Background:This study addresses the pressing need to understand the nuanced relationship between‘mattering’—the perception of being significant to others—and problematic internet use(PIU)among university students....Background:This study addresses the pressing need to understand the nuanced relationship between‘mattering’—the perception of being significant to others—and problematic internet use(PIU)among university students.Unlike previous research that has primarily employed variable-centered approaches,this study first adopts a person-centered approach using Latent Profile Analysis(LPA)to identify distinct mattering profiles.Subsequently,through variable-centered analyses,these profiles are examined in relation to different types of PIU—specifically problematic social media use(PSMU)and problematic gaming(PG)—as well as adaptability.Methods:Data were collected from 3587 university students across 19 universities in China.Participants completed three mattering-related scales(General Mattering Scale,Anti-Mattering Scale,and Fear of Not Mattering Inventory),along with the Bergen Social Media Addiction Scale,the Internet Gaming Disorder Scale-Short Form,and the Nine-item Adaptability Scale.Results:A four-class model identified by LPA was optimally selected:Class 1(high general mattering,low anti-mattering,low fear of not mattering),Class 2(moderate levels),Class 3(moderate general mattering,high antimattering,high fear of not mattering),and Class 4(low general mattering,low fear of not mattering,moderate anti-mattering).Significant differences were found among these classes in both PIU types(PSMU:F=139.66,p<0.001;PG:F=162.96,p<0.001).The pattern of mean differences consistently showed:Class 3>Class 2>Class 4>Class 1.Class 3 participants demonstrated the highest likelihood of meeting the addiction criteria,Class 2 showed moderate probability,while Classes 1 and 4 exhibited lower probabilities(χ^(2)=113.38 to 408.87,all p<0.001).Additionally,Class 3 reported the lowest adaptability(F=131.67,p<0.001).Conclusion:This study reveals that the unique influence of three ways of assessing feelings of mattering and the fear of not mattering on university students’PIU at the personal level,concluding that these factors are integral to understanding PIU among this demographic.展开更多
Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune respons...Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.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
Ultrafast optical spectroscopy was successfully introduced decades ago.Its deep relationship with condensed matter physics profoundly enriched the scientific frontier of light–matter interactions.Previously,materials...Ultrafast optical spectroscopy was successfully introduced decades ago.Its deep relationship with condensed matter physics profoundly enriched the scientific frontier of light–matter interactions.Previously,materials such as metals,insulators,semiconductors,and superconductors were investigated,followed by magnetic materials,strongly correlated materials,complex oxides,nano-materials,topological materials,and metamaterials.展开更多
Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables th...Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.展开更多
Soil organic matter(SOM)is crucial for ecosystem carbon cycling,soil fertility,and environmental quality.As the main component of SOM,humic substances(HS)are considered a unique category of nonuniformly assembled subs...Soil organic matter(SOM)is crucial for ecosystem carbon cycling,soil fertility,and environmental quality.As the main component of SOM,humic substances(HS)are considered a unique category of nonuniformly assembled substances.展开更多
Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and ...Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.展开更多
This study extends the self-propelled particle(SPP)model by incorporating a limited vision cone and local density sensing.The results reveal that clusters can simultaneously exhibit velocity polarization and spatial c...This study extends the self-propelled particle(SPP)model by incorporating a limited vision cone and local density sensing.The results reveal that clusters can simultaneously exhibit velocity polarization and spatial cohesion within specific ranges of vision angle and density threshold.The dependence of the dynamical features,including the order parameter and density variation,on the threshold and visual cone is investigated.Furthermore,a critical threshold is identified,which governs the transition between ordered and disordered states and is closely linked to density fluctuations and noise intensity.The clustering results show that the model is explained by the chasing mechanism responsible for cluster formation,density,and shape.These results may stimulate practical applications in swarm maneuvering.展开更多
The Dongsha area,a key target for gas hydrate exploration,is influenced by multiple factors,including sedimentary processes and the paleoenvironment,which play critical roles in gas hydrate formation.To elucidate the ...The Dongsha area,a key target for gas hydrate exploration,is influenced by multiple factors,including sedimentary processes and the paleoenvironment,which play critical roles in gas hydrate formation.To elucidate the coupling among sedimentary processes,paleoenvironment,and gas hydrate accumulation,this study investigates the Site DS-W16 using particle size analysis,biological component content,and geochemistry data.Oxygen isotope data from foraminifera and biostratigraphic evidence indicate that sedimentation at the bottom of core interval from Site DS-W16 began during MIS 11(Marine isotope stage).The sedimentation dynamics of the studied layers are complex,involving gravity flows,traction currents,and suspended deposition.Organic matter shows a significant correlation with transgressive-regressive cycle.The site DS-W16 contains two distinct gas hydrate reservoirs:a shallow reservoir(10-24 mbsf)and a deep reservoir(below 182 mbsf).The paleomarine environment influences gas hydrate accumulation by altering sedimentary processes and sediment characteristics,especially the distribution of biological components.Both shallow and deep gas hydrate reservoirs formed under dynamic conditions dominated by traction currents and are characterized by a higher abundance of foraminifera.Sedimentary layers rich in foraminifera and modified by traction currents represent key intervals for preferential gas hydrate accumulation.展开更多
Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory syste...Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NFκB neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.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
Conformational entropy,one of the central concepts of polymer physics,is the key to revealing physical characteristics of polymers.Despite an increased repertoire of conformational-entropy effects in the structural fo...Conformational entropy,one of the central concepts of polymer physics,is the key to revealing physical characteristics of polymers.Despite an increased repertoire of conformational-entropy effects in the structural formation,transition,and properties of polymer systems,the physical origin of conformational entropy remains less understood compared to interaction energy and other types of entropy.This review seeks to provide a conceptual framework unveiling several principles and rules of conformational entropy in governing the structures and properties of polymers,from the perspective of fundamental physics and statistical mechanics.First,we focus on the fundamentals of entropy in thermodynamics,leading to the theoretical basis for the elucidation of conformational entropy.Second,we delineate the physical nature of statistics and dissipation of conformational entropy and its essential dependence on the environmental heat bath.Next,we explore the principles of conformational entropy in driving the ordering transitions of various systems of polymers and their nanocomposites,elucidating the emergent and collective behaviors as well as the interplay between energetic interactions and entropy.Moreover,we demonstrate how the concept of conformational entropy is generalized to the biological systems and other soft matters.Finally,we discuss future directions to signify this framework originated from polymers.展开更多
This study presents an integrated assessment of sedimentological,granulometric,physico-chemical,and biological characteristics in three Romanian coastal lakes,based on 2022 field surveys.A total of 59 sediment samples...This study presents an integrated assessment of sedimentological,granulometric,physico-chemical,and biological characteristics in three Romanian coastal lakes,based on 2022 field surveys.A total of 59 sediment samples were analyzed lithologically and granulometrically,and 12 were examined for macrozoobenthic community composition.Water samples were assessed for nutrient and pigment concentrations to evaluate trophic status and ecological condition.Sediments were predominantly silty-clayey,indicating low-energy depositional environments.Organic matter content was highest in Lakes Agigea and Tuzla,suggesting enhanced primary productivity and organic detritus accumulation,while Lake Costinești showed higher biogenic carbonate content from mollusc shells.Macrozoobenthic assemblages were dominated by taxa tolerant to organic enrichment and hypoxia,including Chironomidae larvae,Oligochaeta,and Cyprideis torosa.Water quality analysis indicated good ecological status in Agigea Lake,whereas Tuzla Lake was severely eutrophic,with phosphate and nitrite in Class Ⅳ and chlorophyll-a exceeding Class Ⅴ thresholds(>250μg/L),consistent with cyanobacterial blooms.Elevated sulfate(Class Ⅲ)and suspended solids further impaired Tuzla’s transparency.In Costinești,marine taxa presence and variable salinity reflected periodic seawater exchange.Anthropogenic influences were evident-nutrient enrichment from fisheries in Tuzla and marine species introduction in Costinești-highlighting system vulnerability to human pressure.The integration of sediment,water quality,and biological indicators emphasizes the need for continuous,interdisciplinary monitoring to track ecological shifts,support adaptive management,and conserve biodiversity and ecosystem integrity in Romanian coastal lakes.展开更多
Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an i...Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.展开更多
Interfacial superconductivity(IS)has been a topic of intense interest in condensed matter physics,due to its unique properties and exotic photoelectrical performance.However,there are few reports about IS systems cons...Interfacial superconductivity(IS)has been a topic of intense interest in condensed matter physics,due to its unique properties and exotic photoelectrical performance.However,there are few reports about IS systems consisting of two insulators.Here,motivated by the emergence of an insulator-metal transition in type-Ⅲ heterostructures and the superconductivity in some“special”two-dimensional(2D)semiconductors via electron doping,we predict that the 2D heterostructure SnSe_(2)/PtTe_(2) is a model system for realizing IS by using firstprinciples calculations.Our results show that due to slight but crucial interlayer charge transfer,SnSe_(2)/PtTe_(2) turns to be a type-Ⅲ heterostructure with metallic properties and shows a superconducting transition with the critical temperature(T_(c))of 3.73 K.Similar to the enhanced electron–phonon coupling(EPC)in the electrondoped SnSe_(2) monolayer,the IS in the SnSe_(2)/PtTe_(2) heterostructure mainly originates from the metallized SnSe_(2) layer.Furthermore,we find that its superconductivity is sensitive to tensile lattice strain,forming a domeshaped superconducting phase diagram.Remarkably,at 7%biaxial tensile strain,the superconducting T_(c) can increase more than twofold(8.80 K),resulting from softened acoustic phonons at the𝑀point and enhanced EPC strength.Our study provides a concrete example for realizing IS in type-Ⅲ heterostructures,which waits for future experimental verification.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
In 2005,Richard Conn Henry from Johns Hopkins University published“The Mental Universe”in Nature,advancing the idealistic claim that the universe is fundamentally mental and conscious,and that matter has no objectiv...In 2005,Richard Conn Henry from Johns Hopkins University published“The Mental Universe”in Nature,advancing the idealistic claim that the universe is fundamentally mental and conscious,and that matter has no objective reality.Grounded in a one-sided interpretation of the observational effects in quantum mechanics,this view has sparked long-standing debates across physics,philosophy,neuroscience,and other disciplines.The Unified Complex System Theory(UCST),centered on an ether-mind dualistic ontology,differs from both traditional materialist monism and idealist monism,and offers a more comprehensive account of the mind-matter relationship.Using UCST as a theoretical framework,this paper systematically analyzes multiple fallacies in“The Mental Universe”concerning conceptual definition,logical deduction,and the demarcation of scientific boundaries.It comprehensively reviews both supportive and critical arguments in authoritative journals since 2005,and integrates evidence from interpretive disputes in quantum mechanics,empirical findings in neuroscience,epigenetic mechanisms,and parapsychological phenomena.The study demonstrates that:Quantum measurement essentially involves interactions between material systems,rather than consciousness determining existence;consciousness emerges from the interaction between mind and the physical body,and cannot exist independently of a material substrate;science applies only to the finite,observable world accessible to humans,and cannot pronounce absolute truths about the universe as a whole;monism is unsuitable as a reliable ontological foundation for science,and ether-mind dualistic ontology possesses greater logical completeness and explanatory power.展开更多
Tunable plasmonic structures provide the possibility to actively modify the radiation from atoms through electromagnetic coupling.In this paper,we investigate the decay and radiation behavior of an atom near a dielect...Tunable plasmonic structures provide the possibility to actively modify the radiation from atoms through electromagnetic coupling.In this paper,we investigate the decay and radiation behavior of an atom near a dielectric nanosphere with conductive surface within the framework of macroscopic quantum electrodynamics.The electromagnetic fields including the losses in the materials can be taken as fundamental excitations which interact with the atom through a transition dipole.Both weak and strong coupling regimes have been investigated.The decay rate and the angle-dependent light intensities indeed strongly depend on the parameters of the system,i.e.,the position and orientation of the dipole,the geometric size,and the surface conductivity,providing the opportunity of artificial control over these quantities.Generalizing the formalism in this paper to other systems,like metamaterials,is straightforward,which we believe may pave a way for future active quantum nanophotonic devices.展开更多
Matter and Radiation at Extremes(MRE),is committed to the publication of original and impactful research and review papers that address extreme states of matter and radiation,and the associated science and technology ...Matter and Radiation at Extremes(MRE),is committed to the publication of original and impactful research and review papers that address extreme states of matter and radiation,and the associated science and technology that are employed to produce and diagnose these conditions in the laboratory.Drivers,targets and diagnostics are included along with related numerical simulation and computational methods.It aims to provide a peer-reviewed platform for the international physics community and promote worldwide dissemination of the latest and impactful research in related fields.展开更多
Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In th...Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.展开更多
基金supported by a special grant from the Taishan Scholars Project(Project No.tsqn202211130).
文摘Background:This study addresses the pressing need to understand the nuanced relationship between‘mattering’—the perception of being significant to others—and problematic internet use(PIU)among university students.Unlike previous research that has primarily employed variable-centered approaches,this study first adopts a person-centered approach using Latent Profile Analysis(LPA)to identify distinct mattering profiles.Subsequently,through variable-centered analyses,these profiles are examined in relation to different types of PIU—specifically problematic social media use(PSMU)and problematic gaming(PG)—as well as adaptability.Methods:Data were collected from 3587 university students across 19 universities in China.Participants completed three mattering-related scales(General Mattering Scale,Anti-Mattering Scale,and Fear of Not Mattering Inventory),along with the Bergen Social Media Addiction Scale,the Internet Gaming Disorder Scale-Short Form,and the Nine-item Adaptability Scale.Results:A four-class model identified by LPA was optimally selected:Class 1(high general mattering,low anti-mattering,low fear of not mattering),Class 2(moderate levels),Class 3(moderate general mattering,high antimattering,high fear of not mattering),and Class 4(low general mattering,low fear of not mattering,moderate anti-mattering).Significant differences were found among these classes in both PIU types(PSMU:F=139.66,p<0.001;PG:F=162.96,p<0.001).The pattern of mean differences consistently showed:Class 3>Class 2>Class 4>Class 1.Class 3 participants demonstrated the highest likelihood of meeting the addiction criteria,Class 2 showed moderate probability,while Classes 1 and 4 exhibited lower probabilities(χ^(2)=113.38 to 408.87,all p<0.001).Additionally,Class 3 reported the lowest adaptability(F=131.67,p<0.001).Conclusion:This study reveals that the unique influence of three ways of assessing feelings of mattering and the fear of not mattering on university students’PIU at the personal level,concluding that these factors are integral to understanding PIU among this demographic.
基金supported by National Key R&D Program:Key Special Project on Research for the Prevention and Treatment of Common Diseases-2022 Annual Project,Nos.2022YFC2504900,2022YFC2504902(both to ZL).
文摘Regulatory T cells are crucial immunomodulatory cells that play essential roles in both ischemic stroke and intracerebral hemorrhage.These cells are vital in post-stroke inflammation since they suppress immune responses and promote tissue repair.This review thoroughly examines the dynamic changes in the number and function of regulatory T cells and highlights their distinct roles at various stages of stroke progression.In the acute phase(within 5-7 days),regulatory T cells exert neuroprotective effects primarily by reducing inflammation.In the chronic phase(7 days post-onset),these cells support neuroregeneration and functional recovery.The review also explores the emerging role of regulatory T cells in the brain-gut axis,a key mediator of the systemic immune responses following stroke,and discusses its relevance in modulating post-stroke inflammation and repair.Various strategies aimed at enhancing regulatory T cell responses include adoptive transfer of regulatory T cells,administration of pharmacological agents,and induction of mucosal tolerance.All these approaches can potentially enhance the immunomodulatory and repair functions of regulatory T cells.Nevertheless,despite the promising preclinical results,the translation of regulatory T cell-based therapies into clinical practice is associated with challenges related to optimal timing,dosage,and long-term efficacy.Overall,targeting regulatory T cells is a novel and promising immunoregulatory approach for mitigating stroke-induced injury and promoting neural repair.
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.
文摘Ultrafast optical spectroscopy was successfully introduced decades ago.Its deep relationship with condensed matter physics profoundly enriched the scientific frontier of light–matter interactions.Previously,materials such as metals,insulators,semiconductors,and superconductors were investigated,followed by magnetic materials,strongly correlated materials,complex oxides,nano-materials,topological materials,and metamaterials.
文摘Neurodevelopmental processes represent a finely tuned interplay between genetic and environmental factors,shaping the dynamic landscape of the developing brain.A major component of the developing brain that enables this dynamic is the white matter(WM),known to be affected in neurodevelopmental disorders(NDDs)(Rokach et al.,2024).WM formation is mediated by myelination,a multifactorial process driven by neuro-glia interactions dependent on proper neuronal functionality(Simons and Trajkovic,2006).Another key aspect of neurodevelopmental abnormalities involves neuronal dynamics and function,with recent advances significantly enhancing our understanding of both neuronal and glial mitochondrial function(Devine and Kittler,2018;Rojas-Charry et al.,2021).Energy homeostasis in neurons,attributed largely to mitochondrial function,is critical for proper functionality and interactions with oligodendrocytes(OLs),the cells forming myelin in the brain’s WM.We herein discuss the interplay between these processes and speculate on potential dysfunction in NDDs.
基金financial support from the National Key Research and Development Program of China(No.2022YFD1500304)the Postdoctoral Fellowship Program of CPSF,China(No.GZC20232641)the Postdoctoral Science Foundation of China(No.2024M753215)。
文摘Soil organic matter(SOM)is crucial for ecosystem carbon cycling,soil fertility,and environmental quality.As the main component of SOM,humic substances(HS)are considered a unique category of nonuniformly assembled substances.
基金supported by the National Key Research and Development Program of China(No.2022YFC3702704)the National Natural Science Foundation of China(Nos.22376005,22076006 and 82073506).
文摘Microorganisms constitute an essential component in the indoor environment,which is closely related to hu-man health.However,there is limited evidence regarding the associations between indoor airborne microbiome and systemic inflammation,as well as whether this association is modified by indoor particulate matter and the underlying mechanisms.In this prospective repeated-measure study among 66 participants,indoor airborne mi-crobiome was characterized using amplicon sequencing and qPCR.Indoor fine particulate matter(PM_(2.5))and inhalable particulate matter(PM10)were measured.Systemic inflammatory biomarkers were assessed,including white blood cell(WBC),neutrophil(NEUT),monocyte,eosinophil counts,and their proportions.Targeted serum amino acid metabolomics were conducted to explore the underlying mechanisms.Linear mixed-effect models re-vealed that bacterial and fungal Simpson diversity were significantly associated with decreased WBC and NEUT.For example,for each interquartile range increase in the bacterial Simpson diversity,WBC and NEUT changed by-4.53%(95%CI:-8.25%,-0.66%)and-5.95%(95%CI:-11.3%,-0.27%),respectively.Notably,increased inflammatory risks of airborne microbial exposure were observed when indoor PM_(2.5) and PM10 levels were below the WHO air quality guidelines.Mediation analyses indicated that dopamine metabolism partially mediated the anti-inflammatory effects of fungal diversity exposure.Overall,our study indicated protection from a diverse indoor microbial environment on cardiovascular health and proposed an underlying mechanism through amino acid metabolism.Additionally,health risks associated with microbial exposure deserve more attention in con-texts of low indoor particulate matter pollution.Further research is necessary to fully disentangle the complex relationships between indoor microbiome,air pollutants,and human health.
基金Project supported by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(Grant No.KYCX240139)funded by the Youth Independent Innovation Fund of PLA Army Engineering University(Grant No.KYJBJKQTZQ23006)。
文摘This study extends the self-propelled particle(SPP)model by incorporating a limited vision cone and local density sensing.The results reveal that clusters can simultaneously exhibit velocity polarization and spatial cohesion within specific ranges of vision angle and density threshold.The dependence of the dynamical features,including the order parameter and density variation,on the threshold and visual cone is investigated.Furthermore,a critical threshold is identified,which governs the transition between ordered and disordered states and is closely linked to density fluctuations and noise intensity.The clustering results show that the model is explained by the chasing mechanism responsible for cluster formation,density,and shape.These results may stimulate practical applications in swarm maneuvering.
基金supported by National Natural Science Foundation of China(No.42376217)Fundamental Research Funds for the Central Universities of China(No.3-7-10-2025-03)National Key Research and Development Program of China(No.2024YFC2814702).
文摘The Dongsha area,a key target for gas hydrate exploration,is influenced by multiple factors,including sedimentary processes and the paleoenvironment,which play critical roles in gas hydrate formation.To elucidate the coupling among sedimentary processes,paleoenvironment,and gas hydrate accumulation,this study investigates the Site DS-W16 using particle size analysis,biological component content,and geochemistry data.Oxygen isotope data from foraminifera and biostratigraphic evidence indicate that sedimentation at the bottom of core interval from Site DS-W16 began during MIS 11(Marine isotope stage).The sedimentation dynamics of the studied layers are complex,involving gravity flows,traction currents,and suspended deposition.Organic matter shows a significant correlation with transgressive-regressive cycle.The site DS-W16 contains two distinct gas hydrate reservoirs:a shallow reservoir(10-24 mbsf)and a deep reservoir(below 182 mbsf).The paleomarine environment influences gas hydrate accumulation by altering sedimentary processes and sediment characteristics,especially the distribution of biological components.Both shallow and deep gas hydrate reservoirs formed under dynamic conditions dominated by traction currents and are characterized by a higher abundance of foraminifera.Sedimentary layers rich in foraminifera and modified by traction currents represent key intervals for preferential gas hydrate accumulation.
基金supported by the National Natural Science Foundation of China(Nos.22236006,22076146 and 22036001).
文摘Decades of researches have shown that particulate matter(PM)in cooking oil fumes(COFs)have the capacity to induce neurological diseases,such as cognitive impairment and stroke through multiple pathways.Olfactory system serves as an important route for exogenous PM to invade the central nervous system.Nevertheless,the olfactory injuries caused by PM_(2.5) and its mechanism have remained uncertain.In this study,10-week-old C57BL/6 mice were exposed to COF generated from heating soybean oil via an exposure chamber for 4 weeks and the toxic effects and mechanisms of COF on the olfactory epithelium(OE)and olfactory bulb(OB)in mice were investigated.The results indicated that the COF exposure led to the apoptosis of olfactory epithelial cells and inflammatory responses in the mice OE,which resulted in the olfactory barrier damage.The transformation of microglia cells from a ramified morphology to an amoeboid morphology was observed in the OB,accompanied by the activation of TLR4-NFκB neuroinflammation signaling and the disruption of olfactory transduction signaling in the OB.Our study revealed the potential harm of COF to olfactory system and suggested a potential pathway for PM-induced neuroinflammation.
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financially supported by the National Natural Science Foundation of China (Nos. 22533003 and 22025302)financial support from the Ministry of Science and Technology of China (No. 2022YFA1203203)State Key Laboratory of Chemical Engineering (No. SKL-ChE23T01).
文摘Conformational entropy,one of the central concepts of polymer physics,is the key to revealing physical characteristics of polymers.Despite an increased repertoire of conformational-entropy effects in the structural formation,transition,and properties of polymer systems,the physical origin of conformational entropy remains less understood compared to interaction energy and other types of entropy.This review seeks to provide a conceptual framework unveiling several principles and rules of conformational entropy in governing the structures and properties of polymers,from the perspective of fundamental physics and statistical mechanics.First,we focus on the fundamentals of entropy in thermodynamics,leading to the theoretical basis for the elucidation of conformational entropy.Second,we delineate the physical nature of statistics and dissipation of conformational entropy and its essential dependence on the environmental heat bath.Next,we explore the principles of conformational entropy in driving the ordering transitions of various systems of polymers and their nanocomposites,elucidating the emergent and collective behaviors as well as the interplay between energetic interactions and entropy.Moreover,we demonstrate how the concept of conformational entropy is generalized to the biological systems and other soft matters.Finally,we discuss future directions to signify this framework originated from polymers.
基金financed by the Ministry of Research and Innovation-“Program Nucleu”-13N/08.02.2019-PN19-20-04-01The APC was funded by PN 23.30.02.02,PN 23.30.01.03.
文摘This study presents an integrated assessment of sedimentological,granulometric,physico-chemical,and biological characteristics in three Romanian coastal lakes,based on 2022 field surveys.A total of 59 sediment samples were analyzed lithologically and granulometrically,and 12 were examined for macrozoobenthic community composition.Water samples were assessed for nutrient and pigment concentrations to evaluate trophic status and ecological condition.Sediments were predominantly silty-clayey,indicating low-energy depositional environments.Organic matter content was highest in Lakes Agigea and Tuzla,suggesting enhanced primary productivity and organic detritus accumulation,while Lake Costinești showed higher biogenic carbonate content from mollusc shells.Macrozoobenthic assemblages were dominated by taxa tolerant to organic enrichment and hypoxia,including Chironomidae larvae,Oligochaeta,and Cyprideis torosa.Water quality analysis indicated good ecological status in Agigea Lake,whereas Tuzla Lake was severely eutrophic,with phosphate and nitrite in Class Ⅳ and chlorophyll-a exceeding Class Ⅴ thresholds(>250μg/L),consistent with cyanobacterial blooms.Elevated sulfate(Class Ⅲ)and suspended solids further impaired Tuzla’s transparency.In Costinești,marine taxa presence and variable salinity reflected periodic seawater exchange.Anthropogenic influences were evident-nutrient enrichment from fisheries in Tuzla and marine species introduction in Costinești-highlighting system vulnerability to human pressure.The integration of sediment,water quality,and biological indicators emphasizes the need for continuous,interdisciplinary monitoring to track ecological shifts,support adaptive management,and conserve biodiversity and ecosystem integrity in Romanian coastal lakes.
基金supported by the Natural Science Foundation of Beijing,No.7232279(to XW)the National Natural Science Foundation of China,No.U21A20400(to QW)Key Project of Beijing University of Chinese Medicine,Nos.2022-JYB-JBZR-004(to XW),2024-JYB-JBZD-043(to CL).
文摘Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.
基金supported by the National Key R&D Program of China (Grant Nos.2022YFA1403103 and 2019YFA0308603)the National Natural Science Foundation of China (Grant No.12304167)the Shandong Provincial Natural Science Foundation of China (Grant No.ZR2023QA020)。
文摘Interfacial superconductivity(IS)has been a topic of intense interest in condensed matter physics,due to its unique properties and exotic photoelectrical performance.However,there are few reports about IS systems consisting of two insulators.Here,motivated by the emergence of an insulator-metal transition in type-Ⅲ heterostructures and the superconductivity in some“special”two-dimensional(2D)semiconductors via electron doping,we predict that the 2D heterostructure SnSe_(2)/PtTe_(2) is a model system for realizing IS by using firstprinciples calculations.Our results show that due to slight but crucial interlayer charge transfer,SnSe_(2)/PtTe_(2) turns to be a type-Ⅲ heterostructure with metallic properties and shows a superconducting transition with the critical temperature(T_(c))of 3.73 K.Similar to the enhanced electron–phonon coupling(EPC)in the electrondoped SnSe_(2) monolayer,the IS in the SnSe_(2)/PtTe_(2) heterostructure mainly originates from the metallized SnSe_(2) layer.Furthermore,we find that its superconductivity is sensitive to tensile lattice strain,forming a domeshaped superconducting phase diagram.Remarkably,at 7%biaxial tensile strain,the superconducting T_(c) can increase more than twofold(8.80 K),resulting from softened acoustic phonons at the𝑀point and enhanced EPC strength.Our study provides a concrete example for realizing IS in type-Ⅲ heterostructures,which waits for future experimental verification.
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 scientific research project of Westlake University under Grant Number WU2025A006.
文摘In 2005,Richard Conn Henry from Johns Hopkins University published“The Mental Universe”in Nature,advancing the idealistic claim that the universe is fundamentally mental and conscious,and that matter has no objective reality.Grounded in a one-sided interpretation of the observational effects in quantum mechanics,this view has sparked long-standing debates across physics,philosophy,neuroscience,and other disciplines.The Unified Complex System Theory(UCST),centered on an ether-mind dualistic ontology,differs from both traditional materialist monism and idealist monism,and offers a more comprehensive account of the mind-matter relationship.Using UCST as a theoretical framework,this paper systematically analyzes multiple fallacies in“The Mental Universe”concerning conceptual definition,logical deduction,and the demarcation of scientific boundaries.It comprehensively reviews both supportive and critical arguments in authoritative journals since 2005,and integrates evidence from interpretive disputes in quantum mechanics,empirical findings in neuroscience,epigenetic mechanisms,and parapsychological phenomena.The study demonstrates that:Quantum measurement essentially involves interactions between material systems,rather than consciousness determining existence;consciousness emerges from the interaction between mind and the physical body,and cannot exist independently of a material substrate;science applies only to the finite,observable world accessible to humans,and cannot pronounce absolute truths about the universe as a whole;monism is unsuitable as a reliable ontological foundation for science,and ether-mind dualistic ontology possesses greater logical completeness and explanatory power.
基金supported by Hangzhou Dianzi University(Grant No.KYS075621018)supported by the Natural Science Foundation of Zhejiang Province(Grant No.LY24A050004)。
文摘Tunable plasmonic structures provide the possibility to actively modify the radiation from atoms through electromagnetic coupling.In this paper,we investigate the decay and radiation behavior of an atom near a dielectric nanosphere with conductive surface within the framework of macroscopic quantum electrodynamics.The electromagnetic fields including the losses in the materials can be taken as fundamental excitations which interact with the atom through a transition dipole.Both weak and strong coupling regimes have been investigated.The decay rate and the angle-dependent light intensities indeed strongly depend on the parameters of the system,i.e.,the position and orientation of the dipole,the geometric size,and the surface conductivity,providing the opportunity of artificial control over these quantities.Generalizing the formalism in this paper to other systems,like metamaterials,is straightforward,which we believe may pave a way for future active quantum nanophotonic devices.
文摘Matter and Radiation at Extremes(MRE),is committed to the publication of original and impactful research and review papers that address extreme states of matter and radiation,and the associated science and technology that are employed to produce and diagnose these conditions in the laboratory.Drivers,targets and diagnostics are included along with related numerical simulation and computational methods.It aims to provide a peer-reviewed platform for the international physics community and promote worldwide dissemination of the latest and impactful research in related fields.
基金supported by the National Natural Science Foundation of China,No.82201626(to CC)the Natural Science Foundation of LiaoningProvince,No.2022-MS-442(to CC)the Dalian Municipal Medical Key Specialty Climbing Project,No.2024ZZ040(to MZ).
文摘Cerebral small vessel disease is a major vascular contributor to cognitive impairment and dementia.However,there remains a lack of effective preventative or therapeutic regimens for cerebral small vessel disease.In this study,we investigated the potential therapeutic effects of MCC950,a selective NOD-like receptor family pyrin domain-containing protein 3 inhibitor,on cerebral small vessel disease pathogenesis and cognitive decline in spontaneously hypertensive rats.Our results showed that chronic administration of MCC950(10 mg/kg)to spontaneously hypertensive rats inhibited NOD-like receptor family pyrin domain-containing protein 3 inflammasome activation,thereby considerably suppressing the production of pyroptosis executive protein gasdermin D and pro-inflammatory factors,including interleukin-1βand-18.A decrease in astrocytic and microglial activation was also observed.We also found that MCC950 significantly inhibited autophagy.More importantly,behavioral assessment indicated that MCC950 administration ameliorated impaired neurocognitive function,which was associated with improvements in neuropathological hallmarks in the cerebral small vessel disease brain,such as blood‒brain barrier breakdown,white matter damage,and endothelial dysfunction.Thus,our findings revealed that the NOD-like receptor family pyrin domain-containing protein 3 inflammasome is a key contributor to the onset or progression of cerebral small vessel disease and suggested the potential of NOD-like receptor family pyrin domain-containing protein 3-based therapy as a potential novel strategy for treating cerebral small vessel disease.
