The corrosion behavior of C110 bushing at high temperature and high pressure with a high H2S / CO2 was studied, and a basis for the materials selection of sour gas well bushing was provided in H2S, CO2 and saline coex...The corrosion behavior of C110 bushing at high temperature and high pressure with a high H2S / CO2 was studied, and a basis for the materials selection of sour gas well bushing was provided in H2S, CO2 and saline coexisting environment. Under acidic condiction, hydrogen atoms greatly entered into the material and caused the material properties changed. Weight loss method was used to study the corrosion rate of hydrogen charging samples and original untreated samples in simulated oil field environment. PAR2273 electrochemical workstation was used to examine the electrochemical performance of samples untreated, hydrogen charging after reacting in autoclave. The corrosion product film was observed through SEM. The experimental results show that sample with hydrogen charging has a much more obvious partial corrosion and pitting corrosion than the untreated blank sample even the downhole corrosion speed of bushing is increased after being used for a period of time. Polarization curve shows the corrosion tendency is the same between sample with or without hydrogen charging and corrosion tendency is reduced by corrosion product film. A layer of dense product film formed on the surface of samples provides a certain protective effect to the matrix, but cracked holes which will accelerate partial corrosion of the sample were also observed.展开更多
We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation r...We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.展开更多
Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postu...Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.展开更多
E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a mo...E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.展开更多
Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a p...Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.展开更多
Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulat...Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.展开更多
Excellent fits to a couple of the data-sets on the temperature (T)-dependent upper critical field (Hc2) of H3S (critical temperature, Tc ≈ 200 K at pressure ≈ 150 GPa) reported by Mozaffari, et al. (2019) were obtai...Excellent fits to a couple of the data-sets on the temperature (T)-dependent upper critical field (Hc2) of H3S (critical temperature, Tc ≈ 200 K at pressure ≈ 150 GPa) reported by Mozaffari, et al. (2019) were obtained by Talantsev (2019) in an approach based on an ingenious mix of the Ginzberg-Landau (GL), the Werthamer, Helfand and Hohenberg (WHH), and the Gor’kov, etc., theories which have individually been employed for the same purpose for a long time. Up to the lowest temperature (TL) in each of these data-sets, similarly accurate fits have also been obtained by Malik and Varma (2023) in a radically different approach based on the Bethe-Salpeter equation (BSE) supplemented by the Matsubara and the Landau quantization prescriptions. For T TL, however, while the (GL, WHH, etc.)-based approach leads to Hc2(0) ≈ 100 T, the BSE-based approach leads to about twice this value even at 1 K. In this paper, a fit to one of the said data-sets is obtained for the first time via a thermodynamic approach which, up to TL, is as good as those obtained via the earlier approaches. While this is interesting per se, another significant result of this paper is that for T TL it corroborates the result of the BSE-based approach.展开更多
Ef fective and robust catalyst is the core of water splitting to produce hydrogen.Here, we report an anionic etching method to tailor the sulfur vacancy(VS) of NiS_(2) to further enhance the electrocatalytic performan...Ef fective and robust catalyst is the core of water splitting to produce hydrogen.Here, we report an anionic etching method to tailor the sulfur vacancy(VS) of NiS_(2) to further enhance the electrocatalytic performance for hydrogen evolution reaction(HER). With the VS concentration change from 2.4% to 8.5%, the H* adsorption strength on S sites changed and NiS_(2)-VS 5.9% shows the most optimized H* adsorption for HER with an ultralow onset potential(68 m V) and has long-term stability for 100 h in 1 M KOH media. In situ attenuated-total-reflection Fourier transform infrared spectroscopy(ATR-FTIRS) measurements are usually used to monitor the adsorption of intermediates. The S-H* peak of the Ni S_(2)-VS 5.9% appears at a very low voltage, which is favorable for the HER in alkaline media. Density functional theory calculations also demonstrate the Ni S_(2)-VS 5.9% has the optimal |ΔG^(H*)| of 0.17 e V. This work offers a simple and promising pathway to enhance catalytic activity via precise vacancies strategy.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in spe...●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.展开更多
基金Funded by the National Natural Science Foundation of China(No. 50904050)the Basic Projects of Sichuan Province(2011JY0106)the Postdoctoral Science Foundation(20110490810)
文摘The corrosion behavior of C110 bushing at high temperature and high pressure with a high H2S / CO2 was studied, and a basis for the materials selection of sour gas well bushing was provided in H2S, CO2 and saline coexisting environment. Under acidic condiction, hydrogen atoms greatly entered into the material and caused the material properties changed. Weight loss method was used to study the corrosion rate of hydrogen charging samples and original untreated samples in simulated oil field environment. PAR2273 electrochemical workstation was used to examine the electrochemical performance of samples untreated, hydrogen charging after reacting in autoclave. The corrosion product film was observed through SEM. The experimental results show that sample with hydrogen charging has a much more obvious partial corrosion and pitting corrosion than the untreated blank sample even the downhole corrosion speed of bushing is increased after being used for a period of time. Polarization curve shows the corrosion tendency is the same between sample with or without hydrogen charging and corrosion tendency is reduced by corrosion product film. A layer of dense product film formed on the surface of samples provides a certain protective effect to the matrix, but cracked holes which will accelerate partial corrosion of the sample were also observed.
基金supported by the National Natural Science Foundation of China,Nos.82271327(to ZW),82072535(to ZW),81873768(to ZW),and 82001253(to TL).
文摘We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.
文摘Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.
文摘E-learning platforms support education systems worldwide, transferring theoretical knowledge as well as soft skills. In the present study high-school pupils’, and adult students’ opinions were evaluated through a modern structured MOODLE interactive course, designed for the needs of the laboratory course “Automotive Systems”. The study concerns Greek secondary vocational education pupils aged 18 and vocational training adult students aged 20 to 50 years. The multistage, equal size simple random cluster sample was used as a sampling method. Pupils and adult students of each cluster completed structured 10-question questionnaires both before and after attending the course. A total of 120 questionnaires were collected. In general, our findings disclosed that the majority of pupils and adult students had significantly improved their knowledge and skills from using MOODLE. They reported strengthening conventional teaching, using the new MOODLE technology. The satisfaction indices improved quite, with the differences in their mean values being statistically significant.
基金supported by the National Key Research and Development Program of China,Nos.2017YFE0122900(to BH),2019YFA0110800(to WL),2019YFA0903802(to YW),2021YFA1101604(to LW),2018YFA0108502(to LF),and 2020YFA0804003(to JW)the National Natural Science Foundation of China,Nos.31621004(to WL,BH)and 31970821(to YW)+1 种基金CAS Project for Young Scientists in Basic Research,No.YSBR-041(to YW)Joint Funds of the National Natural Science Foundation of China,No.U21A20396(to BH)。
文摘Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.
基金supported by a grant from the Massachusetts Alzheimer’s Disease Research Center(5P50 AG 005134)(to SL).
文摘Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia.Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental factors.The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction.Throughout life,environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders.These changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity.In this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic plasticity.Moreover,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic mechanisms.Lastly,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease.We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.
文摘Excellent fits to a couple of the data-sets on the temperature (T)-dependent upper critical field (Hc2) of H3S (critical temperature, Tc ≈ 200 K at pressure ≈ 150 GPa) reported by Mozaffari, et al. (2019) were obtained by Talantsev (2019) in an approach based on an ingenious mix of the Ginzberg-Landau (GL), the Werthamer, Helfand and Hohenberg (WHH), and the Gor’kov, etc., theories which have individually been employed for the same purpose for a long time. Up to the lowest temperature (TL) in each of these data-sets, similarly accurate fits have also been obtained by Malik and Varma (2023) in a radically different approach based on the Bethe-Salpeter equation (BSE) supplemented by the Matsubara and the Landau quantization prescriptions. For T TL, however, while the (GL, WHH, etc.)-based approach leads to Hc2(0) ≈ 100 T, the BSE-based approach leads to about twice this value even at 1 K. In this paper, a fit to one of the said data-sets is obtained for the first time via a thermodynamic approach which, up to TL, is as good as those obtained via the earlier approaches. While this is interesting per se, another significant result of this paper is that for T TL it corroborates the result of the BSE-based approach.
基金funded by the National Natural Science Foundation of China (NSFC) (Nos. 22221001, 22201115, 21931001, and 21922105)the Special Fund Project of Guiding Scientific and Technological Innovation Development of Gansu Province (2019ZX–04)+3 种基金the 111 Project (B20027)by the Fundamental Research Funds for the Central Universities (lzujbky-2023-eyt03)support Natural Science Foundation of Gansu Providence (22JR5RA540)Gansu Province Youth Science and Technology Talent Promotion Project (GXH202220530-02)。
文摘Ef fective and robust catalyst is the core of water splitting to produce hydrogen.Here, we report an anionic etching method to tailor the sulfur vacancy(VS) of NiS_(2) to further enhance the electrocatalytic performance for hydrogen evolution reaction(HER). With the VS concentration change from 2.4% to 8.5%, the H* adsorption strength on S sites changed and NiS_(2)-VS 5.9% shows the most optimized H* adsorption for HER with an ultralow onset potential(68 m V) and has long-term stability for 100 h in 1 M KOH media. In situ attenuated-total-reflection Fourier transform infrared spectroscopy(ATR-FTIRS) measurements are usually used to monitor the adsorption of intermediates. The S-H* peak of the Ni S_(2)-VS 5.9% appears at a very low voltage, which is favorable for the HER in alkaline media. Density functional theory calculations also demonstrate the Ni S_(2)-VS 5.9% has the optimal |ΔG^(H*)| of 0.17 e V. This work offers a simple and promising pathway to enhance catalytic activity via precise vacancies strategy.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金Supported by Regional Science Foundation Project of the National Natural Science Foundation of China(No.82060827,No.82260891)The Key Discipline of Universities in the“14th Five-Year Plan”Autonomous Region-Traditional Chinese Medicine at Xinjiang Medical University.
文摘●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-related diseases for further studies.
