Excessive activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation
针对炮钢材料25Cr3Mo3NiNbZr钢,结合可控离子渗入(Programable ion permeation,PIP)与激光淬火(Laser quenching,LQ)两种工艺优势进行复合处理以提升其表面性能。试验材料经调质预处理后,先进行PIP处理,再以不同扫描速度进行激光淬火。...针对炮钢材料25Cr3Mo3NiNbZr钢,结合可控离子渗入(Programable ion permeation,PIP)与激光淬火(Laser quenching,LQ)两种工艺优势进行复合处理以提升其表面性能。试验材料经调质预处理后,先进行PIP处理,再以不同扫描速度进行激光淬火。通过金相观察、XRD分析、显微硬度测试、电化学腐蚀以及中性盐雾试验等方法表征试样性能。结果表明,在2.31~3.00 J/mm^(2)的激光能量密度扫描下,部分化合物层发生了分解,降低了表面硬度;扩散层生成含氮马氏体,次表层硬度峰值得到提高。激光扫描速度为39 mm/s(激光能量密度为2.31 J/mm^(2))时工艺最佳,此时组织细化,含氮马氏体转变较多,表层氮化物损失较少,有效缓解“蛋壳效应”。PIP/LQ复合工艺处理试样的耐腐蚀性能虽低于PIP处理试样,但仍高于未处理试样,因此,PIP/LQ复合工艺在提高炮钢材料表面性能方面具有可行性。展开更多
Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangle...Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.展开更多
Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction （AR）. The mechanisms of these m...Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction （AR）. The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2＋ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase （PI3K） is phosphorylated/activated via a protein kinase A （PKA）-dependent cascade, and downregulated by protein kinase C a （PKCa）. PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP172 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate （cAMP） produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways： first, PIP2 acts as a cofactor for phospholipase D （PLD） activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase （SFK） is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.展开更多
Lactococcus lactis is an important food-grade microorganism that has been successfully applied as a starter to increase the level of 3-methylbutanal produced during the ripening of cheese.Three variants of branched-ch...Lactococcus lactis is an important food-grade microorganism that has been successfully applied as a starter to increase the level of 3-methylbutanal produced during the ripening of cheese.Three variants of branched-chain α-keto acid decarboxylase (KADC) were discovered in L.lactis strains with different 3-methylbutanal production abilities.Three genes encoding KADCs of varying lengths (KADC-long,KADC-middle,and KADC-short) were cloned and heterologously expressed into Escherichia coli.KADC activity was only detected in the E.coli cloned with the KADC-long-encoding gene.Homology modeling of the three KADC recombination proteins showed that an active-site residue (Glu462) and an S-pocket structure were necessary for the ability to catalyze substrates.KADC-long showed maximum activity at pH 7.0 and 30 ℃.The substrate hydrolysis and kinetic parameters demonstrated that KADC-long efficiently produces 2-methylbutanal and 3-methylbutanal.The heterologous expression of the full-length kdcA in low-3-methylbutanal-yield L.lactis strains increased their production yields.The results of this study demonstrate the function of the complete KADC in 3-methylbutanal production.展开更多
In this paper,a high-yield Hf-modified SiHfBOC ceramic precursor was developed,and a high-pressure assisted impregnation pyrolysis method was proposed to achieve the preparation of 3D PyC–Cf/SiHfBOC composites.This h...In this paper,a high-yield Hf-modified SiHfBOC ceramic precursor was developed,and a high-pressure assisted impregnation pyrolysis method was proposed to achieve the preparation of 3D PyC–Cf/SiHfBOC composites.This high-pressure assisted impregnation method significantly improves impregnation filling effect of the precursor in and between fiber bundles compared to dozens of traditional impregnation cycles.After undergoing just 9 precursor infiltration pyrolysis(PIP)cycles,the composites achieved relative density of approximately 90%and density of 1.64 g/cm^(3).The critical temperature difference of the 3D PyC–Cf/SiHfBOC composites after the shock of room temperature(RT)–1000℃is as high as 650℃,which is twice that of traditional ceramic materials,showing good thermal shock resistance.Under the effect of Hf modification,a dense HfO_(2)–SiO_(2)oxide layer(thickness of 93μm)was formed in situ on the surface of the 3D PyC–Cf/SiHfBOC composites,effectively preventing further erosion of the composite matrix by high-temperature oxidation gas.Even in the ultra-high-temperature oxygen-containing environment at 1800℃,it still exhibits an excellent non-ablative result(with a linear ablation rate of 0.83×10^(−4)mm/s).This work not only enriches the basic research on lightweight ultra-high-temperature ceramic composites converted from Hf ceramic precursors,but also provides strong technical support for their applications in ultra-high-temperature non-ablative thermal protection materials for high-speed aircraft.展开更多
文摘Excessive activation of G-protein coupled receptor (GPCR) and receptor tyrosine kinase (RTK) pathways has been linked to prostate cancer metastasis. Rac activation
基金supported by a grant from Key Laboratory of Alzheimer's Disease of Zhejiang Province,Institute of Aging,Wenzhou Medical University,No.ZJAD-2021002(to ZW)。
文摘Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.
文摘Mammalian sperm must undergo a series of biochemical and physiological modifications, collectively called capacitation, in the female reproductive tract prior to the acrosome reaction （AR）. The mechanisms of these modifications are not well characterized though protein kinases were shown to be involved in the regulation of intracellular Ca2＋ during both capacitation and the AR. In the present review, we summarize some of the signaling events that are involved in capacitation. During the capacitation process, phosphatidyl-inositol-3-kinase （PI3K） is phosphorylated/activated via a protein kinase A （PKA）-dependent cascade, and downregulated by protein kinase C a （PKCa）. PKCa is active at the beginning of capacitation, resulting in PI3K inactivation. During capacitation, PKCa as well as PP172 is degraded by a PKA-dependent mechanism, allowing the activation of PI3K. The activation of PKA during capacitation depends mainly on cyclic adenosine monophosphate （cAMP） produced by the bicarbonate-dependent soluble adenylyl cyclase. This activation of PKA leads to an increase in actin polymerization, an essential process for the development of hyperactivated motility, which is necessary for successful fertilization. Actin polymerization is mediated by PIP2 in two ways： first, PIP2 acts as a cofactor for phospholipase D （PLD） activation, and second, as a molecule that binds and inhibits actin-severing proteins such as gelsolin. Tyrosine phosphorylation of gelsolin during capacitation by Src family kinase （SFK） is also important for its inactivation. Prior to the AR, gelsolin is released from PIP2 and undergoes dephosphorylation/activation, resulting in fast F-actin depolymerization, leading to the AR.
基金supported by the National Natural Science Foundation of China(No.31972197).
文摘Lactococcus lactis is an important food-grade microorganism that has been successfully applied as a starter to increase the level of 3-methylbutanal produced during the ripening of cheese.Three variants of branched-chain α-keto acid decarboxylase (KADC) were discovered in L.lactis strains with different 3-methylbutanal production abilities.Three genes encoding KADCs of varying lengths (KADC-long,KADC-middle,and KADC-short) were cloned and heterologously expressed into Escherichia coli.KADC activity was only detected in the E.coli cloned with the KADC-long-encoding gene.Homology modeling of the three KADC recombination proteins showed that an active-site residue (Glu462) and an S-pocket structure were necessary for the ability to catalyze substrates.KADC-long showed maximum activity at pH 7.0 and 30 ℃.The substrate hydrolysis and kinetic parameters demonstrated that KADC-long efficiently produces 2-methylbutanal and 3-methylbutanal.The heterologous expression of the full-length kdcA in low-3-methylbutanal-yield L.lactis strains increased their production yields.The results of this study demonstrate the function of the complete KADC in 3-methylbutanal production.
基金the National Natural Science Foundation of China(No.52032003)National Natural Science Foundation of China(Nos.51972082,52102093,and 52172041)+1 种基金Postdoctoral Research Foundation of China(No.2021M690817)the Science Foundation of National Key Laboratoryof Science and Technology on Advanced Composites in Special Environments.
文摘In this paper,a high-yield Hf-modified SiHfBOC ceramic precursor was developed,and a high-pressure assisted impregnation pyrolysis method was proposed to achieve the preparation of 3D PyC–Cf/SiHfBOC composites.This high-pressure assisted impregnation method significantly improves impregnation filling effect of the precursor in and between fiber bundles compared to dozens of traditional impregnation cycles.After undergoing just 9 precursor infiltration pyrolysis(PIP)cycles,the composites achieved relative density of approximately 90%and density of 1.64 g/cm^(3).The critical temperature difference of the 3D PyC–Cf/SiHfBOC composites after the shock of room temperature(RT)–1000℃is as high as 650℃,which is twice that of traditional ceramic materials,showing good thermal shock resistance.Under the effect of Hf modification,a dense HfO_(2)–SiO_(2)oxide layer(thickness of 93μm)was formed in situ on the surface of the 3D PyC–Cf/SiHfBOC composites,effectively preventing further erosion of the composite matrix by high-temperature oxidation gas.Even in the ultra-high-temperature oxygen-containing environment at 1800℃,it still exhibits an excellent non-ablative result(with a linear ablation rate of 0.83×10^(−4)mm/s).This work not only enriches the basic research on lightweight ultra-high-temperature ceramic composites converted from Hf ceramic precursors,but also provides strong technical support for their applications in ultra-high-temperature non-ablative thermal protection materials for high-speed aircraft.
