Lake Baiyangdian is one of China’s largest macrophyte-derived lakes,facing severe challenges related to water quality maintenance and eutrophication prevention.Dissolved organic matter(DOM)was a huge carbon pool and ...Lake Baiyangdian is one of China’s largest macrophyte-derived lakes,facing severe challenges related to water quality maintenance and eutrophication prevention.Dissolved organic matter(DOM)was a huge carbon pool and its abundance,property,and transformation played important roles in the biogeochemical cycle and energy flow in lake ecosystems.In this study,Lake Baiyangdian was divided into four distinct areas:Unartificial Area(UA),Village Area(VA),Tourism Area(TA),and Breeding Area(BA).We examined the diversity of DOM properties and sources across these functional areas.Our findings reveal that DOM in this lake is predominantly composed of protein-like substances,as determined by excitation-emission matrix and parallel factor analysis(EEM-PARAFAC).Notably,the exogenous tyrosine-like component C1 showed a stronger presence in VA and BA compared to UA and TA.Ultrahigh-resolution mass spectrometry(FT-ICR MS)unveiled a similar DOM molecular composition pattern across different functional areas due to the high relative abundances of lignan compounds,suggesting that macrophytes significantly influence the material structure of DOM.DOM properties exhibited specific associations with water quality indicators in various functional areas,as indicated by the Mantel test.The connections between DOM properties and NO_(3)-N andNH3-Nwere more pronounced in VA and BA than in UA and TA.Our results underscore the viability of using DOM as an indicator for more precise and scientific water quality management.展开更多
To elucidate the geographical differentiation characteristics and driving mechanisms of Dissolved Organic Matter(DOM)in typical rivers,this study conducted a multi-spectral investigation on three representative river ...To elucidate the geographical differentiation characteristics and driving mechanisms of Dissolved Organic Matter(DOM)in typical rivers,this study conducted a multi-spectral investigation on three representative river types within Shandong Province:The mountainous Dawen River,the plain Tuhai River,and the artificial East Grand Canal.The DOM composition was analyzed using Ultraviolet-Visible(UV-Vis)absorption spectroscopy,Excitation-Emission Matrix(EEM)fluorescence spectroscopy,and parallel factor analysis(PARAFAC),while Principal Component Analysis(PCA)was employed to quantify the synergistic effects of natural processes and anthropogenic activities.Results revealed significant spatial heterogeneity in DOM composition and sources.The plain river exhibited the highest aromaticity(humic-like components:43.3%)due to long-term agricultural non-point source inputs and urban wastewater discharge.The mountain stream,shaped by complex terrain and relatively intact ecosystems,was dominated by autochthonous DOM derived from microbial metabolism,with higher Fluorescence Index(FI=2.12)and biological index(BIX=1.35)than other river types.The artificial canal retained protein-like components(64.2%),largely attributed to winter hydrological stagnation and disturbances from shipping activities.Further analysis demonstrated that geographical settings(e.g.,mountain terrain)and anthropogenic activities(e.g.,agriculture,shipping)jointly regulated DOM composition by altering the balance between input and transformation processes.Integrated fluorescence parameters and PCA results suggested differentiated management strategies:protecting ecological integrity in mountain streams to sustain selfpurification,enhancing non-point source interception in plain rivers,and mitigating shipping pollution in canals.This study systematically reveals the natural-anthropogenic coupling mechanisms driving DOM dynamics in northern China rivers,providing critical insights for precision water environment management at the watershed scale.展开更多
Aiming to control lake eutrophication,proposed methods for convenient and faithworthy lake water quality evaluation are warranted.Optical measurement of dissolved organic matter(DOM)demonstrates great potential for es...Aiming to control lake eutrophication,proposed methods for convenient and faithworthy lake water quality evaluation are warranted.Optical measurement of dissolved organic matter(DOM)demonstrates great potential for estimating organic matter(OM)composition,and can thus serve as a proxy for conventional chemical oxygen demand(COD_(Mn))measurements,which are considered as imprecise and environmentally unfriendly.Hence,we conducted a field campaign across 30 lakes in Wuhan's metropolitan area,collecting 255 samples from varying trophic states to evaluate the predictive capability of COD_(Mn)using DOM optical measurements combined with parallel factor(PARAFAC)analysis.The DOM optical properties and chemical composition exhibited considerable variability across varying trophic state levels(TSLs).Fluorescence components C1-C3 and C5,fluorescence index(FI),and absorption at 254 nm(α_(254)),increased as TSL increased,while the DOM spectral slope(SR)decreased.COD_(Mn)was positively and significantly correlated with fluorescence components C1-C3 and C5,freshness index(β/α),autochthonous index(BIX),humification index(HIX),α_(254),the ratio ofα_(250)toα_(365)(E2/E3)while being negatively correlated with SR.Parametersα_(254),C1,C3,C4,FI,β/α,and HIX were identified as key predictors of COD_(Mn).The multiple linear regression model successfully predicted COD_(Mn)(r^(2)=0.63,p<0.01,n=1113)and demonstrated superior performance in mesotrophic lakes.These findings highlight the potential for establishing high-frequency,continuous,and multi-regional COD monitoring programs.展开更多
Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observati...Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observational studies.The objective of this study was to explore the causal association between PM_(2.5)exposure,its absorbance,and IBD.Methods We assessed the association of PM_(2.5)and PM_(2.5)absorbance with the two primary forms of IBD(Crohn’s disease[CD]and ulcerative colitis[UC])using Mendelian randomization(MR)to explore the causal relationship.We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study.Single-nucleotide polymorphisms linked with PM_(2.5)concentrations or their absorbance were used as instrumental variables(IVs).We used inverse variance weighting(IVW)as the primary analytical approach and four other standard methods as supplementary analyses for quality control.Results The results of MR demonstrated that PM_(2.5)had an adverse influence on UC risk(odds ratio[OR]=1.010;95%confidence interval[CI]=1.001–1.019,P=0.020).Meanwhile,the results of IVW showed that PM_(2.5)absorbance was also causally associated with UC(OR=1.012;95%CI=1.004–1.019,P=0.002).We observed no causal relationship between PM_(2.5),PM_(2.5)absorbance,and CD.The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy,ensuring the reliability of MR results.Conclusion Based on two-sample MR analyses,there are potential positive causal relationships between PM_(2.5),PM_(2.5)absorbance,and UC.展开更多
Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have rev...Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.展开更多
Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of...Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of turbulences in the very early universe in sustaining intense and persistent fluctuations in energy or mass density,which could provide a natural mechanism for PBH formation in the primordial universe. We analyze the mass range and abundance of PBHs produced in the magnetohydrodynamic turbulence induced by the electroweak phase transition. Remarkably, we find that the mass range of the produced PBHs falls within the most viable“asteroid mass” window from the present-day observations, and within natural parameter regions their abundance can be sufficiently large. These findings suggest that PBHs produced during magnetohydrodynamic turbulence in the very early universe may comprise a dominant part of dark matter.展开更多
β-glucocerebrosidase in health and disease:Mutations in theβ-glucocerebrosidase(GBA)gene do cause the rare lysosomal storage disorder Gaucher’s disease(GD)with an estimated global prevalence of 1:200,000(Imbalzano ...β-glucocerebrosidase in health and disease:Mutations in theβ-glucocerebrosidase(GBA)gene do cause the rare lysosomal storage disorder Gaucher’s disease(GD)with an estimated global prevalence of 1:200,000(Imbalzano et al.,2024).GBA is a membrane-bound lysosomalenzyme responsible for glucosylceramide and glucosylsphingosine hydrolysis.When this enzyme is mutated and dysfunctional,its substrates progressively accumulate within cells.展开更多
The accurate segmentation of deep gray matter nuclei is critical for neuropathological research,disease diagnosis and treatment.Existing methods employ the supervised learning training approach,which requires large la...The accurate segmentation of deep gray matter nuclei is critical for neuropathological research,disease diagnosis and treatment.Existing methods employ the supervised learning training approach,which requires large labeled datasets.It is challenging and time-consuming to obtain such datasets for medical image analysis.In addition,these methods based on convolutional neural networks(CNNs)only achieve suboptimal performance due to the locality of convolutional operations.Vision Transformers(ViTs)efficiently model long-range dependencies and thus have the potentiality to outperform these methods in segmentation tasks.To address these issues,we propose a novel hybrid network based on self-supervised pre-training for deep gray matter nuclei segmentation.Specifically,we present a CNN-Transformer hybrid network(CTNet),whose encoder consists of 3D CNN and ViT to learn local spatial-detailed features and global semantic information.A self-supervised learning(SSL)approach that integrates rotation prediction and masked feature reconstruction is proposed to pre-train the CTNet,enabling the model to learn valuable visual representations from unlabeled data.We evaluate the effectiveness of our method on 3T and 7T human brain MRI datasets.The results demonstrate that our CTNet achieves better performance than other comparison models and our pre-training strategy outperforms other advanced self-supervised methods.When the training set has only one sample,our pre-trained CTNet enhances segmentation performance,showing an 8.4%improvement in Dice similarity coefficient(DSC)compared to the randomly initialized CTNet.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet li...White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.展开更多
The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions f...The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions for investigating their interactions.Early efforts to parcellate the mammalian brain,using histological cytoarchitecture and myeloarchitecture,as well as recent in vivo magnetic resonance imaging(MRl)[2,3],have primarily involved cortical areas,subcortical structures,and cerebellar nuclei.Human brain parcellations primarily focus on grey matter(GM),which purposefully excludes white matter(WM),hindering the development of next-generation brain atlases.展开更多
The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cel...The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.展开更多
Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle...Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFC3204000).
文摘Lake Baiyangdian is one of China’s largest macrophyte-derived lakes,facing severe challenges related to water quality maintenance and eutrophication prevention.Dissolved organic matter(DOM)was a huge carbon pool and its abundance,property,and transformation played important roles in the biogeochemical cycle and energy flow in lake ecosystems.In this study,Lake Baiyangdian was divided into four distinct areas:Unartificial Area(UA),Village Area(VA),Tourism Area(TA),and Breeding Area(BA).We examined the diversity of DOM properties and sources across these functional areas.Our findings reveal that DOM in this lake is predominantly composed of protein-like substances,as determined by excitation-emission matrix and parallel factor analysis(EEM-PARAFAC).Notably,the exogenous tyrosine-like component C1 showed a stronger presence in VA and BA compared to UA and TA.Ultrahigh-resolution mass spectrometry(FT-ICR MS)unveiled a similar DOM molecular composition pattern across different functional areas due to the high relative abundances of lignan compounds,suggesting that macrophytes significantly influence the material structure of DOM.DOM properties exhibited specific associations with water quality indicators in various functional areas,as indicated by the Mantel test.The connections between DOM properties and NO_(3)-N andNH3-Nwere more pronounced in VA and BA than in UA and TA.Our results underscore the viability of using DOM as an indicator for more precise and scientific water quality management.
基金supported by the National Natural Science Foundation(42472325)the Fundamental Research Funds of Chinese Academy of Geological Science(SK202103).
文摘To elucidate the geographical differentiation characteristics and driving mechanisms of Dissolved Organic Matter(DOM)in typical rivers,this study conducted a multi-spectral investigation on three representative river types within Shandong Province:The mountainous Dawen River,the plain Tuhai River,and the artificial East Grand Canal.The DOM composition was analyzed using Ultraviolet-Visible(UV-Vis)absorption spectroscopy,Excitation-Emission Matrix(EEM)fluorescence spectroscopy,and parallel factor analysis(PARAFAC),while Principal Component Analysis(PCA)was employed to quantify the synergistic effects of natural processes and anthropogenic activities.Results revealed significant spatial heterogeneity in DOM composition and sources.The plain river exhibited the highest aromaticity(humic-like components:43.3%)due to long-term agricultural non-point source inputs and urban wastewater discharge.The mountain stream,shaped by complex terrain and relatively intact ecosystems,was dominated by autochthonous DOM derived from microbial metabolism,with higher Fluorescence Index(FI=2.12)and biological index(BIX=1.35)than other river types.The artificial canal retained protein-like components(64.2%),largely attributed to winter hydrological stagnation and disturbances from shipping activities.Further analysis demonstrated that geographical settings(e.g.,mountain terrain)and anthropogenic activities(e.g.,agriculture,shipping)jointly regulated DOM composition by altering the balance between input and transformation processes.Integrated fluorescence parameters and PCA results suggested differentiated management strategies:protecting ecological integrity in mountain streams to sustain selfpurification,enhancing non-point source interception in plain rivers,and mitigating shipping pollution in canals.This study systematically reveals the natural-anthropogenic coupling mechanisms driving DOM dynamics in northern China rivers,providing critical insights for precision water environment management at the watershed scale.
基金This study was funded by Wuhan Institute of Technology(Grant Nos.24QD26,21QD02,22QD64)National Natural Science Foundation of China(Grant No.32102823).
文摘Aiming to control lake eutrophication,proposed methods for convenient and faithworthy lake water quality evaluation are warranted.Optical measurement of dissolved organic matter(DOM)demonstrates great potential for estimating organic matter(OM)composition,and can thus serve as a proxy for conventional chemical oxygen demand(COD_(Mn))measurements,which are considered as imprecise and environmentally unfriendly.Hence,we conducted a field campaign across 30 lakes in Wuhan's metropolitan area,collecting 255 samples from varying trophic states to evaluate the predictive capability of COD_(Mn)using DOM optical measurements combined with parallel factor(PARAFAC)analysis.The DOM optical properties and chemical composition exhibited considerable variability across varying trophic state levels(TSLs).Fluorescence components C1-C3 and C5,fluorescence index(FI),and absorption at 254 nm(α_(254)),increased as TSL increased,while the DOM spectral slope(SR)decreased.COD_(Mn)was positively and significantly correlated with fluorescence components C1-C3 and C5,freshness index(β/α),autochthonous index(BIX),humification index(HIX),α_(254),the ratio ofα_(250)toα_(365)(E2/E3)while being negatively correlated with SR.Parametersα_(254),C1,C3,C4,FI,β/α,and HIX were identified as key predictors of COD_(Mn).The multiple linear regression model successfully predicted COD_(Mn)(r^(2)=0.63,p<0.01,n=1113)and demonstrated superior performance in mesotrophic lakes.These findings highlight the potential for establishing high-frequency,continuous,and multi-regional COD monitoring programs.
基金supported by the National Natural Science Foundation of China(No.82303169)the Key Research and Development Program of Shaanxi(No.2021ZDLSF02-06).
文摘Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observational studies.The objective of this study was to explore the causal association between PM_(2.5)exposure,its absorbance,and IBD.Methods We assessed the association of PM_(2.5)and PM_(2.5)absorbance with the two primary forms of IBD(Crohn’s disease[CD]and ulcerative colitis[UC])using Mendelian randomization(MR)to explore the causal relationship.We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study.Single-nucleotide polymorphisms linked with PM_(2.5)concentrations or their absorbance were used as instrumental variables(IVs).We used inverse variance weighting(IVW)as the primary analytical approach and four other standard methods as supplementary analyses for quality control.Results The results of MR demonstrated that PM_(2.5)had an adverse influence on UC risk(odds ratio[OR]=1.010;95%confidence interval[CI]=1.001–1.019,P=0.020).Meanwhile,the results of IVW showed that PM_(2.5)absorbance was also causally associated with UC(OR=1.012;95%CI=1.004–1.019,P=0.002).We observed no causal relationship between PM_(2.5),PM_(2.5)absorbance,and CD.The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy,ensuring the reliability of MR results.Conclusion Based on two-sample MR analyses,there are potential positive causal relationships between PM_(2.5),PM_(2.5)absorbance,and UC.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金supported by the International Partnership Program of the Chinese Academy of Sciences (Grant No.025GJHZ2023106GC)。
文摘Primordial black holes(PBHs) offer a compelling candidate for dark matter. The production of PBHs through well-tested and accepted physical processes is highly worthy of investigation. This work highlights the role of turbulences in the very early universe in sustaining intense and persistent fluctuations in energy or mass density,which could provide a natural mechanism for PBH formation in the primordial universe. We analyze the mass range and abundance of PBHs produced in the magnetohydrodynamic turbulence induced by the electroweak phase transition. Remarkably, we find that the mass range of the produced PBHs falls within the most viable“asteroid mass” window from the present-day observations, and within natural parameter regions their abundance can be sufficiently large. These findings suggest that PBHs produced during magnetohydrodynamic turbulence in the very early universe may comprise a dominant part of dark matter.
基金funded by the AFM-Telethon Foundation (#28703)by the Italian Ministry of Education, University and Research (Grant P2022Y2A3L funded in the framework of NRRP, Mission 4.2, Investment 1.1 “progetti di ricerca di Rilevante Interesse Nazionale - PRIN”, funded by the European Union Next Generation EU, CUP C53D23007520001+2 种基金Grant P20227YB93, CUP C53D23003030001) (to MC)the activities of the National Center for Gene Therapy and Drugs based on RNA Technology, funded in the framework of the National Recovery and Resilience Plan (NRRP), Mission 4 “Education and Research”, Component 2 “From Research to Business”, Investment 1.4 “Strengthening research structures for supporting the creation of National Centres, national R&D leaders on some Key Enabling Technologies”funded by the European Union-Next Generation EU, Project CN00000041, CUP B93D21010860004, Spoke n. 5 “Inflammatory and infectious diseases” (to MC)
文摘β-glucocerebrosidase in health and disease:Mutations in theβ-glucocerebrosidase(GBA)gene do cause the rare lysosomal storage disorder Gaucher’s disease(GD)with an estimated global prevalence of 1:200,000(Imbalzano et al.,2024).GBA is a membrane-bound lysosomalenzyme responsible for glucosylceramide and glucosylsphingosine hydrolysis.When this enzyme is mutated and dysfunctional,its substrates progressively accumulate within cells.
基金supported in part by the National Natural Science Foundation of China under Grant 62071405the National Natural Science Foundation of China under Grant 12175189.
文摘The accurate segmentation of deep gray matter nuclei is critical for neuropathological research,disease diagnosis and treatment.Existing methods employ the supervised learning training approach,which requires large labeled datasets.It is challenging and time-consuming to obtain such datasets for medical image analysis.In addition,these methods based on convolutional neural networks(CNNs)only achieve suboptimal performance due to the locality of convolutional operations.Vision Transformers(ViTs)efficiently model long-range dependencies and thus have the potentiality to outperform these methods in segmentation tasks.To address these issues,we propose a novel hybrid network based on self-supervised pre-training for deep gray matter nuclei segmentation.Specifically,we present a CNN-Transformer hybrid network(CTNet),whose encoder consists of 3D CNN and ViT to learn local spatial-detailed features and global semantic information.A self-supervised learning(SSL)approach that integrates rotation prediction and masked feature reconstruction is proposed to pre-train the CTNet,enabling the model to learn valuable visual representations from unlabeled data.We evaluate the effectiveness of our method on 3T and 7T human brain MRI datasets.The results demonstrate that our CTNet achieves better performance than other comparison models and our pre-training strategy outperforms other advanced self-supervised methods.When the training set has only one sample,our pre-trained CTNet enhances segmentation performance,showing an 8.4%improvement in Dice similarity coefficient(DSC)compared to the randomly initialized CTNet.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
基金supported by the National Natural Science Foundation of China,Nos.82172546(to XH),82172547(to ZZ)the Natural ScienceFoundation of Guangdong Province,Nos.2023A1515012695(to XH),2024A1515010419(to ZZ)the Science and Technology Plan Project of Guangzhou,Nos.202201020413(to ZZ),2023A04J1099(to ZZ).
文摘White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.
基金supported by the National Natural Science Foundation of China(62473082,82202250,82121003,62036003,and 62333003)the Fundamental Research Funds for the Central Universities(ZYGX2022YGRH008 and ZYGX2024XJ054)the Medical-Engineering Cooperation Funds from the University of Electronic Science and Technology of China(ZYGX2021YGLH201).
文摘The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions for investigating their interactions.Early efforts to parcellate the mammalian brain,using histological cytoarchitecture and myeloarchitecture,as well as recent in vivo magnetic resonance imaging(MRl)[2,3],have primarily involved cortical areas,subcortical structures,and cerebellar nuclei.Human brain parcellations primarily focus on grey matter(GM),which purposefully excludes white matter(WM),hindering the development of next-generation brain atlases.
基金supported by Grant 3195 from Paralyzed Veterans of America Research Foundation (to BRK)
文摘The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金supported by the National Natural Science Foundation Joint Fund,No.U22A20309(to PY)the Natural Science Foundation of LiaoningProvince,No.2023-MS-07(to HuL)the Unveiling Key Scientific and Technological Projects of Liaoning Province,No.2021JH1/10400051(to HuL).
文摘Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.
