Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite ou...Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.展开更多
Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinf...Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.展开更多
Chemical hydrogen storage in organic materials is a promising method thanks to its high storage density,reversibility,and safety.However,the dehydrogenation process of organic materials requires high temperatures due ...Chemical hydrogen storage in organic materials is a promising method thanks to its high storage density,reversibility,and safety.However,the dehydrogenation process of organic materials requires high temperatures due to their unfavorable thermodynamic properties.This study proposes a strategy to design a new type of hydrogen storage materials,i.e.,alkali metal pyridinolate/piperidinolate pairs,by combining the effects of a heteroatom and an alkali metal in one molecule to achieve suitable dehydrogenation thermodynamics along with high hydrogen storage capacities.These air-stable compounds can be synthesized using low-cost reactants and water as a green solvent.Thermodynamic predictions indicate that enthalpy changes of dehydrogenation(ΔH_(d))can be significantly reduced to the optimal range for efficient hydrogen release,exemplified by lithium 2-piperidinolate with a 5.6 wt%hydrogen capacity and a suitableΔH_(d)of 32.2 kJ/mol-H_(2).Experimental results obtained using sodium systems validate the computational predictions,demonstrating reversible hydrogen storage even below 100℃.The superior hydrogen desorption performance of alkali metal piperidinolates could be attributed to their suitableΔH_(d)induced by the combined effect of ring nitrogen and metal substitution on their structures.This study not only reports new low-cost hydrogen storage materials but also provides a rational design strategy for developing metalorganic compounds possessing high hydrogen capacities and suitable thermodynamics for efficient hydrogen storage.展开更多
Both the thickness effect and surface effect should be important in nano-indentation behavior of coatings due to the finite thickness and small indentation size.As a basic solution,the two-dimensional Boussinesq probl...Both the thickness effect and surface effect should be important in nano-indentation behavior of coatings due to the finite thickness and small indentation size.As a basic solution,the two-dimensional Boussinesq problem of a finite elastic layer bonded to a rigid substrate is studied in this paper,employing the surface-energy-density-based elastic theory.The Airy stress function and Fourier integral transform methods are adopted to solve the problem.A nalytical solutions of both the stress and displacement fields are well achieved for a finite elastic layer under a concentrated force and a uniform pressure.Unlike the classical solutions,it is discovered that both the thickness effect and surface effect will show significant influences on the Boussinesq elastic behaviors.The surface effect would harden the finite elastic layer and induce a more uniformly distributing displacements and stresses.Only when the thickness is sufficiently large,the Boussinesq solution of an elastic half space may represent that of a finite elastic layer case.A generalized hardness is further defined to include the coupling effects of thickness and surface for the Boussinesq problem of a finite elastic layer.Such a study would assist in the design and property evaluation of coatings and micro-devices with layer-substrate structures.展开更多
The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for th...The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.展开更多
生物多样性强烈的时空尺度依赖性和多层次性决定了生物多样性现状与变量的分析需要在不同生态系统进行多空间尺度、全面和连续的监测。因此,构建生物多样性研究监测网络是生物多样性保护和研究的基础工作。近年来,对地观测组织-生物多...生物多样性强烈的时空尺度依赖性和多层次性决定了生物多样性现状与变量的分析需要在不同生态系统进行多空间尺度、全面和连续的监测。因此,构建生物多样性研究监测网络是生物多样性保护和研究的基础工作。近年来,对地观测组织-生物多样性观测网络(GEO BON)、亚太生物多样性监测网络(APBON)等全球、区域以及国家尺度的生物多样性监测网络蓬勃发展。中国陆续在国家尺度上建立了针对生态系统和物种的长期监测网络,其中,中国生物多样性监测与研究网络(China Biodiversity Observation and Research Network,Sino BON)于2013年启动建设,在我国主要生态系统和环境梯度设置30个监测主点和60个监测辅点,目前已建成10个专项网对动物、植物和微生物进行监测,并建立了以数据标准与汇交、近地面遥感为核心的综合监测中心。Sino BON打造了从地下、地面到森林林冠的多尺度、多类群(功能群)以及多营养级交互为重点的监测与研究平台,为理解生物多样性变化趋势及其驱动因素、研究生物多样性维持机制,以及国家履行《生物多样性公约》、保护生物多样性和生物资源提供详实可靠的生物多样性变化数据。为进一步支撑国家生物多样性治理能力、深化全球多样性保护合作,我国生物多样性监测亟需在监测技术、监测区域、数据标准、综合信息平台等方向谋求更大的发展。展开更多
Background:Inflammation-based indexes have been used to predict survival and recurrence in cancer patients.Systemic immune-inflammation index(Sll) was reported to be associated with prognosis in some malignant tumors....Background:Inflammation-based indexes have been used to predict survival and recurrence in cancer patients.Systemic immune-inflammation index(Sll) was reported to be associated with prognosis in some malignant tumors.In the present study,we aimed to explore the association between Sll and the prognosis of patients with gastric cancer.Methods:We retrospectively analyzed data from 444 gastric cancer patients who underwent gastrectomy at the First Affiliated Hospital of Sun Yat-sen University between January 1994 and December 2005.Preoperative Sll was calculated.The Chi square test or Fisher's exact test was used to determine the relationship between preoperative Sll and clinicopathologic characteristics.Overall survival(OS) rates were estimated using the Kaplan-Meier method,and the effect of Sll on OS was analyzed using the Cox proportional hazards model.Receiver operating characteristic(ROC)curves were used to compare the predictive ability of Sll,NLR,and PLR.Results:Sll equal to or higher than 660 was significantly associated with old age,large tumor size,unfavorable Borrmann classification,advanced tumor invasion,lymph node metastasis,distant metastasis,advanced TNM stage,and high carcino-embryonic antigen level,high neutrophil-lymphocyte ratio,and high platelet-lymphocyte ratio(all P<0.05).High Sll was significantly associated with unfavorable prognosis(P<0.001) and Sll was an independent predictor for OS(P=0.015).Subgroups analysis further showed significant associations between high Sll and short OS in stage Ⅰ,Ⅱ,Ⅲ subgroups(all P<0.05).Sll was superior to NLR and PLR for predicting OS in patients with gastric cancer.Conclusion:Preoperative Sll level is an independent prognostic factor for OS in patients with gastric cancer.展开更多
基金supported by the National Natural Science Foundation of China,No.32071033(to MT)Basic and Applied Basic Research Foundation of Guangdong Province,Nos.2023A1515010140(to MT),2022A1515140169(to MT),2022A1515111096(to ZC)+3 种基金Science and Technology Project of Guangzhou,Nos.202201010015(to YL),2023A03J0790(to TJ)Basic and Applied Basic Research Foundation of Guangzhou,No.2023A04J1285(to ZC)Medical Research Foundation of Guangdong Province,No.A2023147(to ZC)Health Science and Technology Project of Guangzhou,No.20221A011039(to TJ)。
文摘Post-translational modification of spastin enables precise spatiotemporal control of its microtubule severing activity.However,the detailed mechanism by which spastin turnover is regulated in the context of neurite outgrowth remains unknown.Here,we found that spastin interacted with ubiquitin and was significantly degraded by K48-mediated poly-ubiquitination.Cullin3 facilitated spastin degradation and ubiquitination.RING-box protein 1,but not RING-box protein 2,acted synergistically with Cullin3 protein to regulate spastin degradation.Overexpression of Culin3 or BRX1 markedly suppressed spastin expression,and inhibited spastin-mediated microtubule severing and promotion of neurite outgrowth.Moreover,USP14 interacted directly with spastin to mediate its deubiquitination.USP14 overexpression significantly increased spastin expression and suppressed its ubiquitination and degradation.Although co-expression of spastin and USP14 did not enhance microtubule severing,it did increase neurite length in hippocampal neurons.Taken together,these findings elucidate the intricate regulatory mechanisms of spastin turnover,highlighting the roles of the Cullin-3–Ring E3 ubiquitin ligase complex and USP14 in orchestrating its ubiquitination and degradation.The dynamic interplay between these factors governs spastin stability and function,ultimately influencing microtubule dynamics and neuronal morphology.These insights shed light on potential therapeutic targets for neurodegenerative disorders associated with spastin defects.
基金supported by the Educational Commission of Shanghai in China(No.2021LK114)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)the Xinglin Young Talent Program at Shanghai University of Traditional Chinese Medicine(No.A1-U17205010430)。
文摘Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
基金partially supported by the National Key R&D Program of China(2023YFE0198900)support provided by the National Natural Science Foundation of China(52171226,22309174)。
文摘Chemical hydrogen storage in organic materials is a promising method thanks to its high storage density,reversibility,and safety.However,the dehydrogenation process of organic materials requires high temperatures due to their unfavorable thermodynamic properties.This study proposes a strategy to design a new type of hydrogen storage materials,i.e.,alkali metal pyridinolate/piperidinolate pairs,by combining the effects of a heteroatom and an alkali metal in one molecule to achieve suitable dehydrogenation thermodynamics along with high hydrogen storage capacities.These air-stable compounds can be synthesized using low-cost reactants and water as a green solvent.Thermodynamic predictions indicate that enthalpy changes of dehydrogenation(ΔH_(d))can be significantly reduced to the optimal range for efficient hydrogen release,exemplified by lithium 2-piperidinolate with a 5.6 wt%hydrogen capacity and a suitableΔH_(d)of 32.2 kJ/mol-H_(2).Experimental results obtained using sodium systems validate the computational predictions,demonstrating reversible hydrogen storage even below 100℃.The superior hydrogen desorption performance of alkali metal piperidinolates could be attributed to their suitableΔH_(d)induced by the combined effect of ring nitrogen and metal substitution on their structures.This study not only reports new low-cost hydrogen storage materials but also provides a rational design strategy for developing metalorganic compounds possessing high hydrogen capacities and suitable thermodynamics for efficient hydrogen storage.
基金supported by the National Natural Science Foundation of China(Grant Nos.12032004,12293000,12293002,and 12272043).
文摘Both the thickness effect and surface effect should be important in nano-indentation behavior of coatings due to the finite thickness and small indentation size.As a basic solution,the two-dimensional Boussinesq problem of a finite elastic layer bonded to a rigid substrate is studied in this paper,employing the surface-energy-density-based elastic theory.The Airy stress function and Fourier integral transform methods are adopted to solve the problem.A nalytical solutions of both the stress and displacement fields are well achieved for a finite elastic layer under a concentrated force and a uniform pressure.Unlike the classical solutions,it is discovered that both the thickness effect and surface effect will show significant influences on the Boussinesq elastic behaviors.The surface effect would harden the finite elastic layer and induce a more uniformly distributing displacements and stresses.Only when the thickness is sufficiently large,the Boussinesq solution of an elastic half space may represent that of a finite elastic layer case.A generalized hardness is further defined to include the coupling effects of thickness and surface for the Boussinesq problem of a finite elastic layer.Such a study would assist in the design and property evaluation of coatings and micro-devices with layer-substrate structures.
基金supported by grants from the National Natural Science Foundation of China(N0.82474525 and No.82074444)the Hunan Provincial Natural Outstanding Young People Science Foundation(2023JJ10032)the Hunan Province Health and High-Level Talent Medical Academic Leader Training Plan(20240304051).
文摘The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms.Testosterone,as one of the most critical sex hormones,is essential for the development of the reproductive system,maintenance of reproductive function,and the overall health of males.The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes.Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis.We also examined the specific effects of these genes on the occurrence,development,and treatment of common male diseases,including late-onset hypogonadism,erectile dysfunction,male infertility,and prostate cancer.
文摘生物多样性强烈的时空尺度依赖性和多层次性决定了生物多样性现状与变量的分析需要在不同生态系统进行多空间尺度、全面和连续的监测。因此,构建生物多样性研究监测网络是生物多样性保护和研究的基础工作。近年来,对地观测组织-生物多样性观测网络(GEO BON)、亚太生物多样性监测网络(APBON)等全球、区域以及国家尺度的生物多样性监测网络蓬勃发展。中国陆续在国家尺度上建立了针对生态系统和物种的长期监测网络,其中,中国生物多样性监测与研究网络(China Biodiversity Observation and Research Network,Sino BON)于2013年启动建设,在我国主要生态系统和环境梯度设置30个监测主点和60个监测辅点,目前已建成10个专项网对动物、植物和微生物进行监测,并建立了以数据标准与汇交、近地面遥感为核心的综合监测中心。Sino BON打造了从地下、地面到森林林冠的多尺度、多类群(功能群)以及多营养级交互为重点的监测与研究平台,为理解生物多样性变化趋势及其驱动因素、研究生物多样性维持机制,以及国家履行《生物多样性公约》、保护生物多样性和生物资源提供详实可靠的生物多样性变化数据。为进一步支撑国家生物多样性治理能力、深化全球多样性保护合作,我国生物多样性监测亟需在监测技术、监测区域、数据标准、综合信息平台等方向谋求更大的发展。
基金supported by the National Natural Science Foundation of China(Grant No.81372341)the PhD Start-up Fund of the Natural Science Foundation of Guangdong Province,China(Grant No.2014A030310111)the"3&3"project of the First Affiliated Hospital of Sun Yat-sen University
文摘Background:Inflammation-based indexes have been used to predict survival and recurrence in cancer patients.Systemic immune-inflammation index(Sll) was reported to be associated with prognosis in some malignant tumors.In the present study,we aimed to explore the association between Sll and the prognosis of patients with gastric cancer.Methods:We retrospectively analyzed data from 444 gastric cancer patients who underwent gastrectomy at the First Affiliated Hospital of Sun Yat-sen University between January 1994 and December 2005.Preoperative Sll was calculated.The Chi square test or Fisher's exact test was used to determine the relationship between preoperative Sll and clinicopathologic characteristics.Overall survival(OS) rates were estimated using the Kaplan-Meier method,and the effect of Sll on OS was analyzed using the Cox proportional hazards model.Receiver operating characteristic(ROC)curves were used to compare the predictive ability of Sll,NLR,and PLR.Results:Sll equal to or higher than 660 was significantly associated with old age,large tumor size,unfavorable Borrmann classification,advanced tumor invasion,lymph node metastasis,distant metastasis,advanced TNM stage,and high carcino-embryonic antigen level,high neutrophil-lymphocyte ratio,and high platelet-lymphocyte ratio(all P<0.05).High Sll was significantly associated with unfavorable prognosis(P<0.001) and Sll was an independent predictor for OS(P=0.015).Subgroups analysis further showed significant associations between high Sll and short OS in stage Ⅰ,Ⅱ,Ⅲ subgroups(all P<0.05).Sll was superior to NLR and PLR for predicting OS in patients with gastric cancer.Conclusion:Preoperative Sll level is an independent prognostic factor for OS in patients with gastric cancer.
