Nowadays,solid-state lighting sources based on white lightemitting diodes(LEDs)are extensively replacing the traditional illumination devices(incandescent and fluorescent lamps)due to their unique and appealing proper...Nowadays,solid-state lighting sources based on white lightemitting diodes(LEDs)are extensively replacing the traditional illumination devices(incandescent and fluorescent lamps)due to their unique and appealing properties,such as high efficiency,high brightness,long working lifetime,small size,fast response time and eco-friendliness[1-4].Because of this,white LEDs have permeated deeply into many important sectors,including indoor and outdoor lightings,signals,displays and therapeutic applications.In order to make sure that white LEDs can provide artificial lighting source with good color quality and high vision performance,there are several important figures of merit that are used to characterize white LEDs:color rendering index(CRI),correlated color temperature,luminous efficacy of radiation and luminous efficacy.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
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
White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fung...White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin(including the muzzle)of hibernating bats.Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS.However,the role of G.destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking.The debate is fuelled,in part,by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction.Additionally,the recent discovery that G.destructans commonly colonizes the skin of bats of Europe,where no unusual bat mortality events have been reported,has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS.展开更多
Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably n...Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably normal gaseous stars whose debris falls onto the BH,sustaining the flares over years.White dwarfs(WDs),which are the most prevalent compact stars and a million times denser-and therefore tougher-than gaseous stars,can only be disrupted by intermediate-mass black holes(IMBHs)of 10^(2)–10^(5) solar masses.WD-TDEs are considered to generate more powerful and short-lived flares,but their evidence has been lacking.Here we report observations of a fast and luminous X-ray transient EP250702a detected by Einstein Probe.Its one-day-long X-ray peak as luminous as 10^(47−49) erg s^(−1) showed strong recurrent flares with hard spectra extending to several tens of MeV gamma-rays,as detected by Fermi/GBM and Konus-Wind,indicating relativistic jet emission.The jet's X-rays dropped sharply from 3×10^(49) erg s^(−1) to around 1044 erg s^(−1) within 20 days(10 days in the source rest frame).These characteristics are inconsistent with any previously known transient phenomena.We suggest that this fast-evolving event over the unprecedentedly short timescale arises likely from disruption of a WD by an IMBH.At late times,a soft component progressively dominates the X-ray spectrum,reaching a luminosity as high as 1044 erg s^(−1),which is consistent with being extreme super-Eddington emission from an accretion disk expected to form in an IMBH-WD TDE.WD-TDEs open a new window for investigating the elusive IMBHs and their surrounding stellar environments,and they are prime sources of gravitational waves in the band of space-based interferometers.展开更多
Blue calico,which dates back more than 800 years,is a traditional blue-and-white-printed fabric in Nantong,a city in East China's Jiangsu Province.Blue calico is renowned for its simple,yet elegant,patterns,the st...Blue calico,which dates back more than 800 years,is a traditional blue-and-white-printed fabric in Nantong,a city in East China's Jiangsu Province.Blue calico is renowned for its simple,yet elegant,patterns,the striking beauty of its blue-and-white harmony and,especially,for its printing and dyeing being performed by hand.展开更多
Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury respons...Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.展开更多
White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet li...White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.展开更多
The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions f...The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions for investigating their interactions.Early efforts to parcellate the mammalian brain,using histological cytoarchitecture and myeloarchitecture,as well as recent in vivo magnetic resonance imaging(MRl)[2,3],have primarily involved cortical areas,subcortical structures,and cerebellar nuclei.Human brain parcellations primarily focus on grey matter(GM),which purposefully excludes white matter(WM),hindering the development of next-generation brain atlases.展开更多
The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cel...The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.展开更多
Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesio...Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.展开更多
Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle...Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.展开更多
As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming cle...As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).展开更多
This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the...This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the effects.A total of 288 Hy-Line Brown layers were randomly assigned into 3 treatments and respectively offered soybean meal(SBM)-based diet,LCSM-based diet,and LCSM-based diet supplemented with 0.435%L-Ser.Dietary Ser supplementation reversed the decrease in quality indices of albumen,including the proportion of thick albumen(P<0.05),thick-to-thin ratio(P<0.05),albumen height(P<0.05),Haugh unit(P<0.05),and apparent viscosity that were caused by LCSM intake.Also,dietary Ser supplementation mitigated the LCSM-induced reduction in ovomucin content of the albumen(P<0.05).FT-IR analysis of ovomucin revealed differences in second derivative spectra at 1,200-800 cm^(-1) between birds received SBM-and LCSM-based diets,meanwhile,the α-helix of ovomucin was decreased by LCSM but increased by Ser addition(P<0.05).Furthermore,Ser addition up-regulated the mRNA expression of β-ovomucin in magnum mucosa at 2 and 7.5 h post-oviposition(P<0.05).Ser mitigated the LCSMinduced impairment of magnum epithelium,increased goblet cell counts(P<0.05),and up-regulated the expression of occludin,mucin 2,and the relevant glycosyltransferases for O-glycosylation in magnum mucosa(P<0.05).Conclusively,the alleviating effect of Ser on declining albumen quality due to dietary LCSM,could be explained by the efficacy of Ser in regulating ovomucin synthesis.This regulation occurred at the levels of transcription and posttranscriptional O-glycosylation modification ofβ-ovomucin,while positive effect on magnum morphology and barrier function could also in part account for the ovomucin content.This would provide a promising research direction on the adoption of nutritional interventions for manipulation of egg white quality from perspectives of albumen protein synthesis.展开更多
Inorganic lead-free double perovskites have the advantages of low toxicity,broadband emission,and good stability,which make them promising luminescent materials for lighting applications.However,due to the limited reg...Inorganic lead-free double perovskites have the advantages of low toxicity,broadband emission,and good stability,which make them promising luminescent materials for lighting applications.However,due to the limited regulation of their self-trapped exciton emission,it is still greatly challenging to achieve white light emitting from a single double perovskite host.Herein,efficient and tunable white light is realized in Cs_(2)NalnCl_(6)∶Sb^(3+),Tb^(3+),Sm^(3+)double perovskite by controlling the ratios of the doped three ions with blue,green,and red emissions,respectively.The steady-state and transient fluorescence spectra of singly-and doubly-doped double perovskites reveal the existence of multiple energy transfer channels in the triply-doped phosphors,including from Sb^(3+)to Tb^(3+),Sb^(3+)to Sm^(3+),and Tb^(3+)to Sm^(3+).Benefiting from these channels,the color coordinates of the triply-doped phosphors can cross the whole white light area of the CIE chromaticity diagram by adjusting the ratios of the three dopants,and the maximum internal quantum yield of the white light phosphors is 66.61%.The white emission phosphors show the characteristic of being independent of excitation wavelength within 310-360 nm.Furthermore,the emission intensity at 430 K of the white light phosphor Cs_(2)NalnCl_(6)∶0.01Sb^(3+),0.65Tb^(3+),0.20Sm^(3+)remains 50% of that at room temperature.A WLED device fabricated with the phosphor and a 365 nm LED chip exhibits a high color rendering index of 90.9,correlated color temperature of 5469 K,and CIE coordinates of(0.333 and 0.328).The results indicate that the as-prepared double perovskite materials are promising candidates in the solid-state lighting field.展开更多
Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
文摘Nowadays,solid-state lighting sources based on white lightemitting diodes(LEDs)are extensively replacing the traditional illumination devices(incandescent and fluorescent lamps)due to their unique and appealing properties,such as high efficiency,high brightness,long working lifetime,small size,fast response time and eco-friendliness[1-4].Because of this,white LEDs have permeated deeply into many important sectors,including indoor and outdoor lightings,signals,displays and therapeutic applications.In order to make sure that white LEDs can provide artificial lighting source with good color quality and high vision performance,there are several important figures of merit that are used to characterize white LEDs:color rendering index(CRI),correlated color temperature,luminous efficacy of radiation and luminous efficacy.
基金supported by the Guangdong Basic and Applied Basic Research Foundation,No.2023A1515030045(to HS)Presidential Foundation of Zhujiang Hospital of Southern Medical University,No.yzjj2022ms4(to HS)。
文摘Intracerebral hemorrhage is the most dangerous subtype of stroke,characterized by high mortality and morbidity rates,and frequently leads to significant secondary white matter injury.In recent decades,studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota–brain axis.This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.The NACHT,LRR,and pyrin domain-containing protein 3(NLRP3)inflammasome plays a crucial role in this context.This review summarizes the dysbiosis of gut microbiota following intracerebral hemorrhage and explores the mechanisms by which this imbalance may promote the activation of the NLRP3 inflammasome.These mechanisms include metabolic pathways(involving short-chain fatty acids,lipopolysaccharides,lactic acid,bile acids,trimethylamine-N-oxide,and tryptophan),neural pathways(such as the vagus nerve and sympathetic nerve),and immune pathways(involving microglia and T cells).We then discuss the relationship between the activated NLRP3 inflammasome and secondary white matter injury after intracerebral hemorrhage.The activation of the NLRP3 inflammasome can exacerbate secondary white matter injury by disrupting the blood–brain barrier,inducing neuroinflammation,and interfering with nerve regeneration.Finally,we outline potential treatment strategies for intracerebral hemorrhage and its secondary white matter injury.Our review highlights the critical role of the gut microbiota–brain axis and the NLRP3 inflammasome in white matter injury following intracerebral hemorrhage,paving the way for exploring potential therapeutic approaches.
基金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.
文摘White-nose syndrome(WNS)has caused recent catastrophic declines among multiple species of bats in eastern North America.The disease's name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin(including the muzzle)of hibernating bats.Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS.However,the role of G.destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking.The debate is fuelled,in part,by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction.Additionally,the recent discovery that G.destructans commonly colonizes the skin of bats of Europe,where no unusual bat mortality events have been reported,has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS.
文摘Stars getting close enough to black holes(BHs)can be torn apart by strong tidal forces,producing electromagnetic flares.To date,more than 100 tidal disruption events(TDEs)have been observed,each involving invariably normal gaseous stars whose debris falls onto the BH,sustaining the flares over years.White dwarfs(WDs),which are the most prevalent compact stars and a million times denser-and therefore tougher-than gaseous stars,can only be disrupted by intermediate-mass black holes(IMBHs)of 10^(2)–10^(5) solar masses.WD-TDEs are considered to generate more powerful and short-lived flares,but their evidence has been lacking.Here we report observations of a fast and luminous X-ray transient EP250702a detected by Einstein Probe.Its one-day-long X-ray peak as luminous as 10^(47−49) erg s^(−1) showed strong recurrent flares with hard spectra extending to several tens of MeV gamma-rays,as detected by Fermi/GBM and Konus-Wind,indicating relativistic jet emission.The jet's X-rays dropped sharply from 3×10^(49) erg s^(−1) to around 1044 erg s^(−1) within 20 days(10 days in the source rest frame).These characteristics are inconsistent with any previously known transient phenomena.We suggest that this fast-evolving event over the unprecedentedly short timescale arises likely from disruption of a WD by an IMBH.At late times,a soft component progressively dominates the X-ray spectrum,reaching a luminosity as high as 1044 erg s^(−1),which is consistent with being extreme super-Eddington emission from an accretion disk expected to form in an IMBH-WD TDE.WD-TDEs open a new window for investigating the elusive IMBHs and their surrounding stellar environments,and they are prime sources of gravitational waves in the band of space-based interferometers.
文摘Blue calico,which dates back more than 800 years,is a traditional blue-and-white-printed fabric in Nantong,a city in East China's Jiangsu Province.Blue calico is renowned for its simple,yet elegant,patterns,the striking beauty of its blue-and-white harmony and,especially,for its printing and dyeing being performed by hand.
基金supported by the National Key Research and Development Program of China,No.2022YFC2704801(to CZhu)the National Natural Science Foundation of China,Nos.U21A20347(to CZhu),82203969(to YX),82371472(to XZ)+3 种基金Health Commission of Henan Province,Nos.SBGJ202303039(to XZ),SBGJ202301009(to CZhu),YQRC2024018(to XZ),YQRC2024019(to YX)Henan Science and Technology Department,Nos.242102311054(to XZ),241111521300(to CZhu),GZS2023003(to XW)Swedish Research Council,Nos.2022-01019(to CZhu),2021-01950(to XW)Swedish Governmental Grants to Scientists Working in Healthcare,Nos.ALFGBG-1005209(to CZhu),ALFBG-1005257(to XW),ALFGBG-965197(to CZhu).
文摘Germinal matrix hemorrhage in preterm neonates often leads to white matter injury,contributing to long-term neurodevelopmental impairments.As resident brain immune cells,microglia play a complex role in injury response,including inflammation and repair.Although colony-stimulating factor 1 receptor inhibitors such as PLX5622 enable the selective depletion of microglia,their therapeutic potential in neonatal germinal matrix hemorrhage remains underexplored.Here,we used a collagenase-induced germinal matrix hemorrhage model in postnatal day 5 mice,and intraperitoneally administered PLX562272 hours post-germinal matrix hemorrhage to achieve targeted,temporary microglial depletion during the peak injury response.We then assessed the effects of this delayed intervention on oligodendrocyte lineage cell maturation,white matter integrity,and neurobehavioral outcomes.Additionally,RNA sequencing data from a germinal matrix hemorrhage rat model were analyzed using weighted gene co-expression network analysis to identify the critical phases for interventions.RNA sequencing data revealed a critical period in which key synaptic functions declined while immune responses intensified post-germinal matrix hemorrhage,thus pinpointing the critical response phases for potential interventions.Delayed PLX5622 treatment effectively depleted activated microglia,protecting against white matter injury and enhancing oligodendrocyte lineage cell maturation and myelination in subcortical white matter regions.Moreover,magnetic resonance imaging analysis revealed reduced brain lesion volumes in treated mice.Behaviorally,PLX5622-treated mice exhibited significant improvements in motor coordination and reduced hyperactivity compared with vehicle-treated germinal matrix hemorrhage model mice.These findings suggest that,when timed to avoid interference with initial oligodendrocyte lineage cell proliferation,targeted microglial depletion with PLX5622 significantly mitigates white matter damage and improves neurobehavioral outcomes in neonatal germinal matrix hemorrhage.The present study highlights the therapeutic potential of selectively modulating microglial reactivity to support neurodevelopment in preterm infants with brain injury.
基金supported by the National Natural Science Foundation of China,Nos.82172546(to XH),82172547(to ZZ)the Natural ScienceFoundation of Guangdong Province,Nos.2023A1515012695(to XH),2024A1515010419(to ZZ)the Science and Technology Plan Project of Guangzhou,Nos.202201020413(to ZZ),2023A04J1099(to ZZ).
文摘White matter injury is a key factor impacting stroke recovery.Physical exercise can promote white matter repair.Immune cells,especially regulatory T(Treg)cells,contribute to strengthening white matter integrity,yet little is known about the underlying mechanism.To examine this,we established a transient middle cerebral artery occlusion male mouse model.We found that physical exercise elevated brain Treg cells,thereby enhancing neurological recovery,reducing neuroinflammation,promoting myelin debris clearance,and accelerating white matter repair.Depletion of Treg cells caused a decrease in these positive effects of physical exercise.Mechanistically,the rise in osteopontin triggered by physical exercise is dampened when Treg cells are depleted.In addition,Treg-conditioned medium reduced oxygen-glucose deprivation/re-oxygenation-induced microglial inflammation and enhanced phagocytosis,which could be blocked by osteopontin antibodies.Importantly,although Treg infusion could mimic the protective effects of physical exercise,osteopontin blockade partially countered the effects of physical exercise and Treg cells.Finally,our sequencing data revealed a marked upregulation of C-X-C motif chemokine ligand 12(CXCL12)mRNA expression subsequent to physical exercise,which was confirmed at the protein level.Stimulation of Treg cells with stroke brain lysates increased C-X-C motif chemokine receptor 4(CXCR4)expression,indicating a potential role for the CXCL12-CXCR4 axis in recruiting Treg cells.These findings suggest that physical exercise promotes white matter repair after ischemic stroke by Treg cells.
基金supported by the National Natural Science Foundation of China(62473082,82202250,82121003,62036003,and 62333003)the Fundamental Research Funds for the Central Universities(ZYGX2022YGRH008 and ZYGX2024XJ054)the Medical-Engineering Cooperation Funds from the University of Electronic Science and Technology of China(ZYGX2021YGLH201).
文摘The brain atlas,or parcellation-delineating spatial partitions,organizes the brain's structure and function[1].The spatial arrangements of highly heterogeneous landscapes represent specialized functional regions for investigating their interactions.Early efforts to parcellate the mammalian brain,using histological cytoarchitecture and myeloarchitecture,as well as recent in vivo magnetic resonance imaging(MRl)[2,3],have primarily involved cortical areas,subcortical structures,and cerebellar nuclei.Human brain parcellations primarily focus on grey matter(GM),which purposefully excludes white matter(WM),hindering the development of next-generation brain atlases.
基金supported by Grant 3195 from Paralyzed Veterans of America Research Foundation (to BRK)
文摘The inter-related pathological cascades following a traumatic spinal cord injury(tSCI)disrupt multiple cell types and physiological processes.Subsequently,motor and sensory functions are disrupted by breakdowns in cellular interactions and circuitry.Therapeutic interventions seek to modify some aspects of the injury course to enable the re-establishment of functional circuitry.Interventions often target one cell type(e.g.,promoting neuroprotection or neural regeneration)or one process(e.g.,modulating inflammation,affecting astrocytic,microglial,or macrophage responses.)Many axons in the spinal cord are myelinated,and after injury oligodendrocyte death causes demyelination.Promoting remyelination of spared or new axons to re-establish conduction seems a logical choice as a therapeutic target.
基金supported by the Qingdao Medical Health Research Project,No.2023-WJZD212(to XX)。
文摘Recent evidence suggests that ferroptosis plays a crucial role in the occurrence and development of white matter lesions.However,the mechanisms and regulatory pathways involved in ferroptosis within white matter lesions remain unclear.Long non-coding RNAs(lnc RNAs)have been shown to influence the occurrence and development of these lesions.We previously identified lnc_011797 as a biomarker of white matter lesions by high-throughput sequencing.To investigate the mechanism by which lnc_011797 regulates white matter lesions,we established subjected human umbilical vein endothelial cells to oxygenglucose deprivation to simulate conditions associated with white matter lesions.The cells were transfected with lnc_011797 overexpression or knockdown lentiviruses.Our findings indicate that lnc_011797 promoted ferroptosis in these cells,leading to the formation of white matter lesions.Furthermore,lnc_011797 functioned as a competitive endogenous RNA(ce RNA)for mi R-193b-3p,thereby regulating the expression of WNK1 and its downstream ferroptosis-related proteins.To validate the role of lnc_011797 in vivo,we established a mouse model of white matter lesions through bilateral common carotid artery stenosis.The results from this model confirmed that lnc_011797 regulates ferroptosis via WNK1 and promotes the development of white matter lesions.These findings clarify the mechanism by which lnc RNAs regulate white matter lesions,providing a new target for the diagnosis and treatment of white matter lesions.
基金supported by the National Natural Science Foundation Joint Fund,No.U22A20309(to PY)the Natural Science Foundation of LiaoningProvince,No.2023-MS-07(to HuL)the Unveiling Key Scientific and Technological Projects of Liaoning Province,No.2021JH1/10400051(to HuL).
文摘Some patients with systemic lupus erythematosus experience neuropsychiatric symptoms.Although magnetic resonance imaging can detect abnormal signals in the white matter of the brain,conventional methods often struggle to accurately capture microstructural changes.Various diffusion models have been used to study white matter in systemic lupus erythematosus;however,comparative analyses of their sensitivity and specificity for detecting microstructural changes remain insufficient.To address this,our team designed a diagnostic trial that used multimodal diffusion imaging techniques to observe white matter microstructural changes in patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with an aim to identify key diagnostic biomarkers for these patients.Patients with active lupus who received treatment at the Department of Rheumatology and Immunology,The First Affiliated Hospital of China Medical University,from September 2023 to March 2024 were recruited.According to the standards of the American College of Rheumatology,patients with systemic lupus erythematosus who had neuropsychiatric symptoms were assigned to the systemic lupus erythematosus group,whereas those without neuropsychiatric symptoms were assigned to the non-systemic lupus erythematosus group.Additionally,healthy volunteers matched by region,sex,and age were recruited as controls.All three groups underwent the same diffusion magnetic resonance imaging examination protocol to compare differences in diffusion parameters.Advanced diffusion imaging models were able to sensitively detect microstructural changes in the white matter fibers of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,with specific diffusion parameters showing significant abnormalities in key brain regions.In the left superior longitudinal fasciculus subregion and the right thalamic radiations of patients with systemic lupus erythematosus who had neuropsychiatric symptoms,we also identified abnormal diffusion characteristics that were clearly correlated with disease activity,suggesting that microstructural changes in these areas may reflect the dynamic process of neuroinflammatory damage.The present study addresses critical challenges in the diagnosis of systemic lupus erythematosus by identifying specific white matter imaging biomarkers and elucidating the association between microstructural damage and clinical manifestations.The main contributions of our study include:1)establishing axial regression probability parameters from mean apparent propagator magnetic resonance imaging as sensitive biomarkers for systemic lupus erythematosus,particularly in the third subregion of the left superior longitudinal fasciculus;2)demonstrating that multimodal diffusion imaging may be superior to conventional diffusion tensor imaging for detecting white matter microstructural abnormalities in patients with systemic lupus erythematosus;and 3)integrating tract-based spatial statistics with clinically relevant analyses to link imaging findings to pathological mechanisms.
文摘As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).
基金financially supported by the National Natural Science Foundation of China(32072774)the China Postdoctoral Science Foundation(2023M733822)+2 种基金the Beijing Innovation Consortium of Agriculture Research System(BAIC04),Chinathe earmarked fund for CARS National System for Layer Production Technology,China(CARS-40)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Sciences。
文摘This study examined the effect of dietary serine(Ser)on egg white quality,ovomucin content of laying hens fed low-gossypol cottonseed meal(LCSM)-based diet and sought to explore the regulatory mechanism underlying the effects.A total of 288 Hy-Line Brown layers were randomly assigned into 3 treatments and respectively offered soybean meal(SBM)-based diet,LCSM-based diet,and LCSM-based diet supplemented with 0.435%L-Ser.Dietary Ser supplementation reversed the decrease in quality indices of albumen,including the proportion of thick albumen(P<0.05),thick-to-thin ratio(P<0.05),albumen height(P<0.05),Haugh unit(P<0.05),and apparent viscosity that were caused by LCSM intake.Also,dietary Ser supplementation mitigated the LCSM-induced reduction in ovomucin content of the albumen(P<0.05).FT-IR analysis of ovomucin revealed differences in second derivative spectra at 1,200-800 cm^(-1) between birds received SBM-and LCSM-based diets,meanwhile,the α-helix of ovomucin was decreased by LCSM but increased by Ser addition(P<0.05).Furthermore,Ser addition up-regulated the mRNA expression of β-ovomucin in magnum mucosa at 2 and 7.5 h post-oviposition(P<0.05).Ser mitigated the LCSMinduced impairment of magnum epithelium,increased goblet cell counts(P<0.05),and up-regulated the expression of occludin,mucin 2,and the relevant glycosyltransferases for O-glycosylation in magnum mucosa(P<0.05).Conclusively,the alleviating effect of Ser on declining albumen quality due to dietary LCSM,could be explained by the efficacy of Ser in regulating ovomucin synthesis.This regulation occurred at the levels of transcription and posttranscriptional O-glycosylation modification ofβ-ovomucin,while positive effect on magnum morphology and barrier function could also in part account for the ovomucin content.This would provide a promising research direction on the adoption of nutritional interventions for manipulation of egg white quality from perspectives of albumen protein synthesis.
基金supported by grants from the National Natural Science Foundation of China(NSFC Nos.51972347 and 21771195).
文摘Inorganic lead-free double perovskites have the advantages of low toxicity,broadband emission,and good stability,which make them promising luminescent materials for lighting applications.However,due to the limited regulation of their self-trapped exciton emission,it is still greatly challenging to achieve white light emitting from a single double perovskite host.Herein,efficient and tunable white light is realized in Cs_(2)NalnCl_(6)∶Sb^(3+),Tb^(3+),Sm^(3+)double perovskite by controlling the ratios of the doped three ions with blue,green,and red emissions,respectively.The steady-state and transient fluorescence spectra of singly-and doubly-doped double perovskites reveal the existence of multiple energy transfer channels in the triply-doped phosphors,including from Sb^(3+)to Tb^(3+),Sb^(3+)to Sm^(3+),and Tb^(3+)to Sm^(3+).Benefiting from these channels,the color coordinates of the triply-doped phosphors can cross the whole white light area of the CIE chromaticity diagram by adjusting the ratios of the three dopants,and the maximum internal quantum yield of the white light phosphors is 66.61%.The white emission phosphors show the characteristic of being independent of excitation wavelength within 310-360 nm.Furthermore,the emission intensity at 430 K of the white light phosphor Cs_(2)NalnCl_(6)∶0.01Sb^(3+),0.65Tb^(3+),0.20Sm^(3+)remains 50% of that at room temperature.A WLED device fabricated with the phosphor and a 365 nm LED chip exhibits a high color rendering index of 90.9,correlated color temperature of 5469 K,and CIE coordinates of(0.333 and 0.328).The results indicate that the as-prepared double perovskite materials are promising candidates in the solid-state lighting field.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
