The direct conversion of greenhouse gas CO_(2) and low-cost CH3OH into valuable dimethyl carbonate(DMC)offers a promising low-carbon synthetic pathway,but the slow CO_(2) activation kinetics and entropy-decreasing nat...The direct conversion of greenhouse gas CO_(2) and low-cost CH3OH into valuable dimethyl carbonate(DMC)offers a promising low-carbon synthetic pathway,but the slow CO_(2) activation kinetics and entropy-decreasing nature of this reaction significantly restrict DMC yield to below 1%.In this work,2-cyanopyridine(2-CP)was employed as a dehydrating agent to suppress the reverse reaction between DMC and H_(2)O,shifting the thermodynamic equilibrium in favor of DMC production.Under this thermodynamic unconstrained condition,increasing oxygen vacancies,especially in the form of oxygen vacancy clusters,promotes catalytic activity significantly.We achieve a catalytic activity of 211 mmol/(g·h)at 140℃ on H_(2)-treated,oxygen-vacancy-clusters-rich CeO_(2) in the presence of 2-CP,a 1.6-fold increase compared to the activity with air-treated CeO_(2) under identical conditions.The DMC yield reaches 8.54%in a 20mL CH3OH solution with 2-CP,surpassing the calculated DMC yield of about 0.66%from the reaction equilibrium constant under the same conditions and without using the dehydrating agent.This work suggests the importance of using a dehydrating agent and also highlights oxygen vacancy clusters as pivotal active sites to promote DMC synthesis.Achieving sustainable DMC synthesis requires further exploration,encompassing strategies such as methods for regeneration of 2-CP.展开更多
Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apopt...Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.展开更多
Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adv...Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.展开更多
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone(6PPDQ) and its parent 6PPD are ubiquitous in the environment and may induce multi-endpoint toxicity. Electronic waste(e-waste) dismantling is an under-rec...N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone(6PPDQ) and its parent 6PPD are ubiquitous in the environment and may induce multi-endpoint toxicity. Electronic waste(e-waste) dismantling is an under-recognized source of 6PPD and 6PPDQ emissions, and there is a lack of epidemiological investigations into their presence and health effects in local populations. This study aimed to determine the urinary concentrations of 6PPD and6PPDQ in children aged 2–7 years from e-waste dismantling areas and evaluate their potential risk to physical growth. We found that children from the e-waste area had significantly elevated urinary concentrations of 6PPD and 6PPDQ(median: 0.073 and 2.34 ng/mL) compared to those in the reference area(0.020 and 0.24 ng/mL, respectively). The estimated urinary excretions of 6PPDQ in the e-waste exposure group were considerably higher than that in the reference group(p < 0.001). Furthermore, a borderline significant association of co-exposure to high levels of 6PPD and 6PPDQ with lower BMI z-score(OR = 1.99, 95% Cl: 1.04,3.82) was observed in the crude model and the model adjusted for age and gender. In conclusion, our study first reported the urinary 6PPD and 6PPDQ concentrations in children from e-waste dismantling areas. The result indicated that e-waste recycling activities contribute to significantly elevated body burdens of 6PPD and 6PPDQ in children, which may be a potential risk factor for physical growth. Further epidemiological and toxicological studies are needed to investigate the exposure and health risks, especially in vulnerable populations.展开更多
Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-asso...Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.展开更多
N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the transl...N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.展开更多
[Objectives]To identify the authenticity of Longgu from the microscopic,infrared spectrum and chemical composition,and provide references for the quality control and evaluation methods of Longgu.[Methods]According to ...[Objectives]To identify the authenticity of Longgu from the microscopic,infrared spectrum and chemical composition,and provide references for the quality control and evaluation methods of Longgu.[Methods]According to the mineral characteristics of Longgu,the identification research was carried out by microscope observation,near-infrared spectroscopy and X-ray fluorescence spectrometer.By comparing the single polarizing and orthogonal polarizing characteristics of genuine and fake Longgu,a qualitative identification model of genuine Longgu was established based on the near-infrared spectrum of genuine Longgu,and the detection results of elements in Longgu were analyzed.[Results]The genuine Longgu had apatite optical properties,and was quite different from the fake Longgu of animal bones.Compared with modern animal bones,genuine Longgus had relatively less P and Ca,but they were enriched in elements Sr and F.The correlation coefficient model with good predictive ability can be established by using the near-infrared characteristic spectrum.[Conclusions]Polarizing microscope,near-infrared spectroscopy and X-ray fluorescence spectroscopy can improve the identification results of Longgu.展开更多
Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH r...Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.展开更多
基金supported by the National Natural Science Foundation of China(Nos.22272078 and 52371196)the National Key Research and Development Programof the Ministry of Science and Technology of China(No.2020YFA0406102)the“Innovation and Entrepreneurship of Talents plan”of Jiangsu Province.
文摘The direct conversion of greenhouse gas CO_(2) and low-cost CH3OH into valuable dimethyl carbonate(DMC)offers a promising low-carbon synthetic pathway,but the slow CO_(2) activation kinetics and entropy-decreasing nature of this reaction significantly restrict DMC yield to below 1%.In this work,2-cyanopyridine(2-CP)was employed as a dehydrating agent to suppress the reverse reaction between DMC and H_(2)O,shifting the thermodynamic equilibrium in favor of DMC production.Under this thermodynamic unconstrained condition,increasing oxygen vacancies,especially in the form of oxygen vacancy clusters,promotes catalytic activity significantly.We achieve a catalytic activity of 211 mmol/(g·h)at 140℃ on H_(2)-treated,oxygen-vacancy-clusters-rich CeO_(2) in the presence of 2-CP,a 1.6-fold increase compared to the activity with air-treated CeO_(2) under identical conditions.The DMC yield reaches 8.54%in a 20mL CH3OH solution with 2-CP,surpassing the calculated DMC yield of about 0.66%from the reaction equilibrium constant under the same conditions and without using the dehydrating agent.This work suggests the importance of using a dehydrating agent and also highlights oxygen vacancy clusters as pivotal active sites to promote DMC synthesis.Achieving sustainable DMC synthesis requires further exploration,encompassing strategies such as methods for regeneration of 2-CP.
基金supported by the National Natural Science Foundation of China,Nos.32271043(to ZW)and 82171047(to YM)the both Science and Technology Major Project of Shanghai,No.2018SHZDZX01 and ZJLabShanghai Center for Brain Science and Brain-Inspired Technology(to ZW)。
文摘Downregulation of the inwardly rectifying potassium channel Kir4.1 is a key step for inducing retinal Müller cell activation and interaction with other glial cells,which is involved in retinal ganglion cell apoptosis in glaucoma.Modulation of Kir4.1 expression in Müller cells may therefore be a potential strategy for attenuating retinal ganglion cell damage in glaucoma.In this study,we identified seven predicted phosphorylation sites in Kir4.1 and constructed lentiviral expression systems expressing Kir4.1 mutated at each site to prevent phosphorylation.Following this,we treated Müller glial cells in vitro and in vivo with the m Glu R I agonist DHPG to induce Kir4.1 or Kir4.1 Tyr^(9)Asp overexpression.We found that both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited activation of Müller glial cells.Subsequently,we established a rat model of chronic ocular hypertension by injecting microbeads into the anterior chamber and overexpressed Kir4.1 or Kir4.1 Tyr^(9)Asp in the eye,and observed similar results in Müller cells in vivo as those seen in vitro.Both Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression inhibited Müller cell activation,regulated the balance of Bax/Bcl-2,and reduced the m RNA and protein levels of pro-inflammatory factors,including interleukin-1βand tumor necrosis factor-α.Furthermore,we investigated the regulatory effects of Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression on the release of pro-inflammatory factors in a co-culture system of Müller glial cells and microglia.In this co-culture system,we observed elevated adenosine triphosphate concentrations in activated Müller cells,increased levels of translocator protein(a marker of microglial activation),and elevated interleukin-1βm RNA and protein levels in microglia induced by activated Müller cells.These changes could be reversed by Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression in Müller cells.Kir4.1 overexpression,but not Kir4.1 Tyr^(9)Asp overexpression,reduced the number of proliferative and migratory microglia induced by activated Müller cells.Collectively,these results suggest that the tyrosine residue at position nine in Kir4.1 may serve as a functional modulation site in the retina in an experimental model of glaucoma.Kir4.1 and Kir4.1 Tyr^(9)Asp overexpression attenuated Müller cell activation,reduced ATP/P2X receptor–mediated interactions between glial cells,inhibited microglial activation,and decreased the synthesis and release of pro-inflammatory factors,consequently ameliorating retinal ganglion cell apoptosis in glaucoma.
基金supported by the National Key Research and Development Program of China(No.2017YFC1600500)。
文摘Exposure to environmental cadmium increases the health risk of residents.Early urine metabolic detection using high-resolution mass spectrometry and machine learning algorithms would be advantageous to predict the adverse health effects.Here,we conducted machine learning approaches to screen potential biomarkers under cadmium exposure in 403 urine samples.In positive and negative ionization mode,4207 and 3558 features were extracted,respectively.We compared seven machine learning algorithms and found that the extreme gradient boosting(XGBoost)and random forest(RF)classifiers showed better accuracy and predictive performance than others.Following 5-fold cross-validation,the value of area under curve(AUC)was both 0.93 for positive and negative ionization modes in XGBoost classifier.In the RF classifier,AUC were 0.80 and 0.84 for positive and negative ionization modes,respectively.We then identified a biomarker panel based on XGBoost and RF classifiers.The incorporation of machine learning models into urine analysis using high-resolution mass spectrometry could allow a convenient assessment of cadmium exposure.
基金supported by the National Natural Science Foundation Major Research Plan(No.91843301)the Hong Kong General Research Fund(No.12302722)the National Natural Science Foundation of China(Nos.22306150 and 22376079).
文摘N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone(6PPDQ) and its parent 6PPD are ubiquitous in the environment and may induce multi-endpoint toxicity. Electronic waste(e-waste) dismantling is an under-recognized source of 6PPD and 6PPDQ emissions, and there is a lack of epidemiological investigations into their presence and health effects in local populations. This study aimed to determine the urinary concentrations of 6PPD and6PPDQ in children aged 2–7 years from e-waste dismantling areas and evaluate their potential risk to physical growth. We found that children from the e-waste area had significantly elevated urinary concentrations of 6PPD and 6PPDQ(median: 0.073 and 2.34 ng/mL) compared to those in the reference area(0.020 and 0.24 ng/mL, respectively). The estimated urinary excretions of 6PPDQ in the e-waste exposure group were considerably higher than that in the reference group(p < 0.001). Furthermore, a borderline significant association of co-exposure to high levels of 6PPD and 6PPDQ with lower BMI z-score(OR = 1.99, 95% Cl: 1.04,3.82) was observed in the crude model and the model adjusted for age and gender. In conclusion, our study first reported the urinary 6PPD and 6PPDQ concentrations in children from e-waste dismantling areas. The result indicated that e-waste recycling activities contribute to significantly elevated body burdens of 6PPD and 6PPDQ in children, which may be a potential risk factor for physical growth. Further epidemiological and toxicological studies are needed to investigate the exposure and health risks, especially in vulnerable populations.
基金supported by the National Natural Science Foundation of China,Nos.82071008(to BL)and 82004001(to XJ)Medical Science and Technology Program of Health Commission of Henan Province,No.LHGJ20210072(to RQ)Science and Technology Department of Henan Province,No.212102310307(to XJ)。
文摘Retinitis pigmentosa is a group of inherited diseases that lead to retinal degeneration and photoreceptor cell death.However,there is no effective treatment for retinitis pigmentosa caused by PDE6B mutation.Adeno-associated virus(AAV)-mediated gene therapy is a promising strategy for treating retinitis pigmentosa.The aim of this study was to explore the molecular mechanisms by which AAV2-PDE6B rescues retinal function.To do this,we injected retinal degeneration 10(rd10)mice subretinally with AAV2-PDE6B and assessed the therapeutic effects on retinal function and structure using dark-and light-adapted electroretinogram,optical coherence tomography,and immunofluorescence.Data-independent acquisition-mass spectrometry-based proteomic analysis was conducted to investigate protein expression levels and pathway enrichment,and the results from this analysis were verified by real-time polymerase chain reaction and western blotting.AAV2-PDE6B injection significantly upregulated PDE6βexpression,preserved electroretinogram responses,and preserved outer nuclear layer thickness in rd10 mice.Differentially expressed proteins between wild-type and rd10 mice were closely related to visual perception,and treating rd10 mice with AAV2-PDE6B restored differentially expressed protein expression to levels similar to those seen in wild-type mice.Kyoto Encyclopedia of Genes and Genome analysis showed that the differentially expressed proteins whose expression was most significantly altered by AAV2-PDE6B injection were enriched in phototransduction pathways.Furthermore,the phototransductionrelated proteins Pde6α,Rom1,Rho,Aldh1a1,and Rbp1 exhibited opposite expression patterns in rd10 mice with or without AAV2-PDE6B treatment.Finally,Bax/Bcl-2,p-ERK/ERK,and p-c-Fos/c-Fos expression levels decreased in rd10 mice following AAV2-PDE6B treatment.Our data suggest that AAV2-PDE6B-mediated gene therapy promotes phototransduction and inhibits apoptosis by inhibiting the ERK signaling pathway and upregulating Bcl-2/Bax expression in retinitis pigmentosa.
基金supported by the National Natural Science Foundation of China(82371083,82471100,82121003,82271084)Program of Science and Technology International Cooperation Project of Qinghai province(China)(2022-HZ-814)。
文摘N6-methyladenosine(m^(6)A)modification of mRNA is a critical post-transcriptional regulatory mechanism that modulates mRNA metabolism and neuronal function.The m^(6)A reader YTHDF1 has been shown to enhance the translational efficiency of m^(6)A-modified mRNAs in the brain and is essential for learning and memory.However,its role in the mature retina remains unclear.Herein,we report a novel role of Ythdf1 in the maintenance of retinal function using a genetic knockout model.Loss of Ythdf1 resulted in impaired scotopic electroretinogram(ERG)responses and progressive retinal degeneration.Detailed analyses of rod photoreceptors confirmed substantial degenerative changes in the absence of ciliary defects.Single-cell RNA sequencing revealed comprehensive molecular alterations across all retinal cell types in Ythdf1-deficient retinas.Integrative analysis of methylated RNA immunoprecipitation(MeRIP)sequencing and RIP sequencing identified Tulp1 and Dhx38,two inheritable retinal degeneration disease-associated gene homologs,as direct targets of YTHDF1 in the retina.Specifically,YTHDF1 recognized and bound m^(6)A-modified Tulp1 and Dhx38 mRNA at the coding sequence(CDS),enhancing their translational efficiency without altering mRNA levels.Collectively,these findings highlight the essential role of YTHDF1 in preserving visual function and reveal a novel regulatory mechanism of m^(6)A reader proteins in retinal degeneration,identifying potential therapeutic targets for severe retinopathies.
基金Supported by the Subject Talent Research Promotion Program for"Xinglin Scholars"of Chengdu University of Traditional Chinese Medicine(ZRQN2020019).
文摘[Objectives]To identify the authenticity of Longgu from the microscopic,infrared spectrum and chemical composition,and provide references for the quality control and evaluation methods of Longgu.[Methods]According to the mineral characteristics of Longgu,the identification research was carried out by microscope observation,near-infrared spectroscopy and X-ray fluorescence spectrometer.By comparing the single polarizing and orthogonal polarizing characteristics of genuine and fake Longgu,a qualitative identification model of genuine Longgu was established based on the near-infrared spectrum of genuine Longgu,and the detection results of elements in Longgu were analyzed.[Results]The genuine Longgu had apatite optical properties,and was quite different from the fake Longgu of animal bones.Compared with modern animal bones,genuine Longgus had relatively less P and Ca,but they were enriched in elements Sr and F.The correlation coefficient model with good predictive ability can be established by using the near-infrared characteristic spectrum.[Conclusions]Polarizing microscope,near-infrared spectroscopy and X-ray fluorescence spectroscopy can improve the identification results of Longgu.
基金This work was supported by grants from the National Natural Science Foundation of China(81790642 and 31872765)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJ Lab,and the Shanghai Center for Brain Science and Brain-Inspired Technology.
文摘Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma.Here,we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension(COH).In COH retinas,the microglial proliferation that occurred was inhibited by the P2X7 receptor(P2X7R)blocker BBG or P2X7R knockout,but not by the P2X4R blocker 5-BDBD.Treatment of primary cultured microglia with BzATP,a P2X7R agonist,mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway.Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration,which was completely blocked by 5-BDBD.In vivo and in vitro experiments demonstrated that ATP,released from activated Müller cells through connexin43 hemichannels,acted on P2X7R to induce microglial proliferation,and acted on P2X4R/P2X7R(mainly P2X4R)to induce microglial migration.Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
