Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A...Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.展开更多
Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydrop...Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydroponic crop nutrient solution. The average production of grape tomatoes was 338.9, 358.9, and 325.7 g/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean of numbers of grape tomatoes were 34.6, 38.8, and 34.2/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean weight of individual grape tomatoes was about 10.4 g for all of the substrates tested. These results confirmed the notion that a composted agave bagasse substrate could replace an expensive imported substrate. The remaining challenge is to produce agave bagasse substrate commercially, because to date, agave bagasse substrates have only been produced on a pilot scale for testing. Therefore, it is necessary to implement a stabilized process for producing agave bagasse at a commercial level. This process must consider economic production costs and market value to ensure that the product is competitive with other substrates typically used in soilless crops.展开更多
Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphoc...Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphocytic leukemia. Patient and Methods: Magnetic Resonance Imaging (MRI), histological picture (H.E., Kluver-Barrera) and immunohistochemical picture (GFAP, neurofilaments, CD68, JC virus) were obtained. Results: 1) Magnetic resonance imaging: Asymmetric and progressive lesions on middle cerebellar peduncles, that were hyperintense in T2/FLAIR, extended towards the pons, had no mass effect and were unmodified after intravenous contrast. 2) Histology: Marked reactive gliosis with cytopathic changes suggesting viral infection, plus demyelination areas with axonal preservation. 3) Immunohistochemistry: Marked positivity for viral (polyoma and JC virus) markers in glial cells showing cytopathic changes. Conclusions: The importance of histological and immunohistochemical diagnosis in everyday assistance;of the collaboration between clinicians, radiologists and pathologists;and the validity of postmortem studies as a key element for research and clinical quality assessment must be stressed.展开更多
There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near t...There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near the Refinery of Cd.Madero,Tam-ps.,had high amounts of both,hydrocarbons and hea-vy metals.展开更多
Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Objective:To evaluate and compare coagulation and hematological parameters in hypertensive and normotensive pregnant women.Methods:This present cross-sectional study was carried out in the Departments of Pathology and...Objective:To evaluate and compare coagulation and hematological parameters in hypertensive and normotensive pregnant women.Methods:This present cross-sectional study was carried out in the Departments of Pathology and Obstetrics&Gynaecology at Dr.D.Y.Patil Medical College,Hospital&Research Centre,Pimpri,Pune,India from September 2023 to March 2025.Hematological parameters[platelet count,mean platelet volume(MPV),platelet distribution width(PDW)]were analyzed using an automated hematology analyzer,while coagulation parameters[prothrombin time(PT)/international normalised ratio,activated partial thromboplastin time(aPTT),and D-dimer]were assessed by standard automated assays.Results were compared between normotensive and hypertensive groups and correlated with disease severity.Results:The study included 212 antenatal females,with 106 normotensive pregnant women and 106 hypertensive women.Hypertensive women include cases of gestational hypertension(n=55);mild preeclampsia(n=39),and severe preeclampsia(n=12).A significant progressive decrease in platelet count and significant increases in MPV,PDW,PT,aPTT,and D-dimer levels were associated with increasing severity of pregnancy-induced hypertension(P<0.001).Women with severe preeclampsia had the lowest mean platelet counts and the highest coagulation parameter values compared to women with gestational hypertension,mild preeclampsia,and normotensive pregnancies.These findings indicate enhanced platelet activation,endothelial dysfunction,and activation of the coagulation–fibrinolytic system with worsening disease severity.Conclusions:Significant hematologic and coagulation abnormalities were present in women with pregnancy-induced hypertension.For better maternal-fetal outcomes and early management,routine monitoring is essential.展开更多
Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately...Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately 80 km along a NW-SE axis.With a summit reaching~3214 m(a.s.l.),Mount Kandil is a stratovolcano that,like many other peaks within the EAHP and the Lesser Caucasus,experienced significant environmental changes during Late Pleistocene.Among these,glacial processes stand out as the most profound,having distinctly shaped the mountains geomorphic landscape.This study presents,for the first time,a comprehensive analysis of the glacial morphology of Mount Kandil based on multiple datasets.Field-based morphological observations indicate that an area of approximately 32.62 km^(2)has been sculpted by glacial activity.Within six glaciated regions on Mount Kandil,25 cirques and 6 glacial valleys have been identified.In addition,moraines in various locations exhibit characteristic morphologies.Furthermore,valley glaciers are inferred to have descended to altitudes as low as~2000 m.The paleoequilibrium line(p ELA)was estimated to use AABR method within GIS,yielding a mean pELA of~2730 m.Ice thickness modelling indicates that the thickness of glaciers in the Kandil Mountain valleys reaches up to~350 m.Due to its orographic extension,Mount Kandil is exposed to humid northwest winds and receives substantial frontal precipitation(~686 mm annually).The compiled geomorphic,cartographic and morphometric parameters suggest that the glaciation dynamics of Mount Kandil—situated between the Southeastern Taurus and the Lesser Caucasus—closely resemble those observed in the Lesser Caucasus.This indicates that glaciation was primarily governed by northern atmospheric systems with additional influences from southerly or westerly winds.The integrated data also underscores the role of multiple atmospheric systems in controlling the glaciation regime around the Lesser Caucasus.Additionally,findings on regional pELA question the common belief that pELA increases eastward in EAHP.展开更多
Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,par...Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
Agile lithology identification can assist mining by providing important information in the exploration and production of mineral resources.This study proposes a new lithology recognition procedure using video-logging ...Agile lithology identification can assist mining by providing important information in the exploration and production of mineral resources.This study proposes a new lithology recognition procedure using video-logging of boreholes with an endoscope,applied to six production blocks in a limestone quarry.Images are automatically extracted from the videos and the lithology is classified into three classes based on clay content,i.e.massive limestone,brecciated limestone,and high amount of clay.The image quality is evaluated with a gray pixel intensity threshold and three no-reference image quality metrics,i.e.perception-based image quality evaluator,natural image quality evaluator,and blind/referenceless image spatial quality evaluator.After removing low-quality images,7583 images are retained and used for developing lithology classification models using six optimized classification techniques.The contrast-limited adaptive histogram equalization(CLAHE)technique is used to improve image quality.Ten color characteristics involving three percentiles of red,green and blue pixel intensities,together with color counting and five texture characteristics-correlation,entropy,homogeneity,contrast and energy-are used as inputs.Bayesian optimized light gradient boosting machine model performs best,with an overall accuracy of 88.04%,and a precision on the classes of massive limestone,brecciated limestone and high amount of clay of 90.72%,83.52%and 85.29%,respectively,for the testing set.The feature importance scores show that the color counting is the most significant parameter for the development of the classification model.Compared with previous image-based methodologies,this study provides a more flexible and cheaper procedure to identify lithology.展开更多
The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in S...The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.展开更多
In April 2016,a moment magnitude(Mw)7.8 earthquake struck near Muisne(Pedernales),Ecuador,causing 671 fatalities,displacing>30,000 people,and generating approximately USD 3.6 billion in economic losses that severel...In April 2016,a moment magnitude(Mw)7.8 earthquake struck near Muisne(Pedernales),Ecuador,causing 671 fatalities,displacing>30,000 people,and generating approximately USD 3.6 billion in economic losses that severely impacted the coastal province of Manabí.Nine years later,the recovery trajectory of its principal urban centers-Pedernales,Manta,Portoviejo,and Chone-offers a critical perspective to assess adaptive resilience in earthquake-prone coastal cities of Latin America.This study conducts a regional assessment of post-earthquake recovery using the 4Rs resilience framework-robustness,redundancy,resourcefulness,and rapidity-applied across housing,health,education,infrastructure,and economic sectors.Official reports,statistical databases,and field validations collected between 2016 and 2025 provide the basis for documenting both progress and persistent challenges.The findings indicate that robustness improved with the enforcement of the Ecuadorian seismic code NEC-15 and the adoption of advanced technologies such as base isolation and supplemental damping in hospitals and high-rise buildings.Redundancy expanded selectively,being stronger in healthcare yet limited in housing and utilities.Resourcefulness varied across cities:municipal leadership and civic oversight in Manta and Portoviejo facilitated adaptive recovery,whereas Pedernales and Chone remained dependent on central agencies.Rapidity was similarly uneven;lifeline services were restored promptly,but complex projects-including hospitals,sewer systems,and residential complexes-faced delays of five to nine years.Structural assessments of 97 buildings revealed that nearly half remain without reinforcement,with recurrent deficiencies such as soft-story mecha-nisms,brittle masonry infill,and reinforcement corrosion sustaining latent seismic risk.Governance fragmen-tation,equity gaps,and insufficient monitoring thus emerged as critical barriers,underscoring the need for integrated governance,community participation,and AI-enabled monitoring to strengthen long-term disaster recovery in coastal cities.展开更多
AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygiu...AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.展开更多
Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortal...Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.展开更多
For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language defi...For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.展开更多
AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided...AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
Achieving uniform X-ray irradiation in indirect-drive inertial confinement fusion(ICF)is a key challenge for successful capsule implosion.Spherical hohlraums,particularly those with octahedral laser entrance holes(LEH...Achieving uniform X-ray irradiation in indirect-drive inertial confinement fusion(ICF)is a key challenge for successful capsule implosion.Spherical hohlraums,particularly those with octahedral laser entrance holes(LEHs),are an alternative to the cylindrical hohlraums currently considered for ICF at NIF(USA)and LMJ(France).These spherical hohlraums are advantageous in terms of irradiation uniformity on the fusion capsule because,owing to their octahedral symmetry,low-order asymmetries cancel out intrinsically.However,they may be less favorable from an energetic point of view,primarily owing to radiation losses through their multiple LEHs.The net balance of these advantages and disadvantages is difficult to determine,because,unlike cylindrical hohlraums,they require fully 3D modeling.To address this,a new version of the MULTI-3D simulation code has been developed.MULTI-3D is a 3D radiation-hydrodynamics code with arbitrary Langrangian-Eulerian(ALE)hydrodynamics,multigroup SN radiation transport,and ray-tracing laser deposition.Using this tool,several aspects of the behavior of spherical hohlraums have been analyzed,with special attention to phenomena inaccessible to 2D modeling.In these targets,laser beams strike the inner walls at very oblique angles,and the expansion of plasma significantly alters the locations where primary X rays are produced.Furthermore,the complex distribution of laser hot spots leads to mutual interactions,where plasma bubbles from one beam intersect the path of another.The laser-to-X-ray energy conversion efficiency has been analyzed as a function of key parameters.The symmetry on the capsule has also been evaluated,revealing nonuniformities of less than 1%.展开更多
Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation...Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures”,is observing 139 massive starforming clumps at ALMA Band 6(λ~1.3 mm).This paper introduces the Atacama Compact Array(ACA)7 m data of the QUARKS survey,describing the ACA observations and data reduction.Combining multiwavelength data,we provide the first edition of QUARKS atlas,offering insights into the multiscale and multiphase interstellar medium in high-mass star formation.The ACA 1.3 mm catalog includes 207 continuum sources that are called ACA sources.Their gas kinetic temperatures are estimated using three formaldehyde transitions with a non-LTE radiation transfer model,and the mass and density are derived from a dust emission model.The ACA sources are massive(16–84 percentile values of 6–160 M_(⊙)),gravity-dominated(M∝R^(1.1))fragments within massive clumps,with supersonic turbulence(M>1)and embedded star-forming protoclusters.We find a linear correlation between the masses of the fragments and the massive clumps,with a ratio of 6%between the two.When considering fragments as representative of dense gas,the ratio indicates a dense gas fraction(DGF)of 6%,although with a wide scatter ranging from 1%to 10%.If we consider the QUARKS massive clumps to be what is observed at various scales,then the size-independent DGF indicates a self-similar fragmentation or collapsing mode in protocluster formation.With the ACA data over four orders of magnitude of luminosity-to-mass ratio(L/M),we find that the DGF increases significantly with L/M,which indicates clump evolutionary stage.We observed a limited fragmentation at the subclump scale,which can be explained by a dynamic global collapse process.展开更多
Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone home...Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone homeostasis,promoting osteoclastogenesis and the accumulation of senescent cells.In line with updated cancer hallmarks,senescent mesenchymal stem/stromal cells(MSCs),osteoblasts,and osteocytes contribute to remodeling of the BM microenvironment,thereby favoring pre-metastatic niche(PMN)formation and subsequent bone metastasis.We previously demonstrated that untreated stage III-B breast cancer patients(BCPs)exhibit increased oxidative stress and elevated reactive oxygen species(ROS)levels,accompanied by senescent and functionally impaired BM-MSCs—key regulators of BM/bone homeostasis.In the present study,we sought to identify the molecular targets affected by oxidative stress that drive MSC senescence in these patients.Methods:BM-MSCs were isolated from untreated stage III-B BCPs and healthy volunteers(HVs).Oxidative stress responses were evaluated by quantitative real-time PCR(qRT-PCR)analysis of stress-and antioxidant-related genes.Oxidative damage to DNA,proteins,and lipids was assessed using alkaline comet assay,chromosomal aberration(CAs)analysis,micronuclei(MN)and nuclear blebs(NBs)quantification,protein carbonyl content,and detection of 4-hydroxynonenal(4-HNE)adducts.The MSC secretome was analyzed by label-free quantitative proteomics followed by Gene Ontology enrichment analysis.Results:Our results show that elevated oxidative stress in BCPs induces the overexpression of oxidative stress-related and antioxidant response genes in BM-MSCs;however,this response is insufficient to prevent extensive ROS-induced damage to deoxyribonucleic acid(DNA),proteins,and lipids.In addition,proteomic analysis of the BM-MSC secretome revealed a distinct protein expression profile in BCPs compared with HVs.Conclusions:Together,these findings highlight oxidative stress-induced MSC damage as a key mechanism contributing to PMN formation and suggest potential therapeutic targets to mitigate bone metastasis in advanced breast cancer.展开更多
文摘Obesity has reached epidemic proportions particularly in western countries. Most non-surgical treatments of this condition are disappointing. Since 2005, several studies evaluating the effect of Botulinum Toxin type A (BT-A) in gastric antrum by means of endoscopy for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BT-A in laparatomized rats induced a significant reduction of food intake and body weight. Nowadays, 6 studies have been published yielding conflicting results. Differences in selection of patients, doses of BT-A, method of administration of the toxin and instruments of evaluation of some parameters among these studies may be the cause of divergent results. We discuss herein some important features of these studies pointing out on differences among them. At the same time, based on the knowledge of physiological characteristics of normal and abnormal gastric function related with feeding, we discuss the probable causes of failure observed in these trials. Finally, we give some guidelines concerning the way that future research in this field may follow, not without calling attention to disadvantages of this treatment.
文摘Here, we evaluated the possibility of growing grape tomatoes on three different mixtures of composted agave bagasse substrate. Tomatoes were grown in 28-L pots for 106 days under a drip irrigation system with a hydroponic crop nutrient solution. The average production of grape tomatoes was 338.9, 358.9, and 325.7 g/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean of numbers of grape tomatoes were 34.6, 38.8, and 34.2/pot/cut for each of the substrates studied, and no significant difference was observed between treatments (p > 0.5). The mean weight of individual grape tomatoes was about 10.4 g for all of the substrates tested. These results confirmed the notion that a composted agave bagasse substrate could replace an expensive imported substrate. The remaining challenge is to produce agave bagasse substrate commercially, because to date, agave bagasse substrates have only been produced on a pilot scale for testing. Therefore, it is necessary to implement a stabilized process for producing agave bagasse at a commercial level. This process must consider economic production costs and market value to ensure that the product is competitive with other substrates typically used in soilless crops.
文摘Objective: To describe the radiological, histological and immunohistochemical findings in a case of Progressive Multifocal Leukoencephalopathy (PML) affecting the cerebellar peduncles in a patient with chronic lymphocytic leukemia. Patient and Methods: Magnetic Resonance Imaging (MRI), histological picture (H.E., Kluver-Barrera) and immunohistochemical picture (GFAP, neurofilaments, CD68, JC virus) were obtained. Results: 1) Magnetic resonance imaging: Asymmetric and progressive lesions on middle cerebellar peduncles, that were hyperintense in T2/FLAIR, extended towards the pons, had no mass effect and were unmodified after intravenous contrast. 2) Histology: Marked reactive gliosis with cytopathic changes suggesting viral infection, plus demyelination areas with axonal preservation. 3) Immunohistochemistry: Marked positivity for viral (polyoma and JC virus) markers in glial cells showing cytopathic changes. Conclusions: The importance of histological and immunohistochemical diagnosis in everyday assistance;of the collaboration between clinicians, radiologists and pathologists;and the validity of postmortem studies as a key element for research and clinical quality assessment must be stressed.
文摘There is a growing concern adout the genetic riskproduced by contamination of coastal lagoons alongthe Gulf of Mexico,it was found recently that oys-ters(Crassostrea virginica)collected from an es-tuary located near the Refinery of Cd.Madero,Tam-ps.,had high amounts of both,hydrocarbons and hea-vy metals.
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
文摘Objective:To evaluate and compare coagulation and hematological parameters in hypertensive and normotensive pregnant women.Methods:This present cross-sectional study was carried out in the Departments of Pathology and Obstetrics&Gynaecology at Dr.D.Y.Patil Medical College,Hospital&Research Centre,Pimpri,Pune,India from September 2023 to March 2025.Hematological parameters[platelet count,mean platelet volume(MPV),platelet distribution width(PDW)]were analyzed using an automated hematology analyzer,while coagulation parameters[prothrombin time(PT)/international normalised ratio,activated partial thromboplastin time(aPTT),and D-dimer]were assessed by standard automated assays.Results were compared between normotensive and hypertensive groups and correlated with disease severity.Results:The study included 212 antenatal females,with 106 normotensive pregnant women and 106 hypertensive women.Hypertensive women include cases of gestational hypertension(n=55);mild preeclampsia(n=39),and severe preeclampsia(n=12).A significant progressive decrease in platelet count and significant increases in MPV,PDW,PT,aPTT,and D-dimer levels were associated with increasing severity of pregnancy-induced hypertension(P<0.001).Women with severe preeclampsia had the lowest mean platelet counts and the highest coagulation parameter values compared to women with gestational hypertension,mild preeclampsia,and normotensive pregnancies.These findings indicate enhanced platelet activation,endothelial dysfunction,and activation of the coagulation–fibrinolytic system with worsening disease severity.Conclusions:Significant hematologic and coagulation abnormalities were present in women with pregnancy-induced hypertension.For better maternal-fetal outcomes and early management,routine monitoring is essential.
基金supported by Van Yüzüncü Yıl University,Scientific Research Projects Coordination Unit(Project No:SDK-2025-11935)Van Yüzüncü Yıl University,Scientific Research Projects Coordination Unit for supporting the study。
文摘Mount Kandil is situated in the eastern sector of the EAHP(Eastern Anatolian High Plateau),to the south of the Lesser Caucasus.The mountain lies at the westernmost end of the Aras Mountains,which extends approximately 80 km along a NW-SE axis.With a summit reaching~3214 m(a.s.l.),Mount Kandil is a stratovolcano that,like many other peaks within the EAHP and the Lesser Caucasus,experienced significant environmental changes during Late Pleistocene.Among these,glacial processes stand out as the most profound,having distinctly shaped the mountains geomorphic landscape.This study presents,for the first time,a comprehensive analysis of the glacial morphology of Mount Kandil based on multiple datasets.Field-based morphological observations indicate that an area of approximately 32.62 km^(2)has been sculpted by glacial activity.Within six glaciated regions on Mount Kandil,25 cirques and 6 glacial valleys have been identified.In addition,moraines in various locations exhibit characteristic morphologies.Furthermore,valley glaciers are inferred to have descended to altitudes as low as~2000 m.The paleoequilibrium line(p ELA)was estimated to use AABR method within GIS,yielding a mean pELA of~2730 m.Ice thickness modelling indicates that the thickness of glaciers in the Kandil Mountain valleys reaches up to~350 m.Due to its orographic extension,Mount Kandil is exposed to humid northwest winds and receives substantial frontal precipitation(~686 mm annually).The compiled geomorphic,cartographic and morphometric parameters suggest that the glaciation dynamics of Mount Kandil—situated between the Southeastern Taurus and the Lesser Caucasus—closely resemble those observed in the Lesser Caucasus.This indicates that glaciation was primarily governed by northern atmospheric systems with additional influences from southerly or westerly winds.The integrated data also underscores the role of multiple atmospheric systems in controlling the glaciation regime around the Lesser Caucasus.Additionally,findings on regional pELA question the common belief that pELA increases eastward in EAHP.
文摘Obesity is widely recognized as a global epidemic,primarily driven by an imbalance between energy expenditure and caloric intake associated with a sedentary lifestyle.Diets high in carbohydrates and saturated fats,particularly palmitic acid,are potent inducers of chronic low-grade inflammation,largely due to disruptions in glucose metabolism and the onset of insulin resistance(Qiu et al.,2022).While many organs are affected,the brain,specifically the hypothalamus,is among the first to exhibit inflammation in response to an unhealthy diet,suggesting that obesity may,in fact,be a brain-centered disease with neuroinflammation as a central factor(Thaler et al., 2012).
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
基金the DigiEcoQuarry project,funded by the European Union's Horizon 2020 research and innovation program under Grant Agreement No.101003750supported by the China Scholarship Council(Grant No.202006370006).
文摘Agile lithology identification can assist mining by providing important information in the exploration and production of mineral resources.This study proposes a new lithology recognition procedure using video-logging of boreholes with an endoscope,applied to six production blocks in a limestone quarry.Images are automatically extracted from the videos and the lithology is classified into three classes based on clay content,i.e.massive limestone,brecciated limestone,and high amount of clay.The image quality is evaluated with a gray pixel intensity threshold and three no-reference image quality metrics,i.e.perception-based image quality evaluator,natural image quality evaluator,and blind/referenceless image spatial quality evaluator.After removing low-quality images,7583 images are retained and used for developing lithology classification models using six optimized classification techniques.The contrast-limited adaptive histogram equalization(CLAHE)technique is used to improve image quality.Ten color characteristics involving three percentiles of red,green and blue pixel intensities,together with color counting and five texture characteristics-correlation,entropy,homogeneity,contrast and energy-are used as inputs.Bayesian optimized light gradient boosting machine model performs best,with an overall accuracy of 88.04%,and a precision on the classes of massive limestone,brecciated limestone and high amount of clay of 90.72%,83.52%and 85.29%,respectively,for the testing set.The feature importance scores show that the color counting is the most significant parameter for the development of the classification model.Compared with previous image-based methodologies,this study provides a more flexible and cheaper procedure to identify lithology.
基金the research project LaTe4PoliticES(PID2022-138099OB-I00)funded by MCIN/AEI/10.13039/501100011033 and the European Fund for Regional Development(ERDF)-a way to make Europe.Tomás Bernal-Beltrán is supported by University of Murcia through the predoctoral programme.
文摘The malicious dissemination of hate speech via compromised accounts,automated bot networks and malware-driven social media campaigns has become a growing cybersecurity concern.Automatically detecting such content in Spanish is challenging due to linguistic complexity and the scarcity of annotated resources.In this paper,we compare two predominant AI-based approaches for the forensic detection of malicious hate speech:(1)finetuning encoder-only models that have been trained in Spanish and(2)In-Context Learning techniques(Zero-and Few-Shot Learning)with large-scale language models.Our approach goes beyond binary classification,proposing a comprehensive,multidimensional evaluation that labels each text by:(1)type of speech,(2)recipient,(3)level of intensity(ordinal)and(4)targeted group(multi-label).Performance is evaluated using an annotated Spanish corpus,standard metrics such as precision,recall and F1-score and stability-oriented metrics to evaluate the stability of the transition from zero-shot to few-shot prompting(Zero-to-Few Shot Retention and Zero-to-Few Shot Gain)are applied.The results indicate that fine-tuned encoder-only models(notably MarIA and BETO variants)consistently deliver the strongest and most reliable performance:in our experiments their macro F1-scores lie roughly in the range of approximately 46%–66%depending on the task.Zero-shot approaches are much less stable and typically yield substantially lower performance(observed F1-scores range approximately 0%–39%),often producing invalid outputs in practice.Few-shot prompting(e.g.,Qwen 38B,Mistral 7B)generally improves stability and recall relative to pure zero-shot,bringing F1-scores into a moderate range of approximately 20%–51%but still falling short of fully fine-tuned models.These findings highlight the importance of supervised adaptation and discuss the potential of both paradigms as components in AI-powered cybersecurity and malware forensics systems designed to identify and mitigate coordinated online hate campaigns.
基金funded by the Chilean National Agency for Research and Development(ANID)through the Beca de Doctorado Nacional 21220089.
文摘In April 2016,a moment magnitude(Mw)7.8 earthquake struck near Muisne(Pedernales),Ecuador,causing 671 fatalities,displacing>30,000 people,and generating approximately USD 3.6 billion in economic losses that severely impacted the coastal province of Manabí.Nine years later,the recovery trajectory of its principal urban centers-Pedernales,Manta,Portoviejo,and Chone-offers a critical perspective to assess adaptive resilience in earthquake-prone coastal cities of Latin America.This study conducts a regional assessment of post-earthquake recovery using the 4Rs resilience framework-robustness,redundancy,resourcefulness,and rapidity-applied across housing,health,education,infrastructure,and economic sectors.Official reports,statistical databases,and field validations collected between 2016 and 2025 provide the basis for documenting both progress and persistent challenges.The findings indicate that robustness improved with the enforcement of the Ecuadorian seismic code NEC-15 and the adoption of advanced technologies such as base isolation and supplemental damping in hospitals and high-rise buildings.Redundancy expanded selectively,being stronger in healthcare yet limited in housing and utilities.Resourcefulness varied across cities:municipal leadership and civic oversight in Manta and Portoviejo facilitated adaptive recovery,whereas Pedernales and Chone remained dependent on central agencies.Rapidity was similarly uneven;lifeline services were restored promptly,but complex projects-including hospitals,sewer systems,and residential complexes-faced delays of five to nine years.Structural assessments of 97 buildings revealed that nearly half remain without reinforcement,with recurrent deficiencies such as soft-story mecha-nisms,brittle masonry infill,and reinforcement corrosion sustaining latent seismic risk.Governance fragmen-tation,equity gaps,and insufficient monitoring thus emerged as critical barriers,underscoring the need for integrated governance,community participation,and AI-enabled monitoring to strengthen long-term disaster recovery in coastal cities.
文摘AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.
基金Instituto de Salud CarlosⅢCB16/10/00435(CIBERFES)(PID2022-142470OB-I00)from the Spanish Ministry of Innovation and Science+3 种基金PROMETEO(CIPROM/2022/56)de"Consellería de Educación,Universidades,y Empleo de la Generalitat Valenciana"EU Funded H2020-DIABFRAIL-LATAM(Ref:825546)Red EXERNET-RED DE EJERCICIO FISICO Y SALUD(RED2022-134800-T)Agencia Estatal de Investigacion(Ministerio de Ciencias e Innovación)funded by Generalitat Valenciana and co-financed with FEDER funds(OP FEDER of Comunitat Valenciana 2014–2020).A.G-G(FPU22/02539)and S.S-R(PREP2022-000563)received a predoctoral grant financed by the Spanish Ministry of Universities.
文摘Aging is characterized by a progressive decline in physiological function,driven by intrinsic mechanisms(primary aging)and modifiable factors(secondary aging),ultimately leading to multimorbidity,disability,and mortality.Mitochondrial dysfunction,a major hallmark of aging,plays a central role in the loss of muscle mass and strength observed in frailty and sarcopenia.With age,mitochondrial quality control processes,including biogenesis,mitophagy,and dynamics,become dysregulated,impairing energy metabolism and muscle homeostasis.Mitochondrial dysfunction correlates with clinical biomarkers of sarcopenia and frailty,such as the decrease in walking speed and muscle strength,making it a therapeutic target for mitohormesis-based strategies aimed at preserving functional capacity.Mitohormetic agents induce reversible mitochondrial stress,triggering adaptive responses that enhance function.Among these interventions,physical exercise,particularly endurance and resistance training(RT),has been reported to be among the most effective,as it may modulate mitochondrial biogenesis,dynamics,and mitophagy through increases in proliferator-activated receptor gamma coactivator 1-alpha(PGC-1α)and mitochondrial transcription factor A(TFAM)expression,mitochondrial deoxyribonucleic acid(mtDNA)copy number,and mitochondrial content.Chronic RT can also elevate fusion and fission markers,potentially as a compensatory mechanism to mitigate mitochondrial damage.Apart from exercise,mitohormetic compounds such as harmol and piceid are emerging as promising supplements in the aging field.By modulating mitochondrial bioenergetics and dynamics,they may complement lifestyle-based interventions to improve mitochondrial fitness and extend health span.
文摘For many decades,Alzheimer's disease research has primarily focused on impairments within cortical and hippocampal regions,which are thought to be related to cognitive dysfunctions such as memory and language deficits.The exact cause of Alzheimer's disease is still under debate,making it challenging to establish an effective therapy or early diagnosis.It is widely accepted that the accumulation of amyloid-beta peptide in the brain parenchyma leads to synaptic dysfunction,a critical step in Alzheimer's disease development.The traditional amyloid cascade model is initiated by accumulating extracellular amyloid-beta in brain areas essential for memory and language.However,while it is possible to reduce the presence of amyloid-beta plaques in the brain with newer immunotherapies,cognitive symptoms do not necessarily improve.Interestingly,recent studies support the notion that early alterations in subcortical brain regions also contribute to brain damage and precognitive decline in Alzheimer's disease.A body of recent evidence suggests that early Alzheimer's disease is associated with alterations(e.g.,motivation,anxiety,and motor impairment)in subcortical areas,such as the striatum and amygdala,in both human and animal models.Also,recent data indicate that intracellular amyloid-beta appears early in subcortical regions such as the nucleus accumbens,locus coeruleus,and raphe nucleus,even without extracellular amyloid plaques.The reported effects are mainly excitatory,increasing glutamatergic transmission and neuronal excitability.In agreement,data in Alzheimer's disease patients and animal models show an increase in neuronal synchronization that leads to electroencephalogram disturbances and epilepsy.The data indicate that early subcortical brain dysfunctions might be associated with non-cognitive symptoms such as anxiety,irritability,and motivation deficits,which precede memory loss and language alterations.Overall,the evidence reviewed suggests that subcortical brain regions could explain early dysfunctions and perhaps be targets for therapies to slow disease progression.Future research should focus on these non-traditional brain regions to reveal early pathological alterations and underlying mechanisms to advance our understanding of Alzheimer's disease beyond the traditionally studied hippocampal and cortical circuits.
文摘AIM:To examine the ocular toxicity linked to sildenafilusage and the possible protective benefits of adenosinetriphosphate(ATP)against this toxicity in rats.METHODS:Twenty-four male albino Wistar-type ratswere divided into four equal groups(n=6/group)as follows:healthy group(HG),ATP-only group(ATPG),sildenafil-onlygroup(SILG),and ATP+sildenafil group(ATP+SLD).ATPG andATP+SLD groups were injected intraperitoneally with ATP(4 mg/kg),while SILG and HG groups were injected withsaline(0.9%NaCl)by the same route as a solvent.One hourafter the administration of ATP and solvent,sildenafil(10 m g/k g)was administered orally to the SILG andATP+SLD groups.This procedure was repeated once a dayfor 4wk.The animals were then sacrificed,eyeballs wereremoved and oxidant and antioxidant parameters weremeasured biochemically.Additionally,the ocular tissueswere evaluated histopathologically.RESULTS:Sildenafil increased oxidant(malondialdehyde)levels and decreased antioxidant levels(total glutathione,superoxide dismutase,catalase)in rat ocular tissues andcaused severe oxidative stress.In addition,sildenafil hasbeen shown histopathologically to cause oxidative damagein retinal layers.ATP treatment suppressed oxidative stressand attenuated histopathological damage in the retinal layers.CONCLUSION:ATP protects retinal tissue againstsildenafil-induced ocular oxidative damage in rats andmay contribute to the development of novel approaches toprevent or treat this damage.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
基金supported by the Project Nos.PID2022-137339OB-C22 of the“Plan Estatal 2021-2023R”of the Spanish Government and ENR-IFE.01.CEA of EUROFUSION.
文摘Achieving uniform X-ray irradiation in indirect-drive inertial confinement fusion(ICF)is a key challenge for successful capsule implosion.Spherical hohlraums,particularly those with octahedral laser entrance holes(LEHs),are an alternative to the cylindrical hohlraums currently considered for ICF at NIF(USA)and LMJ(France).These spherical hohlraums are advantageous in terms of irradiation uniformity on the fusion capsule because,owing to their octahedral symmetry,low-order asymmetries cancel out intrinsically.However,they may be less favorable from an energetic point of view,primarily owing to radiation losses through their multiple LEHs.The net balance of these advantages and disadvantages is difficult to determine,because,unlike cylindrical hohlraums,they require fully 3D modeling.To address this,a new version of the MULTI-3D simulation code has been developed.MULTI-3D is a 3D radiation-hydrodynamics code with arbitrary Langrangian-Eulerian(ALE)hydrodynamics,multigroup SN radiation transport,and ray-tracing laser deposition.Using this tool,several aspects of the behavior of spherical hohlraums have been analyzed,with special attention to phenomena inaccessible to 2D modeling.In these targets,laser beams strike the inner walls at very oblique angles,and the expansion of plasma significantly alters the locations where primary X rays are produced.Furthermore,the complex distribution of laser hot spots leads to mutual interactions,where plasma bubbles from one beam intersect the path of another.The laser-to-X-ray energy conversion efficiency has been analyzed as a function of key parameters.The symmetry on the capsule has also been evaluated,revealing nonuniformities of less than 1%.
基金upported by the National Natural Science Foundation of China(NSFC,Grant No.12033005)the National Key R&D Program of China(No.2022YFA1603102)+2 种基金the China Manned Space Project(CMS-CSST-2021-A09,CMS-CSST-2021-B06)the China-Chile Joint Research Fund(CCJRF No.2211)support from the Tianchi Talent Program of Xinjiang Uygur Autonomous Region。
文摘Leveraging the high resolution,sensitivity,and wide frequency coverage of the Atacama Large Millimeter/submillimeter Array(ALMA),the QUARKS survey,standing for“Querying Underlying mechanisms of massive star formation with ALMA-Resolved gas Kinematics and Structures”,is observing 139 massive starforming clumps at ALMA Band 6(λ~1.3 mm).This paper introduces the Atacama Compact Array(ACA)7 m data of the QUARKS survey,describing the ACA observations and data reduction.Combining multiwavelength data,we provide the first edition of QUARKS atlas,offering insights into the multiscale and multiphase interstellar medium in high-mass star formation.The ACA 1.3 mm catalog includes 207 continuum sources that are called ACA sources.Their gas kinetic temperatures are estimated using three formaldehyde transitions with a non-LTE radiation transfer model,and the mass and density are derived from a dust emission model.The ACA sources are massive(16–84 percentile values of 6–160 M_(⊙)),gravity-dominated(M∝R^(1.1))fragments within massive clumps,with supersonic turbulence(M>1)and embedded star-forming protoclusters.We find a linear correlation between the masses of the fragments and the massive clumps,with a ratio of 6%between the two.When considering fragments as representative of dense gas,the ratio indicates a dense gas fraction(DGF)of 6%,although with a wide scatter ranging from 1%to 10%.If we consider the QUARKS massive clumps to be what is observed at various scales,then the size-independent DGF indicates a self-similar fragmentation or collapsing mode in protocluster formation.With the ACA data over four orders of magnitude of luminosity-to-mass ratio(L/M),we find that the DGF increases significantly with L/M,which indicates clump evolutionary stage.We observed a limited fragmentation at the subclump scale,which can be explained by a dynamic global collapse process.
基金supported by the FONCYT,PICT 2016-#1093,Argentina.CONICET,PIP2014-#300,Argentina.Florencio Fiorini Foundation(#2021-2022),Argentina.
文摘Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone homeostasis,promoting osteoclastogenesis and the accumulation of senescent cells.In line with updated cancer hallmarks,senescent mesenchymal stem/stromal cells(MSCs),osteoblasts,and osteocytes contribute to remodeling of the BM microenvironment,thereby favoring pre-metastatic niche(PMN)formation and subsequent bone metastasis.We previously demonstrated that untreated stage III-B breast cancer patients(BCPs)exhibit increased oxidative stress and elevated reactive oxygen species(ROS)levels,accompanied by senescent and functionally impaired BM-MSCs—key regulators of BM/bone homeostasis.In the present study,we sought to identify the molecular targets affected by oxidative stress that drive MSC senescence in these patients.Methods:BM-MSCs were isolated from untreated stage III-B BCPs and healthy volunteers(HVs).Oxidative stress responses were evaluated by quantitative real-time PCR(qRT-PCR)analysis of stress-and antioxidant-related genes.Oxidative damage to DNA,proteins,and lipids was assessed using alkaline comet assay,chromosomal aberration(CAs)analysis,micronuclei(MN)and nuclear blebs(NBs)quantification,protein carbonyl content,and detection of 4-hydroxynonenal(4-HNE)adducts.The MSC secretome was analyzed by label-free quantitative proteomics followed by Gene Ontology enrichment analysis.Results:Our results show that elevated oxidative stress in BCPs induces the overexpression of oxidative stress-related and antioxidant response genes in BM-MSCs;however,this response is insufficient to prevent extensive ROS-induced damage to deoxyribonucleic acid(DNA),proteins,and lipids.In addition,proteomic analysis of the BM-MSC secretome revealed a distinct protein expression profile in BCPs compared with HVs.Conclusions:Together,these findings highlight oxidative stress-induced MSC damage as a key mechanism contributing to PMN formation and suggest potential therapeutic targets to mitigate bone metastasis in advanced breast cancer.
