Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central ne...Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.展开更多
This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization ...This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization of the adhesive and physical–mechanical testing of the panels according to European standards.The black soldier fly larvae-based adhesive exhibited gel-like viscoelastic behavior,rapid partial structural recovery after shear,and favorable application properties.Particleboards manufactured with this adhesive and sugarcane bagasse achieved promising mechanical performance,with modulus of rupture and modulus of elasticity values of 30.2 and 3500 MPa,respectively.Internal bond strength exceeded 0.4 MPa,complying with European standard 312-3 specifications.For comparative purposes,a panel made with Eucalyptus grandis particles was also produced under the same conditions to demonstrate the versatility of the adhesive system.Compared to other bio-based and synthetic adhesives,this bio-based system showed competitive performance and derives from the bioconversion of organic residues.Protein adhesives were synthesized fromHermetia illucens larvae grown commercially on agriculturalwaste frompotato chip production,emphasizing the renewable origin of both the biomass and the final adhesive.These results highlight the potential of insect proteins as sustainable and circular alternatives for the wood panel industry.展开更多
Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical...Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical action mechanisms of DCD on bridge structures,a three-span continuous suspension bridge was taken as the engineering background in this study.The influence of different forms of DCD on the internal force and displacement of the components in the side span of the bridge and the structural dynamic characteristics were explored through numerical simulations.The results showed that the lack of DCD caused the main cable and main girder to have large vertical displacements.The stresses of other components were redistributed,and the safety factor of the suspenders at the side span was greatly reduced.The setting of DCD improved the vertical stiffness of the structure.The rigid DCD had larger internal forces,but its control effect on the internal forces at the side span was slightly better than that of the flexible DCD.Both forms of DCD effectively coordinated the deformation of the main cable and main girder and the stress distribution of components in the side span area.The choice of DCD form depends on the topographic factors of bridge sites and the design requirements of related components at the side span.展开更多
Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has bee...Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.展开更多
Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus u...Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus using histological,histochemical,and morphological perspectives to elucidate the gonochoric or hermaphrodite sexual system in this genus.Males have a slender and very translucent reproductive system that is challenging to observe.The entire cephalothorax was histologically sectioned to ensure that all regions of the reproductive system could be identified.This non-gambarelloides group shows a gonochoric condition.The caridean pattern of the reproductive system was observed where the male has a pair of testes and a pair of very thin vasa deferentia,ending at the opening of the gonopore.Spermatophore structure is absent,without any layers surrounding the spermatozoa that are aggregated in a sperm mass.In females,the reproductive system consists of a pair of ovaries that extend to the end of the pleon.The extension of the ovary has a particular pattern compared to other caridean shrimps.Here,we hypothesize that males invest energy on somatic morphological structures to protect the host and female,using the larger pistol-like cheliped,while females invest energy in reproduction since all the members of this group are typical"pair-bond"examples.The observed pattern of the reproductive male morphology could also be evidence of a possible synapomorphy for this genus within theinfraorder.展开更多
The Mediterranean region in central Chile is experiencing a significant decrease in precipitation due to climate change and the dynamics of the El Nino Southern Oscillation(ENSO).Droughts have increased in recent deca...The Mediterranean region in central Chile is experiencing a significant decrease in precipitation due to climate change and the dynamics of the El Nino Southern Oscillation(ENSO).Droughts have increased in recent decades,~with the most severe and longest drought of the last millennium occurring since 2010 in central Chile.The impact of ongoing water scarcity is leading to significant drought-related declines in tree growth and forest dieback in the Mediterranean region.A deep understanding of how tree species respond to climate is crucial to accurately predict how forests will respond to climate change.We examined the growth responses to climate of three endemic and threatened tree species of the Mediterranean forests of central Chile,Nothofagus macrocarpa,Cryptocarya alba and Persea lingue,in a protected area.We observed that the growth of all three species was highly dependent on water availability and ENSO,and that the evergreen species C.alba and P.lingue increased their sensitivity to hydroclimate more than the deciduous species N.macrocarpa.These relationships were consistent across much of southern South America,highlighting the dependence of these species on water availability at large geographic scales.We found that there is a relationship between local water availability and ENSO that has intensified temporally and expanded geographically in recent decades.The xerophyllous species C.alba showed greater resistance and increasing resilience to severe droughts,while P.lingue and N.macrocarpa showed greater growth decline during droughts,possibly due to their preference for wetter environments.Our results highlight the crucial role of ENSO-driven water availability and drought in limiting tree growth and threatening the conservation of Mediterranean forests in central Chile.展开更多
Unstable environments intensify the frequency of extreme disasters.Long-term climate changes can lead to agricultural and ecological degradation that threatens population sustainability.To better understand past clima...Unstable environments intensify the frequency of extreme disasters.Long-term climate changes can lead to agricultural and ecological degradation that threatens population sustainability.To better understand past climatic events and consequences,here we present a reconstruction of the self-calibrating Palmer drought severity index(scPDSI)from September to August for the desert margins of northern China,dating back to 1742.The reconstruction accounts for 42.9%of the variation of meteorological data between 1951 and 2020.Our spatial correlation analyses showed significant correlations between scPDSI,runoff,and precipitation.Over the past 279 years,the study area has undergone nine dry and eight wet periods,with the most severe climate extremes between the 1850s and 1890s.This period of prolonged drought in northeastern China coincided with the combined impacts of climatic factors and human influences,contributing to the fall of the Qing Dynasty.Analysis of periodicity and anomalies in sea surface temperatures indicate a strong association between wet and dry cycles and El Niño-Southern Oscillations.Our findings offer insights into long-term dry and wet fluctuations at the desert margins in northern China and elucidate the relationship between drought and the dynamics of civilizations.They also highlight the potential impact of extremes in climate on modern society,especially under the four projected shared socioeconomic pathways climatic scenarios,which predict worsening droughts in northern China.展开更多
In the search for new alternatives to control tropical fungal pathogens,the ethanol extracts(EEs)from Acalypha gaumeri(Euphorbiaceae)roots showed antifungal properties against several tropical fungal phytopathogens.A....In the search for new alternatives to control tropical fungal pathogens,the ethanol extracts(EEs)from Acalypha gaumeri(Euphorbiaceae)roots showed antifungal properties against several tropical fungal phytopathogens.A.gaumeri is classified as endemic to the Yucatan Peninsula,Mexico,an area with distinct rainy,drought and northern seasons.The present study evaluated the antifungal activity of threewild populations of A.gaumeri collected quarterly in different seasons during one year against Alternaria chrysanthemi,Colletotrichumgloeosporioides,andPseudocercospora fijiensis and explored their ex-situ propagation.The highest activity was shown by the EE from the Tinum wild population during the rainy season against A.chrysanthemi,C.gloeosporioides,and P.fijiensis with MIC values of 500–1000μg/mL,followed by Yaxcaba populations during the rainy season and Kiuic and Tinum from November against A.chrysanthemi and P.fijiensis 1000 and 500μg/mL,respectively.The propagation of A.gaumeri was more effective throughmediumcuttings,showing 96%with 0.06%auxin indolbutyric acid,whereas only 51%of seeds germinated.The results indicated that seasonal changes and edaphic conditions in the three populations influence the antifungal efficacy of the extracts from A.gaumeri roots.This study enhances the knowledge of the biology and sustainable management of the A.gaumeri plant and advances the development of a biorational product to control tropical fungal diseases.展开更多
BACKGROUND Kidney disease is a common complication in liver transplant(LT)recipients,contributing to substantial morbidity and mortality.Calcineurin inhibitors are associated with short-and long-term decline in kidney...BACKGROUND Kidney disease is a common complication in liver transplant(LT)recipients,contributing to substantial morbidity and mortality.Calcineurin inhibitors are associated with short-and long-term decline in kidney function.AIM To assess how changes in immunosuppression over three decades have impacted the evolution of renal function in the first year post-LT.METHODS This single-center,observational,retrospective study was conducted in a tertiary hospital in Madrid.Adult patients who received a first LT in our center from 1987 to 2019 were included.Patients with simultaneous or prior transplantation of another organ and patients who required re-transplantation,or were lost to follow-up or died during the first year after transplantation were excluded.The development of chronic kidney disease(CKD)pre-transplant or at the first year after LT was analyzed.RESULTS A total of 594 patients(median age:52.9 years,25th-75th percentiles=45-59.08 years;29.3%female)were included.At 1 year post-transplant,290(48.82%)patients had developed CKD.Older age[odds ratio(OR)=1.03,95%CI:1.01-1.05],female sex(OR=1.88,95%CI:1.23-2.89),pre-transplant renal dysfunction(RD)(OR=2.69,95%CI:1.58-4.58),and treatment with cyclosporine A(CsA)(OR=3.77,95%CI:2.45-5.78)were independent risk factors for CKD at 1 year after LT.In patients treated with tacrolimus(Tac)(n=375),the combination of basiliximab and mycophenolic acid(MPA)resulted in decreased Tac blood levels(P<0.001);additionally,MPA was associated with a lower incidence of RD in the first year(P=0.016).CONCLUSION Age,female sex,pre-transplant RD,and CsA are associated with increased risk of CKD within 1 year after LT.Addition of MPA to Tac is associated with lower RD incidence.展开更多
BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the ...BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.展开更多
Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious a...Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.展开更多
Although mollusks represent Earth’s second most diverse invertebrate group,their natural history and ecology are still scarcely known.The compilation of non-traditional data,such as those from citizen science,represe...Although mollusks represent Earth’s second most diverse invertebrate group,their natural history and ecology are still scarcely known.The compilation of non-traditional data,such as those from citizen science,represents an alternative to fill these gaps,particularly on striking land snail species such as Macrocyclis peruvianus.Based on long-term citizen science,we aimed to update and describe some basic ecological aspects,such as the distribution and protected area types used by M.peruvianus.We performed pairwise comparisons to test potential changes in occurrence and occupancy among administrative regions,forest types,and protected area types using chi-squared tests.The citizen scientists were also asked to provide the number of M.peruvianus individuals observed and the tree species that dominated their habitat.Thus,we tested if the number of land snails found by citizen scientists could be related to forest and protected area types using a generalized linear mixed model.We expanded the northern distributional limit,with Nothofagus,evergreen,and mixed forests far the most frequented by M.peruvianus.Parallelly,the occurrence of M.peruvianus in official protected areas(65.73%)was significantly higher than in privately owned areas.Moreover,we did not find associations between forest and protected area types with the number of M.peruvianus recorded.Although citizen science is a helpful method for obtaining novel information regarding the ecology of neglected species such as M.peruvianus,it also introduces spatial and occurrence biases explained by the access and attractiveness of the officially protected areas compared to privately owned patches of native forest.展开更多
Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative...Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative stress,and causes pro-inflammatory cytokine release,creating a neurotoxic environment.In this context,we explore the intricate connection between hypertension,neuroinflammation,and neurodegeneration,as well as how hypertension interacts with other metabolic disorders,such as obesity and diabetes,to further worsen neuroinflammation.Additionally,we discuss the role of the reninangiotensin-aldosterone system,the impact of the microbiome,and the potential contribution of chronic infections in exacerbating neuroinflammation.It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches.Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs,antioxidants,and neuroprotective compounds,enabling targeted delivery across the BBB.By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation,oxidative stress,and protein aggregation,we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions.Ultimately,hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death,primarily through impaired cerebral blood flow and disruption of the BBB.The interaction of hypertension with metabolic disorders exacerbates these effects.However,advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain,thereby improving treatment outcomes,enhancing adherence,and reducing side effects.展开更多
Tomato is an economically important crop that is susceptible to biotic and abiotic stresses,situations that negatively affect the crop cycle.Biotic stress is caused by phytopathogens such as Fusarium oxysporum f.sp.ly...Tomato is an economically important crop that is susceptible to biotic and abiotic stresses,situations that negatively affect the crop cycle.Biotic stress is caused by phytopathogens such as Fusarium oxysporum f.sp.lycopersici(FOL),responsible for vascular wilt,a disease that causes economic losses of up to 100%in crops of interest.Nanomaterials represent an area of opportunity for pathogen control through stimulations that modify the plant development program,achieving greater adaptation and tolerance to stress.The aim of this study was to evaluate the antimicrobial capacity of the nanoparticles and the concentrations used in tomato plants infected with FOL.To this end,a two-stage experiment was conducted.In Stage 1,the effects of the nanomaterials(Graphene nanoplatelets[GP],Zinc oxide nanoparticles[ZnO NPs],Magnesium oxide nanoparticles[MgO NPs])were evaluated both alone and in combination to determine the most effective method of controlling FOL-induced disease.In Stage 2,the most effective combination of nanomaterials(ZnO+GP)was evaluated at four concentrations ranging from 100 to 400 mg L^(−1).To evaluate the effectiveness of the treatments,we determined the incidence and severity of the disease,agronomic parameters,as well as the following biochemical variables:chlorophylls,β-carotene,vitamin C,phenols,flavonoids,hydrogen peroxide,superoxide anion,and malondialdehyde.The results show various positive effects,highlighting the efficiency of the ZnO+GP at 200mg L^(−1),which reduced the severity by approximately 20%,in addition to increasing agronomic variables and reducing reactive oxygen species.Moreover,the results show that the application of these nanomaterials increases vegetative development and defense against biotic stress.The use of nanomaterials such as zinc oxide,magnesium oxide and graphene can be an effective tool in the control of the severity of Fusarium oxysporum disease.展开更多
Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild fem...Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild females,causing generation-to-generation suppression.Medflies are colonized by microorganisms,primarily the Enterobacteriaceae,with the genera Klebsiella and Enterobacter being the most common.Such microbiota contributes to host fitness.During the SIT,diet with antibiotics and irradiation for sterility of adults alter microbiota.We aimed to determine the role of Medfly microbiota on resistance to abiotic stress conditions,evaluating its function under:(i)starvation,(ii)elevated temperatures,and(iii)dry environments.These conditions simulate challenges Medfly may encounter after release,which differ from controlled rearing environments.We compared adult survival between symbiotic and aposymbiotic individuals,under starvation,two thermal regimes(25 and 30℃)or two humidity regimes(20%-25%and 80%-90%R.H.).Aposymbiotic individuals were obtained after providing them with water containing a mixture of antibiotics and methylparaben.Treatment with antimicrobials effectively reduced the gut microbiota.While starvation had no significant effect on survival,a higher proportion of aposymbiotic individuals died earlier at 30℃ and under dry humidity,with the effect being more pronounced after 48 h.Our results suggest that microbiota plays a role in adaptation of Medfly under environmental stress.We report for the presence of a culturable yeast in the digestive tract of C.capitata,Zygosaccharomyces rouxii.Providing a probiotic adult diet with bacteria and Z.rouxii prior to release could improve SIT outcomes under adverse conditions.展开更多
Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrins...Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.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
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
The selective vulnerability of nigrostriatal dopaminergic neurons is a hallmark of Parkinson’s disease and underlies its progressive motor decline.These neurons are uniquely susceptible to degeneration due to their e...The selective vulnerability of nigrostriatal dopaminergic neurons is a hallmark of Parkinson’s disease and underlies its progressive motor decline.These neurons are uniquely susceptible to degeneration due to their extensive axonal arborization,high energy demands,sustained pacemaking activity,and cytosolic dopamine metabolism,which collectively promote oxidative stress and mitochondrial dysfunction.Advances in single-nucleus RNA sequencing and spatial transcriptomics have revealed transcriptionally distinct dopaminergic subtypes within the human substantia nigra pars compacta,such as AGTR1+/SOX6+and RIT2+populations,which exhibit subtype-specific transcriptional stress signatures and are preferentially lost in Parkinson’s disease.These findings underscore the role of intrinsic vulnerability,influenced by genetic risk loci,mitochondrial stress,and protein misfolding pathways,includingα-synuclein aggregation.Furthermore,neuroinflammation,iron accumulation,and vascular dysfunction act synergistically to amplify neuronal loss.This review integrates molecular,cellular,and systems-level mechanisms contributing to dopaminergic degeneration and evaluates emerging neuroprotective strategies.These include anti-oxidative,anti-inflammatory,mitochondrial therapies,novel biomarkers,gene editing,and cell replacement techniques.Understanding the selective vulnerability of nigrostriatal subtypes offers a promising path toward precision-targeted,disease-modifying treatments for Parkinson’s disease.展开更多
基金supported by funds from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico do Brasil(CNPq)(312286/2023-6,307201/2023-6,and Instituto Nacional Saude Cerebral INSC,No.406020/2022-1)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior(CAPES)Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro-FAPERJ(E-26/010.002260/2019,E-26/010.001652/2019,E-26/010.101036/2018,E-26/202.774/2018,E-26/210.240/2020,E-26/211.138/2021,26/210.823/2021,E-26/211.325/2021,E-26/210.779/2021,E-26/201.086/2022,E-26/210.312/2022,E-26/203.262/2023,E-26/200.195/2023)(to LEBS)。
文摘Recent increases in infectious diseases affecting the central nervous system have raised concerns about their role in neuroinflammation and neurodegeneration.Viral pathogens or their products can invade the central nervous system and cause damage,leading to meningitis,encephalitis,meningoencephalitis,myelitis,or post-infectious demyelinating diseases.Although neuroinflammation initially has a protective function,chronic inflammation can contribute to the development of neurodegenerative diseases.Mechanisms such as protein aggregation and cellular disturbances are implicated with specific viruses such as herpes simplex virus type 1 and Epstein-Barr virus being associated with Alzheimer's disease and multiple sclerosis,respectively.Extracellular nucleotides,particularly adenosine triphosphate and its metabolites are released from activated,infected,and dying cells,acting as alarmins mediating neuroinflammation and neurodegeneration.When viruses infect central nervous system cells,adenosine triphosphate is released as an alarmin,triggering inflammatory responses.This process is mediated by purinergic receptors,divided into two families:P1,which responds to adenosine,and P2,activated by adenosine triphosphate and other nucleotides.This review highlights how specific viruses,such as human immunodeficiency virus type 1,Theiler's murine encephalomyelitis virus,herpes simplex virus type 1,Epstein-Barr virus,dengue virus,Zika virus,and severe acute respiratory syndrome coronavirus 2,can initiate inflammatory responses through the release of extracellular nucleotides,particularly adenosine triphosphate,which act as critical mediators in the progression of neuroinflammation and neurodegenerative disorders.A better understanding of purinergic signaling pathways in these diseases may suggest new potential therapeutic strategies for targeting neuroinflammation to mitigate the long-term consequences of viral infections in the central nervous system.
基金supported by the Consejo Nacional de Investigaciones Cientificas y Tecnicas(CONICET)via grant Proyectos de Investigacion Plurianuales(PIP 2021:2894)Agencia I+D+i via grant Proyectos de Investigacion Cientifica y Tecnologica(PICT-2021-I-A-00294).
文摘This study explores the use of black soldier fly larvae protein as a bio-based adhesive to produce particleboards from sugarcane bagasse.A comprehensive evaluation was conducted,including rheological characterization of the adhesive and physical–mechanical testing of the panels according to European standards.The black soldier fly larvae-based adhesive exhibited gel-like viscoelastic behavior,rapid partial structural recovery after shear,and favorable application properties.Particleboards manufactured with this adhesive and sugarcane bagasse achieved promising mechanical performance,with modulus of rupture and modulus of elasticity values of 30.2 and 3500 MPa,respectively.Internal bond strength exceeded 0.4 MPa,complying with European standard 312-3 specifications.For comparative purposes,a panel made with Eucalyptus grandis particles was also produced under the same conditions to demonstrate the versatility of the adhesive system.Compared to other bio-based and synthetic adhesives,this bio-based system showed competitive performance and derives from the bioconversion of organic residues.Protein adhesives were synthesized fromHermetia illucens larvae grown commercially on agriculturalwaste frompotato chip production,emphasizing the renewable origin of both the biomass and the final adhesive.These results highlight the potential of insect proteins as sustainable and circular alternatives for the wood panel industry.
基金The National Natural Science Foundation of China(No.52338011)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_0067).
文摘Main cable displacement-controlled devices(DCDs)are key components for coordinating the vertical deformation of the main cable and main girder in the side span of continuous suspension bridges.To reveal the mechanical action mechanisms of DCD on bridge structures,a three-span continuous suspension bridge was taken as the engineering background in this study.The influence of different forms of DCD on the internal force and displacement of the components in the side span of the bridge and the structural dynamic characteristics were explored through numerical simulations.The results showed that the lack of DCD caused the main cable and main girder to have large vertical displacements.The stresses of other components were redistributed,and the safety factor of the suspenders at the side span was greatly reduced.The setting of DCD improved the vertical stiffness of the structure.The rigid DCD had larger internal forces,but its control effect on the internal forces at the side span was slightly better than that of the flexible DCD.Both forms of DCD effectively coordinated the deformation of the main cable and main girder and the stress distribution of components in the side span area.The choice of DCD form depends on the topographic factors of bridge sites and the design requirements of related components at the side span.
基金funded by a grant from the Consejo Nacional de humanidades Ciencia y Tecnología(Conahcyt).Fronteras de la Ciencia 1320,Infra-2017280788Universidad Autónoma Metropolitana-Iztapalapa.
文摘Background:Growth differentiation factor 11(GDF11),a transforming growth factor-beta superfamily member,is a crucial protein involved in many differentiation processes in embryogenesis and morphogenesis,and it has been extensively characterized due to its capacity to target poorly differentiated cells,including transformed or cancer cells.Aim:In the present work,we aimed to describe the effects on migration,proliferation,and metabolism in the T-cell acute lymphoblastic leukemia-derived cell line Jurkat.Methods:Based on previous evidence,we analyzed metabolic changes exerted by GDF11 and its relationship with the aggressive phenotype.Results:We found a profound impact on mitochondrial metabolism and reactive oxygen species content;these were related to a decrement in the expression of the transcription factor forkhead-box-protein P3(FOXP3),which is highly involved in aggressiveness in leukemia cells;this was verified by a decrement in invasion capacity exhibited by the Jurkat cells under the GDF11 treatment.Conclusion:The results position the GDF11 response as a good alternative in the search for new therapeutic options for these diseases.
基金I.R.R.M.andA.L.C.were fundedby"Conselho Nacional de Desenvolvimento Cientifico e Tecnologico"(CNPQ grantPQ311034/2018-7)"Coordenacaode Aperfeicoamento deNivelSuperior-CAPES,Brazil(CAPES PRINT 88881.310767/2018-01,CAPES PROEX 23038.000802/2018-25)+2 种基金FJ.Z.would like to thank the laboratory support provided by the_Sao Paulo Research Foundation-FAPESP(JP#2005/04707-5 and Biota Intercrusta#2018/13685-5)CAPES-Ciencias do Mar II program(grant#1989/2014,23038.004309/2014-51)CNPq Research Scholarship(PQ2#309298-2020-2,PQ1D#308324/2023-4),and CNPq PPBio 2023/0723.
文摘Shrimps of the genus Synalpheus(Caridea)are commonly found in subtropical and tropical marine habitats around the world.The present work aims to provide the first description of the reproductive system of this genus using histological,histochemical,and morphological perspectives to elucidate the gonochoric or hermaphrodite sexual system in this genus.Males have a slender and very translucent reproductive system that is challenging to observe.The entire cephalothorax was histologically sectioned to ensure that all regions of the reproductive system could be identified.This non-gambarelloides group shows a gonochoric condition.The caridean pattern of the reproductive system was observed where the male has a pair of testes and a pair of very thin vasa deferentia,ending at the opening of the gonopore.Spermatophore structure is absent,without any layers surrounding the spermatozoa that are aggregated in a sperm mass.In females,the reproductive system consists of a pair of ovaries that extend to the end of the pleon.The extension of the ovary has a particular pattern compared to other caridean shrimps.Here,we hypothesize that males invest energy on somatic morphological structures to protect the host and female,using the larger pistol-like cheliped,while females invest energy in reproduction since all the members of this group are typical"pair-bond"examples.The observed pattern of the reproductive male morphology could also be evidence of a possible synapomorphy for this genus within theinfraorder.
基金funded by Gobierno de Chile with the project“An atlas of droughts for Chile:1000 years of space-time changes and variations throughout the territory”(grant number FONDECYT 1181956).
文摘The Mediterranean region in central Chile is experiencing a significant decrease in precipitation due to climate change and the dynamics of the El Nino Southern Oscillation(ENSO).Droughts have increased in recent decades,~with the most severe and longest drought of the last millennium occurring since 2010 in central Chile.The impact of ongoing water scarcity is leading to significant drought-related declines in tree growth and forest dieback in the Mediterranean region.A deep understanding of how tree species respond to climate is crucial to accurately predict how forests will respond to climate change.We examined the growth responses to climate of three endemic and threatened tree species of the Mediterranean forests of central Chile,Nothofagus macrocarpa,Cryptocarya alba and Persea lingue,in a protected area.We observed that the growth of all three species was highly dependent on water availability and ENSO,and that the evergreen species C.alba and P.lingue increased their sensitivity to hydroclimate more than the deciduous species N.macrocarpa.These relationships were consistent across much of southern South America,highlighting the dependence of these species on water availability at large geographic scales.We found that there is a relationship between local water availability and ENSO that has intensified temporally and expanded geographically in recent decades.The xerophyllous species C.alba showed greater resistance and increasing resilience to severe droughts,while P.lingue and N.macrocarpa showed greater growth decline during droughts,possibly due to their preference for wetter environments.Our results highlight the crucial role of ENSO-driven water availability and drought in limiting tree growth and threatening the conservation of Mediterranean forests in central Chile.
基金supported by the National Natural Science Foundation of China(32061123008).
文摘Unstable environments intensify the frequency of extreme disasters.Long-term climate changes can lead to agricultural and ecological degradation that threatens population sustainability.To better understand past climatic events and consequences,here we present a reconstruction of the self-calibrating Palmer drought severity index(scPDSI)from September to August for the desert margins of northern China,dating back to 1742.The reconstruction accounts for 42.9%of the variation of meteorological data between 1951 and 2020.Our spatial correlation analyses showed significant correlations between scPDSI,runoff,and precipitation.Over the past 279 years,the study area has undergone nine dry and eight wet periods,with the most severe climate extremes between the 1850s and 1890s.This period of prolonged drought in northeastern China coincided with the combined impacts of climatic factors and human influences,contributing to the fall of the Qing Dynasty.Analysis of periodicity and anomalies in sea surface temperatures indicate a strong association between wet and dry cycles and El Niño-Southern Oscillations.Our findings offer insights into long-term dry and wet fluctuations at the desert margins in northern China and elucidate the relationship between drought and the dynamics of civilizations.They also highlight the potential impact of extremes in climate on modern society,especially under the four projected shared socioeconomic pathways climatic scenarios,which predict worsening droughts in northern China.
基金supported by Secihti project PDCPN-2015-266,Mexico.
文摘In the search for new alternatives to control tropical fungal pathogens,the ethanol extracts(EEs)from Acalypha gaumeri(Euphorbiaceae)roots showed antifungal properties against several tropical fungal phytopathogens.A.gaumeri is classified as endemic to the Yucatan Peninsula,Mexico,an area with distinct rainy,drought and northern seasons.The present study evaluated the antifungal activity of threewild populations of A.gaumeri collected quarterly in different seasons during one year against Alternaria chrysanthemi,Colletotrichumgloeosporioides,andPseudocercospora fijiensis and explored their ex-situ propagation.The highest activity was shown by the EE from the Tinum wild population during the rainy season against A.chrysanthemi,C.gloeosporioides,and P.fijiensis with MIC values of 500–1000μg/mL,followed by Yaxcaba populations during the rainy season and Kiuic and Tinum from November against A.chrysanthemi and P.fijiensis 1000 and 500μg/mL,respectively.The propagation of A.gaumeri was more effective throughmediumcuttings,showing 96%with 0.06%auxin indolbutyric acid,whereas only 51%of seeds germinated.The results indicated that seasonal changes and edaphic conditions in the three populations influence the antifungal efficacy of the extracts from A.gaumeri roots.This study enhances the knowledge of the biology and sustainable management of the A.gaumeri plant and advances the development of a biorational product to control tropical fungal diseases.
文摘BACKGROUND Kidney disease is a common complication in liver transplant(LT)recipients,contributing to substantial morbidity and mortality.Calcineurin inhibitors are associated with short-and long-term decline in kidney function.AIM To assess how changes in immunosuppression over three decades have impacted the evolution of renal function in the first year post-LT.METHODS This single-center,observational,retrospective study was conducted in a tertiary hospital in Madrid.Adult patients who received a first LT in our center from 1987 to 2019 were included.Patients with simultaneous or prior transplantation of another organ and patients who required re-transplantation,or were lost to follow-up or died during the first year after transplantation were excluded.The development of chronic kidney disease(CKD)pre-transplant or at the first year after LT was analyzed.RESULTS A total of 594 patients(median age:52.9 years,25th-75th percentiles=45-59.08 years;29.3%female)were included.At 1 year post-transplant,290(48.82%)patients had developed CKD.Older age[odds ratio(OR)=1.03,95%CI:1.01-1.05],female sex(OR=1.88,95%CI:1.23-2.89),pre-transplant renal dysfunction(RD)(OR=2.69,95%CI:1.58-4.58),and treatment with cyclosporine A(CsA)(OR=3.77,95%CI:2.45-5.78)were independent risk factors for CKD at 1 year after LT.In patients treated with tacrolimus(Tac)(n=375),the combination of basiliximab and mycophenolic acid(MPA)resulted in decreased Tac blood levels(P<0.001);additionally,MPA was associated with a lower incidence of RD in the first year(P=0.016).CONCLUSION Age,female sex,pre-transplant RD,and CsA are associated with increased risk of CKD within 1 year after LT.Addition of MPA to Tac is associated with lower RD incidence.
基金Supported by Patronage of the Autonomous University of Nayarit,Quality Postgraduate Program with resources from the 15%Special Tax allocated to the UAN 2022.
文摘BACKGROUND MicroRNAs play a key role in regulating gene expression in human cells.Singlenucleotide variants in these molecules have been linked to cancer development,particularly breast cancer(BrC).AIM To analyze the association of three microRNA polymorphisms with the risk of BrC in women from western Mexico.METHODS This case-control study included 71 women diagnosed with BrC and 215 women without BrC.Genotypes were determined using a real-time polymerase chain reaction allelic discrimination assay.Multiple genetic models-dominant,recessive,over-dominant,additive,and multiple comparison-were applied to assess the risk.RESULTS The over-dominant model showed that the C/T genotype of MIR196A2(rs11614913)is a protective factor against the ductal histological subtype of BrC in women from western Mexico[odds ratio(OR)=0.4687,95%confidence interval(CI):0.2205-0.9963,P=0.0489].A protective effect was also observed for the C/A genotype(OR=0.2612,95%CI:0.0900-0.7582,P=0.0135)and A allele(OR=0.2826,95%CI:0.0993-0.8044,P=0.0179)of MIR618(rs2682818).No significant association was found between MIR200C(rs73262897)and BrC risk.CONCLUSION The C/T genotype of rs11614913 in MIR196A2,and C/A genotype and A allele of rs2682818 in MIR618,are associated with a protective effect against BrC in women from western Mexico.
基金Supported by CONAHCYT Project,No.CF-2023-I-2663Instituto Nacional de Psiquiatría Project,No.NC24208.0(to Pérez-Sánchez G,Pavón L,Sánchez-Huerta K,Maldonado-García JL,Chin-Chan JM,Ponce-Regalado MD,Arreola R,Contis-Montes de Oca A,and Moreno-Lafont MC).
文摘Suicide is defined as the act of a person attempting to take their own life by causing death.Suicide is a complex phenomenon that is influenced by a multitude of factors,including psychosocial,cultural,and religious aspects,as well as genetic,biochemical,and environmental factors.From a biochemical perspective,it is crucial to consider the communication between the endocrine,immune,and nervous systems when studying the etiology of suicide.Several pathologies involve the bidirectional communication between the peripheral activity and the central nervous system by the action of molecules such as cytokines,hormones,and neurotransmitters.These humoral signals,when present in optimal quantities,are responsible for maintaining physiological homeostasis,including mood states.Stress elevates the cortisol and proinflammatory cytokines levels and alter neurotransmitters balance,thereby increasing the risk of developing a psychiatric disorder and subsequently the risk of suicidal behavior.This review provides an integrative perspective about the neurochemical,immunological,and endocrinological disturbances associated with suicidal behavior,with a particular focus on those alterations that may serve as potential risk markers and/or indicators of the state preceding such a tragic act.
基金supported by the Agencia Nacional de Investigacion y Desarrollo(ANID)with the ANID grant[SIA 85220045].
文摘Although mollusks represent Earth’s second most diverse invertebrate group,their natural history and ecology are still scarcely known.The compilation of non-traditional data,such as those from citizen science,represents an alternative to fill these gaps,particularly on striking land snail species such as Macrocyclis peruvianus.Based on long-term citizen science,we aimed to update and describe some basic ecological aspects,such as the distribution and protected area types used by M.peruvianus.We performed pairwise comparisons to test potential changes in occurrence and occupancy among administrative regions,forest types,and protected area types using chi-squared tests.The citizen scientists were also asked to provide the number of M.peruvianus individuals observed and the tree species that dominated their habitat.Thus,we tested if the number of land snails found by citizen scientists could be related to forest and protected area types using a generalized linear mixed model.We expanded the northern distributional limit,with Nothofagus,evergreen,and mixed forests far the most frequented by M.peruvianus.Parallelly,the occurrence of M.peruvianus in official protected areas(65.73%)was significantly higher than in privately owned areas.Moreover,we did not find associations between forest and protected area types with the number of M.peruvianus recorded.Although citizen science is a helpful method for obtaining novel information regarding the ecology of neglected species such as M.peruvianus,it also introduces spatial and occurrence biases explained by the access and attractiveness of the officially protected areas compared to privately owned patches of native forest.
基金Supported by Agencia Nacional de Promoción de la Investigación,el Desarrollo Tecnológico y la Innovación,No.PICT 2020 Serie A 4000.
文摘Hypertension disrupts cerebral blood flow,leading to endothelial dysfunction,breakdown of the blood-brain barrier(BBB),and inflammatory cell infiltration.This cascade triggers glial cell activation,increases oxidative stress,and causes pro-inflammatory cytokine release,creating a neurotoxic environment.In this context,we explore the intricate connection between hypertension,neuroinflammation,and neurodegeneration,as well as how hypertension interacts with other metabolic disorders,such as obesity and diabetes,to further worsen neuroinflammation.Additionally,we discuss the role of the reninangiotensin-aldosterone system,the impact of the microbiome,and the potential contribution of chronic infections in exacerbating neuroinflammation.It is essential to emphasize the potential of nanotechnology to transform therapeutic approaches.Nanoparticle-based drug delivery systems can enhance the bioavailability and selectivity of antihypertensive drugs,antioxidants,and neuroprotective compounds,enabling targeted delivery across the BBB.By combining effective blood pressure management with nanotechnology-enabled therapies that modulate inflammation,oxidative stress,and protein aggregation,we can explore new avenues for preventing and treating hypertension and metabolic disorder-associated neurodegenerative conditions.Ultimately,hypertension significantly contributes to neuroinflammation and neurodegeneration by promoting neuronal cell death,primarily through impaired cerebral blood flow and disruption of the BBB.The interaction of hypertension with metabolic disorders exacerbates these effects.However,advancements in our understanding and new technologies reveal promising nanopharmacological approaches for targeted drug delivery to the brain,thereby improving treatment outcomes,enhancing adherence,and reducing side effects.
文摘Tomato is an economically important crop that is susceptible to biotic and abiotic stresses,situations that negatively affect the crop cycle.Biotic stress is caused by phytopathogens such as Fusarium oxysporum f.sp.lycopersici(FOL),responsible for vascular wilt,a disease that causes economic losses of up to 100%in crops of interest.Nanomaterials represent an area of opportunity for pathogen control through stimulations that modify the plant development program,achieving greater adaptation and tolerance to stress.The aim of this study was to evaluate the antimicrobial capacity of the nanoparticles and the concentrations used in tomato plants infected with FOL.To this end,a two-stage experiment was conducted.In Stage 1,the effects of the nanomaterials(Graphene nanoplatelets[GP],Zinc oxide nanoparticles[ZnO NPs],Magnesium oxide nanoparticles[MgO NPs])were evaluated both alone and in combination to determine the most effective method of controlling FOL-induced disease.In Stage 2,the most effective combination of nanomaterials(ZnO+GP)was evaluated at four concentrations ranging from 100 to 400 mg L^(−1).To evaluate the effectiveness of the treatments,we determined the incidence and severity of the disease,agronomic parameters,as well as the following biochemical variables:chlorophylls,β-carotene,vitamin C,phenols,flavonoids,hydrogen peroxide,superoxide anion,and malondialdehyde.The results show various positive effects,highlighting the efficiency of the ZnO+GP at 200mg L^(−1),which reduced the severity by approximately 20%,in addition to increasing agronomic variables and reducing reactive oxygen species.Moreover,the results show that the application of these nanomaterials increases vegetative development and defense against biotic stress.The use of nanomaterials such as zinc oxide,magnesium oxide and graphene can be an effective tool in the control of the severity of Fusarium oxysporum disease.
基金Fund for Scientific and Technological Research of Argentina(FONCyT PICT 2018 number 03521).
文摘Ceratitis capitata(Wiedemann)is a cosmopolitan pest of economic importance.It is controlled by using the Sterile Insect Technique(SIT),which involves rearing and release of sterile males destined to mate with wild females,causing generation-to-generation suppression.Medflies are colonized by microorganisms,primarily the Enterobacteriaceae,with the genera Klebsiella and Enterobacter being the most common.Such microbiota contributes to host fitness.During the SIT,diet with antibiotics and irradiation for sterility of adults alter microbiota.We aimed to determine the role of Medfly microbiota on resistance to abiotic stress conditions,evaluating its function under:(i)starvation,(ii)elevated temperatures,and(iii)dry environments.These conditions simulate challenges Medfly may encounter after release,which differ from controlled rearing environments.We compared adult survival between symbiotic and aposymbiotic individuals,under starvation,two thermal regimes(25 and 30℃)or two humidity regimes(20%-25%and 80%-90%R.H.).Aposymbiotic individuals were obtained after providing them with water containing a mixture of antibiotics and methylparaben.Treatment with antimicrobials effectively reduced the gut microbiota.While starvation had no significant effect on survival,a higher proportion of aposymbiotic individuals died earlier at 30℃ and under dry humidity,with the effect being more pronounced after 48 h.Our results suggest that microbiota plays a role in adaptation of Medfly under environmental stress.We report for the presence of a culturable yeast in the digestive tract of C.capitata,Zygosaccharomyces rouxii.Providing a probiotic adult diet with bacteria and Z.rouxii prior to release could improve SIT outcomes under adverse conditions.
基金supported by the Argentine Agency for the Promotion of Science and Technology ANPCyT(PICT2019-1472 to GP,PICT2019-4597 to FL,PICT2020-1524 to GP,and PICT2021-00627 to FL)supported by an Independent Career Position from CONICETsupported by a postdoctoral fellowship from ANPCyT。
文摘Stem cell proliferation is tightly regulated in developing and adult tissues through the coordinated action of cell-intrinsic and extracellular signals.Although many extracellular cues were identified,the cell-intrinsic mechanisms underlying the decision of a stem cell to proliferate,enter a dormant quiescent state or differentiate into a specific cell type remains incompletely understood.
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.
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The selective vulnerability of nigrostriatal dopaminergic neurons is a hallmark of Parkinson’s disease and underlies its progressive motor decline.These neurons are uniquely susceptible to degeneration due to their extensive axonal arborization,high energy demands,sustained pacemaking activity,and cytosolic dopamine metabolism,which collectively promote oxidative stress and mitochondrial dysfunction.Advances in single-nucleus RNA sequencing and spatial transcriptomics have revealed transcriptionally distinct dopaminergic subtypes within the human substantia nigra pars compacta,such as AGTR1+/SOX6+and RIT2+populations,which exhibit subtype-specific transcriptional stress signatures and are preferentially lost in Parkinson’s disease.These findings underscore the role of intrinsic vulnerability,influenced by genetic risk loci,mitochondrial stress,and protein misfolding pathways,includingα-synuclein aggregation.Furthermore,neuroinflammation,iron accumulation,and vascular dysfunction act synergistically to amplify neuronal loss.This review integrates molecular,cellular,and systems-level mechanisms contributing to dopaminergic degeneration and evaluates emerging neuroprotective strategies.These include anti-oxidative,anti-inflammatory,mitochondrial therapies,novel biomarkers,gene editing,and cell replacement techniques.Understanding the selective vulnerability of nigrostriatal subtypes offers a promising path toward precision-targeted,disease-modifying treatments for Parkinson’s disease.
