Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derive...Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.展开更多
The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifact...The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse event...Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This st...Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.展开更多
In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a to...In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.展开更多
This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids)...This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids) based on classical rotations cΘand their rates. Contravariant second Piola-Kirchhoff stress and moment tensors, in conjunction with finite deformation measures derived by the authors in recent paper, are utilized in deriving the conservation and balance laws and the constitutive theories based on conjugate pairs in entropy inequality and the representation theorem. This nonlinear MPNCCT for TVES with rheology: 1) incorporates nonlinear ordered rate dissipation mechanism based on Green’s strain rates up to order n;2) also incorporates an additional ordered rate dissipation mechanism due to microconstituents, the viscosity of the medium and the rates of the symmetric part of the rotation gradient (of cΘ) tensor up to order n, referred to as micropolar dissipation or micropolar viscous dissipation mechanism;3) incorporates the primary mechanism of memory or rheology due to long chain molecules of the polymer and the viscosity of the medium by using the contravaraint second Piola-Kirchhoff stress tensor and its rates up to order m, resulting in a relaxation spectrum;4) incorporates second mechanism of memory or rheology due to nonclassical physics, interaction of microconstituents with the viscous medium and long chain molecules by considering rates of the contravariant second Piola-Kirchhoff moment tensor up to order m, resulting in relaxation of second Piola-Kirchhoff moment tensor. This results in another relaxation spectrum for the second Piola-Kirchhoff moment tensor due to microconstituents, referred to as micropolar relaxation spectrum consisting of micropolar relaxation time constants of the material. This nonlinear MPNCCT for TVES with memory is thermodynamically and mathematically consistent, and the mathematical model consisting of conservation and balance laws and the constitutive theories has closure and naturally reduces to linear MPNCCT based on infinitesimal deformation assumption. BMM is the essential balance law for all MPNCCT and is used in the present work as well. In the absence of this balance law, a valid thermodynamically and mathematically consistent nonlinear MPNCCT is not possible. The nonlinear MPNCCT based on rotations (cΘ+αΘ) and αΘ(ignoring cΘ) is not considered due to the fact that even the linear MPNCCT based on these rotations is invalid and is thermodynamically and mathematically inconsistent MPNCCT.展开更多
BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We ...BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.展开更多
Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks...Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.展开更多
Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treat...Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excess...Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.展开更多
Non-selective hunting of waterbirds poses a significant challenge in biodiversity-rich areas such as Important Bird Areas (IBAs), where protected and game species congregate. Here, we present evidence from three conse...Non-selective hunting of waterbirds poses a significant challenge in biodiversity-rich areas such as Important Bird Areas (IBAs), where protected and game species congregate. Here, we present evidence from three consecutive hunting seasons spanning autumn 2021 to spring 2024 at a Natura 2000 site in western Poland, based on analyses of hunting bag photographs, local hunting records, and standardized bird monitoring data. We recorded 1331 hunted individuals from 14 species, 43% of which are protected under national or EU legislation. Among these was the Vulnerable Common Pochard (Aythya ferina), listed on the IUCN Red List. For nearly all species, harvest rates exceeded the sustainable thresholds defined by BirdLife International. Statistical comparisons between species' environmental abundance and their representation in hunting bags indicated no selectivity in shooting, pointing to indiscriminate hunting practices. Simultaneous waterbird monitoring (2018–2024) revealed steep declines in the local waterbird community and a marked decrease in Common Crane (Grus grus) numbers, with average autumn roost counts dropping from over 2000 individuals prior to hunting to 320 during hunting seasons. Although causality cannot be directly confirmed, these patterns suggest substantial disturbance effects. Our findings demonstrate the impracticality of selective hunting in species-rich wetland refuges and highlight the systematic killing of protected species. We recommend banning waterbird hunting in IBAs and implementing mandatory bird identification training and certification for hunters to reduce unintended impacts on vulnerable species.展开更多
In contrast to glaciological studies in Mexico,periglacial studies are very recent and limited to the analysis of the general permafrost cover in the high mountains of the country.Although some of the studies on the r...In contrast to glaciological studies in Mexico,periglacial studies are very recent and limited to the analysis of the general permafrost cover in the high mountains of the country.Although some of the studies on the reconstruction of Pleistocene glaciers in Mexico mention the existence of rock glaciers,to date no work has been done to study their physical properties or determining their state of conservation.Since rock glaciers are the most important visible indicators of mountain permafrost(along with features such as gelifluction lobes and patterned ground)and given that the“Nevado”rock glacier is the main example of its kind in Mexico,this study analyzes its internal temperature and assesses its state of conservation.The investigation was carried out by drilling and thermal monitoring of rock profiles as well as air.The results indicate that at present,the“Nevado”seems to lack permafrost inside.Although there is evidence of surface freezing during the winter months in the upper part of the rock glacier,in the lower portion it is almost unnoticed;and in both parts the internal temperature shows a tendency towards positive values as depth increases,a situation that predominates throughout the year.In addition,according to the records of the climatological station located in the lower part of the rock glacier,although the annual rainfall regime could be favorable for the formation and feeding of interstitial or segregated ice,the air temperature conditions throughout the year prevent permanent freezing.The sum of the above determines that at present the“Nevado”could be considered as an inactive and relict-type rock glacier;the presence of vegetation on the surface of the debris that make it up corroborates its inactivity.展开更多
The development of minimally invasive surgery has transformed the management of gastrointestinal cancer.Notably,three-dimensional visualization systems have increased surgical precision.This editorial discusses a rece...The development of minimally invasive surgery has transformed the management of gastrointestinal cancer.Notably,three-dimensional visualization systems have increased surgical precision.This editorial discusses a recent study by Shen and Zhang,which compared the clinical applications of naked-eye threedimensional laparoscopic systems vs traditional optical systems in radical surgery for gastric and colorectal cancer.Both systems appeared to yield comparable surgical and oncological outcomes in terms of safety parameters,operating times,and quality of lymph node dissection.However,the spectacle-free system’s technical and logistical limitations hindered its effects on the surgical team’s overall competency.This editorial examines the authors’findings within the broader context of the evolution of oncologic laparoscopy,discusses the relevance of the results in light of the current literature,and proposes future research directions focused on multicenter validation,comprehensive ergonomic analysis,and technological advancements aimed at enhancing intraoperative collaboration.As technology continues to evolve,clinical implementation of new methods must be supported by robust scientific evidence and standardized criteria,to ensure tangible improvements in efficiency,safety,and oncologic outcomes.展开更多
Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrat...Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrative review synthesizes recent findings regarding the epidemiology,viral mechanisms,clinical and histopathological features,diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH.This disease predominantly affects children and adolescents from Indigenous American countries,although cases have been increasingly reported in nonendemic regions.MEH manifests clinically as multiple,asymptomatic papules or nodules,typically exhibiting a characteristic cobblestone-like appearance.Histologically,it presents with epithelial hyperplasia,koilocytosis,and altered cytokeratin expression.Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping,while immunohistochemical markers such as CK4/13,Ki-67,and the absence of p16 can be useful adjuncts in differential diagnosis.Despite its self-limiting nature in most cases,treatment may be warranted in symptomatic or immunocompromised patients.This review highlights the need to improve diagnostic access,develop targeted vaccines,and implement public health strategies in vulnerable communities.It also highlights existing gaps in knowledge,particularly regarding host-virus interactions and the absence of standardized treatment protocols.展开更多
Background:Vestibular assessments,such as the video ocular counter roll(vOCR)test,offer valuable insights into the interactions between age,otolith function,and vestibular performance.Objective:To analyze the relation...Background:Vestibular assessments,such as the video ocular counter roll(vOCR)test,offer valuable insights into the interactions between age,otolith function,and vestibular performance.Objective:To analyze the relation between age and vOCR gains as a potential marker of age-related otolith degeneration.Methods:A total of 107 participants underwent vOCR testing.Descriptive statistics and simple linear regression analyses were conducted to explore the association between age and vOCR gains.Results were presented using regression coefficients,95%confidence intervals,p-values,and R-squared values.Results:In the overall sample,statistically significant associations were observed between age and vOCR gains in both ears.For the right ear,vOCR gains decreased with increasing age(coefficient:-0.03;95%CI:-0.05 to-0.01;p<0.001;R^(2)=0.08),while the left ear showed a slightly stronger association(coefficient:-0.04;95%CI:-0.07 to-0.02;p<0.001;R²=0.12).These findings indicate a moderate age-related decline in otolith-mediated vestibular responses.Conclusion:vOCR gains appear to decline with age,reflecting potential age-related otolith degeneration.These results support the clinical value of vOCR as a non-invasive method to assess vestibular function and its changes across the lifespan.展开更多
Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a diffi...Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a difficult task to deal with because the presence of buildings,infrastructures,and human activities usually conceals the morphological signs of these landslide activities.So,in the last decades,numerous researchers have shown new methodologies to deepen the studies of similar instability phenomena.The present research is based on an integrated approach to investigate the landslide boundaries,type of movement,failure surface depth,and vulnerability state of buildings in Rota Greca Village(Calabria region,southern Italy) affected by a slowmoving landslide.For this purpose,multi-source data were acquired through geological and geomorphological surveys,recognition of landslide-induced damage on the built environment,subsurface investigations(e.g.,continuous drill boreholes,Standard Penetration Test,Rock Quality Designation index and inclinometer monitoring),laboratory tests(direct shear tests on undisturbed samples),geophysical survey,and InSAR-derived map of deformation rates.The complete integration of multi-source data allowed for the construction of reliable landslide modelling with relative geotechnical properties.In addition,the cross-comparison between surface deformation data by SAR images and severity damage level collected on the exposed buildings enabled to obtain the vulnerability map of the built area.In particular,the achieved goals highlighted two failure surfaces at about-13 and-25 m depth,causing a high vulnerability value for the buildings allocated in the central portion of the Rota Greca Village.The knowledge acquired by the multi-approach can be used to manage and implement appropriate landslide risk mitigation strategies,providing helpful advice and best practices to state-run organisations and stakeholders for landslide management in urban sites.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
基金supported by project Emerging Infectious Diseases One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,INF-ACT,Spoke 1 and Spoke 5,Project number PE00000007,CUP B53C20040570005(to PP and DN).
文摘Introduction:One of the main events that regulate a cell’s well-being is cell-to-cell communication.This intercellular mechanism of information transfer is often mediated by vesicular trafficking.Mitochondrial-derived vesicles(MDVs)are an emerging subpopulation of extracellular vesicle(EV)first discovered in 2008 that allow mitochondria to communicate with their surroundings.
文摘The rapidly aging population directly contributes to the increasing cases of neurological disorders.Due to the chronic progressive nature of neurodegeneration,numerous neurological conditions are considered“multifactorial”with systemic metabolic alterations.Even so,treatments for neurological disorders have remained unchanged for the past decades.Recently,metabolic drugs such as metformin and glucagon-like peptide 1 agonists have demonstrated promising health outcomes for neurodegeneration.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
文摘Leg-length discrepancy(LLD)in individuals experiencing total hip arthroplasty(THA)is related to a substantially higher fall risk,length of post-operative hospital in-patient stay,elevated implant-related adverse events,and earlier revision.Therefore,it is essential to try to avoid LLD when implanting a THA.Several studies focus on this issue,including the following:Accelerometer-based portable navigation system,preoperative digital templating,robot-assisted surgery,the anatomical marker positioning method(shoulder-to-shoulder)and the artificial intelligence-based three-dimensional planning software system.The aforementioned methods should be familiar to surgeons who perform THA procedures,as a fundamental objective of this surgical intervention is to avoid LLD.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
基金Supported by Sichuan Science and Technology Program(2023YFSY0026,2023YFH0004)Supported by the Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Korean government(MSIT)(No.RS-2022-00155885,Artificial Intelligence Convergence Innovation Human Resources Development(Hanyang University ERICA)).
文摘Two-dimensional endoscopic images are susceptible to interferences such as specular reflections and monotonous texture illumination,hindering accurate three-dimensional lesion reconstruction by surgical robots.This study proposes a novel end-to-end disparity estimation model to address these challenges.Our approach combines a Pseudo-Siamese neural network architecture with pyramid dilated convolutions,integrating multi-scale image information to enhance robustness against lighting interferences.This study introduces a Pseudo-Siamese structure-based disparity regression model that simplifies left-right image comparison,improving accuracy and efficiency.The model was evaluated using a dataset of stereo endoscopic videos captured by the Da Vinci surgical robot,comprising simulated silicone heart sequences and real heart video data.Experimental results demonstrate significant improvement in the network’s resistance to lighting interference without substantially increasing parameters.Moreover,the model exhibited faster convergence during training,contributing to overall performance enhancement.This study advances endoscopic image processing accuracy and has potential implications for surgical robot applications in complex environments.
文摘In this study we review the occurrence of different types (A, B, C, M, and X classes) of solar flares during different solar cycle phases from 1996 to 2019 covering the solar cycles 23 and 24. During this period, a total of 19,126 solar flares were observed regardless the class: 3548 flares in solar cycle 23 (SC23) and 15,668 flares in solar cycle 24 (SC24). Our findings show that the cycle 23 has observed the highest occurrences of M-class and X-class flares, whereas cycle 24 has pointed out a predominance of B-class and C-class flares throughout its different phases. The results indicate that the cycle 23 was magnetically more intense than cycle 24, leading to more powerful solar flares and more frequent geomagnetic storms, capable of generating significant electromagnetic emissions that can affect satellites and GPS signals. The decrease in intense solar flares during cycle 24 compared to cycle 23 reflects an evolution in solar activity patterns over time.
文摘This paper presents a nonlinear micropolar nonclassical continuum theory (MPNCCT) for finite deformation, finite strain deformation physics of thermosviscoelastic solid medium with memory (polymeric micropolar solids) based on classical rotations cΘand their rates. Contravariant second Piola-Kirchhoff stress and moment tensors, in conjunction with finite deformation measures derived by the authors in recent paper, are utilized in deriving the conservation and balance laws and the constitutive theories based on conjugate pairs in entropy inequality and the representation theorem. This nonlinear MPNCCT for TVES with rheology: 1) incorporates nonlinear ordered rate dissipation mechanism based on Green’s strain rates up to order n;2) also incorporates an additional ordered rate dissipation mechanism due to microconstituents, the viscosity of the medium and the rates of the symmetric part of the rotation gradient (of cΘ) tensor up to order n, referred to as micropolar dissipation or micropolar viscous dissipation mechanism;3) incorporates the primary mechanism of memory or rheology due to long chain molecules of the polymer and the viscosity of the medium by using the contravaraint second Piola-Kirchhoff stress tensor and its rates up to order m, resulting in a relaxation spectrum;4) incorporates second mechanism of memory or rheology due to nonclassical physics, interaction of microconstituents with the viscous medium and long chain molecules by considering rates of the contravariant second Piola-Kirchhoff moment tensor up to order m, resulting in relaxation of second Piola-Kirchhoff moment tensor. This results in another relaxation spectrum for the second Piola-Kirchhoff moment tensor due to microconstituents, referred to as micropolar relaxation spectrum consisting of micropolar relaxation time constants of the material. This nonlinear MPNCCT for TVES with memory is thermodynamically and mathematically consistent, and the mathematical model consisting of conservation and balance laws and the constitutive theories has closure and naturally reduces to linear MPNCCT based on infinitesimal deformation assumption. BMM is the essential balance law for all MPNCCT and is used in the present work as well. In the absence of this balance law, a valid thermodynamically and mathematically consistent nonlinear MPNCCT is not possible. The nonlinear MPNCCT based on rotations (cΘ+αΘ) and αΘ(ignoring cΘ) is not considered due to the fact that even the linear MPNCCT based on these rotations is invalid and is thermodynamically and mathematically inconsistent MPNCCT.
文摘BACKGROUND The neutrophil-lymphocyte ratio(NLR)has been proposed as a potential prognostic marker for mortality outcomes in various conditions,yet its association with chronic hemodialysis(HD)remains underexplored.We aim to study its utility by conducting a meta-analysis of this specific population.AIM To determine whether elevated NLR is associated with all-cause mortality(ACM)and cardiovascular mortality(CVM)in patients undergoing chronic HD.METHODS A comprehensive search from PubMed,Google Scholar,and Scopus identified studies showing the association between NLR and mortality outcomes in patients with chronic HD.Random-effects models with 95%CIs were employed to pool adjusted hazard ratios(aHRs),odds ratios(ORs),and I²statistics for evaluating the heterogeneity of findings.Leave-one-out sensitivity and meta-regression analyses assessed changes in overall effects and identified confounders,respectively.The Joanna Briggs Institute(JBI)tool was used to assess the quality of studies.RESULTS 19 studies comprising 9047 patients with a mean age of 59.5±5.86 years and a mean follow-up duration of 46.7 months were included in our study.Our meta-analysis revealed a significant association between NLR>2.5 and increased risks of ACM(aHR:1.25,95%CI:1.14-1.37,P<0.0001)and CVM(aHR:1.24,95%CI:1.02-1.49,P=0.03).Studies reporting outcomes in OR reported similar findings for ACM(OR:4.59,95%CI:1.74-12.11,P=0.002)and CVM(OR:1.11,95%CI:1.01-1.23,P=0.03).Sensitivity analysis revealed no variations.Meta-regression revealed increasing male proportion is positively associated with ACM.Pooled area under the curve(AUC)was 0.71(95%CI:0.63-0.80,P<0.0001).The JBI tool revealed high-quality studies.CONCLUSION This meta-analysis suggests that elevated NLR may serve as a useful prognostic marker for ACM and CVM in patients on chronic HD and can be useful in planning for the prevention of mortality-related strategies.
基金supported by the National Cancer Institute of the National Institutes of Health under Award Number R00CA218603
文摘Background The biological mechanisms by which postdiagnosis physical activity improves disease-free survival in colorectal cancer survivors remain incompletely understood.This trial tested the hypothesis that 12 weeks of moderate-intensity aerobic exercise,when compared with a control group,would change inflammation,circulating tumor cells(CTCs),and circulating tumor DNA(ctDNA)in a manner consistent with an improved cancer prognosis.Methods This trial randomized Stages I–III colorectal cancer survivors to 12 weeks of home-based moderate-intensity aerobic exercise or a waitlist control group.The co-primary endpoints were high-sensitivity C-reactive protein(hs-CRP)and interleukin-6(IL-6),secondary endpoints were soluble tumor necrosis factor-αreceptor 2(sTNFαR2)and CTCs,and the exploratory endpoint was tumor fraction quantified from ctDNA.Results Sixty subjects were randomized(age=60.6±10.8 years,mean±SD;39(65%)females;46(77%)colonic primary tumor),and 59(98%)subjects completed the study.Over 12 weeks,exercise adherence was 92%(95%confidence interval(95%CI):86‒99).Exercise improved submaximal fitness capacity(0.36 metabolic equivalents;95%CI:0.05‒0.67;p=0.025)and objectively measured moderate-to-vigorous-intensity physical activity(34.8%,95%CI:11.3‒63.1;p=0.002)compared to control.Exercise did not change hs-CRP(20.9%,95%CI:−17.1 to 76.2;p=0.32),IL-6(11.4%,95%CI:−7.5 to 34.0;p=0.25),or sTNFαR2(−3.6%,95%CI:−13.7 to 7.7;p=0.52)compared to control.In the subgroup of subjects with elevated baseline hs-CRP(n=35,58.3%),aerobic exercise reduced hs-CRP(−35.5%,95%CI:−55.3 to−3.8;p=0.031).Exercise did not change CTCs(0.59 cells/mL,95%CI:−0.33 to 1.51;p=0.21)or tumor fraction(0.0005,95%CI:−0.0024 to 0.0034;p=0.73).In exploratory analyses,higher aerobic exercise adherence correlated with a reduction in CTCs(ρ=−0.37,95%CI:−0.66 to−0.08;p=0.013).Conclusion Colorectal cancer survivors achieved high adherence to a home-based moderate-intensity aerobic exercise prescription that improved fitness capacity and physical activity but did not reduce inflammation or change tumor endpoints from a liquid biopsy.
文摘Alzheimer's disease and Down syndrome:Down syndrome(DS)is a genetic disorder caused by the presence of an extra complete or partial chromosome 21.Over the past few decades,significant advancements in medical treatment and nursing care have greatly improved the life expectancy of individuals with DS.However,as they age,their risk of developing Alzheimer’s disease(AD)increases considerably(Antonarakis et al.,2020).
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
基金support from the National Science Foundation of China(NSFC)(Grants No.12293031 and No.61905252)the National Science Foundation for Distinguished Young Scholars(Grant No.12022308)the National Key R&D Program of China(Grants No.2021YFC2202200 and No.2021YFC2202204).
文摘Adaptive optics(AO)has significantly advanced high-resolution solar observations by mitigating atmospheric turbulence.However,traditional post-focal AO systems suffer from external configurations that introduce excessive optical surfaces,reduced light throughput,and instrumental polarization.To address these limitations,we propose an embedded solar adaptive optics telescope(ESAOT)that intrinsically incorporates the solar AO(SAO)subsystem within the telescope's optical train,featuring a co-designed correction chain with a single Hartmann-Shack full-wavefront sensor(HS f-WFS)and a deformable secondary mirror(DSM).The HS f-WFS uses temporal-spatial hybrid sampling technique to simultane-ously resolve tip-tilt and high-order aberrations,while the DSM performs real-time compensation through adaptive modal optimization.This unified architecture achieves symmetrical polarization suppression and high system throughput by min-imizing optical surfaces.A 600 mm ESAOT prototype incorporating a 12×12 micro-lens array HS f-WFS and 61-actuator piezoelectric DSM has been developed and successfully conducted on-sky photospheric observations.Validations in-cluding turbulence simulations,optical bench testing,and practical observations at the Lijiang observatory collectively confirm the system's capability to maintain aboutλ/10 wavefront error during active region tracking.This architectural breakthrough of the ESAOT addresses long-standing SAO integration challenges in solar astronomy and provides scala-bility analyses confirming direct applicability to the existing and future large solar observation facilities.
文摘Non-selective hunting of waterbirds poses a significant challenge in biodiversity-rich areas such as Important Bird Areas (IBAs), where protected and game species congregate. Here, we present evidence from three consecutive hunting seasons spanning autumn 2021 to spring 2024 at a Natura 2000 site in western Poland, based on analyses of hunting bag photographs, local hunting records, and standardized bird monitoring data. We recorded 1331 hunted individuals from 14 species, 43% of which are protected under national or EU legislation. Among these was the Vulnerable Common Pochard (Aythya ferina), listed on the IUCN Red List. For nearly all species, harvest rates exceeded the sustainable thresholds defined by BirdLife International. Statistical comparisons between species' environmental abundance and their representation in hunting bags indicated no selectivity in shooting, pointing to indiscriminate hunting practices. Simultaneous waterbird monitoring (2018–2024) revealed steep declines in the local waterbird community and a marked decrease in Common Crane (Grus grus) numbers, with average autumn roost counts dropping from over 2000 individuals prior to hunting to 320 during hunting seasons. Although causality cannot be directly confirmed, these patterns suggest substantial disturbance effects. Our findings demonstrate the impracticality of selective hunting in species-rich wetland refuges and highlight the systematic killing of protected species. We recommend banning waterbird hunting in IBAs and implementing mandatory bird identification training and certification for hunters to reduce unintended impacts on vulnerable species.
文摘In contrast to glaciological studies in Mexico,periglacial studies are very recent and limited to the analysis of the general permafrost cover in the high mountains of the country.Although some of the studies on the reconstruction of Pleistocene glaciers in Mexico mention the existence of rock glaciers,to date no work has been done to study their physical properties or determining their state of conservation.Since rock glaciers are the most important visible indicators of mountain permafrost(along with features such as gelifluction lobes and patterned ground)and given that the“Nevado”rock glacier is the main example of its kind in Mexico,this study analyzes its internal temperature and assesses its state of conservation.The investigation was carried out by drilling and thermal monitoring of rock profiles as well as air.The results indicate that at present,the“Nevado”seems to lack permafrost inside.Although there is evidence of surface freezing during the winter months in the upper part of the rock glacier,in the lower portion it is almost unnoticed;and in both parts the internal temperature shows a tendency towards positive values as depth increases,a situation that predominates throughout the year.In addition,according to the records of the climatological station located in the lower part of the rock glacier,although the annual rainfall regime could be favorable for the formation and feeding of interstitial or segregated ice,the air temperature conditions throughout the year prevent permanent freezing.The sum of the above determines that at present the“Nevado”could be considered as an inactive and relict-type rock glacier;the presence of vegetation on the surface of the debris that make it up corroborates its inactivity.
文摘The development of minimally invasive surgery has transformed the management of gastrointestinal cancer.Notably,three-dimensional visualization systems have increased surgical precision.This editorial discusses a recent study by Shen and Zhang,which compared the clinical applications of naked-eye threedimensional laparoscopic systems vs traditional optical systems in radical surgery for gastric and colorectal cancer.Both systems appeared to yield comparable surgical and oncological outcomes in terms of safety parameters,operating times,and quality of lymph node dissection.However,the spectacle-free system’s technical and logistical limitations hindered its effects on the surgical team’s overall competency.This editorial examines the authors’findings within the broader context of the evolution of oncologic laparoscopy,discusses the relevance of the results in light of the current literature,and proposes future research directions focused on multicenter validation,comprehensive ergonomic analysis,and technological advancements aimed at enhancing intraoperative collaboration.As technology continues to evolve,clinical implementation of new methods must be supported by robust scientific evidence and standardized criteria,to ensure tangible improvements in efficiency,safety,and oncologic outcomes.
文摘Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrative review synthesizes recent findings regarding the epidemiology,viral mechanisms,clinical and histopathological features,diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH.This disease predominantly affects children and adolescents from Indigenous American countries,although cases have been increasingly reported in nonendemic regions.MEH manifests clinically as multiple,asymptomatic papules or nodules,typically exhibiting a characteristic cobblestone-like appearance.Histologically,it presents with epithelial hyperplasia,koilocytosis,and altered cytokeratin expression.Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping,while immunohistochemical markers such as CK4/13,Ki-67,and the absence of p16 can be useful adjuncts in differential diagnosis.Despite its self-limiting nature in most cases,treatment may be warranted in symptomatic or immunocompromised patients.This review highlights the need to improve diagnostic access,develop targeted vaccines,and implement public health strategies in vulnerable communities.It also highlights existing gaps in knowledge,particularly regarding host-virus interactions and the absence of standardized treatment protocols.
文摘Background:Vestibular assessments,such as the video ocular counter roll(vOCR)test,offer valuable insights into the interactions between age,otolith function,and vestibular performance.Objective:To analyze the relation between age and vOCR gains as a potential marker of age-related otolith degeneration.Methods:A total of 107 participants underwent vOCR testing.Descriptive statistics and simple linear regression analyses were conducted to explore the association between age and vOCR gains.Results were presented using regression coefficients,95%confidence intervals,p-values,and R-squared values.Results:In the overall sample,statistically significant associations were observed between age and vOCR gains in both ears.For the right ear,vOCR gains decreased with increasing age(coefficient:-0.03;95%CI:-0.05 to-0.01;p<0.001;R^(2)=0.08),while the left ear showed a slightly stronger association(coefficient:-0.04;95%CI:-0.07 to-0.02;p<0.001;R²=0.12).These findings indicate a moderate age-related decline in otolith-mediated vestibular responses.Conclusion:vOCR gains appear to decline with age,reflecting potential age-related otolith degeneration.These results support the clinical value of vOCR as a non-invasive method to assess vestibular function and its changes across the lifespan.
基金supported by the MIUR-ex 60% Project(responsibility of Fabio Ietto)。
文摘Slow-moving landslides are widespread in the Mediterranean area,causing damage to the exposed facilities and economic losses in many countries.The recognition of slow-moving landslides in urban areas is always a difficult task to deal with because the presence of buildings,infrastructures,and human activities usually conceals the morphological signs of these landslide activities.So,in the last decades,numerous researchers have shown new methodologies to deepen the studies of similar instability phenomena.The present research is based on an integrated approach to investigate the landslide boundaries,type of movement,failure surface depth,and vulnerability state of buildings in Rota Greca Village(Calabria region,southern Italy) affected by a slowmoving landslide.For this purpose,multi-source data were acquired through geological and geomorphological surveys,recognition of landslide-induced damage on the built environment,subsurface investigations(e.g.,continuous drill boreholes,Standard Penetration Test,Rock Quality Designation index and inclinometer monitoring),laboratory tests(direct shear tests on undisturbed samples),geophysical survey,and InSAR-derived map of deformation rates.The complete integration of multi-source data allowed for the construction of reliable landslide modelling with relative geotechnical properties.In addition,the cross-comparison between surface deformation data by SAR images and severity damage level collected on the exposed buildings enabled to obtain the vulnerability map of the built area.In particular,the achieved goals highlighted two failure surfaces at about-13 and-25 m depth,causing a high vulnerability value for the buildings allocated in the central portion of the Rota Greca Village.The knowledge acquired by the multi-approach can be used to manage and implement appropriate landslide risk mitigation strategies,providing helpful advice and best practices to state-run organisations and stakeholders for landslide management in urban sites.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
