Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse...Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca alumina...A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca aluminates)during the impregnation process of the matrix.After cathode activation,the surface Ba:O molar ratio is 0.88:1.00,much higher than the Ba dispenser cathode without Ni doping.The XPS results of the cathode surface showed that the metallic Ba appeared on the activated cathode surface,forming dipoles with oxygen,and effectively reducing the cathode surface work function.The pulse electron emission current density at 1100℃_(b)(brightness temperature)was 18.26 A/cm^(2),and the calculated work function was 1.97 eV.It has a low evaporation rate and the accelerated lifetime test predict a lifetime of over 160000 h.First-principles calculations showed that the charge transfer and dipole moment in the NiW-BaO system were both increased compared to the Ba dispenser cathode,thus improving the emission performance of the Ni-W mixed matrix cathode.展开更多
Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation...Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.展开更多
Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementat...Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.展开更多
Predicting the precise impacts of climate change on extreme winds remains challenging,yet strong storms are widely expected to occur more frequently in a warming climate.Wind barriers are commonly used on bridges to r...Predicting the precise impacts of climate change on extreme winds remains challenging,yet strong storms are widely expected to occur more frequently in a warming climate.Wind barriers are commonly used on bridges to reduce aerodynamic loads on trains through blocking effects.This study develops a novel wind barrier based on Tesla valves,which not only blocks incoming flow but also dissipates mechanical energy through fluid collision.To demonstrate this energy-dissipation capability,a Tesla plate is placed in a circular duct to examine its influence on pressure drop.Experimental tests and numerical simulations comparing a Tesla channel and a straight channel of equal porosity show that the Tesla configuration produces a substantially higher pressure drop.Validated simulations are then used to conduct a parametric study to optimize the design.By varying the channel ratio,diversion angle,number of dissipation units,and porosity,velocity–pressure-drop relationships for different Tesla plates are obtained.The results show that larger channel ratios,larger diversion angles,and more dissipation units,combined with lower porosity,all increase pressure drop and thus enhance energy dissipation.Finally,the aerodynamic coefficients of a high-speed train on a bridge deck equipped with a Tesla-type barrier are evaluated and compared with those for a traditional straight-channel barrier.The Tesla-type barrier reduces the train’s lateral force coefficient to only 15%–25%of that produced by the traditional barrier,and it generates an additional stabilizing force that further improves running safety.展开更多
Objective:To systematically review the current implementation status of nurses’non-pharmacological prescription authority and analyze the barriers encountered during its implementation in China,providing countermeasu...Objective:To systematically review the current implementation status of nurses’non-pharmacological prescription authority and analyze the barriers encountered during its implementation in China,providing countermeasures and references for promoting the standardized implementation of nurses’non-pharmacological prescription authority.Methods:A secondary analysis of literature was conducted to systematically search for domestic and international literature related to nurses’non-pharmacological prescription authority.Meta-analysis was performed on eligible literature to evaluate the implementation effects.Simultaneously,semi-structured in-depth interviews were conducted with healthcare workers,patients,and policymakers.Content analysis was used to organize the interview data and extract core issues and barriers.Results:A total of 46 international articles were included in the Meta-analysis,which revealed that the implementation of nurses’non-pharmacological prescription authority significantly improved patients’health management outcomes,enhanced healthcare service efficiency,and increased patient satisfaction.Conclusion:The implementation of nurses’non-pharmacological prescription authority has demonstrated significant positive effects.However,China faces multiple barriers in its advancement,necessitating efforts in optimizing policy systems,constructing collaborative models,strengthening professional skills training,and improving social awareness to guide the scientific and rational implementation of nurses’non-pharmacological prescription authority.展开更多
Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance...Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.展开更多
In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the e...In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.展开更多
Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a n...Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an imper...The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.展开更多
The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-...The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.展开更多
Railway noise barriers are an essential piece of infrastructure for reducing noise propagation.However,these barriers experience aerodynamic loads generated by high-speed trains,leading to dynamic effects that may com...Railway noise barriers are an essential piece of infrastructure for reducing noise propagation.However,these barriers experience aerodynamic loads generated by high-speed trains,leading to dynamic effects that may compromise their fatigue capacity.The most common structural design for railway noise barriers consists of vertical configurations of posts and panels.However,there have been few dynamic analyses of steel post/wood panel noise barriers under train-induced aerodynamic loads.This study used dynamic finite element analysis to assess the dynamic behavior of such noise barriers.Analysis of a 40-m-long noise barrier model and a triangular simplified load model,the latter of which effectively represented the detailed aerodynamic load,were first used to establish the model and input of the moving load during dynamic simulation.Then,the effects of different parameters on the dynamic response of the noise barrier were evaluated,including the damping ratio,the profile of the steel post,the span length of the panel,the barrier height,and the train speed.Gray relational analysis indicated that barrier height exhibited the highest correlations with the dynamic responses,followed by train speed,post profile,span length,and damping ratio.A reduction in the natural frequency and an increase in the train speed result in a higher peak response and more pronounced fluctuations between the nose and tail waves.The dynamic amplification factor(DAF)was found to be related to both the natural frequency and train speed.A model was proposed showing that the DAF significantly increases as the square of the natural frequency decreases and the cube of the train speed rises.展开更多
Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is cha...Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).展开更多
Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low pe...Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.展开更多
Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are tradition...Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.展开更多
The current global shortage of oil resources and the pollution problems caused by traditional barrier materials urgently require the search for new substitutes.Biodegradable bio-based barrier materials possess the cha...The current global shortage of oil resources and the pollution problems caused by traditional barrier materials urgently require the search for new substitutes.Biodegradable bio-based barrier materials possess the characteristics of being renewable,environmentally friendly,and having excellent barrier properties.They have become an important choice in fields such as food packaging,agricultural film covering,and medical protection.This review systematically analyzes the design and research of this type of material,classifying biobased and biodegradable barrier materials based on the sources of raw materials and synthesis pathways.It also provides a detailed introduction to the latest research progress of biobased and biodegradable barrier materials,discussing the synthesis methods and improvement measures of their barrier properties.Subsequently,it analyzes the related technologies for enhancing the barrier properties of biobased and biodegradable barrier materials,and finally looks forward to the directions that future research should focus on,promoting the transition of biobased and biodegradable barrier materials from the laboratory to industrial applications.展开更多
Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary e...Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.展开更多
基金supported by the National Natural Science Foundation of China,Nos. 32260196 (to JY), 81860646 (to ZY) and 31860274 (to JY)a grant from Yunnan Department of Science and Technology,Nos. 202101AT070251 (to JY), 202201AS070084 (to ZY), 202301AY070001-239 (to JY), 202101AZ070001-012, and 2019FI016 (to ZY)。
文摘Studies have shown that chitosan protects against neurodegenerative diseases. However, the precise mechanism remains poorly understood. In this study, we administered chitosan intragastrically to an MPTP-induced mouse model of Parkinson's disease and found that it effectively reduced dopamine neuron injury, neurotransmitter dopamine release, and motor symptoms. These neuroprotective effects of chitosan were related to bacterial metabolites, specifically shortchain fatty acids, and chitosan administration altered intestinal microbial diversity and decreased short-chain fatty acid production in the gut. Furthermore, chitosan effectively reduced damage to the intestinal barrier and the blood–brain barrier. Finally, we demonstrated that chitosan improved intestinal barrier function and alleviated inflammation in both the peripheral nervous system and the central nervous system by reducing acetate levels. Based on these findings, we suggest a molecular mechanism by which chitosan decreases inflammation through reducing acetate levels and repairing the intestinal and blood–brain barriers, thereby alleviating symptoms of Parkinson's disease.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金supported by the National Natural Science Foundation of China(Nos.U2341209 and 52130407).
文摘A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca aluminates)during the impregnation process of the matrix.After cathode activation,the surface Ba:O molar ratio is 0.88:1.00,much higher than the Ba dispenser cathode without Ni doping.The XPS results of the cathode surface showed that the metallic Ba appeared on the activated cathode surface,forming dipoles with oxygen,and effectively reducing the cathode surface work function.The pulse electron emission current density at 1100℃_(b)(brightness temperature)was 18.26 A/cm^(2),and the calculated work function was 1.97 eV.It has a low evaporation rate and the accelerated lifetime test predict a lifetime of over 160000 h.First-principles calculations showed that the charge transfer and dipole moment in the NiW-BaO system were both increased compared to the Ba dispenser cathode,thus improving the emission performance of the Ni-W mixed matrix cathode.
基金Leducq Trans-Atlantic Network of Excellence,Grant/Award Number:TNE-21CVD04Spanish Ministry of Science and Innovation,Grant/Award Number:PID2020-117765RB-I00 and PID2022-140616OB-I00+1 种基金Instituto de Salud Carlos Ⅲ,European Development Regional Fund,RICORS-ICTUS Grant/Award Number:RD21/0006/0001the FORTALECE program. Grant/Award Number:FORT23/00023。
文摘Stroke induces profound neuroinflammation and systemic immune dysregulation,including disturbances in gut homeostasis.Experimental evidence suggests that intestinal barrier permeability(IBP)and bacterial translocation(BT)critically influence stroke outcomes.However,biological variability among commonly used rodent substrains has received limited attention.In this pilot study,we compared poststroke immune responses in two Wistar rat substrains obtained from different suppliers:RccHan(Envigo)and RjHan(Janvier).Naive animals(n=4)and rats subjected to permanent cerebral ischemia(n=8 per substrain)were evaluated 72 h after middle cerebral artery occlusion and stratified according to the presence or absence of BT.Immune cell populations in blood and bone marrow were analyzed using flow cytometry,and leukocyte infiltration into ischemic brain tissue was quantified using immunohisto-chemistry.Differences were considered statistically significant when p<0.05.Both substrains developed significant infarcts and neurological deficits.RccHan rats exhibited larger infarct volumes and more extensive BT across multiple organs.In contrast,RjHan rats exhibited BT mainly confined to mesenteric lymph nodes but exhibited greater IBP.Although dissemination was broader in RccHan rats,overall bacterial burden was slightly lower compared with RjHan,and extraintestinal bacterial composition differed between groups.Particularly,RjHan rats exhibited stronger systemic and central immune activation,with significant alterations in lymphocyte and monocyte populations and enhanced granulocyte and T-cell infiltration within ischemic lesions.These findings demonstrate that substrain origin profoundly influences poststroke intestinal barrier integrity,bacterial dissemination,and immune responses considering substrain-related variability is essential to improve reproducibility and translational relevance in preclinical stroke research.
基金The National Natural Science Foundation of China(32302759,32372924)the CAST Youth Talent Support Project-Special Program for Doctoral Students(156-O-230-0000375-5)。
文摘Background Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids(SCFAs).Although SCFA supplementation has been proposed to mitigate these issues,the efficacy and optimal dosage of sodium isobutyrate remain unclear.Results We investigated the effects of sodium isobutyrate supplementation(500,1,000,2,000,and 4,000 mg/kg diet)on weaned piglets(Duroc×Landrace×Yorkshire,28 d of age;n=8).After a 28-d feeding trial,supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency,with maximal benefits observed at 1,000 mg/kg(P<0.0001).Additionally,500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein,organic matter,and crude fibre(P<0.05).Serum biochemical parameters were unaffected,although secretory immunoglobulin A(SIgA)levels significantly increased upon supplementation with 500–1,000 mg/kg(P<0.05).16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota.The 1,000 mg/kg group presented the most pronounced effect,with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations(P<0.05).Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg(P<0.05).Transcriptomic analyses indicated activation of protein digestion and absorption pathways,and PI3K-Akt signalling,marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression(P<0.05).Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers,including reduced serum D-lactate,diamine oxidase,and lipopolysaccharide levels,increased tight junction protein expression;activation of G protein-coupled receptors;and inhibition of TLR4/MyD88/NF-κB signalling(P<0.05),suggesting enhanced barrier function.Conclusions In conclusion,dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology,reduced serum permeability,increased expression of tight junction proteins,and enhanced immune function in weaned piglets,suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications.
基金supported by the National Natural Science Foundation of China(52475105)Special Fund for Science and Technology Innovation of Jiangsu Province(BE2022610)National Natural Science Foundation of China(U23A20661).
文摘Predicting the precise impacts of climate change on extreme winds remains challenging,yet strong storms are widely expected to occur more frequently in a warming climate.Wind barriers are commonly used on bridges to reduce aerodynamic loads on trains through blocking effects.This study develops a novel wind barrier based on Tesla valves,which not only blocks incoming flow but also dissipates mechanical energy through fluid collision.To demonstrate this energy-dissipation capability,a Tesla plate is placed in a circular duct to examine its influence on pressure drop.Experimental tests and numerical simulations comparing a Tesla channel and a straight channel of equal porosity show that the Tesla configuration produces a substantially higher pressure drop.Validated simulations are then used to conduct a parametric study to optimize the design.By varying the channel ratio,diversion angle,number of dissipation units,and porosity,velocity–pressure-drop relationships for different Tesla plates are obtained.The results show that larger channel ratios,larger diversion angles,and more dissipation units,combined with lower porosity,all increase pressure drop and thus enhance energy dissipation.Finally,the aerodynamic coefficients of a high-speed train on a bridge deck equipped with a Tesla-type barrier are evaluated and compared with those for a traditional straight-channel barrier.The Tesla-type barrier reduces the train’s lateral force coefficient to only 15%–25%of that produced by the traditional barrier,and it generates an additional stabilizing force that further improves running safety.
基金Scientific Research Fund Project of Yunnan Provincial Department of Education(Project No.:2024J2130)。
文摘Objective:To systematically review the current implementation status of nurses’non-pharmacological prescription authority and analyze the barriers encountered during its implementation in China,providing countermeasures and references for promoting the standardized implementation of nurses’non-pharmacological prescription authority.Methods:A secondary analysis of literature was conducted to systematically search for domestic and international literature related to nurses’non-pharmacological prescription authority.Meta-analysis was performed on eligible literature to evaluate the implementation effects.Simultaneously,semi-structured in-depth interviews were conducted with healthcare workers,patients,and policymakers.Content analysis was used to organize the interview data and extract core issues and barriers.Results:A total of 46 international articles were included in the Meta-analysis,which revealed that the implementation of nurses’non-pharmacological prescription authority significantly improved patients’health management outcomes,enhanced healthcare service efficiency,and increased patient satisfaction.Conclusion:The implementation of nurses’non-pharmacological prescription authority has demonstrated significant positive effects.However,China faces multiple barriers in its advancement,necessitating efforts in optimizing policy systems,constructing collaborative models,strengthening professional skills training,and improving social awareness to guide the scientific and rational implementation of nurses’non-pharmacological prescription authority.
基金supported by Ministry of Science and Technology China Brain Initiative Grant,No.2022ZD0204702(to ZY)the National Natural Science Foundation of China,No.82371357(to LC)+2 种基金Foundation for Military Medicine,No.16QNP085(to ZY)Navy Medical University Basic Medical College“Yi Zhang”Basic Medical Talent Development and Support Program,Nos.JCYZRC-D-022(to TC)and JCYZRC-D-024(to HD)Science and Technology Innovation Special Fund of Shanghai Baoshan District,No.2023-E-05(to YW).
文摘Macrophages in the brain barrier system include microglia in the brain parenchyma,border-associated macrophages at the brain’s borders,and recruited macrophages.They are responsible for neural development,maintenance of homeostasis,and orchestrating immune responses.With the rapid exploitation and development of new technologies,there is a deeper understanding of macrophages in the brain barrier system.Here we review the origin,development,important molecules,and functions of macrophages,mainly focusing on microglia and border-associated macrophages.We also highlight some advances in single-cell sequencing and significant cell markers.We anticipate that more advanced methods will emerge to study resident and recruited macrophages in the future,opening new horizons for neuroimmunology and related peripheral immune fields.
基金funded by the Fundamental Research Funds for the Central Universities (No.2242022R42012)。
文摘In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.
基金funded by Beijing Natural Science Foundation(6252001)Guangdong Basic and Applied Basic Research Foundation(2022A1515140021)Natural Science Foundation of China(31871772).
文摘Probiotics can regulate gut microbes to maintain human health.However,the sensitivity of probiotics to environmental conditions reduces their bioavailability.In contrast,the formation of probiotic biofilm provides a natural physical barrier against external interference.Our previous study established a dynamic culture system of the biofilm-state Bifidobacterium adolescentis Gr19(B-DC-B.adolescentis Gr19),forming higher density and more structurally stable biofilms,which enhanced its potential probiotic properties in vivo.Thus,the protective effect and mechanism of B-DC-B.adolescentis Gr19 on lipopolysaccharide(LPS)-induced intestinal barrier dysfunction were investigated in this study.The results showed that B-DC-B.adolescentis Gr19 not only had high resistance and adhesion activity,but also improved the intestinal barrier by increasing goblet cells and promoting the expression of tight junction(TJ)-related proteins.Moreover,B-DC-B.adolescentis Gr19 effectively attenuated intestinal barrier injury in Caco-2 cells by improving intestinal permeability and integrity.Remarkably,B-DC-B.adolescentis Gr19 enhanced expression of TJ proteins,restored localization of cytoskeleton and reduced intestinal inflammation by suppressing the Ras homolog family member A/Rho-associated coiled-coil-forming kinases/nuclear factor kappa B/myosin light chain kinase/myosin light chain(RhoA/ROCK/NF-κB/MLCK/MLC)pathway.Therefore,B-DC-B.adolescentis Gr19 plays a key role in mitigating LPS-induced intestinal barrier dysfunction.Overall,the present study provides a theoretical basis for ameliorating intestinal barrier dysfunction and developing novel functional foods by using biofilm-state probiotics under dynamic culture.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number K02NS110973 and R01NS126498(to MAP).
文摘The central nervous system(CNS)does not function in isolation-it engages in continuous molecular dialogue with the vascular and immune systems.Traditionally,the blood-brain barrier(BBB)was portrayed solely as an impermeable wall,safeguarding the CNS by excluding blood-derived molecules and circulating cells.However,this view has evolved.The BBB is now recognized as a dynamic interface that selectively regulates the exchange of signals,cells.
基金supported by the National Natural Science Foundation of China,No.82471411(to ZW and TD)the Key Research and DevelopmentProgram of Shaanxi Province,No.2023-ZDLSF-12(to TD).
文摘The blood-spinal cord barrier is crucial for preserving homeostasis of the central nervous system.After spinal cord injury,autophagic flux within endothelial cells is disrupted,compromising the integrity of the blood-spinal cord barrier.This disruption facilitates extensive infiltration of inflammatory cells,resulting in exacerbated neuroinflammatory responses,neuronal death,and impaired neuronal regeneration.Previous research has demonstrated that photobiomodulation promotes the regeneration of damaged nerves following spinal cord injury by inhibiting the recruitment of inflammatory cells to the injured site and restoring neuronal mitochondrial function.However,the precise mechanisms by which photobiomodulation regulates neuroinflammation remain incompletely elucidated.In this study,we established a mouse model of spinal cord injury and assessed the effects of photobiomodulation treatment.Photobiomodulation effectively cleared damaged mitochondria from endothelial cells in mice,promoting recovery of hindlimb motor function.Using microvascular endothelial bEnd.3 cells subjected to oxygen-glucose deprivation,we found that the effects of photobiomodulation were mediated through activation of the PINK1/Parkin pathway.Additionally,photobiomodulation reduced mitochondrial oxidative stress levels and increased the expression of tight junction proteins within the blood-spinal cord barrier.Our findings suggest that photobiomodulation activates mitochondrial autophagy in endothelial cells through the PINK1/Parkin pathway,thereby promoting repair of the blood-spinal cord barrier following spinal cord injury.
基金financially supported by the Swedish Transport Administration(Trafikverket)through the“Excellence Area 4”and FOI-BBT program(Grant Nos.BBT-2019-022 and BBT-TRV 2024/132497).
文摘Railway noise barriers are an essential piece of infrastructure for reducing noise propagation.However,these barriers experience aerodynamic loads generated by high-speed trains,leading to dynamic effects that may compromise their fatigue capacity.The most common structural design for railway noise barriers consists of vertical configurations of posts and panels.However,there have been few dynamic analyses of steel post/wood panel noise barriers under train-induced aerodynamic loads.This study used dynamic finite element analysis to assess the dynamic behavior of such noise barriers.Analysis of a 40-m-long noise barrier model and a triangular simplified load model,the latter of which effectively represented the detailed aerodynamic load,were first used to establish the model and input of the moving load during dynamic simulation.Then,the effects of different parameters on the dynamic response of the noise barrier were evaluated,including the damping ratio,the profile of the steel post,the span length of the panel,the barrier height,and the train speed.Gray relational analysis indicated that barrier height exhibited the highest correlations with the dynamic responses,followed by train speed,post profile,span length,and damping ratio.A reduction in the natural frequency and an increase in the train speed result in a higher peak response and more pronounced fluctuations between the nose and tail waves.The dynamic amplification factor(DAF)was found to be related to both the natural frequency and train speed.A model was proposed showing that the DAF significantly increases as the square of the natural frequency decreases and the cube of the train speed rises.
文摘Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).
基金supported by the NIH RF1 grant NS119477 jointly funded by NINDS and NIA(to RM).
文摘Cells of the central nervous system(CNS)are privileged in lying behind the blood-brain barrier(BBB).Unlike blood vessels in other organs,CNS blood vessels are unique in displaying high electrical resistance and low permeability.With this unique structure and function,the BBB prevents potentially harmful blood components such as serum proteins,inflammatory cytokines,and inflammatory leukocytes from entering the hallowed space of the CNS and wreaking havoc.In addition to these“tightness”properties,the BBB has an array of specialized transporters designed to import essential nutrients.
基金supported by the Key Scientific Research Project of Hubei Provincial Department of Education (No.D20232001)。
文摘Ulcerative colitis (UC) is a persistent,diffuse intestinal inflammation and ranks among the most challenging chronic diseases worldwide.Atractylodes lancea (Thunb.) DC.and Atractylodis macrocephala Koidz.are traditional Chinese medicines (TCMs) with a long history of clinical application,particularly for gastrointestinal disorders.Both Atractylodis Rhizoma (AR)and Atractylodis Macrocephala Rhizoma (AM) have shown significant efficacy in managing UC;however,the underlying mechanism by which the AR-AM herbal pair promotes intestinal mucosal healing remains poorly understood.The therapeutic effects of the ethanolic extract of AR-AM (EEAR-AM) were evaluated in a murine UC model induced by dextran sodium sulfate(DSS).A network pharmacology approach was employed to explore the anti-UC properties of EEAR-AM,including identification of active compounds,prediction of potential targets,and construction of a protein-protein interaction (PPI) network.Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to preliminarily elucidate the mechanisms of EEAR-AM in UC treatment.Finally,the proposed molecular mechanisms were validated in both DSS-induced UC mice and Caco-2 cells.In vivo results demonstrated that EEAR-AM significantly attenuated DSS-induced weight loss,reduced colon shortening,lowered the disease activity index (DAI) score,and modulated the spleen coefficient.Moreover,EEAR-AM improved colonic tissue architecture,reduced inflammatory infiltration,restored goblet cell density,enhanced mucin MUC2 expression,and elevated levels of tight junction (TJ) proteins.Additionally,EEAR-AM suppressed the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9.Network pharmacology analyses indicated that EEAR-AM may ameliorate intestinal mucosal dysfunction through modulation of the exchange protein directly activated by cAMP 1 (Epac1)/Ras-associated protein 1 (Rap1) pathway and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathways.These actions potentially enhance cellular barrier integrity and reduce the release of inflammatory mediators.Western blotting results confirmed that EEAR-AM activated the Epac1/Rap1 pathway while downregulating the PI3K/AKT pathway in both DSS-induced UC mice and Caco-2cells,consistent with predictions from network pharmacology.This study represents the first evidence that the EEAR-AM herbal pair improves intestinal mucosal barrier function in UC,with therapeutic effects likely mediated by activation of the Epac1/Rap1 pathway and inhibition of the PI3K/AKT pathway.
基金supported by the Science and Technology Research Project of Henan Province(222102230031)Key Scientific Research Projects of Colleges and Universities in Henan Province(23A430018)Natural Science Foundation of Henan(252300420267).
文摘The current global shortage of oil resources and the pollution problems caused by traditional barrier materials urgently require the search for new substitutes.Biodegradable bio-based barrier materials possess the characteristics of being renewable,environmentally friendly,and having excellent barrier properties.They have become an important choice in fields such as food packaging,agricultural film covering,and medical protection.This review systematically analyzes the design and research of this type of material,classifying biobased and biodegradable barrier materials based on the sources of raw materials and synthesis pathways.It also provides a detailed introduction to the latest research progress of biobased and biodegradable barrier materials,discussing the synthesis methods and improvement measures of their barrier properties.Subsequently,it analyzes the related technologies for enhancing the barrier properties of biobased and biodegradable barrier materials,and finally looks forward to the directions that future research should focus on,promoting the transition of biobased and biodegradable barrier materials from the laboratory to industrial applications.
基金supported by the National Key R&D Program of China(2023YFA1800100and 2024YFF1206600)the National Natural Science Foundation of China(32100664)the Basic and Applied Basic Research Foundation of Guangdong Province(2024B1515040019 and 2022A1515012042).
文摘Inflammatory bowel disease(IBD)comprises a heterogeneous group of chronic inflammatory conditions of the intestine.Current therapeutic strategies primarily focus on maintaining remission and mitigating the secondary effects rather than reversing its pathogenic mechanisms(Jeong et al.,2019).The pathogenesis of IBD involves intestinal barrier dysfunction,tissue damage,and dysregulated innate and adaptive immune responses(de Souza et al.,2017).Elevated neutrophil activity has been reported in IBD(Danne et al.,2024),yet the precise roles and mechanisms of neutrophils in disease progression remain to be elucidated.
