Design and Application of Intelligent Control System for Molten Iron Transportation Based on 5G Technology

Molten transport is an important link in the iron and steel enterprise production,involves many complex factors,artificial management is difficult.Therefore,puts forward a kind of molten iron transport wisdom control system based on 5G technology,which mainly contains the intelligent identification tracking system,equipment status collection information acquisition system,locomotive vehicle terminal system,etc.Combined with the analysis of the actual application situation,the system could integrate all the processes and elements of molten iron produc-tion and transportation,realize the integration of operation and management,and also promote the improvement of the turnover efficiency of molten iron tank,reduce the demand for personnel,and reduce the labor cost.

Possible association of the 5-HTTLPR serotonin transporter promoter gene polymorphism with premature ejaculation in a Turkish population

We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.

The PcHY5 methylation is associated with anthocyanin biosynthesis and transport in ‘Max Red Bartlett' and ‘Bartlett' pears

The red coloring of pear fruits is mainly caused by anthocyanin accumulation. Red sport, represented by the green pear cultivar ‘Bartlett’(BL) and the red-skinned derivative ‘Max Red Bartlett’(MRB), is an ideal material for studying the molecular mechanism of anthocyanin accumulation in pear. Genetic analysis has previously revealed a quantitative trait locus(QTL) associated with red skin color in MRB. However, the key gene in the QTL and the associated regulatory mechanism remain unknown. In the present study, transcriptomic and methylomic analyses were performed using pear skin for comparisons between BL and MRB. These analyses revealed differential PcHY5 DNA methylation levels between the two cultivars;MRB had lower PcHY5 methylation than BL during fruit development, and PcHY5 was more highly expressed in MRB than in BL. These results indicated that PcHY5 is involved in the variations in skin color between BL and MRB. We further used dual luciferase assays to verify that PcHY5 activates the promoters of the anthocyanin biosynthesis and transport genes PcUFGT, PcGST, PcMYB10 and PcMYB114, confirming that PcHY5 not only regulates anthocyanin biosynthesis but also anthocyanin transport. Furthermore, we analyzed a key differentially methylated site between MRB and BL, and found that it was located in an intronic region of PcHY5. The lower methylation levels in this PcHY5 intron in MRB were associated with red fruit color during development, whereas the higher methylation levels at the same site in BL were associated with green fruit color. Based on the differential expression and methylation patterns in PcHY5 and gene functional verification, we hypothesize that PcHY5, which is regulated by methylation levels, affects anthocyanin biosynthesis and transport to cause the variations in skin color between BL and MRB.

5-Fluorocytosine–Sugar Conjugates for Glucose Transporter-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism

Two novel sugar-conjugated 5-fluorocytosine(5-FC)antineoplastic compounds were designed and synthesized to improve the selective drug uptake by targeting the tumor-specific glucose transporter(GLUT).The antitumor activity of these compounds was evaluated in four different human cancer cell lines:A549(human lung cancer cell line),HT29(human colorectal cancer cell line),H460(human lung cancer cell line),and PC3(human prostate cancer cell line).The sugar conjugates exhibited cytotoxicity similar to or higher than 5-FC and 1-hexylcarbamoyl-5-FC in A549,HT29,H460,and PC3.Furthermore,GLUT-mediated transport of the glycoconjugate was investigated with GLUT inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing HT29 cell line.The cell-killing potency of 5-FC glycoconjugate was found to depend significantly on the GLUT inhibitor,and the cellular uptake of molecules was regulated by GLUT-mediated transport.All the results demonstrate the potential advantages of glycoconjugation for Warburg effect-targeted drug design.

A novel oral prodrug-targeting transporter MCT 1: 5-fluorouracil-dicarboxylate monoester conjugates

Monocarboxylate transporter 1(MCT1)is responsible for oral absorption of short-chain monocarboxylic acids from small intestine,hence,it’s likely to serve as an ideal design target for the development of oral prodrugs.However,potential application of MCT1 to facilitate the oral delivery is still unclear.Irregular oral absorption,poor permeability and bioavailability greatly limit the oral delivery efficiency of 5-fluorouracil(5-FU).Herein,we design three 5-FU-fatty acid conjugates targeting intestinal MCT1 with different lipophilic linkages.Interestingly,due to high MCT1 affinity and good gastrointestinal stability,5-FUoctanedioic acid monoester prodrug exhibited significant improvement in membrane permeability(13.1-fold)and oral bioavailability(4.1-fold)compared to 5-FU.More surprisingly,stability experiment in intestinal homogenates showed that 5-FU prodrugs could be properly activated to release 5-FU within intestinal cells,which provides an ideal foundation for the improvement of oral bioavailability.In summary,good gastrointestinal stability,high membrane permeability and appropriate intestinal cell bioactivation are the important factors for high-efficiency 5-FU oral prodrugs,and such work provides a good platform for the development of novel oral prodrugs targeting intestinal transporters.

Transforming liquid flow fuel cells to controllable reactors for highlyefficient oxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid at low temperature

Highly-efficient oxidation of 5-hydroxymethylfurtural(HMF) to 2,5-furandicarboxylic acid(FDCA) at low temperature with air as the oxidant is still challenging.Herein,inspired by the respirato ry electron transport chain(ETC) of living cells mediated by electron carriers,we constructed artificial ETCs and transformed liquid flow fuel cells(LFFCs) to flexible reactors for efficient oxidation of HMF to produce FDCA under mild conditions.This LFFC reactor employed an electrodeposition modified nickel foam as an anode to promote HMF oxidation and(VO_(2))_(2)SO_(4) as a cathode electron carrier to facilitate the electron transfer to air.The reaction rate could be easily controlled by selecting the anode catalyst,adjusting the external loading and changing the cathodic electron carrier or oxidants.A maximal power density of 44.9 mW cm^(-2) at room temperature was achieved,while for FDCA production,short-circuit condition was preferred to achieve quick transfer of electrons.For a single batch operation with 0.1 M initial HMF,FDCA yield reached 97.1%.By fed-batch operation,FDCA concentration reached 144.5 g L^(-1) with a total yield of 96%.Ni^(2+)/Ni^(3+) redox couple was the active species mediating the electron transfer,while both experimental and DFT calculation results indicated that HMFCA pathway was the preferred reaction mechanism.

基于天牛须搜索算法和内点法的运输类飞机5×5谱编制方法

载荷谱作为运输类飞机疲劳分析和试验的输入,其编制具有重要意义。针对运输类飞机载荷谱编制需求,本文基于天牛须搜索算法和内点法,提出了一种编制5×5谱的方法。首先确定飞机的任务剖面,通过对飞机实测数据进行处理与统计获得过载累积超越数曲线,依据极值载荷对数正态分布准则,采用基于天牛须搜索算法和内点法耦合的5×5谱求解方法对各类飞行类型次数和载荷水平比进行迭代和选取;依据载荷谱形状相似准则,提出了载荷谱形状相似性指标,采用天牛须算法对5×5谱中各类飞行类型中各级载荷出现次数进行迭代,形成各任务段的5×5谱。最后给出了一个示例以阐明该5×5谱编制方法。实现了运输类飞机5×5谱的快速和高质量编制。

Diversity of Sodium Transporter HKT1;5 in Genus Oryza

Asian cultivated rice shows allelic variation in sodium transporter,OsHKT1;5,correlating with shoot sodium exclusion(salinity tolerance).These changes map to intra/extracellularly-oriented loops that occur between four transmembrane-P loop-transmembrane(MPM)motifs in OsHKT1;5.HKT1;5 sequences from more recently evolved Oryza species(O.sativa/O.officinalis complex species)contain two expansions that involve two intracellularly oriented loops/helical regions between MPM domains,potentially governing transport characteristics,while more ancestral HKT1;5 sequences have shorter intracellular loops.We compared homology models for homoeologous OcHKT 1;5-K and OcHKT1;5-L from halophytic O.coarctata to identify complementary amino acid residues in OcHKT1;5-L that potentially enhance affinity for Na+.Using haplotyping,we showed that Asian cultivated rice accessions only have a fraction of HKT1;5 diversity available in progenitor wild rice species(O.nivara and O.rufipogon).Progenitor HKT1;5 haplotypes can thus be used as novel potential donors for enhancing cultivated rice salinity tolerance.Within Asian rice accessions,10 non-synonymous HKT1;5 haplotypic groups occur.More HKT1;5 haplotypic diversities occur in cultivated indica gene pool compared to japonica.Predominant Haplotypes 2 and 10 occur in mutually exclusive japonica and indica groups,corresponding to haplotypes in O.sativa salt-sensitive and salt-tolerant landraces,respectively.This distinct haplotype partitioning may have originated in separate ancestral gene pools of indica and japonica,or from different haplotypes selected during domestication.Predominance of specific HKT1;5 haplotypes within the 3000 rice dataset may relate to eco-physiological fitness in specific geo-climatic and/or edaphic contexts.

Evaluation of the 5-HTTLPR and 5-HTTVNTR Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Objective: The purpose of the present study was to evaluate the association between the 5-HTTLPR and 5-HTTVNTR polymorphisms in the serotonin transporter gene (SLC6A4) in Brazilian women with diagnosed postpartum depression (PPD) and the presence of depressive symptoms. Method: The cohort consisted of 128 white women who were charac-terized based on skin color and morphological characteristics. The Beck Depression Inventory was used to diagnose PPD and to score the depressive symptoms. The 5-HTTLPR and 5-HTTVNTR polymorphisms were analyzed by PCR-based methods. Results: No association was observed between the PPD diagnosis and either the 5-HTTLPR (p = 0.48) or the 5-HTTVNTR (p = 0.77) polymorphism. When the polymorphisms were analyzed together with haplotype data, the analyses demonstrated that women carriers of the L-12/L-12 diplotype have lower Beck Depression Inventory scores than women carrying other diplotypes (p = 0.04). Discussion: Few studies have investigated the association of SLC6A4 polymorphisms with PPD, and the role of 5-HTTLPR and 5-HTTVNTR polymorphisms in PPD susceptibility has not been established to date. Therefore, our findings link the haplotypes of these two variants with depression symptoms, thereby contributing to our understanding of PPD susceptibility.

5G Flexible Optical Transport Networks with Large-Capacity, Low-Latency and High-Efficiency

The fifth generation(5G) of mobile communications are facing big challenges, due to the proliferation of diversified terminals and unprecedented services such as internet of things(IoT), high-definition videos, virtual/augmented reality(VR/AR). To accommodate massive connections and astonish mobile traffic, an efficient 5G transport network is required. Optical transport network has been demonstrated to play an important role for carrying 5G radio signals. This paper focuses on the future challenges, recent studies and potential solutions for the 5G flexible optical transport networks with the performances on large-capacity, low-latency and high-efficiency. In addition, we discuss the technology development trends of the 5G transport networks in terms of the optical device, optical transport system, optical switching, and optical networking. Finally, we conclude the paper with the improvement of network intelligence enabled by these technologies to deterministic content delivery over 5G optical transport networks.

Water Vapor Transport and Cross-Equatorial Flow over the Asian-Australia Monsoon Region Simulated by CMIP5 Climate Models

The summer mean water vapor transport （WVT） and cross-equatorial flow （CEF） over the Asian- Australian monsoon region simulated by 22 coupled atmospheric-oceanic general circulation models （AOGCMs） from the World Climate Research Programme＇s Coupled Model Intercomparison Project Phase 5 （CMIP5） were evaluated. Based on climatology of the twentieth-century simulations, most of models have a reason- ably realistic representation of summer monsoon WVT characterized by southeast water vapor conveyor belt over the South Indian Ocean and southwest belt from the Arabian Sea to the East Asian. The correlation coefficients between NCEP reanalysis and simulations of BCC-CSMI-1, BNU-ESM, CanESM2, FGOALS-s2, MIROC4h and MPI-ESM-LR are up to 0.8. The simulated CEF depicted by the meridional wind along the equator includes the Somali jet and eastern CEF in low atmosphere and the reverse circulation in upper atmosphere, which were generally consistent with NCEP reanalysis. Multi-model ensemble means （MME） can reproduce more reasonable climatological features in spatial distribution both of WVT and CEF. Ten models with more reasonable WVT simulations were selected for future projection studies, including BCC- CSMI-1, BNU-ESM, CanESM2, CCSM4, FGOALS-s2, FIO-ESM, GFDL-ESM2G, MRIOCS, MPI-ESM-LR and NorESM-1M. Analysis based on the future projection experiments in RCP （Representative Concentra- tion Pathway） 2.6, RCP4.5, RCP6 and RCP8.5 show that the global warming forced by different RCP scenarios will results in enhanced WVT over the Indian area and the west Pacific and weaken WVT in the low latitudes of tropical Indian Ocean.

Flex Ethernet Technology and Application in 5G Mobile Transport Network

With the advent of 5G era,the rise of cloud services,virtual reality/virtual reality(AR/VR),vehicle networking and other technologies has put forward new requirements for the bandwidth and delay of the bearer network.Traditional Ethernet technology cannot meet the new requirements very well.Flex Ethernet(FlexE)technology has emerged as the times require.This paper introduces the background,standardization process,functional principle,application mode and technical advantages of FlexE technology,and finally analyses its application prospects and shortcomings in 5G mobile transport network.

5-羟色胺转运体基因多态性与不同民族创伤后应激障碍患者的关联性研究

目的探讨5-羟色胺转运体(5-HTTLPR)基因多态性与海南省黎、汉民族创伤后应激障碍(PTSD)患者的相关性。方法选取2017年10月至2018年7月在海南省人民医院就诊的308例PTSD患者作为研究组,其中黎族167例,汉族141例;另选2017年10月至2018年7月间未经受创伤性事件并在我院健康体检中心体检的158例健康志愿者作为对照组。收集研究对象的一般资料,采用PTSD临床评定量表、埃森创伤问卷(ETI)评定入组患者PTSD严重程度,另采用汉诺塔(TOH)、威斯康星卡片分类测试(WCST)、连线测验(TMT)与韦氏成人智力量表(WAIS)对评定入组对象认知功能,应用多聚酶链式反应(PCR)方法检测研究对象5-HTTLPR基因多态性。结果三组被试者的平均年龄、性别构成、婚姻状况和受教育程度比较差异均无统计学意义(P>0.05);黎族PTSD患者和汉族PTSD患者的各ETI评分与PTSD总分、TMT时间、TOH计划时间和执行时间、WCST的错误数明显高于对照组,而WAIS-RC中领悟、相似、木块图、物体拼凑及操作智商和TOH总分明显低于对照组,差异均有统计学意义(P<0.05);黎族PTSD患者各ETI评分与PTSD总分、TMT时间明显高于汉族PTSD患者,而WAIS-RC中领悟、操作智商与低于汉族PTSD患者,差异均具有统计学意义(P<0.05);黎族PTSD患者5-HTTLPR等位基因与基因型分布与对照组比较差异均无统计学意义(P>0.05),而在汉族PTSD患者与对照组中比较差异均有统计学意义(P<0.05):与LL基因型比较,SS基因型可能会增加汉族人群患PTSD的风险(OR=2.157,95%CI=1.098~4.237,P=0.024);与L等位基因比较,S等位基因可能会增加汉族人群患PTSD的风险(OR=1.456,95%CI=1.045~2.207,P=0.026);汉族PTSD患者中5-HTTLPR的SS基因型患者各ETI评分与PTSD总分、TMT时间明显高于LL基因型患者,WAIS-RC中的领悟和算术及木块图明显低于LL基因型患者,差异均具有统计学意义(P<0.05),而在黎族PTSD患者中SS基因型与LL基因型的认知功能比较差异无统计学意义(P>0.05)。结论5-HTTLPR的SS基因型和S等位基因可能增加PTSD发病风险及导致患者的认知功能损害更加严重。

5-HTTLPR基因多态性与惊恐障碍发病风险关系的Meta分析

目的系统评价5-羟色胺转运体启动子区(5-HTTLPR)基因多态性与惊恐障碍(PD)发病风险的关系。方法利用PubMed、Embase、中国知网、维普网和万方数据知识服务平台等数据库检索5-HTTLPR基因多态性与PD发病风险关系的相关文献,根据异质性检验结果,采用固定效应模型分析总体人群及以种族划分为亚组人群5种基因遗传模型下5-HTTLPR基因多态性与PD发病风险的关系。结果共纳入合格文献11篇,包括PD组1431例,对照组2148例。在总体人群及以种族划分为亚组人群中,5种基因遗传模型下5-HTTLPR基因多态性与PD发病风险均无关(均P>0.05)。结论5-HTTLPR基因多态性可能与PD发病风险无关。

Multi-carrier transport in ZrTe_5 film

Single-layered zirconium pentatelluride （ZrTes） has been predicted to be a large-gap two-dimensional （2D） topolog- ical insulator, which has attracted particular attention in topological phase transitions and potential device applications. Herein, we investigated the transport properties in ZrTe5 films as a function of thickness, ranging from a few nm to several hundred nm. We determined that the temperature of the resistivity anomaly peak （Tp） tends to increase as the thickness decreases. Moreover, at a critical thickness of ~ 40 rim, the dominating carriers in the films change from n-type to p-type. A comprehensive investigation of Shubnikov-de Hass （SdH） oscillations and Hall resistance at variable temperatures revealed a multi-carrier transport tendency in the thin films. We determined the carrier densities and mobilities of two majority car- riers using the simplified two-carrier model. The electron carriers can be attributed to the Dirac band with a non-trivial Berry phase ~, while the hole carriers may originate from surface chemical reaction or unintentional doping during the microfabrication process. It is necessary to encapsulate the ZrTe5 film in an inert or vacuum environment to potentially achieve a substantial improvement in device quality.

Effect of GTA on Gas Transporting SHS of Ti_5Si_3

By doping gas transport agents (GTA), the combustion process and structural formation of SHS can be significantly varied. In this paper, Ti5Sis was synthesized by SHS method using AICI3·6H2O as GTA. The effect of GTA was studied by measuring combustion process parameters. XRD and SEM were used to determine the phases and microstructures of products. The structural formation of 7V6Si3 with different GTA contents was studied by CFQ method. Three mechanisms were deduced.

An assessment of the CMIP5 models in simulating the Argo geostrophic meridional transport in the North Pacifi c Ocean

Eleven climate system models that participate in the Coupled Model Intercomparison Project phase 5(CMIP5)were evaluated based on an assessment of their simulated meridional transports in comparison with the Sverdrup transports.The analyses show that the simulated North Pacifi c Ocean circulation is essentially in Sverdrup balance in most of the 11 models while the Argo geostrophic meridional transports indicate signifi cant non-Sverdrup gyre circulation in the tropical North Pacifi c Ocean.The climate models overestimated the observed tropical and subtropical volume transports signifi cantly.The non-Sverdrup gyre circulation leads to non-Sverdrup heat and salt transports,the absence of which in the CMIP5 simulations suggests defi ciencies of the CMIP5 model dynamics in simulating the realistic meridional volume,heat,and salt transports of the ocean.

Structural determinants specific for retromer protein sorting nexin 5 in regulating subcellular retrograde membrane trafficking

The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting trimer and a membrane-deforming subunit of sorting nexin proteins. Recent studies have shown that the isoforms, sorting nexin 5 (SNX5) and SNX6, have played distinctive regulatory roles in retrograde membrane trafficking. However, the molecular insight determined functional differences within the proteins remains unclear. We reported that SNX5 and SNX6 had distinct binding affinity to the cargo protein vesicular monoamine transporter 2 (VMAT2). SNX5, but not SNX6, specifically interacted with VMAT2 through the Phox domain, which contains an alpha-helix binding motif. Using chimeric mutagenesis, we identified that several key residues within this domain were unique in SNX5, but not SNX6, and played an auxiliary role in its binding to VMAT2. Importantly, we generated a set of mutant SNX6, in which the corresponding key residues were mutated to those in SNX5. In addition to the gain in binding affinity to VMAT2, their overexpression functionally rescued the altered retrograde trafficking of VMAT2 induced by siRNA-mediated depletion of SNX5. These data strongly suggest that SNX5 and SNX6 have different functions in retrograde membrane trafficking, which is determined by the different structural elements within the Phox domain of two proteins. Our work provides a new information on the role of SNX5 and SNX6 in the molecular regulation of retrograde membrane trafficking and vesicular membrane targeting in monoamine neurotransmission and neurological diseases.

SLC1A5协同TM4SF1通过mTOR信号通路调控食管鳞癌细胞迁移

目的探讨氨基酸转运载体溶质载体家族1成员5(SLC1A5)在食管鳞癌(ESCC)中的表达及其与临床病理特征的相关性,以及SLC1A5对ESCC细胞迁移的影响及潜在分子机制。方法采用TNM plot在线数据库分析SLC1A5基因在ESCC组织和正常组织中的表达情况。通过实时定量逆转录聚合酶链反应(qRT-PCR)法检测ESCC组织和癌旁组织中SLC1A5 mRNA表达情况;采用免疫组化(IHC)法检测SLC1A5蛋白表达情况,并分析其与患者临床病理资料的相关性。分别构建SLC1A5过表达(SLC1A5-OE组)、四跨膜蛋白超家族成员1过表达(TM4SF1-OE组)、SLC1A5和TM4SF1共同过表达的Eca109细胞。采用细胞增殖试验、Transwell实验检测Eca109细胞的增殖、迁移和侵袭能力。通过免疫共沉淀(IP)实验证实SLC1A5和TM4SF1的相互作用;采用蛋白质免疫印迹(WB)法检测哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白的表达水平。结果TNM plot数据库分析显示,ESCC组织中SLC1A5基因表达水平高于正常组织,差异有统计学意义(P<0.05)。ESCC组织中SLC1A5 mRNA表达高于成对的癌旁组织,差异有统计学意义(P<0.01)。IHC结果显示,SLC1A5蛋白在癌组织中高表达,并且与临床分期(P=0.036)、淋巴结转移(P=0.029)显著相关。细胞增殖实验结果显示,SLC1A5-OE组和对照细胞(Con组)增殖能力比较,差异无统计学意义(P>0.05)。Transwell实验结果显示,与Con组比较,SLC1A5-OE组细胞迁移及侵袭能力增强,差异有统计学意义(P<0.01)。IP结果表明,SLC1A5与TM4SF1存在相互作用。WB结果显示,相对于SLC1A5-OE组或TM4SF1-OE组,p-mTOR、p-S6蛋白表达水平在SLC1A5和TM4SF1共同过表达的细胞中最高。Transwell实验证实,共同过表达SLC1A5和TM4SF1的ESCC细胞迁移能力最强。结论ESCC中SLC1A5呈高表达,且与患者临床分期、淋巴结转移显著相关,SLC1A5可能通过与TM4SF1相互作用,激活mTOR信号通路,进而促进ESCC细胞迁移。

瞬时受体电位通道香草醛亚型-5通过调控NF-κB通路改善免疫微环境治疗小鼠动脉粥样硬化的作用机制

目的:分析瞬时受体电位通道香草醛亚型-5(transient receptor potential vanilloid type 5,TRPV5)对载脂蛋白E基因敲除(apolipoprotein E gene knockout,ApoE^(−/−))小鼠动脉粥样硬化发病机制的影响。方法:构建过表达TRPV5的携带绿色荧光蛋白重组腺病毒(adeno-associated virus-TRPV5-green fluorescent protein,AAV-TRPV5-GFP),将其转染RAW264.7细胞以及经静脉注射到ApoE^(−/−)小鼠体内。ApoE^(−/−)小鼠喂食含21%脂肪和0.15%胆固醇的西方式高脂食物8周后,随机分为2组:AAV-TRPV5-GFP组(n=10)和AAV-GFP组(n=10)。采用油红O染色检测主动脉病变大小,ELISA试剂盒法测定血脂、炎症因子水平,高效液相色谱法测定细胞的胆固醇酯,液体闪烁光谱法检测细胞的3H-胆固醇放射性,以及蛋白质印迹法分析胆固醇转运、炎症调节蛋白表达。结果:与0周相比,ApoE^(−/−)小鼠血管组织中的TRPV5水平随着西方饮食喂养时间延长持续降低。在西方饮食喂养第14周时,与AAV-GFP组小鼠相比,AAV-TRPV5-GFP组小鼠整个主动脉的油红O阳性区域减少,主动脉根部病变显著减小,并且小鼠血浆甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)、白细胞介素(interleukin,IL)-1β和IL-6水平显著降低,血浆高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平显著提高并改善了HDL功能。此外,注射AAV-TRPV5-GFP的ApoE^(−/−)小鼠的腹腔巨噬细胞中磷酸化β-连环素(phosphoβ-catenin,P-β-catenin)和磷酸化核因子κB(phospho nuclear factor kappa-B,P-NF-κB)的表达水平低于AAV-GFP小鼠。体外实验中,与转染AAV-GFP的细胞相比,转染AAV-TRPV5-GFP的RAW264.7细胞的油红O染色降低了34.4%,细胞胆固醇含量降低43.9%,胆固醇外流至载脂蛋白AI(apolipoprotein AI,apoAI)增加了38.3%。蛋白质印迹法显示:转染AAVTRPV5-GFP的RAW264.7细胞的三磷酸腺苷结合盒转运体A1(ATP binding cassette transporter A1,ABCA1)、ATP结合盒转运体G1(ATP binding cassette transporter G1,ABCG1)、B类1型清道夫受体(scavenger receptor class B type 1,SR-B1)、过氧化酶活化增生受体γ(peroxisome proliferator activated receptor gamma,PPAR-γ)、肝X受体α(liver X receptorα,LXR-α)蛋白水平显著增高(均P<0.05),而清道夫受体A1(scavenger receptor A1,SR-A1)和低密度脂蛋白受体(low-density lipoprotein receptor,LDLR)蛋白水平显著降低(均P<0.05)。结论:TRPV5通过调节巨噬细胞中的胆固醇转运和抑制炎症因子的释放来防止动脉粥样硬化。