VEGF-A,BDNF,c-Jun,and ATF3.
基金funded by"MED-Star"(Grant No.E88H19000120007)“Med-Foreste”(grant no.B85I1900010007)+5 种基金“Med-Coopfi re”(Grant No.B81I1900010007)projectssupported by the European Union under the cross-border Programma Italia-Francia Marittimo 2014–2020the“FOE2019-Climate Change:risk mitigation for sustainable development”(Ministerial Decree no.856/19)projectfunded by the Italian Ministry of EducationUniversity and Research(MIUR)co-financed by the University of Sassari,Fondo di Ateneo per la Ricerca Scientifica(FAR)2020。
文摘Effective landscape-scale fuel management strategies are essential for reducing wildfire risk in Mediterranean fire-prone areas.In this study,the minimum travel time(MTT)fire-spread algorithm as implemented in FlamMap was applied to assess the potential of alternative fuel treatments for lowering wildfire losses in a 5,740-ha study area in eastern Sardinia,Italy.Twenty-seven wildfires at 10-m resolution were simulated considering three wind speeds(15,18,and 21 km h-1)to compare fuel treatments:no treatment(NT),irrigated agroforestry areas with shrub clearing(T1),prescribed fire in eucalyptus stands(T2),and irrigated grasslands(T3).The simulations replicated a recent large wildfire that occurred in the study area(Orrìwildfire,2019)and considered the weather and fuel moisture conditions associated with this event.The average wildfire exposure outputs(burned area,probability of burning,conditional flame length,potential crown fire occurrence,and surfaces withflame lengths above 2.5 m)decreased after fuel treatments,compared to no treatment.T1 was the most effective strategy in mitigating wildfire hazards and provided the most significant performance for several wildfire exposure indicators.Treating only 0.5%of the study area(~30 ha)resulted in a decrease in all wildfire exposure metrics to~10%within the study area.In addition,the total surface characterized by high flame length(average>2.5 m)was the lowest in the T1 treatment.This study can help land and fire managers optimize fuel treatment opportunities and wildfire risk mitigation strategies in Mediterranean areas.
基金supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)(NRF-2022R1A2C2093415) and (NRF-2018R1A2B6006721)Institute for Basic Science of Korea (IBS-R011-D1)the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (Project Number: KMDF_PR_20200901_0004)。
文摘Herein, a stable and efficient CoS_(2)-ReS_(2) electrocatalyst is successfully constructed by using the different molar ratios of CoS_(2) on ReS_(2). The size and morphology of the catalysts are significantly changed after the CoS_(2) is grown on ReS_(2), providing regulation of the catalytic activity of ReS_(2). Particularly, the optimized CoS_(2)-ReS_(2) shows superior electrocatalytic properties with a low voltage of 1.48 V at 20 mA cm^(-2) for overall water splitting in 1.0 M KOH, which is smaller than the noble metal-based catalysts(1.77 V at 20 mA cm^(-2)). The XPS, XAS, and theoretical data confirm that the interfacial regulation of ReS_(2) by CoS_(2) can provide rich edge catalytic sites, which greatly optimizes the catalytic kinetics and drop the energy barrier for oxygen/hydrogen evolution reactions. Our results demonstrated that interfacial engineering is an efficient route for fabricating high-performance water splitting electrocatalysts.
基金the National Natural Science Foundation of China(51676096)supported by the Australian Research Council(DP170104264 and DP190103548).
文摘Van der Waals(VDW)heterojunctions in a 2D/2D contact provide the highest area for the separation and transfer of charge carriers.In this work,a top-down strategy with a gas erosion process was employed to fabricate a 2D/2D carbon nitride VDW heterojunction in carbon nitride(g-C_(3)N_(4))with carbon-rich carbon nitride.The created 2D semiconducting channel in the VDW structure exhibits enhanced electric field exposure and radiation absorption,which facilitates the separation of the charge carriers and their mobility.Consequently,compared with bulk g-C_(3)N_(4)and its nanosheets,the photocatalytic performance of the fabricated carbon nitride VDW heterojunction in the water splitting reaction to hydrogen is improved by 8.6 and 3.3 times,respectively,while maintaining satisfactory photo-stability.Mechanistically,the finite element method(FEM)was employed to evaluate and clarify the contributions of the formation of VDW heterojunction to enhanced photocatalysis,in agreement quantitatively with experimental ones.This study provides a new and effective strategy for the modification and more insights to performance improvement on polymeric semiconductors in photocatalysis and energy conversion.