Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion a...Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.展开更多
In-optical-sensor computing architectures based on neuro-inspired optical sensor arrays have become key milestones for in-sensor artificial intelligence(AI)technology,enabling intelligent vision sensing and extensive ...In-optical-sensor computing architectures based on neuro-inspired optical sensor arrays have become key milestones for in-sensor artificial intelligence(AI)technology,enabling intelligent vision sensing and extensive data processing.These architectures must demonstrate potential advantages in terms of mass production and complementary metal oxide semiconductor compatibility.Here,we introduce a visible-light-driven neuromorphic vision system that integrates front-end retinomorphic photosensors with a back-end artificial neural network(ANN),employing a single neuro-inspired indium-g allium-zinc-oxide photo transistor(NIP)featuring an aluminum sensitization layer(ASL).By methodically adjusting the ASL coverage on IGZO phototransistors,a fast-switching response-type and a synaptic response-type of IGZO photo transistors are successfully developed.Notably,the fabricated NIP shows a remarkable retina-like photoinduced synaptic plasticity under wavelengths up to 635 nm,with over256-states,weight update nonlinearity below 0.1,and a dynamic range of 64.01.Owing to this technology,a 6×6 neuro-inspired optical image sensor array with the NIP can perform highly integrated sensing,memory,and preprocessing functions,including contrast enhancement,and handwritten digit image recognition.The demonstrated prototype highlights the potential for efficient hardware implementations in in-sensor AI technologies.展开更多
Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has becom...Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.展开更多
How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polypheno...How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polyphenol,has anti-inflammatory and immunomodulatory effects.Therefore,the aim of this study was to investigate the effect of GA on peanut protein(PP)sensitization under high moisture extrusion conditions.The contents of free sulfhydryl groups and disulfide bonds in the PP-GA complex were determined,and the structure of the complex was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Fourier transform infrared spectroscopy.The results showed that with increasing GA content,the number of free sulfhydryl groups increased while the number of disulfide bonds decreased.The secondary structure of PP-GA showed that the random coils andβ-turns were transformed toα-helices andβ-sheets.A BALB/c mouse model was also established,wherein Al(OH)3 was used as an adjuvant when the complex was administered via intraperitoneal injection,and the mice showed mild allergic symptoms and a decreased immune organ index.In addition,the serum levels of specific antibodies(immunoglobulin E(IgE),immunoglobulin G1(IgG1),and immunoglobulin G2a(IgG2a)),cytokines(interleukin-5(IL-5),interleukin 13(IL-13),and interferon gamma(IFN-γ))and histamine were reduced.In summary,this study proved that GA can relieve the sensitization of PP induced by high moisture extrusion.展开更多
Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue b...Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].展开更多
Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD i...Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].展开更多
Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24...Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24),global Panx1 KO(n=24),neuron-specific Panx1 KO(n=20),and glia-specific Panx1 KO(n=20)mice were used in this study at Albert Einstein College of Medicine.The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant(CFA)injection(7,14,and 21 d).The qRT-PCR was employed to measure mRNA levels of Panx1,Panx2,Panx3,Cx43,Calhm1,andβ-catenin.Laser scanning confocal microscopy imaging,Sholl analysis,and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons(DRGNs)in which Panx1 expression or function was manipulated.Ethidium bromide(EtBr)dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate(ATP)sensitivity.β-galactosidase(β-gal)staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia(TG)and DRG of transgenic mice.Results:Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli(7,14,and 21 d;P<0.01 vs.WT group),indicating that Panx1 was positively correlated with pain sensitivity.In Neuro2a,global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group(P<0.05),revealing that Panx1 enhanced neurogenesis and excitability.Similarly,global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor(NGF)treatment(P<0.01 vs.WT group).Moreover,Panx1 channels enhanced DRG neuron response to ATP after CFA injection(P<0.01 vs.Panx1 KO group).Furthermore,ATP release increased Ca2+responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment(P<0.01 vs.Panx1 KO group),suggesting that Panx1 in glia also impacts exaggerated neuronal excitability.Interestingly,neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs,as evidenced by stunted neurite outgrowth(P<0.05 vs.Panx1 KO group;P<0.01 vs.WT group or GFAP-Cre group),blunted activation of Wnt/β-catenin signaling(P<0.01 vs.WT,Panx1 KO and GFAP-Cre groups),and diminished cell excitability(P<0.01 vs.GFAP-Cre group)and response to ATP stimulation(P<0.01 vs.WT group).Analysis ofβ-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher(2.5-fold increase)in the DRG than in the TG.Conclusions:The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability.This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain,where similar studies revealed a prominent role for glial Panx1.The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.展开更多
In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensit...In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensitive information.How to effectively categorize and protect sensitive data has become an urgent issue in educational data security.This paper systematically researches and constructs a multi-dimensional classification framework for sensitive educational data,and discusses its security protection strategy from the aspects of identification and desensitization,aiming to provide new ideas for the security management of sensitive educational data and to help the construction of an educational data security ecosystem in the era of digital intelligence.展开更多
基金supported by JSPS KAKENHI Grant Number(22K11779).
文摘Background:While mild itching may seem harmless,it can worsen over time,necessitating early treatment.Epicutaneous sensitization has recently gained attention.Oral exposure may promote immune tolerance,but ingestion after epicutaneous sensitization can trigger severe allergic responses.Therefore,this study focused on the initial stages of allergic symptoms before they become severe and investigated the mechanisms underlying food ingestion-induced mild itching following epicutaneous sensitization.Methods:Female mice were epicutaneously sensitized with ovalbumin(OVA).Scratching behavior was recorded,and serum and tissue samples were collected.Levels of OVA-specific immunoglobulin(Ig)E/IgG1,histamine,and mast cell protease-1(MCPT-1)were measured by ELISA.Histological analysis of skin tissues and immune cell infiltration was performed via staining.Results:OVA challenge following epicutaneous sensitization induced mild itching in the OVA group.Scratching behavior peaked between 1 and 2 h and persisted for 8 h before returning to baseline.This itching was accompanied by dynamic fluctuations in OVA-specific IgE and IgG1,histamine,and MCPT-1 levels.Histological analysis revealed increased epidermal thickness and granulocytic infiltration,particularly of mast cells and eosinophils,within 2 h of OVA challenge.Mast cell and eosinophil migration into the skin tissues was significant,with eosinophil migration into the dermis persisted despite normalization of histamine levels and mast cell degranulation.These results suggest that mast cells and eosinophils play significant roles even in mild itching.Conclusion:This study provides insights into the early immune responses involved in food allergies,contributing to a better understanding of how mild symptoms can progress to more severe reactions.
基金supported by the National Research Foundation of Korea(NRF)Grant funded by the Korea government(MSIT)(Grant No.RS-2023-00256917)Samsung Display。
文摘In-optical-sensor computing architectures based on neuro-inspired optical sensor arrays have become key milestones for in-sensor artificial intelligence(AI)technology,enabling intelligent vision sensing and extensive data processing.These architectures must demonstrate potential advantages in terms of mass production and complementary metal oxide semiconductor compatibility.Here,we introduce a visible-light-driven neuromorphic vision system that integrates front-end retinomorphic photosensors with a back-end artificial neural network(ANN),employing a single neuro-inspired indium-g allium-zinc-oxide photo transistor(NIP)featuring an aluminum sensitization layer(ASL).By methodically adjusting the ASL coverage on IGZO phototransistors,a fast-switching response-type and a synaptic response-type of IGZO photo transistors are successfully developed.Notably,the fabricated NIP shows a remarkable retina-like photoinduced synaptic plasticity under wavelengths up to 635 nm,with over256-states,weight update nonlinearity below 0.1,and a dynamic range of 64.01.Owing to this technology,a 6×6 neuro-inspired optical image sensor array with the NIP can perform highly integrated sensing,memory,and preprocessing functions,including contrast enhancement,and handwritten digit image recognition.The demonstrated prototype highlights the potential for efficient hardware implementations in in-sensor AI technologies.
基金supported by the National Natural Science Foundation of China(U21A20418).
文摘Sleep is an indispensable part of life−its deficiency has significant implications for overall health and wellbeing[1].In today’s fast-paced society,sleep loss from either stressful or non-stressful origins has become prevalent.Specifically,active sleep deprivation(ASD),resulting from extended use of smartphones and other recreational activities,has risen as a global health issue.Clinical research has underscored a strong correlation between chronic pain and inadequate sleep[2].The relationship between pain and sleep is reciprocal:pain disturbs sleep,while poor sleep quality,in turn,reduces pain tolerance and exacerbates spontaneous pain sensations[3].While these interplays are well-documented in cases of passive sleep deprivation(PSD)associated with external pressures or illnesses,understanding how and which regions of the brain collaborate to recalibrate the intricate neural circuitry governing pain perception during ASD remains a crucial yet unresolved frontier.
基金supported by the Natural Science Foundation of China(32072139)Liaoning Province Natural Science Foundation Project(2022-MS-307).
文摘How to reduce peanut allergies has always been a main food safety concern.Plant polyphenol complex peanut sensitizing protein was proposed as a new desensitization strategy.Gallic acid(GA),as a natural plant polyphenol,has anti-inflammatory and immunomodulatory effects.Therefore,the aim of this study was to investigate the effect of GA on peanut protein(PP)sensitization under high moisture extrusion conditions.The contents of free sulfhydryl groups and disulfide bonds in the PP-GA complex were determined,and the structure of the complex was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE)and Fourier transform infrared spectroscopy.The results showed that with increasing GA content,the number of free sulfhydryl groups increased while the number of disulfide bonds decreased.The secondary structure of PP-GA showed that the random coils andβ-turns were transformed toα-helices andβ-sheets.A BALB/c mouse model was also established,wherein Al(OH)3 was used as an adjuvant when the complex was administered via intraperitoneal injection,and the mice showed mild allergic symptoms and a decreased immune organ index.In addition,the serum levels of specific antibodies(immunoglobulin E(IgE),immunoglobulin G1(IgG1),and immunoglobulin G2a(IgG2a)),cytokines(interleukin-5(IL-5),interleukin 13(IL-13),and interferon gamma(IFN-γ))and histamine were reduced.In summary,this study proved that GA can relieve the sensitization of PP induced by high moisture extrusion.
基金supported by the National Natural Science Foundation of China(Nos.12474418,U22A20398,and 22135008).
文摘Lanthanide(Ln^(3+))-doped luminescent nanocrystals(NCs)with excitation and emission in the second near-infrared biological window(NIRII,1000-1700 nm)have attracted considerable attention in the fields of deep-tissue bioimaging and non-invasive biodetection,owing to their superior advantages including good photochemical stability,sharp emission peaks,large penetration depth,and high signal-to-noise ratio[1].Conventionally,Yb3t-and Nd3t-sensitized NCs have been utilized as NIR-II luminescent nanoprobes for in vivo bioimaging upon excitation with 980 and 808 nm diode laser,respectively[2].
基金support was provided by the European Regional Development Fund(ERDF),through the Centro 2020 Regional Operational Programme,Portugal(Project No.:CENTRO-01-0145-FEDER-000012(HealthyAging2020))through the COMPETE 2020-Operational Programme for Competitiveness and Internationalisation and Portuguese National Funds via Fundaçao para a Ciencia e a Tecnologia,Portugal(Project Nos.:POCI-01-0145-FEDER-029369 UIDB/04539/2020,iBiMED UIDB/04501/2020,DOI identifier https://doi.org/10.54499/UIDB/04501/2020 and project reference UIDP/04501/2020,DOI identifier https://doi.org/10.54499/UIDP/04501/2020,and LA/P/0058/2020)supported by Fundaçao para a Ciencia e a Tecnologia through the individual PhD fellowships,Portugal(Grant Nos.:PD/BDE/142926/2018 and SFRH/BD/110717/2015)。
文摘Skin sensitization is a common adverse effect of a wide range of small reactive chemicals,leading to allergic contact dermatitis(ACD),the most frequent manifestation of immunotoxicity in humans.The prevalence of ACD is increasing,affecting up to 20%of the Western European population.This trend was particularly pronounced in high-risk occupational sectors,including healthcare,food services,metal and construction workers,and hairdressers[1].The skin sensitization adverse outcome pathway(AOP)comprises 11 elements,with four designated key events(KEs):formation of proteinhapten complexes(KE-1),inflammatory keratinocyte response(KE-2),dendritic cell(DC)activation(KE-3),and T-cell proliferation(KE-4)[2].As there is no cure for ACD,preventive strategies are of great relevance.In addition to avoiding exposure,preventive measures,such as the use of latex gloves,barrier creams,emollients,and moisturizers,often have limited effectiveness[3].
基金This work was NIH(R01NS092466),NSFC(U2004201)Central Plains Thousand People Plan of Henan Province(204200510013)+1 种基金Henan Overseas Expertise Introduction Center for Discipline Innovation(CXJD2021002)Key Special Project of Zhengzhou University Disciplinary Construction(XKZDJC202001)。
文摘Background:The channel-forming protein Pannexin1(Panx1)has been implicated in both human studies and animal models of chronic pain,but the underlying mechanisms remain incompletely understood.Methods:Wild-type(WT,n=24),global Panx1 KO(n=24),neuron-specific Panx1 KO(n=20),and glia-specific Panx1 KO(n=20)mice were used in this study at Albert Einstein College of Medicine.The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant(CFA)injection(7,14,and 21 d).The qRT-PCR was employed to measure mRNA levels of Panx1,Panx2,Panx3,Cx43,Calhm1,andβ-catenin.Laser scanning confocal microscopy imaging,Sholl analysis,and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons(DRGNs)in which Panx1 expression or function was manipulated.Ethidium bromide(EtBr)dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate(ATP)sensitivity.β-galactosidase(β-gal)staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia(TG)and DRG of transgenic mice.Results:Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli(7,14,and 21 d;P<0.01 vs.WT group),indicating that Panx1 was positively correlated with pain sensitivity.In Neuro2a,global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group(P<0.05),revealing that Panx1 enhanced neurogenesis and excitability.Similarly,global Panx1 deletion significantly suppressed Wnt/β-catenin dependent DRG neurogenesis following 5 d of nerve growth factor(NGF)treatment(P<0.01 vs.WT group).Moreover,Panx1 channels enhanced DRG neuron response to ATP after CFA injection(P<0.01 vs.Panx1 KO group).Furthermore,ATP release increased Ca2+responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment(P<0.01 vs.Panx1 KO group),suggesting that Panx1 in glia also impacts exaggerated neuronal excitability.Interestingly,neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs,as evidenced by stunted neurite outgrowth(P<0.05 vs.Panx1 KO group;P<0.01 vs.WT group or GFAP-Cre group),blunted activation of Wnt/β-catenin signaling(P<0.01 vs.WT,Panx1 KO and GFAP-Cre groups),and diminished cell excitability(P<0.01 vs.GFAP-Cre group)and response to ATP stimulation(P<0.01 vs.WT group).Analysis ofβ-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher(2.5-fold increase)in the DRG than in the TG.Conclusions:The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability.This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain,where similar studies revealed a prominent role for glial Panx1.The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.
基金Education Science planning project of Jiangsu Province in 2024(Grant No:B-b/2024/01/152)2025 Jiangsu Normal University Graduate Research and Innovation Program school-level project“Research on the Construction and Desensitization Strategies of Education Sensitive Data Classification from the Perspective of Educational Ecology”。
文摘In the era of digital intelligence,data is a key element in promoting social and economic development.Educational data,as a vital component of data,not only supports teaching and learning but also contains much sensitive information.How to effectively categorize and protect sensitive data has become an urgent issue in educational data security.This paper systematically researches and constructs a multi-dimensional classification framework for sensitive educational data,and discusses its security protection strategy from the aspects of identification and desensitization,aiming to provide new ideas for the security management of sensitive educational data and to help the construction of an educational data security ecosystem in the era of digital intelligence.
