Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-i...Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.展开更多
The van der Waals heterojunctions,stacking of different two-dimensional materials,have opened unprecedented opportunities to explore new physics and device concepts.Here,combining the density functional theory with no...The van der Waals heterojunctions,stacking of different two-dimensional materials,have opened unprecedented opportunities to explore new physics and device concepts.Here,combining the density functional theory with non-equilibrium Green’s function technique,we systematically investigate the spin-polarized transport properties of van der Waals magnetic tunnel junctions(MTJs),Cu/MnBi_(2)Te_(4)/MnBi_(2)Te_(4)/Cu and Cu/MnBi_(2)Te_(4)/hBN/n·MnBi_(2)Te_(4)/Cu(n=1,2,3).It is found that the maximum tunnel magnetoresistance of Cu/MnBi_(2)Te_(4)/hBN/3·MnBi_(2)Te_(4)/Cu MTJs can reach 162.6%,exceeding the system with only a single layer MnBi_(2)Te_(4).More interestingly,our results indicate that Cu/MnBi_(2)Te_(4)/h-BN/n·MnBi_(2)Te_(4)/Cu(n=2,3)MTJs can realize the switching function,while Cu/MnBi_(2)Te_(4)/h-BN/3·MnBi_(2)Te_(4)/Cu MTJs exhibit the negative differential resistance.The Cu/MnBi_(2)Te_(4)/h-BN/3·MnBi_(2)Te_(4)/Cu in the parallel state shows a spin injection efficiency of more than 83.3%.Our theoretical findings of the transport properties will shed light on the possible experimental studies of MnBi_(2)Te_(4)-based van der Waals magnetic tunneling junctions.展开更多
Background:JUNO and IZUMO1 are the first receptor-ligand protein pairs discovered to be essential for spermoocyte fusion;their interaction is indispensable for fertilization.Methods:PCR was used to clone the full-leng...Background:JUNO and IZUMO1 are the first receptor-ligand protein pairs discovered to be essential for spermoocyte fusion;their interaction is indispensable for fertilization.Methods:PCR was used to clone the full-length DNA sequence of the Juno gene in sheep.The single nucleotide polymorphism(SNP)loci of Juno were genotyped by Sequenom MassARRAY®.PCR combined with rapid amplification of cDNA Ends were used to clone the full-length cDNA sequence of Juno and Izumo1.Reverse transcriptase-PCR(RT-PCR)and real time-quantitative-PCR(RT-qPCR)were used to analyze the genes’expression in tissues of sheep,and single cell RNA-seq was used to analyze the genes’expression in oocytes,granulosa cells and follicular theca of polytocous and monotocous Small Tail Han ewes.Bioinformatics was used to analyze advanced structure and phylogeny of JUNO and IZUMO1 proteins.Results:The full-length DNA sequence of the Juno gene in sheep was cloned and nine SNPs were screened.We found a significant association between the g.848253 C>A locus of Juno and litter size of Small Tail Han sheep(P<0.05).The full-length cDNA sequence of Juno and Izumo1 genes from Small Tail Han sheep were obtained.We found a new segment of the Izumo1 CDS consisting of 35 bp,and we confirmed the Izumo1 gene has 9 exons,not 8.RT-qPCR showed that Juno and Izumo1 genes were highly expressed in ovarian and testicular tissues,respectively(P<0.01).Single cell RNA-seq showed Juno was specifically expressed in oocytes,but not in granulosa cells or follicular theca,while Izumo1 displayed little to no expression in all three cell types.There was no difference in expression of the Juno gene in oocyte and ovarian tissue in sheep with different litter sizes,indicating expression of Juno is not related to litter size traits.Bioinformatic analysis revealed the g.848253 C>A locus of Juno results in a nonconservative missense point mutation leading to a change from Phe to Leu at position 219 in the amino acid sequence.Conclusions:For the first time,this study systematically analyzed the expression,structure and function of Juno and Izumo1 genes and their encoded proteins in Small Tail Han sheep,providing the basis for future studies of the regulatory mechanisms of Juno and Izumo1 genes.展开更多
The two-dimensional magnetic van der Waals heterojunctions have opened unprecedented opportunities to explore new physics due to their potential for spintronic applications.Here,combing density functional theory with ...The two-dimensional magnetic van der Waals heterojunctions have opened unprecedented opportunities to explore new physics due to their potential for spintronic applications.Here,combing density functional theory with non-equilibrium Green’s function technique.展开更多
基金supported by research grants from the Ningbo Science and Technology Plan Project,No.2022Z143hezuo(to BL)the National Natural Science Foundation of China,No.82201520(to XD)。
文摘Although microglial polarization and neuroinflammation are crucial cellular responses after traumatic brain injury,the fundamental regulatory and functional mechanisms remain insufficiently understood.As potent anti-inflammato ry agents,the use of glucoco rticoids in traumatic brain injury is still controversial,and their regulatory effects on microglial polarization are not yet known.In the present study,we sought to determine whether exacerbation of traumatic brain injury caused by high-dose dexamethasone is related to its regulatory effects on microglial polarization and its mechanisms of action.In vitro cultured BV2 cells and primary microglia and a controlled cortical impact mouse model were used to investigate the effects of dexamethasone on microglial polarization.Lipopolysaccharide,dexamethasone,RU486(a glucocorticoid receptor antagonist),and ruxolitinib(a Janus kinase 1 antagonist)were administered.RNA-sequencing data obtained from a C57BL/6 mouse model of traumatic brain injury were used to identify potential targets of dexamethasone.The Morris water maze,quantitative reverse transcription-polymerase chain reaction,western blotting,immunofluorescence and confocal microscopy analysis,and TUNEL,Nissl,and Golgi staining were performed to investigate our hypothesis.High-throughput sequencing results showed that arginase 1,a marker of M2 microglia,was significantly downregulated in the dexamethasone group compared with the traumatic brain injury group at3 days post-traumatic brain injury.Thus dexamethasone inhibited M1 and M2 microglia,with a more pronounced inhibitory effect on M2microglia in vitro and in vivo.Glucocorticoid receptor plays an indispensable role in microglial polarization after dexamethasone treatment following traumatic brain injury.Additionally,glucocorticoid receptor activation increased the number of apoptotic cells and neuronal death,and also decreased the density of dendritic spines.A possible downstream receptor signaling mechanism is the GR/JAK1/STAT3 pathway.Overactivation of glucocorticoid receptor by high-dose dexamethasone reduced the expression of M2 microglia,which plays an antiinflammatory role.In contrast,inhibiting the activation of glucocorticoid receptor reduced the number of apoptotic glia and neurons and decreased the loss of dendritic spines after traumatic brain injury.Dexamethasone may exe rt its neurotoxic effects by inhibiting M2 microglia through the GR/JAK1/STAT3 signaling pathway.
基金supported the National Key Research and Development Program of China(Grant No.2022YFB3505301)the Natural Science Basic Research Program of Shanxi(Grant Nos.20210302124252,202203021222219)。
文摘The van der Waals heterojunctions,stacking of different two-dimensional materials,have opened unprecedented opportunities to explore new physics and device concepts.Here,combining the density functional theory with non-equilibrium Green’s function technique,we systematically investigate the spin-polarized transport properties of van der Waals magnetic tunnel junctions(MTJs),Cu/MnBi_(2)Te_(4)/MnBi_(2)Te_(4)/Cu and Cu/MnBi_(2)Te_(4)/hBN/n·MnBi_(2)Te_(4)/Cu(n=1,2,3).It is found that the maximum tunnel magnetoresistance of Cu/MnBi_(2)Te_(4)/hBN/3·MnBi_(2)Te_(4)/Cu MTJs can reach 162.6%,exceeding the system with only a single layer MnBi_(2)Te_(4).More interestingly,our results indicate that Cu/MnBi_(2)Te_(4)/h-BN/n·MnBi_(2)Te_(4)/Cu(n=2,3)MTJs can realize the switching function,while Cu/MnBi_(2)Te_(4)/h-BN/3·MnBi_(2)Te_(4)/Cu MTJs exhibit the negative differential resistance.The Cu/MnBi_(2)Te_(4)/h-BN/3·MnBi_(2)Te_(4)/Cu in the parallel state shows a spin injection efficiency of more than 83.3%.Our theoretical findings of the transport properties will shed light on the possible experimental studies of MnBi_(2)Te_(4)-based van der Waals magnetic tunneling junctions.
基金This research was funded by National Natural Science Foundation of China,grant number 31501941Central Public-interest Scientific Institution Basal Research Fund,grant number 2018-YWF-YB-1,and 2015ywf-zd-2+1 种基金the Earmarked Fund for China Agriculture Research System,grant number CARS-38the Agricultural Science and Technology Innovation Program of China,grant number ASTIP-IAS13.
文摘Background:JUNO and IZUMO1 are the first receptor-ligand protein pairs discovered to be essential for spermoocyte fusion;their interaction is indispensable for fertilization.Methods:PCR was used to clone the full-length DNA sequence of the Juno gene in sheep.The single nucleotide polymorphism(SNP)loci of Juno were genotyped by Sequenom MassARRAY®.PCR combined with rapid amplification of cDNA Ends were used to clone the full-length cDNA sequence of Juno and Izumo1.Reverse transcriptase-PCR(RT-PCR)and real time-quantitative-PCR(RT-qPCR)were used to analyze the genes’expression in tissues of sheep,and single cell RNA-seq was used to analyze the genes’expression in oocytes,granulosa cells and follicular theca of polytocous and monotocous Small Tail Han ewes.Bioinformatics was used to analyze advanced structure and phylogeny of JUNO and IZUMO1 proteins.Results:The full-length DNA sequence of the Juno gene in sheep was cloned and nine SNPs were screened.We found a significant association between the g.848253 C>A locus of Juno and litter size of Small Tail Han sheep(P<0.05).The full-length cDNA sequence of Juno and Izumo1 genes from Small Tail Han sheep were obtained.We found a new segment of the Izumo1 CDS consisting of 35 bp,and we confirmed the Izumo1 gene has 9 exons,not 8.RT-qPCR showed that Juno and Izumo1 genes were highly expressed in ovarian and testicular tissues,respectively(P<0.01).Single cell RNA-seq showed Juno was specifically expressed in oocytes,but not in granulosa cells or follicular theca,while Izumo1 displayed little to no expression in all three cell types.There was no difference in expression of the Juno gene in oocyte and ovarian tissue in sheep with different litter sizes,indicating expression of Juno is not related to litter size traits.Bioinformatic analysis revealed the g.848253 C>A locus of Juno results in a nonconservative missense point mutation leading to a change from Phe to Leu at position 219 in the amino acid sequence.Conclusions:For the first time,this study systematically analyzed the expression,structure and function of Juno and Izumo1 genes and their encoded proteins in Small Tail Han sheep,providing the basis for future studies of the regulatory mechanisms of Juno and Izumo1 genes.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3505301)the Natural Science Basic Research Program of Shanxi(Grant No.20210302124252)the Innovation Project For Teaching Reform of Shanxi(Grant No.J20230616)。
文摘The two-dimensional magnetic van der Waals heterojunctions have opened unprecedented opportunities to explore new physics due to their potential for spintronic applications.Here,combing density functional theory with non-equilibrium Green’s function technique.
