The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease...The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.展开更多
The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for ea...The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for each DR operation. A recursion symmetry Hungarian method （RSHM）, modified from the Hungarian method, is proposed for generating a DR operation sequence with minimal total travel time, in which symmetry marking is introduced to ensure a feasible solution and recursion is adopted to break the endless loop caused by the symmetry marking. Simulation experiments are conducted to evaluate the cost effectiveness and the performance of the proposed method. Experimental results illustrate that compared to the single-shuttle machine, the dual-shuttle machine can reduce more than 40% of the total travel time of retrieval operations, and the RSHM saves about 5% to 10% of the total travel time of retrieval operations compared to the greedy-based heuristic.展开更多
目的以GEO(Gene Expression Omnibus)数据库为基础分析活化的蛋白激酶C受体1(receptor for activated C kinase1,RACK1)在糖尿病肾小管病中的表达及可能的机制。方法通过搜索Nephroseq数据库及KEGG(Kyoto Encyclopedia of Genes and Gen...目的以GEO(Gene Expression Omnibus)数据库为基础分析活化的蛋白激酶C受体1(receptor for activated C kinase1,RACK1)在糖尿病肾小管病中的表达及可能的机制。方法通过搜索Nephroseq数据库及KEGG(Kyoto Encyclopedia of Genes and Genomes),明确RACK1在人的糖尿病肾小管病中表达情况及可能的通路。将培养的肾小管上皮细胞分为对照组、甘露醇组和高糖组,实时定量PCR测定其下游靶基因STAT1和STAT3的变化。FVB/N小鼠分为对照组和糖尿病肾病组,糖尿病肾病组小鼠给予腹腔注射链脲佐菌素构建糖尿病肾病的模型,实时定量PCR测定STAT1和STAT3 mRNA水平,免疫荧光染色明确p-STAT1和p-STAT3的表达情况。结果数据库数据分析发现RACK1在人糖尿病肾小管中表达明显升高。KEGG提示RACK1可能通过激活Jak-STAT信号通路发挥作用。与对照组比较,高糖组肾小管上皮细胞的RACK1、STAT1及STAT3的mRNA水平均明显升高,差异有统计学意义(P<0.05)。糖尿病肾病动物模型中,肾小管的RACK1、STAT1及STAT3的mRNA水平均明显升高,差异有统计学意义(P<0.05);免疫荧光示p-STAT1阳性,主要位于肾小管上皮细胞中。结论 RACK1在糖尿病肾小管中高表达,可能是通过磷酸化STAT1激活Jak-STAT信号通路参与糖尿病肾小管病的发生发展。展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant No.82071395)the Natural Science Foundation of Chongqing(Grant Nos.cstc2021ycjh-bgzxm0186,cstc2020jcyj-zdxmX0004,and cstc2021jcyj-bsh0023)the CQMU Program for Youth Innovation in Future Medicine(Grant No.W0044).
文摘The receptor for activated C kinase 1(RACK1)is a protein that plays a crucial role in various signaling pathways and is involved in the pathogenesis of Alzheimer's disease(AD),a prevalent neurodegenerative disease.RACK1 is highly expressed in neuronal cells of the central nervous system and regulates the pathogenesis of AD.Specifically,RACK1 is involved in regulation of the amyloid-β precursor protein processing through α-or β-secretase by binding to different protein kinase C isoforms.Additionally,RACK1 promotes synaptogenesis and synaptic plasticity by inhibiting N-methyl-D-aspartate receptors and activating gamma-aminobutyric acid A receptors,thereby preventing neuronal excitotoxicity.RACK1 also assembles inflammasomes that are involved in various neuroinflammatory pathways,such as nuclear factor-kappa B,tumor necrosis factor-alpha,and NOD-like receptor family pyrin domain-containing 3 pathways.The potential to design therapeutics that block amyloid-β accumulation and inflammation or precisely regulate synaptic plasticity represents an attractive therapeutic strategy,in which RACK1 is a potential target.In this review,we summarize the contribution of RACK1 to the pathogenesis of AD and its potential as a therapeutic target.
基金The National Natural Science Foundation of China(No.61003158,61272377)the Specialized Research Fund for the Doctoral Program of Higher Education(No.20120092110027)
文摘The dual-retrieval （DR） operation sequencing problem in the flow-rack automated storage and retrieval system （AS/RS） is modeled as an assignment problem since it is equivalent to pairing outgoing unit-loads for each DR operation. A recursion symmetry Hungarian method （RSHM）, modified from the Hungarian method, is proposed for generating a DR operation sequence with minimal total travel time, in which symmetry marking is introduced to ensure a feasible solution and recursion is adopted to break the endless loop caused by the symmetry marking. Simulation experiments are conducted to evaluate the cost effectiveness and the performance of the proposed method. Experimental results illustrate that compared to the single-shuttle machine, the dual-shuttle machine can reduce more than 40% of the total travel time of retrieval operations, and the RSHM saves about 5% to 10% of the total travel time of retrieval operations compared to the greedy-based heuristic.
文摘目的以GEO(Gene Expression Omnibus)数据库为基础分析活化的蛋白激酶C受体1(receptor for activated C kinase1,RACK1)在糖尿病肾小管病中的表达及可能的机制。方法通过搜索Nephroseq数据库及KEGG(Kyoto Encyclopedia of Genes and Genomes),明确RACK1在人的糖尿病肾小管病中表达情况及可能的通路。将培养的肾小管上皮细胞分为对照组、甘露醇组和高糖组,实时定量PCR测定其下游靶基因STAT1和STAT3的变化。FVB/N小鼠分为对照组和糖尿病肾病组,糖尿病肾病组小鼠给予腹腔注射链脲佐菌素构建糖尿病肾病的模型,实时定量PCR测定STAT1和STAT3 mRNA水平,免疫荧光染色明确p-STAT1和p-STAT3的表达情况。结果数据库数据分析发现RACK1在人糖尿病肾小管中表达明显升高。KEGG提示RACK1可能通过激活Jak-STAT信号通路发挥作用。与对照组比较,高糖组肾小管上皮细胞的RACK1、STAT1及STAT3的mRNA水平均明显升高,差异有统计学意义(P<0.05)。糖尿病肾病动物模型中,肾小管的RACK1、STAT1及STAT3的mRNA水平均明显升高,差异有统计学意义(P<0.05);免疫荧光示p-STAT1阳性,主要位于肾小管上皮细胞中。结论 RACK1在糖尿病肾小管中高表达,可能是通过磷酸化STAT1激活Jak-STAT信号通路参与糖尿病肾小管病的发生发展。
