The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmento...The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.展开更多
Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understoo...Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.展开更多
This article presents a detailed theoretical hybrid analysis of the magnetism and the thermal radiative heat transfer in the presence of heat generation affecting the behavior of the dispersed gold nanoparticles(AuNPs...This article presents a detailed theoretical hybrid analysis of the magnetism and the thermal radiative heat transfer in the presence of heat generation affecting the behavior of the dispersed gold nanoparticles(AuNPs)through the blood vessels of the human body.The rheology of gold-blood nanofluid is treated as magnetohydrodynamic(MHD)flow with ferromagnetic properties.The AuNPs take different shapes as bricks,cylinders,and platelets which are considered in changing the nanofluid flow behavior.Physiologically,the blood is circulated under the kinetics of the peristaltic action.The mixed properties of the slip flow,the gravity,the space porosity,the transverse ferromagnetic field,the thermal radiation,the nanoparticles shape factors,the peristaltic amplitude ratio,and the concentration of the AuNPs are interacted and analyzed for the gold-blood circulation in the inclined tube.The appropriate model for the thermal conductivity of the nanofluid is chosen to be the effective Hamilton-Crosser model.The undertaken nanofluid can be treated as incompressible non-Newtonian ferromagnetic fluid.The solutions of the partial differential governing equations of the MHD nanofluid flow are executed by the strategy of perturbation approach under the assumption of long wavelength and low Reynolds number.Graphs for the streamwise velocity distributions,temperature distributions,pressure gradients,pressure drops,and streamlines are presented under the influences of the pertinent properties.The practical implementation of this research finds application in treating cancer through a technique known as photothermal therapy(PTT).The results indicate the control role of the magnetism,the heat generation,the shape factors of the AuNPs,and its concentration on the enhancement of the thermal properties and the streamwise velocity of the nanofluid.The results reveal a marked enhancement in the temperature profiles of the nanofluid,prominently influenced by both the intensified heat source and the heightened volume fractions of the nanoparticles.Furthermore,the platelet shape is regarded as most advantageous for heat conduction owing to its highest effective thermal conductivity.AuNPs proved strong efficiency in delivering and targeting the drug to reach the affected area with tumors.These results offer valuable insights into evaluating the effectiveness of PTT in addressing diverse cancer conditions and regulating their progression.展开更多
This work demonstrates experimentally the close relation between return currents from relativistic laser-driven target polarization and the quality of the relativistic laser–plasma interaction for laser-driven second...This work demonstrates experimentally the close relation between return currents from relativistic laser-driven target polarization and the quality of the relativistic laser–plasma interaction for laser-driven secondary sources,taking as an example ion acceleration by target normal sheath acceleration.The Pearson linear correlation of maximum return current amplitude and proton spectrum cutoff energy is found to be in the range from~0.70 to 0.94.kA-scale return currents rise in all interaction schemes where targets of any kind are charged by escaping laser-accelerated relativistic electrons.Their precise measurement is demonstrated using an inductive scheme that allows operation at high repetition rates.Thus,return currents can be used as a metrological online tool for the optimization of many laser-driven secondary sources and for diagnosing their stability.In particular,in two parametric studies of laser-driven ion acceleration,we carry out a noninvasive online measurement of return currents in a tape target system irradiated by the 1 PW VEGA-3 laser at Centro de Láseres Pulsados:first the size of the irradiated area is varied at best compression of the laser pulse;second,the pulse duration is varied by means of induced group delay dispersion at best focus.This work paves the way to the development of feedback systems that operate at the high repetition rates of PW-class lasers.展开更多
Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss o...Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.展开更多
The Internet of Things(IoT)is integral to modern infrastructure,enabling connectivity among a wide range of devices from home automation to industrial control systems.With the exponential increase in data generated by...The Internet of Things(IoT)is integral to modern infrastructure,enabling connectivity among a wide range of devices from home automation to industrial control systems.With the exponential increase in data generated by these interconnected devices,robust anomaly detection mechanisms are essential.Anomaly detection in this dynamic environment necessitates methods that can accurately distinguish between normal and anomalous behavior by learning intricate patterns.This paper presents a novel approach utilizing generative adversarial networks(GANs)for anomaly detection in IoT systems.However,optimizing GANs involves tuning hyper-parameters such as learning rate,batch size,and optimization algorithms,which can be challenging due to the non-convex nature of GAN loss functions.To address this,we propose a five-dimensional Gray wolf optimizer(5DGWO)to optimize GAN hyper-parameters.The 5DGWO introduces two new types of wolves:gamma(γ)for improved exploitation and convergence,and theta(θ)for enhanced exploration and escaping local minima.The proposed system framework comprises four key stages:1)preprocessing,2)generative model training,3)autoencoder(AE)training,and 4)predictive model training.The generative models are utilized to assist the AE training,and the final predictive models(including convolutional neural network(CNN),deep belief network(DBN),recurrent neural network(RNN),random forest(RF),and extreme gradient boosting(XGBoost))are trained using the generated data and AE-encoded features.We evaluated the system on three benchmark datasets:NSL-KDD,UNSW-NB15,and IoT-23.Experiments conducted on diverse IoT datasets show that our method outperforms existing anomaly detection strategies and significantly reduces false positives.The 5DGWO-GAN-CNNAE exhibits superior performance in various metrics,including accuracy,recall,precision,root mean square error(RMSE),and convergence trend.The proposed 5DGWO-GAN-CNNAE achieved the lowest RMSE values across the NSL-KDD,UNSW-NB15,and IoT-23 datasets,with values of 0.24,1.10,and 0.09,respectively.Additionally,it attained the highest accuracy,ranging from 94%to 100%.These results suggest a promising direction for future IoT security frameworks,offering a scalable and efficient solution to safeguard against evolving cyber threats.展开更多
BACKGROUND Glucocorticoids(GC)are the cornerstone in the treatment of severe alcoholassociated hepatitis(SAH)but may be associated with adverse events.CASE SUMMARY We report a prospective series of patients with SAH w...BACKGROUND Glucocorticoids(GC)are the cornerstone in the treatment of severe alcoholassociated hepatitis(SAH)but may be associated with adverse events.CASE SUMMARY We report a prospective series of patients with SAH who were treated with GC and developed de novo arthropathy within 2 weeks of GC cessation.Five patients were included in this series,three of whom were women.All patients underwent ultrasound evaluation and were referred to the Rheumatology Clinics.Final diagnoses were:Arthralgia associated with GC cessation(n=3),polymyalgia rheumatica(n=1)and psoriatic arthritis(n=1).Joint soreness was the main symptom,whereas arthritis occurred rarely.Patients with arthralgia associated with GC cessation required longer regimes of GC and tapering strategies but remained free of symptoms and specific treatment in the long term.CONCLUSION De novo arthropathy may occur following GC for SAH.Close monitoring and tapering regimes are advised.展开更多
We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are ...We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are obtained for both the thermal equation and the one-dimensional thermoelastic system,where the impossibility of localization with respect to time is also established.Then,the space estimates are deduced for the multidimensional thermoelastic problem,which allow to show the exponential decay of the energy.展开更多
We extend a well-known mass-gap equation for pure gluodynamics in global colour models(formulated in equal-time quantization in Coulomb gauge)to one in which gluons are split into two sets,each exhibiting different ma...We extend a well-known mass-gap equation for pure gluodynamics in global colour models(formulated in equal-time quantization in Coulomb gauge)to one in which gluons are split into two sets,each exhibiting different masses.If the theory is SU(N)×SU(M)with gluons in both groups having identical couplings(as suggested by Grand Unification arguments at large scales)it is immediate to see that different masses are generated for each subgroup.This global symmetry is not broken,but the split masses erase accidental symmetries that might be present due to the two couplings being the same at a large scale,such as SU(N×M)or similar.We also numerically explore a couple of low-dimensional examples of simple Lie groups,but in spite of the system of equations having a form that would seem to allow spontaneous symmetry breaking,it is not triggered for these groups whose algebra has no ideal,and the dispersion relations for the various gluons converge to the same form.展开更多
For songbirds,the post-fledging period is critical for development and survival,as young must learn to get food,practice flying,and identify predators to become independent from their parents and disperse or migrate.O...For songbirds,the post-fledging period is critical for development and survival,as young must learn to get food,practice flying,and identify predators to become independent from their parents and disperse or migrate.Obligate avian brood parasites,like cuckoos and cowbirds,lay eggs in nests of other bird species that provide parental care until the parasite’s young become independent.The information on the post-fledging period in songbirds is limited due to the difficulty in following and observing fledglings and it is even scarcer for brood parasites.We studied the behavior,survival,and age of independence of Shiny Cowbird(Molothrus bonariensis)fledglings raised by 2 hosts that differ markedly in body size:the House Wren(Troglodytes aedon)and the Chalk-Browed Mockingbird(Mimus saturninus).We radio-tracked individuals from a few days before they left the nest until they disappeared from the natal territory.We found:(1)chicks left the nest when they were 11-15 days of age and the age of fledgling did not differ between the 2 host species,(2)after leaving the nest,they spent most of the time perched in a hidden place without begging but as they grew,the proportion of time perched without begging decreased and begging in hidden and exposed places increased,(3)we observed approaches between adult parasitic females and young in host territories,(4)young abandoned the host territory and joined conspecific flocks when they were 35-39 days of age,and(5)the estimated post-fledging survival was between 12.5%and 20.8%.展开更多
The Chilean subduction zone is one of the most seismically active regions globally,characterized by extensive intermediatedepth seismicity in the slab.In this study,we construct a new earthquake catalog for northern C...The Chilean subduction zone is one of the most seismically active regions globally,characterized by extensive intermediatedepth seismicity in the slab.In this study,we construct a new earthquake catalog for northern Chile using seismic waveforms assembled for the period of 2014-2019,from which 320,070 P-wave and 232,907 S-wave first arrivals are obtained for 25,763 earthquakes.Grid search location method NonLinLoc is applied to determine initial earthquake locations and double-difference location method is used to improve relative event locations.The distribution of earthquakes exhibits distinct patterns to the north and south of 21°S.There are many more earthquakes deeper than~150 km to the south of 21°S,while relatively fewer to the north.The intraslab earthquakes shallower than~80 km generally reveal a distinct double seismic zone,and the gap between the two seismic planes disappears at a depth of approximately~80 km,followed by a concentration of seismicity in the depth range of~80-150 km.In the deeper slab,there exist several seismicity clusters with distinct earthquake activities down to~300 km.These characteristics shown in slab seismicity are likely caused by different mechanisms and can be helpful for understanding the subduction process.展开更多
Green cover and human disturbance are important local factors shaping urban bird communities, while climatic and topographic variables can be important when analyzing cities in different biomes. However, the roles of ...Green cover and human disturbance are important local factors shaping urban bird communities, while climatic and topographic variables can be important when analyzing cities in different biomes. However, the roles of large-scale and local variables influencing bird species composition have been scarcely explored in urban areas. This study aimed to analyze the association of climatic, topographic, landscape, and local variables with bird species composition in streets dominated by buildings and urban parks. I expected park bird composition to be more related to large-scale variables, whereas bird species in streets to be more associated with local-scale variables. Bird surveys were conducted in nine cities along a climatic and topographic gradient. Bird species composition in urban parks and streets were related to climatic and topographic variables, local vegetation greenness, and distance to non-urban areas. However, bird composition in streets was also related to noise and pedestrian traffic. The classification of bird composition in urban parks aligned with the phytogeographic provinces, whereas the streets’ bird composition was unrelated to phytogeographic provinces. The results showed that urban habitats with increased vegetation cover allow the colonization of native bird communities and are more aligned with natural large-scale environmental gradients. In contrast, more urbanized sites are decoupled from climatic and topographic gradients and invaded by exotic and widespread native species.展开更多
The differential system ẋ=ax−yz,ẏ=−by+xz,ż=−cz+x^(2),where a,b and c are positive real parameters,has been studied numerically due to the big variety of strange attractors that it can exhibit.This system has a Darboux...The differential system ẋ=ax−yz,ẏ=−by+xz,ż=−cz+x^(2),where a,b and c are positive real parameters,has been studied numerically due to the big variety of strange attractors that it can exhibit.This system has a Darboux invariant when c=2b.Using this invariant and the Poincarécompactification technique we describe analytically its global dynamics.展开更多
The Chilean Pampean flat slab subduction segment is characterized by the nearly horizontal subduction of the Nazca Plate within the depth range of 100-120 km.Numerous seismic tomography studies have been conducted to ...The Chilean Pampean flat slab subduction segment is characterized by the nearly horizontal subduction of the Nazca Plate within the depth range of 100-120 km.Numerous seismic tomography studies have been conducted to investigate its velocity structure;however,they have used only seismic body wave data or surface wave data.As a result,the existing velocity models in the region may have relatively large uncertainties.In this study,we use body wave arrival times from earthquakes occurring in central Chile between 2014 and 2019,as well as Rayleigh wave phase velocity maps at periods of 5-80 s from ambient noise empirical Green’s functions in Chile.By jointly using body wave arrival times and surface wave dispersion data,we refine the VS model and improve earthquake locations in the central Chile subduction zone.Compared with previous velocity models,our velocity model better reveals an eastward-dipping high-velocity plate representing the subducting Nazca Plate,which is 40-50 km thick and is more consistent with the slab thickness estimated by receiver function imaging and thermal modeling.Overall,the intraslab seismicity distribution spatially correlates well with the slab high-velocity anomalies except along the subduction paths of the CopiapóRidge and Juan Fernández Ridge.Additionally,parallel low-velocity stripes are imaged beneath the subducting plate,which are likely associated with the accumulated melts.The joint inversion velocity model also resolves widespread low-velocity anomalies in the crust beneath the Central Volcanic Zone of the central Andes,likely representing crustal magma chambers for various volcanoes.展开更多
BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagn...Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.展开更多
Understanding the evolutionary processes that influence the distribution of genetic diversity in natural populations is a key issue in evolutionary biology. Both species' distribution ranges and environmental grad...Understanding the evolutionary processes that influence the distribution of genetic diversity in natural populations is a key issue in evolutionary biology. Both species' distribution ranges and environmental gradients can influence this diversity through mechanisms such as gene flow, selection, and genetic drift. To explore how these forces interact, we assessed neutral and adaptive genetic variation in three widely distributed and two narrowly distributed bird species co-occurring along the Cauca River canyon in Antioquia, Colombia—a region of pronounced environmental heterogeneity. We sampled individuals across eight sites spanning the canyon's gradient and analyzed genetic diversity and structure using microsatellites and toll-like receptors (TLRs), a gene family involved in innate immunity. Widely distributed species consistently exhibited higher genetic diversity at both marker types compared to their narrowly distributed counterparts. Although we did not find a significant relationship between microsatellite heterozygosity and TLR heterozygosity, we evidenced a negative trend for widely distributed species and a positive trend for narrowly distributed species. This result suggests that there is a stronger effect of genetic drift in narrowly distributed species. Our results highlight the role of distribution range in maintaining genetic diversity and suggest that environmental gradients, by interacting with gene flow and selection, may influence patterns of adaptive variation.展开更多
Hydrogel strain sensors represent an importan development for research into flexible electronics,being able to convert external stimuli into easily monitored electrical signals.However,finding simple and rapid prepara...Hydrogel strain sensors represent an importan development for research into flexible electronics,being able to convert external stimuli into easily monitored electrical signals.However,finding simple and rapid preparation methods,as well as ensuring compatibility between conductive fillers and the polymer matrix are stil the main challenges for conductive hydrogel applications In this work,we utilize MXene to coat liquid metal dro plets that have been broken by ultrasound while incorpo rating cellulose nanofibers to make them stably dispersed Electron paramagnetic resonance spectroscopy revealed that the obtained composite filler could catalyze the releas of additional hydroxyl radicals from ammonium persulfat to enable the rapid gelation of acrylic acid under ambien conditions.This unique property allows for the mold-based fabrication of hydrogels in various shapes,and we also explored the use of microfluidic devices for printing.Th conductive hydrogels showed good tensile properties small hysteresis loops,high self-healing efficiency(97%conductive recovery),and antimicrobial properties.When assembled into flexible sensors,the hydrogel can accu rately monitor body movements with stable repeatability The outstanding characteristics of the hydrogel not only offer a material basis for the development of novel flexibl sensors,but also have the potential for rapid,large-scale and customized preparation through fast gelation.展开更多
Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of ...Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a group of chronic,inflammatory disorders that include Crohn’s disease and ulcerative colitis.IBD arises from the interaction of various environmental and genetic factors....BACKGROUND Inflammatory bowel disease(IBD)is a group of chronic,inflammatory disorders that include Crohn’s disease and ulcerative colitis.IBD arises from the interaction of various environmental and genetic factors.Altered gut permeability and mitochondrial stress in the colonic mucosa are two mechanisms previously implicated in IBD pathogenesis.We have previously demonstrated activation of the mitochondrial unfolded protein response(UPRmt)in the colonic mucosa of IBD patients and linked this activation to pro-inflammatory signaling.Growth differentiation factor 15(GDF15)is an important downstream mediator of the UPRmt.AIM To investigate whether GDF15 has a role in IBD and how GDF15 impacts colonic epithelium.METHODS Circulating levels of GDF15 were assessed in plasma samples from IBD patients and healthy controls using an enzyme-linked immunosorbent assay.To study the effects of GDF15 on the colonic mucosa,we employed two different in vitro culture models:Colonic organoids and T84 cells.RESULTS We found that circulating GDF15 Levels were elevated in IBD patients and correlated with markers of inflammation(C-reactive protein)and intestinal permeability[haptoglobin and lipopolysaccharide-binding protein(LBP)].Additionally,we demonstrated that GDF15 alters the intestinal barrier and increases permeability by decreasing the levels of zonula occludens 1 and claudin 1,critical components of tight junctions.Thus,our findings confirm previous reports of increased circulating GDF15 levels in IBD patients and the activation of UPR^(mt).CONCLUSION In the present study,we describe a novel mechanism in IBD pathophysiology,linking mitochondrial stress to the disruption of the intestinal barrier and increased intestinal permeability.展开更多
基金Fundação de AmparoàPesquisa do Estado de São Paulo(FAPESP,Brazil,#2020/11667-0)and Universidade Federal do ABC(UFABC,Brazil)were recipients of fellowships from FAPESP:THLV(#2021/11969-9 and#2024/00828-3),GBS(#2021/14227-3),and GMB(#2024/10858-7)+1 种基金recipients of fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,Brazil):MIM(Finance Code 001,#88887.597402/2021-00)recipients of fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,Brazil.):GKD(#145164/2024-1),and DRA(#308819/2022-5).
文摘The intricate landscape of neurodegenerative diseases complicates the search for effective therapeutic approaches.Photoreceptor degeneration,the common endpoint in various retinal diseases,including retinitis pigmentosa and age-related macular degeneration,leads to vision loss or blindness.While primary cell death is driven by genetic mutations,oxidative stress,and neuroinflammation,additional mechanisms contribute to disease progression.In retinitis pigmentosa,a multitude of genetic alterations can trigger the degeneration of photoreceptors,while other retinopathies,such as agerelated macular degeneration,are initiated by combinations of environmental factors,such as diet,smoking,and hypertension,with genetic predispositions.Nutraceutical therapies,which blend the principles of nutrition and pharmaceuticals,aim to harness the health benefits of bioactive compounds for therapeutic applications.These compounds generally possess multi-target effects.Polyphenols and flavonoids,secondary plant metabolites abundant in plant-based foods,are known for their antioxidant,neuroprotective,and anti-inflammatory properties.This review focuses on the potential of polyphenols and flavonoids as nutraceuticals to treat neurodegenerative diseases such as retinitis pigmentosa.Furthermore,the importance of developing reliable delivery methods to enhance the bioavailability and therapeutic efficacy of these compounds will be discussed.By combining nutraceuticals with other emerging therapies,such as genetic and cell-based treatments,it is possible to offer a more comprehensive approach to treating retinal degenerative diseases.These advancements could lead to a viable and accessible option,improving the quality of life for patients with retinal diseases.
文摘Races using kitefoil and windfoil surfboards have been in the Olympic Games for the first time in Paris 2024,signalling their relevance in sailing sports.However,the dynamics of these devices is yet not well understood,in particular the influence on the hydrodynamic forces and moments of the distance of the foil to the free surface.Considering this,the present paper documents an experimental investigation in which forces and torque produced,under uniform flow,by a full-scale state-of-the-art hydrofoil(suitable both for kitesurf and windsurf)were measured.A range of velocities,angles of attack,and submergences were tested,leading to Froude numbers based on submergence with maximum values around five,a typical range in actual sailing conditions.From these tests,formulae for the hydrodynamic coefficients have been proposed.They can be used for developing Velocity Prediction Programs(VPP)for this kind of craft,a necessary tool to plan racing configurations and to analyze their racing performance.With the aim of making the experimental data useful for benchmarking numerical models and for future research on related topics such as foil ventilation and transition to turbulence,the specimen’s 3D file is provided as supplementary material to this paper.
文摘This article presents a detailed theoretical hybrid analysis of the magnetism and the thermal radiative heat transfer in the presence of heat generation affecting the behavior of the dispersed gold nanoparticles(AuNPs)through the blood vessels of the human body.The rheology of gold-blood nanofluid is treated as magnetohydrodynamic(MHD)flow with ferromagnetic properties.The AuNPs take different shapes as bricks,cylinders,and platelets which are considered in changing the nanofluid flow behavior.Physiologically,the blood is circulated under the kinetics of the peristaltic action.The mixed properties of the slip flow,the gravity,the space porosity,the transverse ferromagnetic field,the thermal radiation,the nanoparticles shape factors,the peristaltic amplitude ratio,and the concentration of the AuNPs are interacted and analyzed for the gold-blood circulation in the inclined tube.The appropriate model for the thermal conductivity of the nanofluid is chosen to be the effective Hamilton-Crosser model.The undertaken nanofluid can be treated as incompressible non-Newtonian ferromagnetic fluid.The solutions of the partial differential governing equations of the MHD nanofluid flow are executed by the strategy of perturbation approach under the assumption of long wavelength and low Reynolds number.Graphs for the streamwise velocity distributions,temperature distributions,pressure gradients,pressure drops,and streamlines are presented under the influences of the pertinent properties.The practical implementation of this research finds application in treating cancer through a technique known as photothermal therapy(PTT).The results indicate the control role of the magnetism,the heat generation,the shape factors of the AuNPs,and its concentration on the enhancement of the thermal properties and the streamwise velocity of the nanofluid.The results reveal a marked enhancement in the temperature profiles of the nanofluid,prominently influenced by both the intensified heat source and the heightened volume fractions of the nanoparticles.Furthermore,the platelet shape is regarded as most advantageous for heat conduction owing to its highest effective thermal conductivity.AuNPs proved strong efficiency in delivering and targeting the drug to reach the affected area with tumors.These results offer valuable insights into evaluating the effectiveness of PTT in addressing diverse cancer conditions and regulating their progression.
基金funding from the European Union’s Horizon 2020 research and innovation program through the European IMPULSE project under Grant Agreement No.871161from LASERLAB-EUROPE V under Grant Agreement No.871124+6 种基金from the Grant Agency of the Czech Republic(Grant No.GM23-05027M)Grant No.PDC2021120933-I00 funded by MCIN/AEI/10.13039/501100011033by the European Union Next Generation EU/PRTRsupported by funding from the Ministerio de Ciencia,Innovación y Universidades in Spain through ICTS Equipment Grant No.EQC2018-005230-Pfrom Grant No.PID2021-125389O A-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER,UEby“ERDF A Way of Making Europe”by the European Unionfrom grants of the Junta de Castilla y León with Grant Nos.CLP263P20 and CLP087U16。
文摘This work demonstrates experimentally the close relation between return currents from relativistic laser-driven target polarization and the quality of the relativistic laser–plasma interaction for laser-driven secondary sources,taking as an example ion acceleration by target normal sheath acceleration.The Pearson linear correlation of maximum return current amplitude and proton spectrum cutoff energy is found to be in the range from~0.70 to 0.94.kA-scale return currents rise in all interaction schemes where targets of any kind are charged by escaping laser-accelerated relativistic electrons.Their precise measurement is demonstrated using an inductive scheme that allows operation at high repetition rates.Thus,return currents can be used as a metrological online tool for the optimization of many laser-driven secondary sources and for diagnosing their stability.In particular,in two parametric studies of laser-driven ion acceleration,we carry out a noninvasive online measurement of return currents in a tape target system irradiated by the 1 PW VEGA-3 laser at Centro de Láseres Pulsados:first the size of the irradiated area is varied at best compression of the laser pulse;second,the pulse duration is varied by means of induced group delay dispersion at best focus.This work paves the way to the development of feedback systems that operate at the high repetition rates of PW-class lasers.
基金supported by the Spanish Government(ISCIII-FEDER)PI20/01063by Navarra Government(PC 060-061 and PC 192-193)Fundación Gangoiti(to MSA).LA was funded by FPU19/03255.
文摘Neuroinflammation is associated with Parkinson’s disease:Reactive gliosis and neuroinflammation are hallmarks of Parkinson’s disease(PD),a multisystem neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons.Neuroinflammation has long been considered a mere consequence of neuronal loss,but whether it promotes PD or is a key player in disease progression remains to be determined.Human leukocyte antigen.
基金described in this paper has been developed with in the project PRESECREL(PID2021-124502OB-C43)。
文摘The Internet of Things(IoT)is integral to modern infrastructure,enabling connectivity among a wide range of devices from home automation to industrial control systems.With the exponential increase in data generated by these interconnected devices,robust anomaly detection mechanisms are essential.Anomaly detection in this dynamic environment necessitates methods that can accurately distinguish between normal and anomalous behavior by learning intricate patterns.This paper presents a novel approach utilizing generative adversarial networks(GANs)for anomaly detection in IoT systems.However,optimizing GANs involves tuning hyper-parameters such as learning rate,batch size,and optimization algorithms,which can be challenging due to the non-convex nature of GAN loss functions.To address this,we propose a five-dimensional Gray wolf optimizer(5DGWO)to optimize GAN hyper-parameters.The 5DGWO introduces two new types of wolves:gamma(γ)for improved exploitation and convergence,and theta(θ)for enhanced exploration and escaping local minima.The proposed system framework comprises four key stages:1)preprocessing,2)generative model training,3)autoencoder(AE)training,and 4)predictive model training.The generative models are utilized to assist the AE training,and the final predictive models(including convolutional neural network(CNN),deep belief network(DBN),recurrent neural network(RNN),random forest(RF),and extreme gradient boosting(XGBoost))are trained using the generated data and AE-encoded features.We evaluated the system on three benchmark datasets:NSL-KDD,UNSW-NB15,and IoT-23.Experiments conducted on diverse IoT datasets show that our method outperforms existing anomaly detection strategies and significantly reduces false positives.The 5DGWO-GAN-CNNAE exhibits superior performance in various metrics,including accuracy,recall,precision,root mean square error(RMSE),and convergence trend.The proposed 5DGWO-GAN-CNNAE achieved the lowest RMSE values across the NSL-KDD,UNSW-NB15,and IoT-23 datasets,with values of 0.24,1.10,and 0.09,respectively.Additionally,it attained the highest accuracy,ranging from 94%to 100%.These results suggest a promising direction for future IoT security frameworks,offering a scalable and efficient solution to safeguard against evolving cyber threats.
基金Supported by the Instituto de Salud Carlos III,No.PI22/00910.
文摘BACKGROUND Glucocorticoids(GC)are the cornerstone in the treatment of severe alcoholassociated hepatitis(SAH)but may be associated with adverse events.CASE SUMMARY We report a prospective series of patients with SAH who were treated with GC and developed de novo arthropathy within 2 weeks of GC cessation.Five patients were included in this series,three of whom were women.All patients underwent ultrasound evaluation and were referred to the Rheumatology Clinics.Final diagnoses were:Arthralgia associated with GC cessation(n=3),polymyalgia rheumatica(n=1)and psoriatic arthritis(n=1).Joint soreness was the main symptom,whereas arthritis occurred rarely.Patients with arthralgia associated with GC cessation required longer regimes of GC and tapering strategies but remained free of symptoms and specific treatment in the long term.CONCLUSION De novo arthropathy may occur following GC for SAH.Close monitoring and tapering regimes are advised.
基金part of the project“Qualitative and numerical analyses of some thermomechanics problems(ACUANUTER)”(Ref.PID2024-156827NB-I00)。
文摘We consider the space and time decays of certain problems within the second gradient thermal law.Notably,for this thermal theory,the exponential time decay is precluded.First,the time estimates of polynomial type are obtained for both the thermal equation and the one-dimensional thermoelastic system,where the impossibility of localization with respect to time is also established.Then,the space estimates are deduced for the multidimensional thermoelastic problem,which allow to show the exponential decay of the energy.
基金supported by the EU under grant 824093(STRONG2020)spanish MICINN under PID2019-108655GBI00/AEI/10.13039/501100011033,PID2019-106080GB-C21 and PRX23/00225(estancias en el extranjero)Univ.Complutense de Madrid under research group 910309 and the IPARCOS institute。
文摘We extend a well-known mass-gap equation for pure gluodynamics in global colour models(formulated in equal-time quantization in Coulomb gauge)to one in which gluons are split into two sets,each exhibiting different masses.If the theory is SU(N)×SU(M)with gluons in both groups having identical couplings(as suggested by Grand Unification arguments at large scales)it is immediate to see that different masses are generated for each subgroup.This global symmetry is not broken,but the split masses erase accidental symmetries that might be present due to the two couplings being the same at a large scale,such as SU(N×M)or similar.We also numerically explore a couple of low-dimensional examples of simple Lie groups,but in spite of the system of equations having a form that would seem to allow spontaneous symmetry breaking,it is not triggered for these groups whose algebra has no ideal,and the dispersion relations for the various gluons converge to the same form.
基金supported by Grants from the Agencia Nacional de Promoción Científica y Tecnológica,from Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)and the University of Buenos Aires.
文摘For songbirds,the post-fledging period is critical for development and survival,as young must learn to get food,practice flying,and identify predators to become independent from their parents and disperse or migrate.Obligate avian brood parasites,like cuckoos and cowbirds,lay eggs in nests of other bird species that provide parental care until the parasite’s young become independent.The information on the post-fledging period in songbirds is limited due to the difficulty in following and observing fledglings and it is even scarcer for brood parasites.We studied the behavior,survival,and age of independence of Shiny Cowbird(Molothrus bonariensis)fledglings raised by 2 hosts that differ markedly in body size:the House Wren(Troglodytes aedon)and the Chalk-Browed Mockingbird(Mimus saturninus).We radio-tracked individuals from a few days before they left the nest until they disappeared from the natal territory.We found:(1)chicks left the nest when they were 11-15 days of age and the age of fledgling did not differ between the 2 host species,(2)after leaving the nest,they spent most of the time perched in a hidden place without begging but as they grew,the proportion of time perched without begging decreased and begging in hidden and exposed places increased,(3)we observed approaches between adult parasitic females and young in host territories,(4)young abandoned the host territory and joined conspecific flocks when they were 35-39 days of age,and(5)the estimated post-fledging survival was between 12.5%and 20.8%.
基金supported by National Natural Science Foundation of China(No.41861134009)the PIA ANID(AFB180004)the ANID(PCI PII-180003).
文摘The Chilean subduction zone is one of the most seismically active regions globally,characterized by extensive intermediatedepth seismicity in the slab.In this study,we construct a new earthquake catalog for northern Chile using seismic waveforms assembled for the period of 2014-2019,from which 320,070 P-wave and 232,907 S-wave first arrivals are obtained for 25,763 earthquakes.Grid search location method NonLinLoc is applied to determine initial earthquake locations and double-difference location method is used to improve relative event locations.The distribution of earthquakes exhibits distinct patterns to the north and south of 21°S.There are many more earthquakes deeper than~150 km to the south of 21°S,while relatively fewer to the north.The intraslab earthquakes shallower than~80 km generally reveal a distinct double seismic zone,and the gap between the two seismic planes disappears at a depth of approximately~80 km,followed by a concentration of seismicity in the depth range of~80-150 km.In the deeper slab,there exist several seismicity clusters with distinct earthquake activities down to~300 km.These characteristics shown in slab seismicity are likely caused by different mechanisms and can be helpful for understanding the subduction process.
基金funded by the Agencia Nacional de Promoción de la Investigación,el Desarrollo Tecnológico y la Innovación,PICT 2018–03871.
文摘Green cover and human disturbance are important local factors shaping urban bird communities, while climatic and topographic variables can be important when analyzing cities in different biomes. However, the roles of large-scale and local variables influencing bird species composition have been scarcely explored in urban areas. This study aimed to analyze the association of climatic, topographic, landscape, and local variables with bird species composition in streets dominated by buildings and urban parks. I expected park bird composition to be more related to large-scale variables, whereas bird species in streets to be more associated with local-scale variables. Bird surveys were conducted in nine cities along a climatic and topographic gradient. Bird species composition in urban parks and streets were related to climatic and topographic variables, local vegetation greenness, and distance to non-urban areas. However, bird composition in streets was also related to noise and pedestrian traffic. The classification of bird composition in urban parks aligned with the phytogeographic provinces, whereas the streets’ bird composition was unrelated to phytogeographic provinces. The results showed that urban habitats with increased vegetation cover allow the colonization of native bird communities and are more aligned with natural large-scale environmental gradients. In contrast, more urbanized sites are decoupled from climatic and topographic gradients and invaded by exotic and widespread native species.
基金supported by the Agencia Estatal de Investigación grant PID2019-104658GB-I00the H2020 European Research Council grant MSCA-RISE-2017-777911+2 种基金AGAUR(Generalitat de Catalunya)grant 2021SGR00113the Reial Acadèmia de Ciències i Arts de Barcelonasupported by FCT/Portugal through CAMGSD,IST-ID,projects UIDB/04459/2020 and UIDP/04459/2020.
文摘The differential system ẋ=ax−yz,ẏ=−by+xz,ż=−cz+x^(2),where a,b and c are positive real parameters,has been studied numerically due to the big variety of strange attractors that it can exhibit.This system has a Darboux invariant when c=2b.Using this invariant and the Poincarécompactification technique we describe analytically its global dynamics.
基金funded by the National Natural Science Foundation of China under Grant 42230101the National Agency for Research and Development of Chile(ANID)by Projects AFB180004 and AFB220002the ANID Programa de Cooperación Internacional(PCI)Grant PII-180003.
文摘The Chilean Pampean flat slab subduction segment is characterized by the nearly horizontal subduction of the Nazca Plate within the depth range of 100-120 km.Numerous seismic tomography studies have been conducted to investigate its velocity structure;however,they have used only seismic body wave data or surface wave data.As a result,the existing velocity models in the region may have relatively large uncertainties.In this study,we use body wave arrival times from earthquakes occurring in central Chile between 2014 and 2019,as well as Rayleigh wave phase velocity maps at periods of 5-80 s from ambient noise empirical Green’s functions in Chile.By jointly using body wave arrival times and surface wave dispersion data,we refine the VS model and improve earthquake locations in the central Chile subduction zone.Compared with previous velocity models,our velocity model better reveals an eastward-dipping high-velocity plate representing the subducting Nazca Plate,which is 40-50 km thick and is more consistent with the slab thickness estimated by receiver function imaging and thermal modeling.Overall,the intraslab seismicity distribution spatially correlates well with the slab high-velocity anomalies except along the subduction paths of the CopiapóRidge and Juan Fernández Ridge.Additionally,parallel low-velocity stripes are imaged beneath the subducting plate,which are likely associated with the accumulated melts.The joint inversion velocity model also resolves widespread low-velocity anomalies in the crust beneath the Central Volcanic Zone of the central Andes,likely representing crustal magma chambers for various volcanoes.
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
基金Supported by the Instituto de Salud Carlos III,No.PI24/00784,No.PI24/00737,No.PI21/01181,No.PI21/00333 and No.INT22/00112Departamento de Universidad,Innovación y Transformación Digital Gobierno de Navarra,No.0011-1408-2024-000011,No.0011-1408-2022-000010.
文摘Gastric cancer(GC)is both the fifth most common cancer worldwide and the fifth in mortality.Owing to a lack of symptoms in the early stages and unspecific cli-nical presentation in the later stages,GC is usually diagnosed at advanced stages.This means that only approximately 60%of patients are eligible for curative treat-ment,and overall,GC patients have a 5-year survival rate of only 28.3%,under-scoring the importance of developing new treatment strategies.Drug repurposing involves identifying new therapeutic uses for approved drugs and is a promising strategy for cancer treatment because of its lower cost and faster development time.A variety of targetable pathways are involved in GC progression,including the mitogen-activated protein kinase,phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin,p53,Janus kinase 2/signal transducer and activator of transcription 3,hypoxia-inducible factor-1α,wingless-type mouse mammary tumor virus integration site family/beta-catenin(Wnt/β-catenin),nuclear factor kappa B,and Hippo pathways.Therefore,the repurposing of drugs targeting these pathways represents an interesting option in the search for new treatments for GC.In this review,we explore some relevant pathways involved in the development of GC and the possibilities of repurposing drugs that target them.
基金funded by the Empresas Públicas de Medellín and Universidad de Antioquia.
文摘Understanding the evolutionary processes that influence the distribution of genetic diversity in natural populations is a key issue in evolutionary biology. Both species' distribution ranges and environmental gradients can influence this diversity through mechanisms such as gene flow, selection, and genetic drift. To explore how these forces interact, we assessed neutral and adaptive genetic variation in three widely distributed and two narrowly distributed bird species co-occurring along the Cauca River canyon in Antioquia, Colombia—a region of pronounced environmental heterogeneity. We sampled individuals across eight sites spanning the canyon's gradient and analyzed genetic diversity and structure using microsatellites and toll-like receptors (TLRs), a gene family involved in innate immunity. Widely distributed species consistently exhibited higher genetic diversity at both marker types compared to their narrowly distributed counterparts. Although we did not find a significant relationship between microsatellite heterozygosity and TLR heterozygosity, we evidenced a negative trend for widely distributed species and a positive trend for narrowly distributed species. This result suggests that there is a stronger effect of genetic drift in narrowly distributed species. Our results highlight the role of distribution range in maintaining genetic diversity and suggest that environmental gradients, by interacting with gene flow and selection, may influence patterns of adaptive variation.
基金financially supported by China Scholarship Council program(No.202306380028)the National Natural Science Foundation of China(No.11204097)+3 种基金the Spanish Ministry of Science(Nos.RYC2020-945030119-I and PID2023-151682NA-I00 funded by MCIN/AEI/10.13039/501100011033/and FEDER)Unidades de Excelencia Maria de Maeztu 2021(No.CEX2021-001202-M)the Spanish Ministry of Science,Innovation and Universities(MCIU),State Bureau of Investigation(AIE),the European Regional Development Fund(FEDER)(No.PGC2018-096958-B-I00)the Catalonian Government(No.2021 SGR00646)
文摘Hydrogel strain sensors represent an importan development for research into flexible electronics,being able to convert external stimuli into easily monitored electrical signals.However,finding simple and rapid preparation methods,as well as ensuring compatibility between conductive fillers and the polymer matrix are stil the main challenges for conductive hydrogel applications In this work,we utilize MXene to coat liquid metal dro plets that have been broken by ultrasound while incorpo rating cellulose nanofibers to make them stably dispersed Electron paramagnetic resonance spectroscopy revealed that the obtained composite filler could catalyze the releas of additional hydroxyl radicals from ammonium persulfat to enable the rapid gelation of acrylic acid under ambien conditions.This unique property allows for the mold-based fabrication of hydrogels in various shapes,and we also explored the use of microfluidic devices for printing.Th conductive hydrogels showed good tensile properties small hysteresis loops,high self-healing efficiency(97%conductive recovery),and antimicrobial properties.When assembled into flexible sensors,the hydrogel can accu rately monitor body movements with stable repeatability The outstanding characteristics of the hydrogel not only offer a material basis for the development of novel flexibl sensors,but also have the potential for rapid,large-scale and customized preparation through fast gelation.
基金supported through the European Union’s Horizon 2020 Research and Innovation Program(818318)。
文摘Deep phenotyping and genetic characterization of individuals are fundamental to assessing the metabolic status and determining nutrition-specific requirements.This study aimed to ascertain the utmost effectiveness of personalized interventions by aligning dietary adjustments with both the genotype and metabolotype of individuals.Therefore,we assessed here the usefulness of a polygenic score(PGS)characterizing a potential pro-inflammatory profile(PGSi)as a nutrigenetic tool to discern individuals from the Danish PREVENTOMICS cohort that could better respond to precision nutrition(PN)plans,specifically targeted at counteracting the low-grade inflammatory profile typically found in obesity.The cohort followed a PN plan to counteract the pro-inflammatory profile(PNi group)or generic dietary recommendations(Control)for 10 weeks.PGSi was applied for genetic stratification(Low/High).The effects of the intervention on anthropometrics and biomarkers related to inflammatory profile and carbohydrate metabolism were assessed.Around 30%of subjects had a high genetic predisposition to pro-inflammatory status(high-PGSi).These individuals demonstrated the most effective response to the dietary plan,experiencing improved body composition,with significant decreases in body weight(∆:-4.84%;P=0.039)and body fat(∆:-4.86%;P=0.007),and beneficial changes in pro-and anti-inflammatory biomarkers,with significant increases in IL-10(∆:71.3%;P=0.025)and decreases in TNF-α(∆:-3.0%;P=0.048),CRP(∆:-31.1%),ICAM1(∆:-5.8%),and MCP1(∆:-4.2%)circulating levels,compared to low-PGSi individuals.Both phenotypic and genetic stratification contributed to a better understanding of metabolic heterogeneity in response to diet.This approach allows for refinement of the prediction of individual requirements and potentially for better management of obesity.
基金Supported by the Ministerio de Ciencia,Innovación y Universidades(Spain),No.IJCI-2017-31466the Consejería de Salud y Familia de la Junta de Andalucía,Spain,No.PI-0244-2021+12 种基金No.PI-0245-2021No.PI-0131-2020FEDER funds/Consejería de Economía y Conocimiento,Empresas y Universidad,de la Junta de Andalucía(“A way to make Europe”)(“Andalucía se mueve con Europa”,University of Málaga,No.UMA20-FEDERJA-081No.UMA20-FEDERJA-074the Consejería de Empleo,Empresa y Trabajo Autónomo de la Junta de Andalucía(Investigo program),No.MA-INV-0031-2022-04Sara Borrell grant from the Instituto de Salud Carlos III(ISCIII),No.CD23/00117PFIS contract from the ISCIII,No.FI23-00016Juan Rodés contract from the ISCIII,No.JR22/00067the Miguel Servet program from the ISCIII,No.CP23/00088the Nicolas Monardes Program from the Consejería de Salud de la Junta de Andalucía(Spain),No.RC-0005-2020the Consejería Salud y Familias-Junta de Andalucía,No.RH-0078-2021the University of Málaga(Incorporación de Doctores del II Plan Propio de Investigación,Transferencia y Divulgación Científica de la Universidad de Málaga en 2023)the Miguel Servet program from ISCIII,Spain,No.CP22/00050.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a group of chronic,inflammatory disorders that include Crohn’s disease and ulcerative colitis.IBD arises from the interaction of various environmental and genetic factors.Altered gut permeability and mitochondrial stress in the colonic mucosa are two mechanisms previously implicated in IBD pathogenesis.We have previously demonstrated activation of the mitochondrial unfolded protein response(UPRmt)in the colonic mucosa of IBD patients and linked this activation to pro-inflammatory signaling.Growth differentiation factor 15(GDF15)is an important downstream mediator of the UPRmt.AIM To investigate whether GDF15 has a role in IBD and how GDF15 impacts colonic epithelium.METHODS Circulating levels of GDF15 were assessed in plasma samples from IBD patients and healthy controls using an enzyme-linked immunosorbent assay.To study the effects of GDF15 on the colonic mucosa,we employed two different in vitro culture models:Colonic organoids and T84 cells.RESULTS We found that circulating GDF15 Levels were elevated in IBD patients and correlated with markers of inflammation(C-reactive protein)and intestinal permeability[haptoglobin and lipopolysaccharide-binding protein(LBP)].Additionally,we demonstrated that GDF15 alters the intestinal barrier and increases permeability by decreasing the levels of zonula occludens 1 and claudin 1,critical components of tight junctions.Thus,our findings confirm previous reports of increased circulating GDF15 levels in IBD patients and the activation of UPR^(mt).CONCLUSION In the present study,we describe a novel mechanism in IBD pathophysiology,linking mitochondrial stress to the disruption of the intestinal barrier and increased intestinal permeability.
