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Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK

Life Metabolism 2023年第3期2卷 19-32页

作者： Mengqi Li Xiaoyan wei jinye Xiong jin-wei feng Chen-Song Zhang Sheng-Cai Lin State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamenFujian 361102China

When glucose is replete,mammalian/mechanistic target of rapamycin complex 1(mTORC1)is active and anchored to the lysosomal surface via the two GTPases,Ras-related GTPase(RAG)and Ras homolog enriched in brain(Rheb),which are regulated by Ragulator and tuberous sclerosis complex 2(TSC2),*** glucose is low,aldolase senses low fructose-1,6-bisphosphate level and promotes the translocation of AXIN−liver kinase B1(LKB1)to the lysosomal surface,which leads to the activation of AMP-activated protein kinase(AMPK)and the inhibition of RAGs,sundering mTORC1 from the lysosome and causing its *** can also inactivate mTORC1 by phosphorylating Raptor and ***,the hierarchy of AXIN-and AMPK-mediated inhibition of mTORC1 remains poorly ***,we show that AXIN translocation does not require AMPK expression or *** glucose starvation conditions,knockout of AXIN extended the half-life of mTORC1 inhibition from 15 to 60 min,whereas knockout of AMPK only extended it to 30 ***(constitutively active RAGB)almost entirely blocked the lysosomal dissociation and inhibition of mTORC1 under glucose starvation,but it did not inhibit AMPK,indicating that under these conditions,it is AXIN lysosomal translocation that inhibits mTORC1,and it does so via inhibition of RAGs.5-aminoimidazole-4-carboxamide ribonucleoside(AICAR),a mimetic of AMP,which activates both cytosolic AMPK and lysosomal AMPK,fully inhibited mTORC1 even when it is stably anchored to the lysosome by RAGBGTP,whereas glucose starvation mildly inhibited such anchored ***,we demonstrate that the lysosomal translocation of AXIN plays a primary role in glucose starvation-triggered inhibition of mTORC1 by inhibiting RAGs,and that AMPK activity inhibits mTORC1 through phosphorylating Raptor and TSC2,especially under severe stress.

关键词： mTORC1 glucose sensing AMPK

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Differentially expressed miRNAs in anthers may contribute to the fertility of a novel Brassica napus genic male sterile line CN12A

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Journal of Integrative Agriculture 2020年第7期19卷 1731-1742页

作者： DONG Yun WANG Yi jin feng-wei XING Lijuan FANG Yan ZHANG Zheng-ying ZOU Jun-jie WANG Lei XU Miao-yun Crop Research Institute Gansu Academy of Agricultural SciencesLanzhou 730070P.R.China National Key Facility for Crop Gene Resources and Genetic ImprovementBiotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081P.R.China Gansu Provincial Key Lab of Aridland Crop Sciences/Gansu Agricultural University Lanzhou 730070.P.R.China

In Brassica napus L.(rapeseed),complete genic male sterility(GMS)plays an important role in the utilization of *** microRNAs(miRNAs)play essential regulatory roles during bud development,knowledge of how GMS is regulated by miRNAs in rapeseed is rather *** this study,we obtained a novel recessive GMS system,*** sterile line CN12A has defects in tapetal diferentiation and *** sequencing was employed to examine the expression of miRNAs in the buds of CN12A and the fertile line *** identifed 85 known miRNAs and 120 novel miRNAs that were expressed during rapeseed anther *** comparing the expression levels of miRNAs between CN12A and CN12B,19 and 18 known miRNAs were found to be difrentially expressed in 0.5--1.0 mm buds and in 2.5--3.0 mm buds,*** these,the expression levels of 14 miRNAs were higher and the levels of 23 miRNAs were lower in CN12A compared with *** predicted target genes of these iferentially expressed miRNAS encode protein kinases,F-box domain-containing proteins,MADS-box family proteins,SBP-box gene family members,HD ZIP proteins,floral homeotic protein APETAL A 2(AP2)。and nuclear factor Y,subunit *** targets have previously been reported to be involved in pollen development and male sterility,suggesting that miRNAs might act as regulators of GMS in rapeseed ***,RT-qPCR data suggest that one of the dffrentially expressed miRNAs,bna-miR159,plays a role in tapetal differentiation by regulating the expression of transcription factor BnMYB101 and participates in tapetal degradation and infuences callose degradation by manipulating the expression of *** findings contibute to our understanding of the roles of miRNAs during anther development and the occurrence of GMS in rapeseed.

关键词： Brassica napus L. genic male sterility miRNAs targets molecular regulation network

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基于耦合方法的挡土墙地震响应的数值模拟

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岩土力学 2010年第12期31卷 3949-3957页

作者：周健金炜枫同济大学地下建筑与工程系上海200092 同济大学岩土及地下工程教育部重点实验室上海200092

为有效描述动力灾变过程中挡土墙附近土体的细观特性,并大量减小离散元模拟的颗粒数目,节省计算时间,利用离散-连续耦合动力数值模型,模拟了已有离心机试验中重力式挡土墙的地震响应。靠近挡土墙的土体区域用相互作用的离散颗粒模拟,远... 详细信息

为有效描述动力灾变过程中挡土墙附近土体的细观特性,并大量减小离散元模拟的颗粒数目,节省计算时间,利用离散-连续耦合动力数值模型,模拟了已有离心机试验中重力式挡土墙的地震响应。靠近挡土墙的土体区域用相互作用的离散颗粒模拟,远离挡土墙的土体采用连续模型模拟,编写结构的动力有限元程序并嵌入离散元软件中来模拟挡土墙。通过离散元软件PFC2D和有限差分软件FLAC2D的交互运算实现耦合过程。耦合方法的核心在于:①在离散-连续土体的交界面保证连续性;②模拟中离散区域土体的宏观性质与连续土体模型一致。为进一步满足以上两点,分别提出了新的边界耦合力提取方法和自振柱模拟方法。研究表明耦合方法可以从细观尺度上有效描述土体与结构的相互作用和关心区域的土体特性。

关键词：耦合模型离散元法自振柱挡土墙

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Research and application of absorbable screw in orthopedics： a clinical review comparing PDLLA screw with metal screw in patients with simple medial malleolus fracture

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Chinese Journal of Traumatology 2013年第1期16卷 27-30页

作者： TANG jin HU jin-feng GUO wei-chun YU Ling ZHAO Sheng-hao Foxconn Clinic Renmin Hospital of Wuhan UniversityWuhan 430060 China

Objective： To observe the therapeutic effect of absorbable screw in medial malleolus fracture and discuss its clinical application in orthopedics. Methods： A total of 129 patients with simple medial malleolus fracture were studied. Among them, 64 patients were treated with poly-D, L-lactic acid （PDLLA） absorbable screws, while the others were treated with metal screws. All the patients were followed up for 12-20 months （averaged 18.4 months） and the therapeutic effect was evaluated according to the American Orthopaedic Foot and Ankle Society clinical rating systems. Results： In absorbable screw group, we obtained excel- lent and good results in 62 cases （96.88%）; in steel screw group, 61 cases （93.85%） achieved excellent and good results. There was no significant difference between the two groups. Conclusion： In the treatment of malleolus fracture, absorbable screw can achieve the same result compared with metal screw fixation. Absorbable screw is preferred due to its advantages of safety, cleanliness and avoiding the removal procedure associated with metallic implants.

关键词： Ankle Bone screws Fractures, bone

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建立我国行政诉讼中的确认无效诉讼制度

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政法论坛 2005年第3期23卷 142-148页

作者：金伟峰浙江大学浙江杭州310028

虽然我国已有确认行政行为无效的司法实践和关于确认无效判决的司法解释,但不能据此认为我国行政诉讼中已经建立了确认无效诉讼制度。要使确认无效判决真正具有其独立存在的价值,必须在诉讼程序上使确认无效诉讼与一般的行政诉讼相分离:... 详细信息

虽然我国已有确认行政行为无效的司法实践和关于确认无效判决的司法解释,但不能据此认为我国行政诉讼中已经建立了确认无效诉讼制度。要使确认无效判决真正具有其独立存在的价值,必须在诉讼程序上使确认无效诉讼与一般的行政诉讼相分离:1·确认无效诉讼不受起诉期限的限制;2·确认无效诉讼应以行政确认程序为前置条件;3·在确认无效诉讼中原告负有举证责任。在确认无效诉讼与撤销诉讼的关系上,宜把确认无效诉讼看成撤销诉讼的补充诉讼类型。

关键词：行政诉讼诉讼制度无效司法解释司法实践行政行为起诉期限诉讼程序前置条件确认程序举证责任诉讼类型判决撤销限制原告

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玻璃体腔注射TA联合激光治疗非缺血型CRVO继发黄斑水肿

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国际眼科杂志 2010年第7期10卷 1365-1367页

作者：冯金伟中国河南省延津县位邱中心乡卫生院眼科 453200

目的:评价玻璃体腔注射曲安奈德(intravitreal triamcinolo-ne acetonide,IVTA)联合激光治疗非缺血型视网膜中央静脉阻塞继发黄斑水肿的临床效果。方法:将非缺血型视网膜中央静脉阻塞继发黄斑水肿56眼随机分为两组:IVTA联合532半导体激... 详细信息

目的:评价玻璃体腔注射曲安奈德(intravitreal triamcinolo-ne acetonide,IVTA)联合激光治疗非缺血型视网膜中央静脉阻塞继发黄斑水肿的临床效果。方法:将非缺血型视网膜中央静脉阻塞继发黄斑水肿56眼随机分为两组:IVTA联合532半导体激光黄斑部光凝(治疗组)30眼,单独行532半导体激光黄斑部光凝治疗(对照组)26眼。每组在治疗前后查最佳矫正视力、眼压、眼底荧光血管造影(fluorescein fundus angiography,FFA)了解黄斑部荧光渗漏情况、光学相干断层扫描(optic coher-ent tomography,OCT)测量黄斑区视网膜厚度变化。治疗组为先行黄斑格栅样光凝,2wk后进行IVTA4mg。结果:治疗后3mo时,在治疗组中,23眼(77%)视力提高,7眼(23%)视力不变;FFA示黄斑部荧光渗漏明显减轻;黄斑中心凹平均厚度为(170±32)μm。在对照组中,15眼(58%)视力提高,11眼(42%)视力不变;FFA示黄斑部荧光渗漏减轻;黄斑中心凹平均厚度为(223±57)μm。两组视力变化及黄斑中心凹平均厚度改变比较差异有统计学意义(χ2=4.20,χ2=5.13,P<0.01)。结论:IVTA联合激光治疗非缺血型视网膜中央静脉阻塞继发黄斑水肿效果较好。

关键词：视网膜静脉阻塞黄斑水肿药物疗法视网膜光凝

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Comparison of antioxidant activities between salvianolic acid B and Ginkgo biloba extract(EGb 761)

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Acta Pharmacologica Sinica 2006年第9期27卷 1137-1145页

作者： Chang-suo LIU Yong CHENG jin-feng HU wei ZHANG Nai-hong CHEN Jun-tian ZHANG~2 Department of Neuropharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050.China Department of Neuropharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim:To investigate and compare the antioxidant activities of salvianolic acid B(SalB)and Ginkgo biloba extract(EGb 761)in aqueous solution,rat microsomesand the cellular ***:Superoxide anion(O2~-)was generated usingxanthine/xanthine oxidase system and phenazine methosulate/NADH system,andthe effects of SalB and EGb 761 on the generation of O2~- were achieved by spectro-photometric measurement of the product formed on reduction of nitro *** different methods were used to assess the scavenging effects ofthe extracts on hydroxyl radical(.OH):HPLC method was used for quantitation *** by oxy-radical trapping of 5,5-dimethyl- 1-pyrroline-N-oxide(DMPO)to formDMPO-OH adducts in Fe2+-*** confirm the HPLC data,.OHwas also measured by spectrophotometry using a commercial detection ***-lipid peroxidation effects of the extracts in microsomes of rat brain,liver andkidney induced by ascorbate-NADPH were determined by thiobarbituric acid(TBA)*** protective effects of the extracts on peroxide hydrogen(H2O2)-induced oxidative damage in SH-SY5Y cells were investigated by assessing cellviability assay,the level of lipid peroxidation,and the lactate dehydrogenase(LDH)***:Both SalB and EGb 761 were able to scavenge O2~- ***,inhibit lipid peroxidation of microsomes,and protect SH-SY5Y ceils againstH2O2-induced oxidative ***,the concentration of SalB was far lowerthan that of EGb 761 when a similar effect was ***:The antioxi-dant efficiency of SalB was greater than that of EGb *** results suggestthat SalB,like EGb 761,has promising potential in treating oxidative damage-derived neurodegenerative disorders.

关键词： antioxidant Ginkgo biloba extract 761 free radical salvianolic acid B SH-SY5Y cells

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国产尼卡地平治疗高血压急症的疗效观察

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高血压杂志 2005年第8期13卷 481-482页

作者：封金伟河南省太康县人民医院心内科河南太康461400

目的观察静脉注射尼卡地平对高血压急症的疗效。方法选择45例高血压住院患者使用静脉注射尼卡地平治疗,并记录0·5、1、2、4、6、12h血压和心率。结果45例中除1例不能耐受退出外,44例患者在0·5h内血压明显下降,收缩压由(191·0±11·5)... 详细信息

目的观察静脉注射尼卡地平对高血压急症的疗效。方法选择45例高血压住院患者使用静脉注射尼卡地平治疗,并记录0·5、1、2、4、6、12h血压和心率。结果45例中除1例不能耐受退出外,44例患者在0·5h内血压明显下降,收缩压由(191·0±11·5)mmHg降至(164·5±9·6)mmHg(P<0·01),舒张压由(110·0±7.5)降至(96·9±12·5)mmHg(P<0·01),显效率100%,副作用少见。结论静脉注射尼卡地平降低血压疗效肯定,使用安全,简单。

关键词：高血压尼卡地平疗高血压急症疗效观察平治国产静脉注射住院患者降低血压收缩压

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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

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Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang feng Miao Peifeng wei College of Pharmacy and First Clinical Medical College Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug Clinical Trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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行政补偿范围的经济分析

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浙江大学学报（人文社会科学版） 2006年第2期36卷 130-138页

作者：金伟峰姜裕富浙江大学法学院浙江杭州310028 衢州行政学院浙江衢州324002

财产征收、征用的行政补偿原则已经得到我国宪法的确认,但补偿的范围应该包括哪些行为和得到多大程度的补偿等具体问题则有待解决。运用经济分析方法,可以对行政补偿的范围作出更形象的解释。从行政主体对相对人侵权的原因来看,行政补... 详细信息

财产征收、征用的行政补偿原则已经得到我国宪法的确认,但补偿的范围应该包括哪些行为和得到多大程度的补偿等具体问题则有待解决。运用经济分析方法,可以对行政补偿的范围作出更形象的解释。从行政主体对相对人侵权的原因来看,行政补偿应包括财产征用、特别限制、行政行为派生的效果等。确定行政补偿标准要兼顾到公共利益和私人利益最大化,即行政决策者必须充分考虑行政行为所产生的成本(个人成本和社会成本)与效益(个人效率和社会效率),促使行政主体将公益成本内在化。

关键词：行政补偿补偿范围补偿标准经济分析

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