Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for...Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for tinnitus while emotional disorders are risk factors for developing intrusive or bothersome tinnitus.Moreover,aging has also been identified as another risk factor.The aim of this paper was to analyse the correlation between hearing loss,age and tinnitus severity in a cohort of 610 tinnitus sufferers.Methods:Age,audiometric(hearing condition)and tinnitus(time duration and severity)data were assessed and analysed for all subjects just after recruiting(baseline).Furthermore,the average hearing loss(HL)curves of the participants for age groups were compared to these with the corresponding Age Related HL(ARHL).Results:For most of the age groups,the measured HL curves exceeded in 10-20 dB those of the ARHL.The average age of tinnitus onset(age minus tinnitus duration)was found to be 44-46 years in both men and women.Weak correlation between audiometric feature and tinnitus distress was observed.Conclusions:Hearing loss has been shown to be a clear risk factor for triggering tinnitus(86%of participants were hearing impaired).In this cohort,average measures of hearing loss showed,at most,weak associations with tinnitus-related distress,suggesting that non-audiological factors may play a predominant role.展开更多
Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis...Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.展开更多
The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurologica...The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.展开更多
Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating ...Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating neurological disorders and brain cancer.Additionally,this mechanism enhances the effectiveness of magnetic-guided drug delivery.The alternating magnetic field is applied to control the directions of the MNPs to target the tumor cells.This study approaches the radiotherapy techniques of magnetic hyperthermia therapy(MHT),wherein the thermal radiative heat transfer effect is applied to achieve homogenous heating to destroy cancer cells.MNPs are injected through the cerebrospinal fluid(CSF)transport in the glymphatic system.The elastic properties of the cerebral arteries cause peristaltic propulsion for the resulting nanofluid.Therefore,the effective Maxwell model for the nanofluid thermal conductivity is selected.The nanofluid governing equations are solved using the perturbation technique under small wavelength number and long wavelength approximation with small Reynolds number.Additionally,the effects of thermal slip and elastic properties boundary conditions are incorporated.The graphical results for the streamwise velocity,pressure,and temperature distributions are plotted using MATLAB package considering the different effects of the magnetic flux intensity,thermal radiation parameter,thermal slipping at boundaries,elastic wall properties,and nanoparticle concentration.The results demonstrate the strong impact of the magnetic field and radiation heating in terms of enhancing the nanofluid CSF flow behavior and destroying cancer.展开更多
Neotropical forests encompass a diverse array of forest types,each with distinct structures and species compositions shaped by varying soil and climate conditions.Despite their global importance in carbon(C)cycling,th...Neotropical forests encompass a diverse array of forest types,each with distinct structures and species compositions shaped by varying soil and climate conditions.Despite their global importance in carbon(C)cycling,their diversity is underrepresented in Earth system models due to our limited understanding of the abiotic and biotic factors influencing above-ground carbon(AGC)and soil organic carbon(SOC)stocks.We conducted a forest inventory across five neotropical forest types-cloud forest(CF),transition forest(TF),riparian forest(RF),pineoak forest(POF),and tropical dry forest(TDF)-in Nicaragua's Miraflor-Moropotente Protected Landscape(MMPL)to explore these relationships.Across 40 plots,we identified 4,495 trees belonging to 239 species and 62 families,with Fabaceae being the most species-rich.RF exhibited the highest alpha diversity,followed by CF,TF,and TDF,while POF had the lowest.C stocks varied significantly among forest types,averaging 147.8 Mg C⋅ha^(-1)for AGC and 46.3 Mg C⋅ha^(-1)for SOC.RF and CF stored the most AGC,while TF had the highest SOC.AGC correlated strongly with basal area,species richness,and climatic factors such as precipitation and temperature,while SOC was primarily influenced by soil chemical properties(e.g.,total nitrogen,pH)and precipitation.Notably,no significant relationship was found between SOC and AGC.Our C mapping estimated~3,700 Gg of C in the MMPL,with TDF covering the largest area and contributing most to AGC.However,RF and CF,despite occupying smaller areas,harbored the highest species richness and disproportionately contributed to AGC.These findings highlight the need to treat the different neotropical forest types as distinct ecosystems and prioritize the conservation and expansion of endangered cloud and RF across the Neotropics.展开更多
The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well define...The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.展开更多
The methanol oxidation reaction(MOR)to formic acid offers a promising alternative to the anodic oxygen evolution reaction(OER)in water electrolysis.However,the development of efficient and cost-effective catalysts rem...The methanol oxidation reaction(MOR)to formic acid offers a promising alternative to the anodic oxygen evolution reaction(OER)in water electrolysis.However,the development of efficient and cost-effective catalysts remains a primary challenge.In this study,an enhancement in catalytic MOR performance is achieved through the incorporation of Mn atoms with unsaturated t_(2g)orbitals into Ni_(3)Se_(4).Comprehensive experimental analyses and theoretical calculations reveal that substituting Ni with Mn induces strong electron-withdrawing effects,effectively modulating the local coordination environment of the metal centers.The presence of Mn also elongates Ni–Se(O)bonds,which reduces eg orbital occupancy and modifies the spin state of the material.Electrochemical measurements demonstrate that electrodes based on this optimized material exhibit a high spin state and deliver excellent catalytic activity,achieving a MOR current density up to∼190 mA cm^(−2)at 1.6 V.This performance enhancement is attributed to the favorable electronic configuration and reduced reaction energy barriers associated with the high-spin state.展开更多
The root-to-shoot(R/S)ratio is a critical indicator of the balance between root biomass and shoot biomass,representing the ecological strategies and adaptive responses of plants to environmental conditions.However,the...The root-to-shoot(R/S)ratio is a critical indicator of the balance between root biomass and shoot biomass,representing the ecological strategies and adaptive responses of plants to environmental conditions.However,the patterns of change in community R/S ratios during forest succession and their response to moisture levels across broad geographic gradients remains unclear.Based on forest biomass data from a national field inventory of 5,825 plots conducted across China between 2011 and 2015,this study looked into allocating biomass shoots and roots at the early,middle,and late stages of growth in plantations and succession in natural forests,and evaluated how moisture availability influences this allocation.The results revealed a significant decline in R/S ratios from early to late stages for both plantations and natural forests.Shoot and root biomass in plantations grew isometrically during the early and middle succession stages but shifted to allometric growth in the late stage,with the slope of the log-transformed shoot-root biomass relationship differing significantly across growth stages.Natural forests,in contrast,maintained isometric growth across successional stages,showing no significant variation in the slope of the log-transformed shoot-root biomass relationship.Environmental factors,particularly moisture levels,strongly influenced R/S ratios.Moisture levels significantly affected size-corrected R/S ratios,particularly in the middle stage of plantations and the early and middle stages of natural forests,supporting the hypothesis of optimal allocation.These findings suggest that in water-limited regions,forest management should prioritize drought-tolerant,deep-rooted native species,encourage mixed-species planting in the early stage,and reduce logging intensity in mature plantations.Conserving natural forests to maintain successional dynamics is essential for long-term ecological resilience.These findings emphasize the importance of balancing productivity with ecological sustainability by adapting practices to specific environments and forest types under climate change.展开更多
The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting...The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.展开更多
Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably n...Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably normal gaseous stars whose debris falls onto the BH,sustaining the flares over years.White dwarfs(WDs),which are the most prevalent compact stars and a million times denser-and therefore tougher-than gaseous stars,can only be disrupted by intermediate-mass black holes(IMBHs)of 10^(2)–10^(5) solar masses.WD-TDEs are considered to generate more powerful and short-lived flares,but their evidence has been lacking.Here we report observations of a fast and luminous X-ray transient EP250702a detected by Einstein Probe.Its one-day-long X-ray peak as luminous as 10^(47−49) erg s^(−1) showed strong recurrent flares with hard spectra extending to several tens of MeV gamma-rays,as detected by Fermi/GBM and Konus-Wind,indicating relativistic jet emission.The jet's X-rays dropped sharply from 3×10^(49) erg s^(−1) to around 1044 erg s^(−1) within 20 days(10 days in the source rest frame).These characteristics are inconsistent with any previously known transient phenomena.We suggest that this fast-evolving event over the unprecedentedly short timescale arises likely from disruption of a WD by an IMBH.At late times,a soft component progressively dominates the X-ray spectrum,reaching a luminosity as high as 1044 erg s^(−1),which is consistent with being extreme super-Eddington emission from an accretion disk expected to form in an IMBH-WD TDE.WD-TDEs open a new window for investigating the elusive IMBHs and their surrounding stellar environments,and they are prime sources of gravitational waves in the band of space-based interferometers.展开更多
文摘Tinnitus:the hearing of a sound that has not been produced by any external or internal source,is a rather heterogeneous hearing disorder.Background/Objectives:Hearing loss has been shown to be the main risk factor for tinnitus while emotional disorders are risk factors for developing intrusive or bothersome tinnitus.Moreover,aging has also been identified as another risk factor.The aim of this paper was to analyse the correlation between hearing loss,age and tinnitus severity in a cohort of 610 tinnitus sufferers.Methods:Age,audiometric(hearing condition)and tinnitus(time duration and severity)data were assessed and analysed for all subjects just after recruiting(baseline).Furthermore,the average hearing loss(HL)curves of the participants for age groups were compared to these with the corresponding Age Related HL(ARHL).Results:For most of the age groups,the measured HL curves exceeded in 10-20 dB those of the ARHL.The average age of tinnitus onset(age minus tinnitus duration)was found to be 44-46 years in both men and women.Weak correlation between audiometric feature and tinnitus distress was observed.Conclusions:Hearing loss has been shown to be a clear risk factor for triggering tinnitus(86%of participants were hearing impaired).In this cohort,average measures of hearing loss showed,at most,weak associations with tinnitus-related distress,suggesting that non-audiological factors may play a predominant role.
基金supported by the Spanish Ministerio de Ciencia e Innovación/Agencia Española de Investigación(PID2021-124096OB-I00)(to JLV)JGR was granted by Demensfonden,The Royal Physiografic Society of Lund,Neurofonden,The Greta och Johan Kocks stiftelser,and Bertil och Ebon Norlins stiftelse.
文摘Different forms of programmed cell death have been described to participate in the degeneration of dopaminergic neurons in Parkinson’s disease(PD).Given the critical role that disturbance of mitochondrial homeostasis plays in the pathogenesis of PD,apoptosis can be reasonably considered as one of the cell death pathways involved in neuronal loss(Schon and Przedborski,2011).Multiple lines of evidence support that proposal such as the observations in postmortem human brain samples of PD patients including mitochondrial complex I deficiency,reactive oxygen species generation,and oxidative damage to lipids,proteins,and DNA,among others.
基金funded by the Ministerio de Ciencia e Innovación Spain(PID2020-113388RB-I00,AEI/10.13039/501100011033)Consellería de Innovación,Universidades,Ciencia y Sociedad Digital,Generalitat Valenciana(CIPROM/2021/082)+2 种基金co-funded with European Regional Development Funds(ERDF)(PID2020-113388RB-I00,and CIPROM/2021/082)PID2022-136874OB-C33 from MCIN/AEI/10.13039/501100011033by the European Union NextGenerationEU/PRTR(to VF).
文摘The mechanisms leading to neurological and neurodegenerative diseases are not completely known,and new,more effective,therapeutic treatments are necessary for most neurological pathologies.The treatment of neurological and neurodegenerative diseases is complicated due to the blood-brain barrier,which makes it difficult for drugs to access the brain areas in which they must act to improve the pathology.A tool that can help to overcome this difficulty is the use of extracellular vesicles,which can easily cross the blood-brain barrier.The extracellular vesicles are considered a main way of communication between the brain and the rest of the body,with important implications for the physiopathology and therapy of neurological diseases.In recent years,the involvement of microbiota in many neurological pathologies,as well as its possible therapeutic role,has also become evident.A key mediator in the pathologic and beneficial effects of microbiota seems to be the bacterial extracellular vesicles.There is an important communication between the brain and the intestinal microbiota(the gut-brain axis),by which the microbiota influences brain function,impacts on mental health,and plays a role in different neurological and neurodegenerative diseases.The identification of the mechanisms involved in this gut-brain axis is essential to understanding the mechanisms of neurological pathologies and to developing more effective treatments for these diseases.Bacterial extracellular vesicles would play a relevant role in these processes.This review compiles the recent information and evidence on the role of bacterial extracellular vesicles in brain pathologies and on the therapeutic utility of bacterial extracellular vesicles in neurological and neurodegenerative diseases.One advantage of bacterial extracellular vesicles compared to extracellular vesicles derived from other cell types,such as stem cells,is that bacterial extracellular vesicles are generally easier to produce and modify.Bacterial extracellular vesicles may be easily modified to target a specific pathology and/or to enhance its therapeutic efficacy.Although the studies are still scarce,they open a wide field of possibilities for future studies,which will lead to a deeper understanding of the role of microbiota and bacterial extracellular vesicles in neurological pathologies and the underlying mechanisms,as well as to the development of new treatments based on the use of bacterial extracellular vesicles in neurological diseases.
基金Fundación Mujeres por Africa for supporting this work through the fellowship awarded to her。
文摘Neuronanomedicine is a promising interdisciplinary field combining two critical fields,neuroscience and nanotechnology.This study focuses on the engineering of magnetized nanoparticles(MNPs)in diagnosing and treating neurological disorders and brain cancer.Additionally,this mechanism enhances the effectiveness of magnetic-guided drug delivery.The alternating magnetic field is applied to control the directions of the MNPs to target the tumor cells.This study approaches the radiotherapy techniques of magnetic hyperthermia therapy(MHT),wherein the thermal radiative heat transfer effect is applied to achieve homogenous heating to destroy cancer cells.MNPs are injected through the cerebrospinal fluid(CSF)transport in the glymphatic system.The elastic properties of the cerebral arteries cause peristaltic propulsion for the resulting nanofluid.Therefore,the effective Maxwell model for the nanofluid thermal conductivity is selected.The nanofluid governing equations are solved using the perturbation technique under small wavelength number and long wavelength approximation with small Reynolds number.Additionally,the effects of thermal slip and elastic properties boundary conditions are incorporated.The graphical results for the streamwise velocity,pressure,and temperature distributions are plotted using MATLAB package considering the different effects of the magnetic flux intensity,thermal radiation parameter,thermal slipping at boundaries,elastic wall properties,and nanoparticle concentration.The results demonstrate the strong impact of the magnetic field and radiation heating in terms of enhancing the nanofluid CSF flow behavior and destroying cancer.
基金supported by the UNAN-Managua through the research project No.43201804by The Rufford Foundation through the Small Grants Program(ID-32146-1)by the project 2022-20 granted by The Franklinia Foundation。
文摘Neotropical forests encompass a diverse array of forest types,each with distinct structures and species compositions shaped by varying soil and climate conditions.Despite their global importance in carbon(C)cycling,their diversity is underrepresented in Earth system models due to our limited understanding of the abiotic and biotic factors influencing above-ground carbon(AGC)and soil organic carbon(SOC)stocks.We conducted a forest inventory across five neotropical forest types-cloud forest(CF),transition forest(TF),riparian forest(RF),pineoak forest(POF),and tropical dry forest(TDF)-in Nicaragua's Miraflor-Moropotente Protected Landscape(MMPL)to explore these relationships.Across 40 plots,we identified 4,495 trees belonging to 239 species and 62 families,with Fabaceae being the most species-rich.RF exhibited the highest alpha diversity,followed by CF,TF,and TDF,while POF had the lowest.C stocks varied significantly among forest types,averaging 147.8 Mg C⋅ha^(-1)for AGC and 46.3 Mg C⋅ha^(-1)for SOC.RF and CF stored the most AGC,while TF had the highest SOC.AGC correlated strongly with basal area,species richness,and climatic factors such as precipitation and temperature,while SOC was primarily influenced by soil chemical properties(e.g.,total nitrogen,pH)and precipitation.Notably,no significant relationship was found between SOC and AGC.Our C mapping estimated~3,700 Gg of C in the MMPL,with TDF covering the largest area and contributing most to AGC.However,RF and CF,despite occupying smaller areas,harbored the highest species richness and disproportionately contributed to AGC.These findings highlight the need to treat the different neotropical forest types as distinct ecosystems and prioritize the conservation and expansion of endangered cloud and RF across the Neotropics.
基金supported by the Lanzadera TCUE and C2 program(Universidad de Salamanca)(to ASL)the Spanish National Research Council(CSIC)funded by the Junta de Castilla y León and co-financed by the European Regional Development Fund(ERDF“Europe drives our growth”):Internationalization Project“CL-EI-2021-08-IBFG Unit of Excellence”,Grant(PID2022-138478OA-100)funded by MICIU/AEI/10.13039/501100011033 and,by FEDER,UE(to MGM)+3 种基金Junta de Castilla y León(SA225P23)Gerencia Regional de Salud(2701/A1/2023)(to AV)the Plan Especial Grado Medicina(USAL)(to CPM)a Ramón y Cajal researcher:Grant RYC2021-033684-I funded by MICIU/AEI/10.13039/501100011033 and,by European Union NextGenerationEU/PRTR.
文摘The visual system of teleost fish grows continuously,which is a useful model for studying regeneration of the central nervous system.Glial cells are key for this process,but their contribution is still not well defined.We followed oligodendrocytes in the visual system of adult zebrafish during regeneration of the optic nerve at 6,24,and 72 hours post-lesion and at 7 and 14 days post-lesion via the sox10:tagRFP transgenic line and confocal microscopy.To understand the changes that these oligodendrocytes undergo during regeneration,we used Sox2 immunohistochemistry,a stem cell marker involved in oligodendrocyte differentiation.We also used the Click-iT™ Plus TUNEL assay to study cell death and a BrdU assay to determine cell proliferation.Before optic nerve crush,sox10:tagRFP oligodendrocytes are located in the retina,in the optic nerve head,and through all the entire optic nerve.Sox2-positive cells are present in the peripheral germinal zone,the mature retina,and the optic nerve.After optic nerve crush,sox10:tagRFP cells disappeared from the optic nerve crush zone,suggesting that they died,although they were not TUNEL positive.Concomitantly,the number of Sox2-positive cells increased around the crushed area,the optic nerve head,and the retina.Then,between 24 hours post-lesion and 14 days post-lesion,double sox10:tagRFP/Sox2-positive cells were detected in the retina,optic nerve head,and whole optic nerve,together with a proliferation response at 72 hours post-lesion.Our results confirm that a degenerating process may occur prior to regeneration.First,sox10:tagRFP oligodendrocytes that surround the degenerated axons stop wrapping them,change their“myelinating oligodendrocyte”morphology to a“nonmyelinating oligodendrocyte”morphology,and die.Then,residual oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate for the purpose of remyelination.As new axons arise from the surviving retinal ganglion cells,new sox10:tagRFP oligodendrocytes arise from residual oligodendrocyte progenitor cells to guide,nourish and myelinate them.Thus,oligodendrocytes play an active role in zebrafish axon regeneration and remyelination.
基金financially supported by the Sichuan Science and Technology Program (Grant No. 2025NSFSC0139)the China Postdoctoral Science Foundation (Grant No.2023MD734228)+10 种基金funding from Generalitat de Catalunya 2021SGR00457supported by MCIN with funding from European Union NextGenerationEU(PRTR-C17.I1)by Generalitat de Catalunya (In-CAEM Project)the support from the project AMaDE(PID2023-149158OB-C43)funded by MCIN/AEI/10.13039/501100011033/by “ERDF A way of making Europe”by the “European Union”supported by the Severo Ochoa program from Spanish MCIN/AEI (Grant No.:CEX2021-001214-S)funded by the CERCA Programme/Generalitat de Catalunyaperformed in the framework of Universitat Autònoma de Barcelona Materials Science PhD programfunding from the CSC-UAB PhD scholarship program. ICN2 is founding member of e-DREAM[87]
文摘The methanol oxidation reaction(MOR)to formic acid offers a promising alternative to the anodic oxygen evolution reaction(OER)in water electrolysis.However,the development of efficient and cost-effective catalysts remains a primary challenge.In this study,an enhancement in catalytic MOR performance is achieved through the incorporation of Mn atoms with unsaturated t_(2g)orbitals into Ni_(3)Se_(4).Comprehensive experimental analyses and theoretical calculations reveal that substituting Ni with Mn induces strong electron-withdrawing effects,effectively modulating the local coordination environment of the metal centers.The presence of Mn also elongates Ni–Se(O)bonds,which reduces eg orbital occupancy and modifies the spin state of the material.Electrochemical measurements demonstrate that electrodes based on this optimized material exhibit a high spin state and deliver excellent catalytic activity,achieving a MOR current density up to∼190 mA cm^(−2)at 1.6 V.This performance enhancement is attributed to the favorable electronic configuration and reduced reaction energy barriers associated with the high-spin state.
基金supported by the China National Science Foundation(No.42130506,42071031)the Special Technology Innovation Fund of Carbon Peak and Carbon Neutrality in Jiangsu Province(BK20231515)+1 种基金the Spanish Government grant PID2022-140808NB-I00 funded by MICIU/AEI/https://doi.org/10.13039/501100011033the Catalan Government grants SGR 2021-1333 and AGAUR2023 CLIMA 00118.
文摘The root-to-shoot(R/S)ratio is a critical indicator of the balance between root biomass and shoot biomass,representing the ecological strategies and adaptive responses of plants to environmental conditions.However,the patterns of change in community R/S ratios during forest succession and their response to moisture levels across broad geographic gradients remains unclear.Based on forest biomass data from a national field inventory of 5,825 plots conducted across China between 2011 and 2015,this study looked into allocating biomass shoots and roots at the early,middle,and late stages of growth in plantations and succession in natural forests,and evaluated how moisture availability influences this allocation.The results revealed a significant decline in R/S ratios from early to late stages for both plantations and natural forests.Shoot and root biomass in plantations grew isometrically during the early and middle succession stages but shifted to allometric growth in the late stage,with the slope of the log-transformed shoot-root biomass relationship differing significantly across growth stages.Natural forests,in contrast,maintained isometric growth across successional stages,showing no significant variation in the slope of the log-transformed shoot-root biomass relationship.Environmental factors,particularly moisture levels,strongly influenced R/S ratios.Moisture levels significantly affected size-corrected R/S ratios,particularly in the middle stage of plantations and the early and middle stages of natural forests,supporting the hypothesis of optimal allocation.These findings suggest that in water-limited regions,forest management should prioritize drought-tolerant,deep-rooted native species,encourage mixed-species planting in the early stage,and reduce logging intensity in mature plantations.Conserving natural forests to maintain successional dynamics is essential for long-term ecological resilience.These findings emphasize the importance of balancing productivity with ecological sustainability by adapting practices to specific environments and forest types under climate change.
基金supported by the grants from the Spanish Ministry of Economy and Competitiveness(SAF2017-85602-R)the Spanish Ministry of Science and Innovation(PID2020-119638RB-I00 to EGR)FPU-program(FPU17/02616 to JCG)。
文摘The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral circulation.It tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain homeostasis.Despite the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its breakdown.Moreover,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be understood.This review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier integrity.By moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier dysfunction.Furthermore,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case study.Through this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.
文摘Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably normal gaseous stars whose debris falls onto the BH,sustaining the flares over years.White dwarfs(WDs),which are the most prevalent compact stars and a million times denser-and therefore tougher-than gaseous stars,can only be disrupted by intermediate-mass black holes(IMBHs)of 10^(2)–10^(5) solar masses.WD-TDEs are considered to generate more powerful and short-lived flares,but their evidence has been lacking.Here we report observations of a fast and luminous X-ray transient EP250702a detected by Einstein Probe.Its one-day-long X-ray peak as luminous as 10^(47−49) erg s^(−1) showed strong recurrent flares with hard spectra extending to several tens of MeV gamma-rays,as detected by Fermi/GBM and Konus-Wind,indicating relativistic jet emission.The jet's X-rays dropped sharply from 3×10^(49) erg s^(−1) to around 1044 erg s^(−1) within 20 days(10 days in the source rest frame).These characteristics are inconsistent with any previously known transient phenomena.We suggest that this fast-evolving event over the unprecedentedly short timescale arises likely from disruption of a WD by an IMBH.At late times,a soft component progressively dominates the X-ray spectrum,reaching a luminosity as high as 1044 erg s^(−1),which is consistent with being extreme super-Eddington emission from an accretion disk expected to form in an IMBH-WD TDE.WD-TDEs open a new window for investigating the elusive IMBHs and their surrounding stellar environments,and they are prime sources of gravitational waves in the band of space-based interferometers.
