Present mobile communication system suffers from the exponentially increased mobile traffic and research on the fifth generation(5G) mobile network architectures is ongoing to solve this problem. We investigate the fe...Present mobile communication system suffers from the exponentially increased mobile traffic and research on the fifth generation(5G) mobile network architectures is ongoing to solve this problem. We investigate the feasibility of the proposals used for the network architecture evolution from 4G to 5G and first propose a compatible network architecture, which decouples the management plane, the control plane and the user plane based on NO Stack framework proposed in our previous study. We mainly design detail procedures including UE attachment, service request and dedicated bearer activation/deactivation for our proposal network architecture. Finally, we establish a clear analytical mode of the application and system states to evaluate the signaling loads of new architecture. Simulation results show that our proposal network architecture with elaborated signaling procedures has much impact on the total signaling loads of system and could obviously decrease the signaling overhead compared with LTE.展开更多
In the future the fifth generation( 5 G) communication systems,channel models may be very complicated and it is difficult to calculate equivalent signal to interference plus noise ratio( SINR)of a random fading channe...In the future the fifth generation( 5 G) communication systems,channel models may be very complicated and it is difficult to calculate equivalent signal to interference plus noise ratio( SINR)of a random fading channel. Therefore,methods for the calculation of equivalent SINR of a random fading channel are very necessary.In this paper,an enhanced algorithm on the exponential effective SINR mapping( EESM) model for random fading channels was proposed. First, the optimal adjustment parameters of typical channel fading models including extended pedestrian A( EPA)model,extended vehicular A( EVA) model and extended typical urban( ETU) model were obtained by simulation. Then the proposed solution was used to actualize channel classification according to the maximum multipath delay and the average power of the random channel. The solution can determine the typical channel closest to random channel for obtaining the optimal adjustment value of EESM. The evaluation results indicate that the proposed one can improve the whole system throughput significantly and meanwhile the accuracy of the link prediction algorithm is also guaranteed.展开更多
采用RT-PCR方法扩增并克隆麦洼牦牛G蛋白信号转导调节因子5(regulator of G protein signaling 5,RGS5)基因序列,利用ClustalX 1.83和Mega 5.0软件构建系统进化树,并选用多种生物信息学软件进行序列分析和蛋白结构预测。结果表明,所得...采用RT-PCR方法扩增并克隆麦洼牦牛G蛋白信号转导调节因子5(regulator of G protein signaling 5,RGS5)基因序列,利用ClustalX 1.83和Mega 5.0软件构建系统进化树,并选用多种生物信息学软件进行序列分析和蛋白结构预测。结果表明,所得麦洼牦牛RGS5基因长度为863bp,包含1个546bp的完整开放阅读框,编码181个氨基酸,GenBank登录号为KJ867514。系统进化树分析发现,麦洼牦牛RGS5氨基酸序列与普通牛亲缘关系最近,其次是山羊和绵羊。RGS5基因编码的蛋白质分子质量为20.94ku,理论等电点(PI)为6.35,它是一种以α-螺旋为主,不含信号肽的非跨膜、不稳定性蛋白。三级结构预测显示,麦洼牦牛与人RGS5蛋白三级结构相似性高达90.51%。以上结果为深入研究RGS蛋白功能积累科学资料。展开更多
G蛋白配对的生理过程需要微调附属分子如G蛋白信号调节蛋白(regulator of G-protein signaling,RGS)。作为肿瘤血管周细胞的标记物,RGS5最近已被确定在致癌的血管成熟和血管再造过程中起中枢作用。值得注意的是,缺乏RGS5肿瘤的血管形态...G蛋白配对的生理过程需要微调附属分子如G蛋白信号调节蛋白(regulator of G-protein signaling,RGS)。作为肿瘤血管周细胞的标记物,RGS5最近已被确定在致癌的血管成熟和血管再造过程中起中枢作用。值得注意的是,缺乏RGS5肿瘤的血管形态标准化且血流丰富。同时,发现肿瘤血管的形态变化也导致淋巴细胞功能的改善和抗肿瘤免疫疗法的成功。因此,研究RGS5与肿瘤血管形态学的关系,可增强对血管再造的理解,促进抗癌治疗的改善。展开更多
5G network is expected to support massive user connections and exponentially increasing wireless services,which makes network security unprecedentedly important.Unlike traditional security-guaranteeing techniques whic...5G network is expected to support massive user connections and exponentially increasing wireless services,which makes network security unprecedentedly important.Unlike traditional security-guaranteeing techniques which rely heavily on cryptographic approaches at upper layers of the protocol stack,physical-layer security(PLS) solutions fully take advantages of the characteristics of wireless channels to degrade the received signal qualities at the malicious users,and realize keyless secure transmission via signal design and signal processing techniques.PLS avoids the difficulties in the distribution and management of secret keys,and provides flexible security levels through adaptive transmission protocol design.Moreover,PLS techniques match the features of 5G networks well.Therefore,the application of PLS to 5G networks is a promising solution to address the security threats.This article presents a comprehensive review of the state-of-the-art PLS techniques,and discusses their applications in 5G networks.We first summarize the principle and advantages of PLS techniques,and point out the reasons why PLS is suitable for 5G networks.Then,we review the existing PLS methods in literature,and highlight severalPLS solutions that are expected to be applied in 5G networks.Finally,we conclude this article and figure out some further research directions.展开更多
目的通过检测G蛋白偶联受体家族C群5成员A(G protein coupled receptor C type group 5 member A,GPRC5A)在肝癌组织及细胞中的表达,探讨GPRC5A对肝癌细胞增殖、凋亡、氧化应激的影响及其相关作用机制。方法收集2018年12月~2019年11月...目的通过检测G蛋白偶联受体家族C群5成员A(G protein coupled receptor C type group 5 member A,GPRC5A)在肝癌组织及细胞中的表达,探讨GPRC5A对肝癌细胞增殖、凋亡、氧化应激的影响及其相关作用机制。方法收集2018年12月~2019年11月在解放军联勤保障部队第九六九医院行手术治疗的38例肝癌患者癌组织及配对癌旁正常组织样本;另选取人正常肝上皮细胞株HL-7702和人肝癌细胞株(HepG2,HCCLM3,HuH-7和MHCC-97H)进行研究。采用实时荧光定量聚合酶链反应(qRT-PCR)检测肝癌组织、癌旁正常组织及肝癌细胞、正常肝上皮细胞中GPRC5A表达量。通过转染pcDNA3.1-GPRC5A质粒构建过表达GPRC5A肝癌细胞株,采用MTT实验和V-FITC/PI凋亡试剂盒分别检测过表达GPRC5A对肝癌细胞增殖、凋亡的影响。采用活性氧指示剂DCFH-DA检测细胞中氧化应激相关因子活性氧(ROS),NAD+/NADH和三磷酸腺苷(ATP)水平。采用Western blot实验检测凋亡相关蛋白caspase-3及上皮生长因子(VEGF)蛋白表达水平。结果肝癌组织中GPRC5A表达较癌旁正常组织显著降低(0.34±0.09 vs 0.73±0.10),差异有统计学意义(t=17.869,P<0.01)。肝癌细胞HepG2(0.35±0.06),HCCLM3(0.38±0.10),HuH-7(0.53±0.07),MHCC-97H(0.67±0.06)中GPRC5A表达量显著低于人正常肝上皮细胞HL-7702中的GPRC5A表达量(1.00±0.08),差异有统计学意义(t=5.716~11.258,均P<0.05)。pcDNA3.1-GPRC5A组转染36 h细胞增殖吸光度(A)值(0.94±0.16)显著低于对照组(1.49±0.05)和pcDNA3.1组(1.45±0.07)(F=25.640,P<0.01)。GPRC5A过表达组VEGF(0.98±0.04)表达量较对照组(2.94±0.15)和pcDNA3.1组(2.89±0.11)显著降低(F=310.450,P<0.001)。pcDNA3.1-GPRC5A组细胞中ROS(182.12±13.42)水平显著高于对照组(101.23±11.20)和pcDNA3.1组(98.30±10.26)(F=49.577,P<0.001);NAD+/NADH(35.24±6.43)及ATP(55.34±6.51)水平显著低于对照组(100.25±12.41,100.17±14.36)和pcDNA3.1组(97.86±9.67,102.23±11.02)(F=42.338,17.077,P<0.05)。GPRC5A过表达组细胞凋亡率高于对照组和pcDNA3.1组;细胞凋亡蛋白caspase-3(2.61±0.16)表达量也高于对照组(1.00±0.11)和pcDNA3.1组(1.01±0.02)(F=202.843,P<0.001)。pcDNA3.1-GPRC5A组细胞中p-STAT3表达量(0.43±0.06)显著低于对照组(1.00±0.13)和pcDNA3.1组(1.03±0.12)(F=29.476,P<0.001);pcDNA3.1-GPRC5A组下游基因Socs3(0.47±0.05),c-MYC(0.54±0.06)表达量也显著低于对照组(1.01±0.05,1.00±0.04)和pcDNA3.1组(0.98±0.09,1.02±0.06)(F=63.275,75.409,P<0.001)。肝癌组织中STAT3与GPRC5A表达量呈显著负相关(r=-0.746,P<0.01)。过转染pcDNA3.1-STAT3或pcDNA3.1-NLRP3后显著逆转了pcDNA3.1-GPRC5A对肝癌细胞的抑制作用(P<0.05)。结论GPRC5A低表达可能通过调节STAT3/Socs3/c-MYC信号和炎症反应抑制了肝癌细胞的增殖,诱导肝癌细胞的氧化应激和凋亡。展开更多
Ultra-densification of radio access network(RAN)is a key to efficiently support the exponentially growing mobile data traffic in 5 G era.Furthermore,extremely high frequency band like mm Wave band was utilized to solv...Ultra-densification of radio access network(RAN)is a key to efficiently support the exponentially growing mobile data traffic in 5 G era.Furthermore,extremely high frequency band like mm Wave band was utilized to solve the bandwidth shortage problem.However,untra-dense reusing the same radio resource produced severe interference.And the mm Wave link was very harsh due to frequent blockage by obstacles.Therefore a new RAN architecture needed to be introduced to realize ultra-reliable communications in such a severe radio propagation environment.An architecture of distributed MIMO based RAN was presented.Then,enhanced interference coordination(e IC)was described.Finally,the effectiveness of distributed MIMO based RAN with e IC by computer simulation was showed.展开更多
Due to 5G's stringent and uncertainty traffic requirements,open ecosystem would be one inevitable way to develop 5G.On the other hand,GPP based mobile communication becomes appealing recently attributed to its str...Due to 5G's stringent and uncertainty traffic requirements,open ecosystem would be one inevitable way to develop 5G.On the other hand,GPP based mobile communication becomes appealing recently attributed to its striking advantage in flexibility and re-configurability.In this paper,both the advantages and challenges of GPP platform are detailed analyzed.Furthermore,both GPP based software and hardware architectures for open 5G are presented and the performances of real-time signal processing and power consumption are also evaluated.The evaluation results indicate that turbo and power consumption may be another challengeable problem should be further solved to meet the requirements of realistic deployments.展开更多
The heterogeneous network with the separation of the control plane and user plane(C/U) is an evolutionary approach to the fifth generation(5 G) to achieve high system coverage and capacity. To minimize signaling load ...The heterogeneous network with the separation of the control plane and user plane(C/U) is an evolutionary approach to the fifth generation(5 G) to achieve high system coverage and capacity. To minimize signaling load of the core network when there is a macro base station(BS) failure in the control plane, a scheme of transferring the control of small cells under the coverage of the failure macro BS to the neighbor macro BSs is proposed. The average handover rates between small cells related to user mobilities, the extended coverage of the neighboring macro BSs under the constraint of transmitting power and the load balance index of the system are analyzed, based on which the formula of maximizing the handovers processed by macro BSs is constructed and further solved by the convex optimization methods. Simulation results indicate that the proposed scheme can effectively increase the total handovers processed by the macro BSs and thus reduce the signaling load of the core network.展开更多
BACKGROUND In the heart,aldosterone(Aldo)binds the mineralocorticoid receptor(MR)to exert damaging,adverse remodeling-promoting effects.We recently showed that G protein-coupled receptor-kinase(GRK)-5 blocks the cardi...BACKGROUND In the heart,aldosterone(Aldo)binds the mineralocorticoid receptor(MR)to exert damaging,adverse remodeling-promoting effects.We recently showed that G protein-coupled receptor-kinase(GRK)-5 blocks the cardiac MR by directly phosphorylating it,thereby repressing its transcriptional activity.MR antagonist(MRA)drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure.Non-steroidal MRAs,such as finerenone,may provide better cardio-protection against Aldo than classic,steroidal MRAs,like spironolactone and eplerenone.AIM To investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade.METHODS We used H9c2 cardiomyocytes,which endogenously express the MR and GRK5.RESULTS GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone.Unlike eplerenone,finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity,thus displaying inverse agonism.GRK5 is necessary for finerenone’s inverse agonism,since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity.Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels.Finally,GRK5 is necessary for the antiapoptotic,anti-oxidative,and anti-fibrotic effects of both finerenone and eplerenone against Aldo,as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis,oxidative stress,and fibrosis.CONCLUSION Finerenone,but not eplerenone,induces GRK5-dependent cardiac MR inhibition,which underlies,at least in part,its higher potency and efficacy,compared to eplerenone,as an MRA in the heart.GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.展开更多
基金supported by the Chinas 863 Project (No.2015AA01A706)the National Science and Technology Major Project (No. 2016ZX03001017)+1 种基金the Science and Technology Program of Beijing (No. D161100001016002)the Science and Technology Cooperation Projects (No. 2015DFT10160B)
文摘Present mobile communication system suffers from the exponentially increased mobile traffic and research on the fifth generation(5G) mobile network architectures is ongoing to solve this problem. We investigate the feasibility of the proposals used for the network architecture evolution from 4G to 5G and first propose a compatible network architecture, which decouples the management plane, the control plane and the user plane based on NO Stack framework proposed in our previous study. We mainly design detail procedures including UE attachment, service request and dedicated bearer activation/deactivation for our proposal network architecture. Finally, we establish a clear analytical mode of the application and system states to evaluate the signaling loads of new architecture. Simulation results show that our proposal network architecture with elaborated signaling procedures has much impact on the total signaling loads of system and could obviously decrease the signaling overhead compared with LTE.
基金Institute of Nonlinear Science of Donghua University,China
文摘In the future the fifth generation( 5 G) communication systems,channel models may be very complicated and it is difficult to calculate equivalent signal to interference plus noise ratio( SINR)of a random fading channel. Therefore,methods for the calculation of equivalent SINR of a random fading channel are very necessary.In this paper,an enhanced algorithm on the exponential effective SINR mapping( EESM) model for random fading channels was proposed. First, the optimal adjustment parameters of typical channel fading models including extended pedestrian A( EPA)model,extended vehicular A( EVA) model and extended typical urban( ETU) model were obtained by simulation. Then the proposed solution was used to actualize channel classification according to the maximum multipath delay and the average power of the random channel. The solution can determine the typical channel closest to random channel for obtaining the optimal adjustment value of EESM. The evaluation results indicate that the proposed one can improve the whole system throughput significantly and meanwhile the accuracy of the link prediction algorithm is also guaranteed.
文摘采用RT-PCR方法扩增并克隆麦洼牦牛G蛋白信号转导调节因子5(regulator of G protein signaling 5,RGS5)基因序列,利用ClustalX 1.83和Mega 5.0软件构建系统进化树,并选用多种生物信息学软件进行序列分析和蛋白结构预测。结果表明,所得麦洼牦牛RGS5基因长度为863bp,包含1个546bp的完整开放阅读框,编码181个氨基酸,GenBank登录号为KJ867514。系统进化树分析发现,麦洼牦牛RGS5氨基酸序列与普通牛亲缘关系最近,其次是山羊和绵羊。RGS5基因编码的蛋白质分子质量为20.94ku,理论等电点(PI)为6.35,它是一种以α-螺旋为主,不含信号肽的非跨膜、不稳定性蛋白。三级结构预测显示,麦洼牦牛与人RGS5蛋白三级结构相似性高达90.51%。以上结果为深入研究RGS蛋白功能积累科学资料。
文摘G蛋白配对的生理过程需要微调附属分子如G蛋白信号调节蛋白(regulator of G-protein signaling,RGS)。作为肿瘤血管周细胞的标记物,RGS5最近已被确定在致癌的血管成熟和血管再造过程中起中枢作用。值得注意的是,缺乏RGS5肿瘤的血管形态标准化且血流丰富。同时,发现肿瘤血管的形态变化也导致淋巴细胞功能的改善和抗肿瘤免疫疗法的成功。因此,研究RGS5与肿瘤血管形态学的关系,可增强对血管再造的理解,促进抗癌治疗的改善。
基金supported in part by the National Natural Science Foundation of China under Grants No.61671369 and 61431011the National Science and Technology Major Project of China under Grant No.2016ZX03001012004+1 种基金the Open Research Fund of the State Key Laboratory of Integrated Services Networks,Xidian University,under Grant No.ISN18-02the Fundamental Research Funds for the Central Universities of China
文摘5G network is expected to support massive user connections and exponentially increasing wireless services,which makes network security unprecedentedly important.Unlike traditional security-guaranteeing techniques which rely heavily on cryptographic approaches at upper layers of the protocol stack,physical-layer security(PLS) solutions fully take advantages of the characteristics of wireless channels to degrade the received signal qualities at the malicious users,and realize keyless secure transmission via signal design and signal processing techniques.PLS avoids the difficulties in the distribution and management of secret keys,and provides flexible security levels through adaptive transmission protocol design.Moreover,PLS techniques match the features of 5G networks well.Therefore,the application of PLS to 5G networks is a promising solution to address the security threats.This article presents a comprehensive review of the state-of-the-art PLS techniques,and discusses their applications in 5G networks.We first summarize the principle and advantages of PLS techniques,and point out the reasons why PLS is suitable for 5G networks.Then,we review the existing PLS methods in literature,and highlight severalPLS solutions that are expected to be applied in 5G networks.Finally,we conclude this article and figure out some further research directions.
文摘目的通过检测G蛋白偶联受体家族C群5成员A(G protein coupled receptor C type group 5 member A,GPRC5A)在肝癌组织及细胞中的表达,探讨GPRC5A对肝癌细胞增殖、凋亡、氧化应激的影响及其相关作用机制。方法收集2018年12月~2019年11月在解放军联勤保障部队第九六九医院行手术治疗的38例肝癌患者癌组织及配对癌旁正常组织样本;另选取人正常肝上皮细胞株HL-7702和人肝癌细胞株(HepG2,HCCLM3,HuH-7和MHCC-97H)进行研究。采用实时荧光定量聚合酶链反应(qRT-PCR)检测肝癌组织、癌旁正常组织及肝癌细胞、正常肝上皮细胞中GPRC5A表达量。通过转染pcDNA3.1-GPRC5A质粒构建过表达GPRC5A肝癌细胞株,采用MTT实验和V-FITC/PI凋亡试剂盒分别检测过表达GPRC5A对肝癌细胞增殖、凋亡的影响。采用活性氧指示剂DCFH-DA检测细胞中氧化应激相关因子活性氧(ROS),NAD+/NADH和三磷酸腺苷(ATP)水平。采用Western blot实验检测凋亡相关蛋白caspase-3及上皮生长因子(VEGF)蛋白表达水平。结果肝癌组织中GPRC5A表达较癌旁正常组织显著降低(0.34±0.09 vs 0.73±0.10),差异有统计学意义(t=17.869,P<0.01)。肝癌细胞HepG2(0.35±0.06),HCCLM3(0.38±0.10),HuH-7(0.53±0.07),MHCC-97H(0.67±0.06)中GPRC5A表达量显著低于人正常肝上皮细胞HL-7702中的GPRC5A表达量(1.00±0.08),差异有统计学意义(t=5.716~11.258,均P<0.05)。pcDNA3.1-GPRC5A组转染36 h细胞增殖吸光度(A)值(0.94±0.16)显著低于对照组(1.49±0.05)和pcDNA3.1组(1.45±0.07)(F=25.640,P<0.01)。GPRC5A过表达组VEGF(0.98±0.04)表达量较对照组(2.94±0.15)和pcDNA3.1组(2.89±0.11)显著降低(F=310.450,P<0.001)。pcDNA3.1-GPRC5A组细胞中ROS(182.12±13.42)水平显著高于对照组(101.23±11.20)和pcDNA3.1组(98.30±10.26)(F=49.577,P<0.001);NAD+/NADH(35.24±6.43)及ATP(55.34±6.51)水平显著低于对照组(100.25±12.41,100.17±14.36)和pcDNA3.1组(97.86±9.67,102.23±11.02)(F=42.338,17.077,P<0.05)。GPRC5A过表达组细胞凋亡率高于对照组和pcDNA3.1组;细胞凋亡蛋白caspase-3(2.61±0.16)表达量也高于对照组(1.00±0.11)和pcDNA3.1组(1.01±0.02)(F=202.843,P<0.001)。pcDNA3.1-GPRC5A组细胞中p-STAT3表达量(0.43±0.06)显著低于对照组(1.00±0.13)和pcDNA3.1组(1.03±0.12)(F=29.476,P<0.001);pcDNA3.1-GPRC5A组下游基因Socs3(0.47±0.05),c-MYC(0.54±0.06)表达量也显著低于对照组(1.01±0.05,1.00±0.04)和pcDNA3.1组(0.98±0.09,1.02±0.06)(F=63.275,75.409,P<0.001)。肝癌组织中STAT3与GPRC5A表达量呈显著负相关(r=-0.746,P<0.01)。过转染pcDNA3.1-STAT3或pcDNA3.1-NLRP3后显著逆转了pcDNA3.1-GPRC5A对肝癌细胞的抑制作用(P<0.05)。结论GPRC5A低表达可能通过调节STAT3/Socs3/c-MYC信号和炎症反应抑制了肝癌细胞的增殖,诱导肝癌细胞的氧化应激和凋亡。
基金The Research and Development for Further Advancement of the 5th Generation Mobile Communication System(No.JP1000254)。
文摘Ultra-densification of radio access network(RAN)is a key to efficiently support the exponentially growing mobile data traffic in 5 G era.Furthermore,extremely high frequency band like mm Wave band was utilized to solve the bandwidth shortage problem.However,untra-dense reusing the same radio resource produced severe interference.And the mm Wave link was very harsh due to frequent blockage by obstacles.Therefore a new RAN architecture needed to be introduced to realize ultra-reliable communications in such a severe radio propagation environment.An architecture of distributed MIMO based RAN was presented.Then,enhanced interference coordination(e IC)was described.Finally,the effectiveness of distributed MIMO based RAN with e IC by computer simulation was showed.
基金funded in part by National Natural Science Foundation of China(grant NO.61471347)National S&T Mayor Project of the Ministry of S&T of China(grant NO.2016ZX03001020-003)+1 种基金key program for international S&T Cooperation Program of China(grant NO.2014DFA11640)Shanghai Natural Science Foundation(grant NO.16ZR1435100)
文摘Due to 5G's stringent and uncertainty traffic requirements,open ecosystem would be one inevitable way to develop 5G.On the other hand,GPP based mobile communication becomes appealing recently attributed to its striking advantage in flexibility and re-configurability.In this paper,both the advantages and challenges of GPP platform are detailed analyzed.Furthermore,both GPP based software and hardware architectures for open 5G are presented and the performances of real-time signal processing and power consumption are also evaluated.The evaluation results indicate that turbo and power consumption may be another challengeable problem should be further solved to meet the requirements of realistic deployments.
基金Supported by Basic Research Program of BJUT(No.040000546317525)National Natural Science Foundation of China(No.61571021)+1 种基金Foundation of Beijing Municipal Commission of Education(No.KM201610005004,KM201510005006)Beijing Postdoctoral Research Foundation(No.2018ZZ029)
文摘The heterogeneous network with the separation of the control plane and user plane(C/U) is an evolutionary approach to the fifth generation(5 G) to achieve high system coverage and capacity. To minimize signaling load of the core network when there is a macro base station(BS) failure in the control plane, a scheme of transferring the control of small cells under the coverage of the failure macro BS to the neighbor macro BSs is proposed. The average handover rates between small cells related to user mobilities, the extended coverage of the neighboring macro BSs under the constraint of transmitting power and the load balance index of the system are analyzed, based on which the formula of maximizing the handovers processed by macro BSs is constructed and further solved by the convex optimization methods. Simulation results indicate that the proposed scheme can effectively increase the total handovers processed by the macro BSs and thus reduce the signaling load of the core network.
文摘BACKGROUND In the heart,aldosterone(Aldo)binds the mineralocorticoid receptor(MR)to exert damaging,adverse remodeling-promoting effects.We recently showed that G protein-coupled receptor-kinase(GRK)-5 blocks the cardiac MR by directly phosphorylating it,thereby repressing its transcriptional activity.MR antagonist(MRA)drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure.Non-steroidal MRAs,such as finerenone,may provide better cardio-protection against Aldo than classic,steroidal MRAs,like spironolactone and eplerenone.AIM To investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade.METHODS We used H9c2 cardiomyocytes,which endogenously express the MR and GRK5.RESULTS GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone.Unlike eplerenone,finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity,thus displaying inverse agonism.GRK5 is necessary for finerenone’s inverse agonism,since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity.Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels.Finally,GRK5 is necessary for the antiapoptotic,anti-oxidative,and anti-fibrotic effects of both finerenone and eplerenone against Aldo,as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis,oxidative stress,and fibrosis.CONCLUSION Finerenone,but not eplerenone,induces GRK5-dependent cardiac MR inhibition,which underlies,at least in part,its higher potency and efficacy,compared to eplerenone,as an MRA in the heart.GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.