A new detector array with a large solid angle coverage for the coincidence measurement of charged fragments was developed to study the breakup reaction mechanisms of weakly bound nuclear systems at energies around the...A new detector array with a large solid angle coverage for the coincidence measurement of charged fragments was developed to study the breakup reaction mechanisms of weakly bound nuclear systems at energies around the Coulomb barrier.The array has been used to explore the breakup reaction mechanisms of^(6,7)Li+^(209)Bi systems at E_(beam)=30,40,47 MeV,showing good performance in particle identification and complete kinematic measurements.Based on this,different breakup modes and breakup components were clearly distinguished,and some new breakup modes were discovered,such as^(7)Li→α+t breakup mode in6Li+209Bi system and^(7)Li→^(6)He+p breakup mode in^(7)Li+^(209)Bi system.This array can also be used to explore other breakup reaction mechanisms induced by weakly bound nuclei.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Background:This study aims to investigate the underlying mechanisms between parental marital conflict and adolescent short video dependence by constructing a chain mediation model,focusing on the mediating roles of ex...Background:This study aims to investigate the underlying mechanisms between parental marital conflict and adolescent short video dependence by constructing a chain mediation model,focusing on the mediating roles of experiential avoidance and emotional disturbance(anxiety,depression,and stress).Methods:Conducted in January 2025,the research recruited 4125 adolescents from multiple Chinese provinces through convenience sampling;after data cleaning,3957 valid participants(1959 males,1998 females)were included.Using a cross-sectional design,measures included parental marital conflict,experiential avoidance,anxiety,depression,stress,and short video dependence.Results:Pearson correlation analysis revealed significant positive correlations among all variables.Mediation analysis using the SPSS PROCESS macro showed that parental marital conflict directly predicted short video dependence(β=0.269,p<0.001),and also significantly predicted experiential avoidance(β=0.519,p<0.001),anxiety(β=0.072,p<0.001),depression(β=0.067,p<0.001),and stress(β=0.048,p<0.05).Experiential avoidance further predicted anxiety(β=0.521,p<0.001),depression(β=0.489,p<0.001),stress(β=0.408,p<0.001),and short video dependence(β=0.244,p<0.001).While both anxiety(β=0.050,p<0.05)and depression(β=0.116,p<0.001)positively predicted short video dependence,stress did not(β=0.019,p=0.257).Overall,experiential avoidance,anxiety,depression,and stress significantly mediated the relationship between parental marital conflict and short video dependence.Conclusion:These findings confirm that parental marital conflict not only directly influences adolescent short video dependence but also operates through a chain mediation pathway involving experiential avoidance and emotional disturbance,highlighting central psychological mechanisms and providing theoretical support for integrated mental health and behavioral interventions.展开更多
Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“dou...Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“double-muscle”phenotype.However,the specific regulatory mechanism is still unclear.Here,we found that Ca^(2+)content in muscle tissue and muscle satellite cells of MSTN mutated(MSTN^(–/–))cattle were significantly increased compared to wild-type(WT).Furthermore,transcriptome analysis of muscle satellite cells revealed that TRPC4 was significantly increased in MSTN^(–/–)cattle.And the expression of TRPC4 in muscle tissue of MSTN^(–/–)cattle was detected by RT-qPCR and Western blot,which was significantly higher than that of WT.These results suggested that MSTN mutation promoted muscle satellite cells proliferation through activation of TRPC4 channel.To further verify,ML204,a specific inhibitor of TRPC4,was used to treat MSTN^(–/–)muscle satellite cells.We found that cell proliferation was inhibited,calcineurin expression was downregulated,and the entry of NFATc3 into nuclei was reduced,which was similar to WT group.Thus,MSTN mutation leads to the activation of TRPC4 channel,which increases intracellular Ca^(2+)content,further activates calcineurin/NFATc3 pathway,and ultimately promotes the proliferation of muscle satellite cells.展开更多
This study presents a comprehensive analysis of 132 tornadic events in northeastern China from 2004 to 2023,utilizing radar and ERA5 reanalysis data to investigate the climatology,environmental drivers,and synoptic li...This study presents a comprehensive analysis of 132 tornadic events in northeastern China from 2004 to 2023,utilizing radar and ERA5 reanalysis data to investigate the climatology,environmental drivers,and synoptic linkages with Northeast China cold vortices(NCCVs)of tornadic storms under different convective modes.Results reveal that discrete storms account for 70%of events,with clustered cells(CC)being the most frequent mode,while significant tornadoes(EF2+)are primarily associated with isolated cells(IC)and broken lines(BL).The storm mode distribution in northeastern China resembles that of the central United States but with a higher proportion of CC and lower IC.In contrast,southern China exhibits a higher frequency of quasi-linear(QL)modes(>50%),similar to European patterns.Although no single parameter clearly differentiates between all tornado modes,distinct morphological characteristics emerge through specific parameter combinations:NL modes are characterized by high 0-1 km storm-relative helicity(SRH1)and humidity but low 0-6 km shear(SR6),whereas IC modes display contrasting features with low SRH1 and high CAPE.Notably,83%of tornadoes are associated with NCCVs,preferentially forming in southeastern/southwestern quadrants.Strong tornadoes favor southeastern quadrants,while NCCV intensity correlates with tornadic distance from vortex centers.Three characteristic synoptic configurations emerge:(T1)strong deep vortices with vertically aligned cold troughs,generating southeast-dominant tornado clusters characterized by a high proportion of BL and QL modes;(T2)weaker vortices featuring sub-synoptic troughs,with southern-distributed events dominated by a predominance of the CC mode;(T3)transverse-trough systems exhibiting CAPE-SRH decoupling and reduced tornadic activity.This study enhances our understanding of tornadoes in northeastern China,informing future research on formation mechanisms,prediction methods,and disaster prevention strategies.展开更多
Doxorubicin(DOX)is known to elicit potent antitumor immune responses through the induction of immunogenic cell death(ICD).However,its therapeutic efficacy is undermined by the adaptive upregulation of programmed cell ...Doxorubicin(DOX)is known to elicit potent antitumor immune responses through the induction of immunogenic cell death(ICD).However,its therapeutic efficacy is undermined by the adaptive upregulation of programmed cell death ligand 1(PD-L1),which hijacked the antitumor immunity.In this study,we developed a reactive oxygen species(ROS)-responsive dihydroartemisinin(DHA)prodrug to facilitate the delivery of DOX via hydrophobic and electrostatic interactions.Upon internalization by tumor cells,the nanoparticles(NPs)preferentially accumulated in endoplasmic reticulum(ER),exacerbating ER stress and amplifying ICD to enhance tumor immunogenicity.Simultaneously,the oxidative intracellular environment trigged the degradation of NPs,releasing DHA,which downregulated PD-L1 by disrupting signal transducer and activator of transcription 3(STAT3)phosphorylation and inactivating the nuclear factor kappa-B(NF-κB)pathway.Consequently,the effective PD-L1 blockade and robust ICD response,synergistically inhibited breast cancer progression,significantly enhancing the chemo-immunotherapy efficacy of doxorubicin.展开更多
The calculation of viewing and solar geometry angles is a critical first step in retrieving atmospheric and surface variables from geostationary satellite observations.Whereas the viewing angles for geostationary sate...The calculation of viewing and solar geometry angles is a critical first step in retrieving atmospheric and surface variables from geostationary satellite observations.Whereas the viewing angles for geostationary satellites are not timevarying,a primary source of inaccuracy in solar positioning is the use of a single timestamp.Since pixel scanning times can differ significantly across the field-of-view disk(e.g.,by approximately 13 min for Fengyun-4B),this practice leads to errors of up to±2°in solar zenith angle,which translates to±50 W m^(−2) in extraterrestrial irradiance;the errors in solar azimuth angle can exceed±100°.Beyond scanning time,this work also quantifies the impact of other inputs—including altitude,surface pressure,air temperature,difference between Terrestrial Time and Universal Time,and atmospheric refraction—on the resulting angles.A comparison of our precise calculations with the official National Satellite Meteorological Center L1_GEO product shows an accuracy within 0.1°,confirming its utility for most retrieval tasks.To facilitate higher precision when required,this work releases the corresponding satellite and solar positioning codes in both R and Python.展开更多
Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological prop...Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.展开更多
基金supported by the National Key R&D Program of China(Nos.2022YFA1602302 and 2023YFA1606402)the National Natural Science Foundation of China(Nos.U2167204,12175314,12235020 and 12275360)+2 种基金the Continuous-Support Basic Scientific Research Projectthe"111 Center"the China Scholarship Council(CSC)。
文摘A new detector array with a large solid angle coverage for the coincidence measurement of charged fragments was developed to study the breakup reaction mechanisms of weakly bound nuclear systems at energies around the Coulomb barrier.The array has been used to explore the breakup reaction mechanisms of^(6,7)Li+^(209)Bi systems at E_(beam)=30,40,47 MeV,showing good performance in particle identification and complete kinematic measurements.Based on this,different breakup modes and breakup components were clearly distinguished,and some new breakup modes were discovered,such as^(7)Li→α+t breakup mode in6Li+209Bi system and^(7)Li→^(6)He+p breakup mode in^(7)Li+^(209)Bi system.This array can also be used to explore other breakup reaction mechanisms induced by weakly bound nuclei.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
文摘Background:This study aims to investigate the underlying mechanisms between parental marital conflict and adolescent short video dependence by constructing a chain mediation model,focusing on the mediating roles of experiential avoidance and emotional disturbance(anxiety,depression,and stress).Methods:Conducted in January 2025,the research recruited 4125 adolescents from multiple Chinese provinces through convenience sampling;after data cleaning,3957 valid participants(1959 males,1998 females)were included.Using a cross-sectional design,measures included parental marital conflict,experiential avoidance,anxiety,depression,stress,and short video dependence.Results:Pearson correlation analysis revealed significant positive correlations among all variables.Mediation analysis using the SPSS PROCESS macro showed that parental marital conflict directly predicted short video dependence(β=0.269,p<0.001),and also significantly predicted experiential avoidance(β=0.519,p<0.001),anxiety(β=0.072,p<0.001),depression(β=0.067,p<0.001),and stress(β=0.048,p<0.05).Experiential avoidance further predicted anxiety(β=0.521,p<0.001),depression(β=0.489,p<0.001),stress(β=0.408,p<0.001),and short video dependence(β=0.244,p<0.001).While both anxiety(β=0.050,p<0.05)and depression(β=0.116,p<0.001)positively predicted short video dependence,stress did not(β=0.019,p=0.257).Overall,experiential avoidance,anxiety,depression,and stress significantly mediated the relationship between parental marital conflict and short video dependence.Conclusion:These findings confirm that parental marital conflict not only directly influences adolescent short video dependence but also operates through a chain mediation pathway involving experiential avoidance and emotional disturbance,highlighting central psychological mechanisms and providing theoretical support for integrated mental health and behavioral interventions.
基金supported by the National Natural Science Foundation of China(32360837 and 32341052)the STI2030 Major Projects,China(2023ZW0404803)+8 种基金the Inner Mongolia Open Competition Projects,China(2022JBGS0025)the Inner Mongolia Science and Technology Leading Team,China(2022LJRC0006)the Inner Mongolia Science and Technology Major Projects,China(2021ZD0009,2021ZD0008,2022ZD0008,2023KJHZ0028)the Inner Mongolia Young Talents Projects,China(NJYT23138)the Inner Mongolia Natural Science Foundation,China(2023MS03004)the Central Government Guides Development,China(2022ZY0212)the National Agricultural Science and Technology Project of China(NK2022130203)the Collaborative Innovation among Universities in Hohhot,China(XTCX2023-06)the Ministry of Education Engineering Centre Project,China(JYBGCSYS2022)。
文摘Myostatin(MSTN)is principally expressed in skeletal muscle and negatively regulates muscle growth and development.MSTN mutation can induce muscle overgrowth in cattle by activating cell proliferation,presenting a“double-muscle”phenotype.However,the specific regulatory mechanism is still unclear.Here,we found that Ca^(2+)content in muscle tissue and muscle satellite cells of MSTN mutated(MSTN^(–/–))cattle were significantly increased compared to wild-type(WT).Furthermore,transcriptome analysis of muscle satellite cells revealed that TRPC4 was significantly increased in MSTN^(–/–)cattle.And the expression of TRPC4 in muscle tissue of MSTN^(–/–)cattle was detected by RT-qPCR and Western blot,which was significantly higher than that of WT.These results suggested that MSTN mutation promoted muscle satellite cells proliferation through activation of TRPC4 channel.To further verify,ML204,a specific inhibitor of TRPC4,was used to treat MSTN^(–/–)muscle satellite cells.We found that cell proliferation was inhibited,calcineurin expression was downregulated,and the entry of NFATc3 into nuclei was reduced,which was similar to WT group.Thus,MSTN mutation leads to the activation of TRPC4 channel,which increases intracellular Ca^(2+)content,further activates calcineurin/NFATc3 pathway,and ultimately promotes the proliferation of muscle satellite cells.
基金supported by the National Natural Science Foundation of China(Grant No.42305013)Joint Research Project for Meteorological Capacity Improvement(Grant Nos.23NLTSQ002 and 24NLTSQ001)+2 种基金China Meteorological Administration Tornado Key Laboratory(Grant No.TKL202307)the China Meteorological Administration Youth Innovation Team Fund(Grant No.CMA2024QN05)a research project of the Chinese Academy of Meteorological Science(Grant No.2023Z019)。
文摘This study presents a comprehensive analysis of 132 tornadic events in northeastern China from 2004 to 2023,utilizing radar and ERA5 reanalysis data to investigate the climatology,environmental drivers,and synoptic linkages with Northeast China cold vortices(NCCVs)of tornadic storms under different convective modes.Results reveal that discrete storms account for 70%of events,with clustered cells(CC)being the most frequent mode,while significant tornadoes(EF2+)are primarily associated with isolated cells(IC)and broken lines(BL).The storm mode distribution in northeastern China resembles that of the central United States but with a higher proportion of CC and lower IC.In contrast,southern China exhibits a higher frequency of quasi-linear(QL)modes(>50%),similar to European patterns.Although no single parameter clearly differentiates between all tornado modes,distinct morphological characteristics emerge through specific parameter combinations:NL modes are characterized by high 0-1 km storm-relative helicity(SRH1)and humidity but low 0-6 km shear(SR6),whereas IC modes display contrasting features with low SRH1 and high CAPE.Notably,83%of tornadoes are associated with NCCVs,preferentially forming in southeastern/southwestern quadrants.Strong tornadoes favor southeastern quadrants,while NCCV intensity correlates with tornadic distance from vortex centers.Three characteristic synoptic configurations emerge:(T1)strong deep vortices with vertically aligned cold troughs,generating southeast-dominant tornado clusters characterized by a high proportion of BL and QL modes;(T2)weaker vortices featuring sub-synoptic troughs,with southern-distributed events dominated by a predominance of the CC mode;(T3)transverse-trough systems exhibiting CAPE-SRH decoupling and reduced tornadic activity.This study enhances our understanding of tornadoes in northeastern China,informing future research on formation mechanisms,prediction methods,and disaster prevention strategies.
基金The National Natural Science Foundation of China(Nos.82473864,82400095)the Natural Science Foundation of Jiangsu Province(No.BK20231009)+2 种基金the National Center of Technology Innovation for Biopharmaceuticals(No.NCTIB2022HS01015)“Double First-Class”Initiative Program in China Pharmaceutical Universitythe National Innovation and Entrepreneurship Training Program for Undergraduate(Nos.202310316007Z,2023103161133,2023103161333).
文摘Doxorubicin(DOX)is known to elicit potent antitumor immune responses through the induction of immunogenic cell death(ICD).However,its therapeutic efficacy is undermined by the adaptive upregulation of programmed cell death ligand 1(PD-L1),which hijacked the antitumor immunity.In this study,we developed a reactive oxygen species(ROS)-responsive dihydroartemisinin(DHA)prodrug to facilitate the delivery of DOX via hydrophobic and electrostatic interactions.Upon internalization by tumor cells,the nanoparticles(NPs)preferentially accumulated in endoplasmic reticulum(ER),exacerbating ER stress and amplifying ICD to enhance tumor immunogenicity.Simultaneously,the oxidative intracellular environment trigged the degradation of NPs,releasing DHA,which downregulated PD-L1 by disrupting signal transducer and activator of transcription 3(STAT3)phosphorylation and inactivating the nuclear factor kappa-B(NF-κB)pathway.Consequently,the effective PD-L1 blockade and robust ICD response,synergistically inhibited breast cancer progression,significantly enhancing the chemo-immunotherapy efficacy of doxorubicin.
基金supported by the National Natural Science Foundation of China(Grant No.42375192).
文摘The calculation of viewing and solar geometry angles is a critical first step in retrieving atmospheric and surface variables from geostationary satellite observations.Whereas the viewing angles for geostationary satellites are not timevarying,a primary source of inaccuracy in solar positioning is the use of a single timestamp.Since pixel scanning times can differ significantly across the field-of-view disk(e.g.,by approximately 13 min for Fengyun-4B),this practice leads to errors of up to±2°in solar zenith angle,which translates to±50 W m^(−2) in extraterrestrial irradiance;the errors in solar azimuth angle can exceed±100°.Beyond scanning time,this work also quantifies the impact of other inputs—including altitude,surface pressure,air temperature,difference between Terrestrial Time and Universal Time,and atmospheric refraction—on the resulting angles.A comparison of our precise calculations with the official National Satellite Meteorological Center L1_GEO product shows an accuracy within 0.1°,confirming its utility for most retrieval tasks.To facilitate higher precision when required,this work releases the corresponding satellite and solar positioning codes in both R and Python.
基金supported by the Shenzhen Hong Kong Joint Funding Project,No.SGDX20230116093645007(to LY)the Shenzhen Science and Technology Innovation Committee International Cooperation Project,No.GJHZ20200731095608025(to LY)+7 种基金Shenzhen Development and Reform Commission’s Intelligent Diagnosis,Treatment and Prevention of Adolescent Spinal Health Public Service Platform,No.S2002Q84500835(to LY)Shenzhen Medical Research Fund,No.B2303005(to LY)Team-based Medical Science Research Program,No.2024YZZ02(to LY)Zhejiang Provincial Natural Science Foundation of China,No.LWQ20H170001(to RL)Basic Research Project of Shenzhen Science and Technology from Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324103010029(to BY)Shenzhen Second People’s Hospital Clinical Research Fund of Guangdong Province High-level Hospital Construction Project,Nos.2023yjlcyj029(to BY),2023yjlcyj021(to LL)Guangdong Basic and Applied Basic Research Foundation,No.2022A1515110679(to LL)China Postdoctoral Science Foundation,No.2022M722203(to GL).
文摘Peripheral nerve injury causes severe neuroinflammation and has become a global medical challenge.Previous research has demonstrated that porcine decellularized nerve matrix hydrogel exhibits excellent biological properties and tissue specificity,highlighting its potential as a biomedical material for the repair of severe peripheral nerve injury;however,its role in modulating neuroinflammation post-peripheral nerve injury remains unknown.Here,we aimed to characterize the anti-inflammatory properties of porcine decellularized nerve matrix hydrogel and their underlying molecular mechanisms.Using peripheral nerve injury model rats treated with porcine decellularized nerve matrix hydrogel,we evaluated structural and functional recovery,macrophage phenotype alteration,specific cytokine expression,and changes in related signaling molecules in vivo.Similar parameters were evaluated in vitro using monocyte/macrophage cell lines stimulated with lipopolysaccharide and cultured on porcine decellularized nerve matrix hydrogel-coated plates in complete medium.These comprehensive analyses revealed that porcine decellularized nerve matrix hydrogel attenuated the activation of excessive inflammation at the early stage of peripheral nerve injury and increased the proportion of the M2 subtype in monocytes/macrophages.Additionally,porcine decellularized nerve matrix hydrogel negatively regulated the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB axis both in vivo and in vitro.Our findings suggest that the efficacious anti-inflammatory properties of porcine decellularized nerve matrix hydrogel induce M2 macrophage polarization via suppression of the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway,providing new insights into the therapeutic mechanism of porcine decellularized nerve matrix hydrogel in peripheral nerve injury.
