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常春藤皂苷元通过调控巨噬细胞Mincle介导的炎症减轻银屑病小鼠皮肤损伤的作用机制

◇基础研究◇摘要目的：观察常春藤皂苷元（hederagenin ，HDG ）改善银屑病小鼠皮肤损伤和炎症的作用与机制。

方法：通过在C57小鼠背部祛毛并连续涂抹咪喹莫特7d 建立小鼠银屑病动物模型，造模后1h 给予HDG 灌胃治疗。

总计设置正常组、模型组、模型+HDG 低剂量（25mg ·kg -1·d -1）、模型+HDG 高剂量（50mg ·kg -1·d -1）和模型+卤米松阳性对照组（每组8只小鼠）。

给药7d 后，对患处皮肤进行病理检测，以及炎症指标进行ELISA 、实时定量PCR 检测，Mincle 及其下游信号进行免疫组织化学、免疫荧光和Western blot 检测。

结果：与模型组比较，HDG 干预组皮肤病理损伤以及炎性细胞浸润均得到不同程度改善；实时定量PCR 和皮肤组织悬液ELISA 结果证实HDG 干预后小鼠皮肤中炎症因子IL-1β、IL-6和TNF-α的mRNA 及蛋白水平均比模型组降低（P <0.01），说明HDG 具有显著抗炎症作用；免疫组织化学和Western blot 结果表明，与正常组相比，模型组小鼠皮肤中Min-cle 的蛋白表达量显著增加（P <0.01），给予HDG 干预后明显下调（P <0.01）；免疫荧光证实模型组皮肤中Mincle 表达与巨噬细胞标志物F4/80共定位；Western blot 实验发现，HDG 在治疗组中不仅下调了Mincle 的蛋白表达，同时也下调了Mincle 下游信号Syk 和NF-κB 的蛋白磷酸化水平。

结论：HDG 可显著改善银屑病小鼠皮肤损伤和巨噬细胞相关炎症，其潜在分子机制可能与下调Min-cle/Syk/NF-κB 信号途径相关。

关键词常春藤皂苷元；Mincle ；皮肤损伤；炎症；银屑病中图分类号：R965.2文献标志码：A文章编号：1009-2501(2023)12-1339-08doi ：10.12092/j.issn.1009-2501.2023.12.003银屑病是一种慢性丘疹鳞状皮肤病，其主要特点是遗传性和复发性，还可能并发其他疾病，如心血管疾病、糖尿病和关节炎等［1-4］。

鸟声在生态学研究中的应用

and so on…
声音分析 - 分析方法
语图：结构+频率和时间参数
回放实验
声音分析 - 分析方法 - 语图结构
Element(音素)
Element group（音节）: Fixed group of two or more different element types.
Verse（句子）: Separated by pauses
NATURE|29 January 2009 The first evidence of within-species dialects among neotropical primates has beห้องสมุดไป่ตู้n revealed. recorded the vocal patterns of adult pygmy marmosets (Callithrix pygmaea) from 14 groups found in five geographically distinct regions researchers discovered consistent structural differences in calls between regions.
Potter, Science, 1945, 102, 463-470.
Introduction
Bird song research are focus on
Development of Song in the Individual The Syrinx: Organ of Vocal Production Brain Mechanisms and the Vocal Control System Bird Song as a Communication System Evolution of Song and of Vocal Learning Systemic Taxon Individual Identification

灵长类动物卵巢衰老的分子标记物被揭示

灵长类动物卵巢衰老的分子标记物被揭示作者：来源：《科学中国人·下旬刊》2020年第05期灵长类动物卵巢衰老的分子标记物被揭示中国科学院动物研究所刘光慧研究组和曲静研究组与北京大学汤富酬研究组及美国索尔克（Salk）研究所Juan Carlos Izpisua Belmonte研究组等合作，绘制了食蟹猴卵巢的单细胞衰老图谱，同时利用人类卵巢细胞研究体系，发现增龄伴随的抗氧化能力的下降是灵长类卵巢衰老的主要特征之一。

研究论文发表于Cell。

文章报道了非人灵长类器官衰老的高精度單细胞转录组图谱研究，揭示细胞类型特异性的氧化还原调控的失稳是包括人类在内的灵长类卵巢衰老的共性分子机制。

加深了对卵巢组织结构增龄性变化的认识，解析了衰老过程中不同卵巢细胞类型的易感性及易感分子，提供了灵长类卵巢衰老的潜在调控靶标信息。

转基因猕猴与部分自闭症患者的脑功能网络异常相似中国科学院脑科学与智能技术卓越创新中心（神经科学研究所）、上海脑科学与类脑研究中心王征研究组发现转基因猕猴与部分自闭症患者的脑功能网络异常相似。

研究论文发表于Journal of Neuroscience。

该研究联合运用基因组学、行为学、多通道脑电以及功能磁共振成像技术对转基因猕猴系统性分析发现，MECP2基因过表达引起一连串生理事件变化，包括GABA信号通路，β频段脑电信号同步性以及脑功能网络连接异常变化，并进一步展示转基因猕猴的脑功能网络异常与小部分临床自闭症患者的磁共振脑影像结果非常相似，为非人灵长类模型未来的转化应用奠定神经环路基础。

魏氏准噶尔翼龙头骨腭区研究进展中国科学院古脊椎动物与古人类研究所汪筱林团队关于魏氏准噶尔翼龙的头骨腭区研究最新进展发表于PeerJ。

魏氏准噶尔翼龙（Dsungaripterus weii）是我国发现的第一具较完整的翼龙化石骨架，1964年杨钟健研究命名并建立了准噶尔翼龙科，当时认为这是第一次在我国发现的翼龙类化石。

吲哚菁绿纳米探针在结肠癌诊疗一体化中的应用探索

吲哚菁绿纳米探针在结肠癌诊疗一体化中的应用探索目的:结肠癌（Colon cancer,CC）是常见的消化系统恶性肿瘤之一,近年来的发病率和死亡率不断增加,据统计,近年我国结肠癌的发病率已上升到恶性肿瘤发病率的第五位。

早发现、早治疗可以有效提高结肠癌患者的治愈率、生存率,改善患者的生存质量,结肠癌的精确诊断以及高效治疗已经成为临床研究的热点及难点。

传统的治疗方法包括外科手术、化学治疗、放射治疗等存在的毒副作用、多药耐药、复发等问题目前尚难以克服。

融合多学科交叉协作的纳米探针技术,有望克服现有结肠癌治疗手段产生的靶向生物利用率低、对人体不良反应多等缺陷,把结肠癌诊断和治疗有机结合,为结肠癌诊治提供了新思路。

本研究拟使用已在临床医疗应用的近红外荧光染料吲哚菁绿（Indocyanine green,ICG）标记人血清白蛋白（Human serum albumin,HSA）,基于ICG的光热特性,设计生物相容性好、可生物降解的HSA-ICG纳米探针,观察HSA-ICG纳米探针在肿瘤成像诊断和光热治疗方面的作用,为实现结肠癌诊疗一体化探索新的方法。

方法:1.采用有机溶剂沉淀技术制备出还原的HSA,HSA与ICG混合后,重新复合形成HSA-ICG纳米微粒。

在透射电镜下观察HSA-ICG的形貌特征,采用动态光散色（Dynamic light scattering,DLS）法测定HSA-ICG粒径大小,近红外（Near infra-red,NIR）激光进行照射,测试探针光热转换性质及稳定性。

2.培养制备结肠癌HCT116细胞,建立裸鼠结肠癌皮下移植瘤模型,利用980nm NIR激光照射加入HSA-ICG探针的结肠癌细胞样液,MTT比色法检测不同浓度下加入HSA-ICG的HCT116细胞存活率;测定其光热转换的性质,并使用Annexin V FITC/PI双荧光标记法,流式细胞仪观察细胞凋亡情况。

3.分别将Folate Rsense<sup>TM</sup>680、HSA-ICG、ICG探针注入每组同一批、各同样数量的6只裸鼠结肠癌皮下移植瘤模型中,使用活体成像仪（In vivo imaging system,IVIS）进行荧光发光成像（Fluorescence luminescence imaging,FLI）,测量各时间点感兴趣区域（Region of interest,ROI）的平均荧光信号强度。

Exogenous Alanine and or Glucose plus Kanamycin Kills Antibiotic-Resistant Bacteria

Article Exogenous Alanine and/or Glucose plus Kanamycin Kills Antibiotic-Resistant BacteriaGraphical AbstractHighlightsd Glucose and alanine abundances are suppressed inkanamycin-resistant E.tardad Alanine or glucose,via the TCA cycle,restores bacterialsusceptibility to antibioticsd NADH and proton motive force increases,which stimulatesuptake of antibioticd A functional metabolomics-based strategy to kill bacteria isdeveloped AuthorsBo Peng,Yu-bin Su,...,Yao-mei Tian, Xuan-xian PengCorrespondencepxuanx@In BriefPeng et al.show that exogenous alanine and/or glucose restores susceptibility to antibiotics in antibiotic-resistant bacteria by increasing TCAﬂux,NADH production, and proton motive force to enhance kanamycin uptake,both in vitro and in a mouse model for urinary tractinfection. Peng et al.,2015,Cell Metabolism21,249–261February3,2015ª2015Elsevier Inc./10.1016/j.cmet.2015.01.008Cell MetabolismArticleExogenous Alanine and/or Glucoseplus Kanamycin KillsAntibiotic-Resistant BacteriaBo Peng,1,2,3Yu-bin Su,1,3Hui Li,1,3Yi Han,1Chang Guo,1Yao-mei Tian,1and Xuan-xian Peng1,*1Center for Proteomics and Metabolomics,State Key Laboratory of Biocontrol,School of Life Sciences,MOE Key Lab Aquat Food Safety, School of Life Sciences,Sun Yat-sen University,Guangzhou510275,People’s Republic of China2Molecular Foundry,Lawrence Berkeley National Laboratory,Berkeley,CA94720-8197,USA3Co-ﬁrst author*Correspondence:pxuanx@/10.1016/j.cmet.2015.01.008SUMMARYMultidrug-resistant bacteria are an increasinglyserious threat to human and animal health.However,novel drugs that can manage infections by multi-drug-resistant bacteria have proved elusive.Herewe show that glucose and alanine abundances aregreatly suppressed in kanamycin-resistant Edward-siella tarda by GC-MS-based metabolomics.Exoge-nous alanine or glucose restores susceptibility ofmultidrug-resistant E.tarda to killing by kanamycin,demonstrating an approach to killing multidrug-resistant bacteria.The mechanism underlying thisapproach is that exogenous glucose or alanine pro-motes the TCA cycle by substrate activation,whichin turn increases production of NADH and protonmotive force and stimulates uptake of antibiotic.Similar results are obtained with other Gram-nega-tive bacteria(Vibrio parahaemolyticus,Klebsiellapneumoniae,Pseudomonas aeruginosa)and Gram-positive bacterium(Staphylococcus aureus),and the results are also reproduced in a mouse model for urinary tract infection.This study establishes a functional metabolomics-based strategy to manage infection by antibiotic-resistant bacteria.INTRODUCTIONBacterial antibiotic resistance is a threat to human health and to the viability of animal and plant species in the human food chain. Because efforts to develop antimicrobials that kill multidrug-resistant bacteria have not been successful to date(Raju et al., 2012;Coates and Hu,2007),there is an urgent need and high demand for agents that can kill or prevent infection with these bacteria.Unfortunately,the existing arsenal of antibiotics no longer provides protection against infection with Gram-negative bacteria and other pathogenic bacterial species or subspecies (Piddock,2012;Carlet et al.,2012).It has been noted that antibi-otics tend to achieve a lower intracellular concentration in antibi-otic-resistant bacteria than in closely related antibiotic-sensitive strains,indicating either lower rate of drug uptake or higher rate of drug exported(or both)(Page`s et al.,2008;Alekshun and Levy,2007).To overcome this phenomenon,novel approaches must be developed to achieve an intracellular drug concentra-tion sufﬁciently high that the intended biological effect is observed(Hancock et al.,2012;Lee and Collins,2012;Roemer and Boone,2013).Some evidence suggests that agents that increase the trans-membrane proton motive force(PMF)stimulate uptake of amino-glycoside antibiotics(Allison et al.,2011;Wang et al.,2009).We propose that the metabolic state of a bacterium signiﬁcantly in-ﬂuences its relative susceptibility to killing by antibiotic drugs, and that speciﬁc metabolic proﬁles correlate with antibiotic resistance.Furthermore,reagents that revert the metabolome of an antibiotic-resistant strain to that of an antibiotic-sensitive strain could potentially revert the phenotype of antibiotic resis-tance.In particular,we propose that exogenous metabolites might have this effect,if they increase transmembrane PMF, converting drug-resistant bacteria to drug-sensitive bacteria. Edwardsiella tarda is represented in the normal gutﬂora of humans andﬁsh,but it is also an opportunistic intracellular pathogen in humans,ﬁsh,and other species(Haenen et al., 2013;Park et al.,2012).In humans,E.tarda can cause gastroen-teritis,colitis,dysentery-like disease,septicemia,and meningitis (Nelson et al.,2009;Kawai et al.,2011).Infants can become in-fected with E.tarda during birth(Mowbray et al.,2003),and it has been linked to devastating declines inﬁsh populations (Park et al.,2012;Liu et al.,2013).Multidrug-resistant E.tarda has been isolated fromﬁsh and human(Wang et al.,2009;Yu et al.,2012;Kawai et al.,2011),presenting signiﬁcant challenge for its control.Here,we describe the metabolic state of antibi-otic-resistant E.tarda and demonstrate that exogenous alanine or glucose revert the bacterium to kanamycin susceptibility. RESULTSMetabolic Proﬁle and Potential Biomarkers ofDrug-Resistant E.tardaTo study antibiotic resistance in E.tarda,wild-type kanamycin-susceptible E.tarda LTB4(LTB4-S)were grown in media con-taining kanamycin.Single cells that survived and proliferated in the presence of the antibiotic were used to establish a homog-enous kanamycin-resistant cell line,andkanamycin-resistant Cell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.249E.tarda LTB4(LTB4-R)were selected(Figure S1A).Metabolomic proﬁlings of LTB4-S and LTB-R,both of which were cultured in medium without kanamycin,were analyzed by gas chromatog-raphy-mass spectrometry(GC-MS).Eight biological and two technical replicates were performed,covering63metabolites in each strain(Figure S1B).The Z scores for LTB4-S were À17.5to+13.8(Figure S1C).Forty-nine of63metabolites (77.8%)showed signiﬁcant difference(p<0.01)corresponding to a false discovery rate of3.2%,with19metabolites at lower abundance and29at higher abundance in LTB4-R.Unsuper-vised hierarchical clustering and Z scores were used to rank metabolites whose abundance differed signiﬁcantly in the two strains(Figures1A and1B).Independent component analysis identiﬁed two principal components,IC01and IC02,where IC01discriminates between the two strains,and IC02discrimi-nates within each strain(Figure1C).Glucose abundance was suppressed to a greater extent in LTB4-R than all other metabo-lites tested and may have the most impact(Figures1B,1D and S1D).However,the most strongly impacted KEGG pathway is alanine,aspartate,and glutamate metabolism(Figure1E). Decreased abundance of alanine and glutamate was observed (Figure1B),with higher impact on alanine(Figures1D and S1D).The concentration of alanine and glucose modulates the concentration of NADH;consistent with this,NADH abundance was lower in LTB4-R than in LTB4-S(Figure S1E).These results prompted us to explore whether the suppressed levels of alanine and glucose are useful biomarkers of antibiotic resistance and whether the phenotype of LTB4-R cells changes in the presence of exogenous alanine and/or glucose.Exogenous Metabolites Alter Susceptibility ofDrug-Resistant E.tarda to KanamycinAn earlier study reported that exogenous glucose stimulates up-take of aminoglycoside antibiotics by E.coli persisters(Allison et al.,2011).Here,we tested whether two metabolites,alanine or/and glucose,suppressed in LTB4-R,can be used to kill drug-resistant E.tarda with kanamycin including LTB4-R and E.tarda EIB202.EIB202is a wild multidrug-resistant strain car-rying a43.7kbp conjugative plasmid that confers resistance to tetracycline,streptomycin,sulfonamide,and chloramphenicol (Figure S2A)(Wang et al.,2009).The two drug-resistant bacteria were co-incubated with alanine with or without glucose and chal-lenged with an antibiotic,because we predicted the two metab-olites might act in a synergistic manner,by virtue of their ability to stimulate amino acid and carbon metabolisms,respectively. As predicted,cell survival decreased with increasing dose of alanine(Figure2A),glucose(Figure2B),or alanine plus glucose (Figures2C and2D),when grown in the presence of kanamycin. Relative to LTB4-R cells grown in the presence of1,000m g kana-mycin alone,cell survival decreased101-,3,228-,or276,000-fold in the presence of40mM alanine,10mM glucose,or both (Figure2E);cell survival of LTB4-R and EIB202was201-,927-, and123,600-fold and527-,2,916-,and283,089-fold lower for cells grown in the presence of kanamycin plus alanine,glucose, or both,respectively(Figure S2B).Similar experiments were performed with three other E.tarda wild strains,WY28,WY37,and ATCC15947,and three other LTB4-S-derived the beta-lactam ampicillin-,the quinolone balo-ﬂoxacin-,and the tetracyclins tetracycline-resistant strains.Minimum inhibitory concentration of these strains is shown in Figures S2A and S2C,respectively.The results were similar to those observed with LTB4-R and EIB202(Figure S2D),suggest-ing a common mechanism in glucose and/or alanine-mediated drug susceptibility.A more detailed analysis of cell survival of EIB202was performed by titrating the metabolite concentration, counting the number of surviving cells over time,and generating a two-dimensional heat map(Figure S3A)since EIB202is a wild strain with multidrug resistance.The degree of synergy was calculated using the combination index(CI)algorithm of Chou and Talalay(Chou and Talalay,1981),revealing CI97values 0.066–0.197for kanamycin and alanine(Table S1A),0.053–0.192for kanamycin and glucose(Table S1B),and0.0442–0.106for alanine and glucose(Table S1C).Synergy was also analyzed using isobolograms,conﬁrming the above results. Optimal conditions to promote kanamycin sensitivity and the highest level of synergy are revealed in Figure S3A.The dose-reduction index(DRI)for kanamycin is presented in Tables S1D–S1F.At97%effective dose ED97,for kanamycin with alanine(1:8),glucose(1:2),or both,the DRI is93.6%,93.7%, or88.1%,respectively.Alanine and/or glucose also potentiated gentamicin,an aminoglycoside antibiotic to replace kanamycin, to eliminate EIB202(Figure S3B).However,only weak effect was detected when aminoglycoside antibiotic kanamycin was re-placed with the beta-lactam ampicillin,ceftazidime,or the quino-lone baloﬂoxacin(Figure S3B),which is similar to previously reported data(Allison et al.,2011).Replacement of alanine or glucose with threonine or maltose showed similar effects,but not isoleucine(Figure S3C).Correspondingly,lower PMF was detected in cells incubated with isoleucine than with threonine or maltose(Figure S3D).To exclude the possibility that the ef-fects of exogenous metabolite were associated with growth state,survival rate of EIB202was monitored in M9medium or M9/LB mixed medium supplemented with or without metabolic stimuli(glucose or alanine).As shown in Figure S3E,the only fac-tor that makes the survival rate different is the supplementation of metabolic stimuli together with kanamycin rather than meta-bolic stimuli alone(Figure S3E).Treating Clinically Relevant Bacterial Bioﬁlms and PersistersInfection with bacterial bioﬁlms and persisters are a signiﬁcant concern in the clinical environment(Cohen et al.,2013;Corona and Martinez,2013;Drenkard and Ausubel,2002);therefore, it would be clinically useful if bioﬁlms and persisters were sus-ceptible to killing by kanamycin in the presence of alanine and/ or glucose.To test this possibility,ﬁsh-derived pathogenic E.tarda EIB202and human-derived pathogenic E.tarda ATCC15947were cultured in vitro as bioﬁlms in the presence of kanamycin without or with alanine and/or glucose.In this sys-tem,EIB202and ATCC15947bioﬁlm growth was inhibited372-and162-fold by kanamycin plus alanine and glucose(Figure2F), respectively.Pathogenic E.tarda EIB202and ATCC15947bio-ﬁlms were also injected via catheter into the urinary tracts of mice,and in this in vivo system,kanamycin plus alanine and glucose also inhibited infection in the urinary tract and sup-pressed spread of infection to kidneys(Figures2G and2H).In all cases,cell killing required kanamycin and was more severe in the presence of alanine and glucose.250Cell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.Figure1.Metabolic Proﬁling and Bioinformatics Analysis of Drug-Sensitive—LTB4-S—and Drug-Resistant—LTB4-R—E.tarda Strains (A)Heat map showing relative abundance of metabolites(Wilcoxon p<0.01)in E.tarda LTB4-R and LTB4-S.Heat map scale(green to red:low to high abundance) is shown at bottom.(B)Z scores(standard deviation from average)corresponding to data in(A).Each point represents one technical repeat in one metabolite.Black,LTB4-S;blue, LTB4-R.(C)Independent component analysis(ICA)of E.tarda LTB4-S and LTB4-R.Each dot shows one technical replicate.(D)Hierarchical clustering of decreased abundance of metabolites in E.tarda LTB4-R.(E)Enriched pathways in E.tarda LTB4-R(p<0.01).Cell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.251Bacterial persisters are a small phenotypically different sub-population of specialized survivor cells found within bioﬁlms and planktonic bacterial populations.They have been shown to be highly tolerant to antimicrobials and have been reported to be the cause of persistent and difﬁcult-to-treat infections (Co-hen et al.,2013).Here,the frequency of persisters of EIB202and ATCC15947decreased 2,320-and 1,373-fold in the presence of kanamycin plus alanine and glucose,respectively (Figure 2I).Other relevant human and/or ﬁsh pathogens,including Vibrio parahaemolyticus ,Klebsiella pneumonia ,methicillin-resistant Staphylococcus aureus (MRSA),and Pseudomonas aeruginosa ,are also susceptible to killing by kanamycin plus alanine and glucose (Figure S3F).These ﬁndings suggest that kanamycin plus alanine and glucose could be useful for managing or pre-venting infection with drug-resistant pathogens,many of which cause diseases in humans and other economically and/or envi-ronmentally important species.Increased PMF Stimulates Uptake of AntibioticGlucose promotes uptake of aminoglycoside antibiotics by increasing PMF (Allison et al.,2011).A similar mechanism was observed here (Figures 3A–3C and S4A).Speciﬁcally,higher concentration of NADH,higher PMF,and higher kanamycin-induced cell death were detected in in E.tarda EIB202incubated with exogenous alanine and/or glucose,effects that abolished by carbonylcyanide m-chlorophenyl hydrazone (CCCP).To iden-tify PMF as the leading factor for glucose-and/or alanine-medi-ated bacterial killing,we validate this by four ways.First,theFigure 2.Effect of Exogenous Alanine and/or Glucose on Susceptibility of Antibiotic-Resistant E.tarda ,Bioﬁlms,and Persisters to Kanamycin(A and B)LTB4-R or EIB202were incubated with increasing concentrations of alanine (A)or glucose (B)for 6hr in the presence of kanamycin.(C and D)Synergic effects of alanine and glucose on bacterial survival.Experiments were performed similarly to (A)and (B),except for the presence of 10mM glucose (C)or 40mM alanine (D).(E)Percent survival of LTB4-R in the presence or absence of metabolite(s)in the indicated kanamycin concentrations.(F)Percent survival of EIB202and ATCC15947in bioﬁlms treated with 40m g and 30m g/ml kanamycin,respectively,in the presence of alanine and/or glucose as indicated.(G)Mouse urinary tracts were catheterized and infected with EIB202and ATCC15947.Mice were treated with 3,000m g/kg kanamycin as indicated and 3g/kg alanine,1.5g/kg glucose,or both twice daily for 3days.(H)Kidney biopsies were obtained,and cfu/g kidney tissue was measured for mice treated as indicated.(I)Percent survival of EIB202and ATCC15947persisters in the presence or absence of alanine and/or glucose plus kanamycin.Results are displayed as mean ±SEM,and signiﬁcant differences are identiﬁed (*p <0.05,**p <0.01;which caused by dose gradient are not marked)as determined by Student’s t test.Three biological repeats were carried out.252Cell Metabolism 21,249–261,February 3,2015ª2015Elsevier Inc.kanamycin-mediated killing was sensitive to pH,indicating that the killing is attributed to PMF(Figure S4B)(Allison et al., 2011).Second,the level of pyruvate rather than lactate was elevated with increased concentration of alanine and/or glucose. Therefore,the pyruvate/lactate ratio was increased in a dose-dependent manner(Figures3D and S4C).This suggests the pri-ority to generating pyruvate over lactate,which is consistent with the elevated NADH and PMF.Third,the expression of NuoI and NuoE,the two enzymes for NADH oxidation,and respiratory chain dehydrogenase activity,which contribute to cytochrome quinol oxidases activity,were increased by exogenous alanine and/or glucose(Figures3E and3F).Forth,three inhibitors—rote-none,antimycin A,and NaN3—of the aerobic respiratory chain partly abolished increased PMF and acquired sensitivity to kana-mycin(Figures3G–3I and S4D),in which rotenone inhibits the transfer of electrons from iron-sulfur centers in complex I to ubiquinone and antimycin A and NaN3are inhibitors of the ubiq-uinoloxidation and the oxidases,respectively.One noticeable observation is that glucose but not alanine stimulated PMF and partially reverted the phenotype of drug resistance in E.tarda un-der anaerobic condition(Figures3J and S4E),a result consistent with the fact that glucose supports anaerobic respiration. Alanine and/or glucose stimulate antibiotic uptake.Intracel-lular concentration of kanamycin was signiﬁcantly higher in E.tarda grown in the presence of alanine and/or glucose than in the absence of alanine and glucose(Figure3K).And lower kanamycin was detected in LTB4-R than in LTB4-S in medium with one-half MIC drug of LTB4-S,which may be owed to higher rate of drug exported and/or lower rate of drug uptake in the resistant strain.The absence of alanine and glucose led to 9.5ng/ml drug difference between LTB4-R and LTB4-R(36.5 versus46.0ng/ml),whereas alanine and/or glucose promote more65–123ng/ml and113–231ng/ml drug uptake in LTB4-R and LTB4-S,respectively,suggesting the increased drug uptake overcomes the effects by drug efﬂux pump(Figure3L).It is sup-ported by the events that no mutations of AcrAB-TolC were de-tected(data not shown),and alanine and/or glucose did not affect expression of TolC(Figure S4F).These results suggest that increased PMF contributes to the mechanism by which alanine and/or glucose stimulates uptake of kanamycin by E.tarda and decreases cell survival.Exogenous Metabolites Promote Metabolic Flux of the TCA CycleWe propose that exogenous alanine or glucose acts in a manner to revert multidrug-resistant E.tarda EIB202,which contributes to elevation of NADH and PMF.To investigate this possibility, metabolic proﬁles(63metabolites,5biological and2technical replicates)of EIB202were compared in the presence and absence of alanine,glucose,or alanine plus glucose.Data were analyzed as described above,and the results are pre-sented in Figures4,S5,and S6.The four groups are clearly separately using ICA(Figure4A).Based on Z score analysis, exogenous alanine,glucose,or alanine plus glucose signiﬁcantly altered the metabolic state(Figure S5A).Forty-eight,ﬁfty-one, and forty-nine of the63metabolites(76.20%,80.95%,and 77.78%)had signiﬁcant change in abundance,corresponding to a false discovery rate of5.9%,8.3%,and16.3%(Figures S5B–S5D).Unsupervised hierarchical clustering and pathway enrichment analysis identiﬁed16biological pathways(Figures S5E and S5F),out of which theﬁrst three impact values are listed in Figure4B.The largest effects were observed on decreased amino acid metabolism(glycine,serine,asparagine,valine,and proline)(Figure S6)and increased the TCA cycle(Figure4C). The synergy of alanine and glucose increased higher production of succinate,malate,and citrate,but not fumarate,than alanine or glucose alone(Figure4D).These results indicate that the metabolicﬂux of the TCA cycle increases in the presence of alanine and/or glucose.Recently developed NTFD(non-targeted tracer fate detection) is a powerful tool to provide information about relativeﬂux magnitudes into each metabolite pool by determining the mass isotopomer distribution for all labeled compounds(Hiller et al., 2011;Walther et al.,2012).To further demonstrate the promotion in the TCA cycle as a result of exogenous alanine and/or glucose, we performed13C3-alanine and13C6-glucose tracer experiments in EIB202by GC-MS(Table S2).As shown in Figures4C and S6B,13C3-alanine or13C6-glucose is converted by acetyle-CoA synthase to produce labeled acetyl-CoA,which provides an acetyl group to citrate,succinate,fumarate,malate,and aspar-tate to generate M2label in the initial cycle.In the second cycle, both labeled and unlabeled acetyl-CoA are entered into the TCA cycle and are added to the M2label to generate M3and M1label through oxidative decarboxylation,respectively.Since the unla-beled acetyl-CoA has exogenous and endogenous sources,M1 is higher than M3label.Similarly,the labeled acetyl-CoA adding to M3label would produce M4label.Since an equal amount of M2is required for the M3generation,(M1+M3)/(M2+M3)ratio of each pool represents relativeﬂux for that metabolite in the TCA cycle(y TCA/y ALA,y GLC,or y BOTH),where y TCA refers to the turnover of a particular metabolite pool and y ALA and/or y GLC re-fers to theﬂux of alanine and/or glucose carbon atoms to the TCA cycle.M1label is lower in citrate than in succinate,fuma-rate,or malate pools,which is due to the oxidative decarboxyl-ation of a-ketoglutarate.Low M1-fumarate and-aspartate and high M1-malate as well as low M2-and high M4-malate in the 13C3-alanine tracer experiment suggest glyoxylic acid cycle may be involved in theﬂux,which is supported by elevated fatty acid synthesis in the13C3-alanine(data not shown).Thus,the relativeﬂux for13C3-alanine in the malate of glyoxylic acid cycle can be represented by(M1+M3)/(M2+M4+M3)(y MALAT/y ALA) (Figure S6C).In addition,most of M2-labeled metabolites are from labeled acetyl-CoA and unlabeled oxaloacetate.Although oxaloacetate and glutamate are interconverted to each other via alanine aminotransferase,the detection of few labeled gluta-mate indicates that the labeled metabolites are not converted to glutamate.The enriched M2-aspartate alone in aspartate pool indicates that L-aspartate may contribute to M2regulation of the TCA cycle through fumarate and oxaloacetate(Figure4C). In summary,the tracer experiments suggest that the exogenous glucose and/or alanine are converted to acetyl-CoA and thenﬂux to the TCA cycle,which is regulated by glutamate,aspartate,and glyoxylic acid cycle.Promotion of the TCA Cycle Is Required for Restoring Sensitivity to KanamycinTo understand how the TCA cycle was activated by alanine and/ or glucose and also further validate theﬁnding that activation ofCell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.253Figure3.Effect of Exogenous Alanine and/or Glucose on NADH,PMF,and Intracellular Kanamycin(A)Intracellular NADH concentration in EIB202in the presence of alanine and/or glucose as indicated.(B)PMF in EIB202in the presence of alanine and/or glucose and effect of CCCP as indicated.(C)Percent survival of EIB202in the presence or absence of CCCP and in the presence of alanine and/or glucose.(D)The pyruvate/lactate ratio of EIB202in the presence of alanine and/or glucose.(E)Western blot for detection of NuoL and NuoF expression in the presence of alanine and/or glucose.Protein loading amounts were normalized to SDS-PAGE gel.(F)Activity of respiration chain dehydrogenase in the presence of alanine and/or glucose.(G–I)Percent survival of EIB202in the presence or absence of increasing doses of rotenone(G),antimycin A(H),and NaN3(I)and in the presence of alanine and/or glucose.(J)Percent survival of EIB202cultured under aerobic or anaerobic conditions in the presence of alanine and/or glucose as indicated.(legend continued on next page)254Cell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.the TCA cycle is required for the potential,we evaluated expres-sion and activity of enzymes in the TCA cycles by western blot and enzyme inhibitors (Figure 5A).The expressions of succinyl-CoA synthetase b subunit (SucC)and citrate synthase (GltA)were increased with alanine and/or glucose dose (Figure 5B).Similarly,the activity of three key enzymes,citrate synthase (CS),isocitrate dehydrogenase (ICDH),and a -oxoglutarate de-(K)Intracellular kanamycin concentration in EIB202and ATCC15947in the presence of alanine and/or glucose as indicated.(L)Comparison of intracellular kanamycin between LTB4-R and LTB4-S in the presence of alanine and/or glucose as indicated.Results in (A)–(E)and (G)–(L)are displayed as mean ±SEM,and signiﬁcant differences are identiﬁed (*p <0.05,**p <0.01;which caused by dose gradient are not marked)as determined by Student’s t test.Three biological repeats were carried out(A)–(L).Figure 4.Metabolic Pathway Analysis(A)Independent component analysis of cells grown in the presence or absence of alanine and/or glucose.(B)Enriched pathways in the presence of alanine and/or glucose.(C)Elevated abundance of metabolites (in red)in the TCA cycle and mass isotopomer distributions for 13C-labeled alanine or glucose detected in a nontargeted manner (histogram)in the presence of alanine,glucose,or both.Elevation of glutamate is detected only in the presence of glucose and plus alanine.(D)Scatter plot showing normalized abundance of four TCA cycle metabolites.Each dot shows a technical replicate.*p <0.05and **p <0.01as determined by Student’s t test.hydrogenase (OGD),of the TCA cycle were elevated in the presence of alanine and/or glucose (Figure 5C).We further validate this by using two inhibitors,bro-mopyruvate or malonate.Bromopyruvate is an active-site-directed inhibitor of the pyruvate decarboxylase (El),a compo-nent of the pyruvate dehydrogenase complex,which converts pyruvate to acetyl-CoA (Figure 5A).Malonate is a competitive inhibitor of succinate dehy-drogenase (Figure 5A).As shown in Fig-ure 5C,the activities of the three enzymes were elevated in the presence of alanine and/or glucose.Bromopyruvate inhibited the activities of CS and ICDH in the pres-ence of glucose and glucose plus alanine but not alanine paratively,the activity of OGD was inhibited at all cases,indicating it may play more critical roles than CS and ICDH.These enzymes were affected because the rate of inhibi-tion by bromopyruvate was signiﬁcantly increased in the presence of pyruvate (Lowe and Perham,1984;Brown et al.,1997),which caused less pyruvate and then acetyl-CoA to enter the TCA cycle and affect the activity of these enzymes.Malonate and bromopyruvate inhibited NADH and PMF genera-tion promoted by alanine and/or glucose (Figures 5D and 5E).Furthermore,malonate rescued higher viability of EIB202than bromopyruvate (Figures 5F and 5G),which is consistent with the fact that pyruvate decarboxylase regulates concentration of pyruvate as a source of the TCA cycle,whereas succinate dehydrogenase plays a role in the TCA cycle and generation ofCell Metabolism 21,249–261,February 3,2015ª2015Elsevier Inc.255Figure5.Effect of Exogenous Alanine and/or Glucose on Enzymes of the TCA Cycle(A)Superimposed on metabolic pathways related to glucose,alanine,and the TCA cycle.PDH,pyruvate dehydrogenase;GltA,citrate synthase;ICDH,isocitrate dehydrogenase;OGD,oxoglutarate dehydrogenase complex;SucC,succinyl-CoA synthetase b subunit;SDH,succinate dehydrogenase.(B)Western blot analysis for SucC and GltA expression in the increasing concentration of alanine and/or glucose.(C)Activity of three key enzymes of the TCA cycle in the presence or absence of exogenous alanine and/or glucose and effect of bromopyruvate.(legend continued on next page)256Cell Metabolism21,249–261,February3,2015ª2015Elsevier Inc.。

第七章分子系统发育分析进化树

D C F GA B E†
系统进化树的概念
直系同源(orthol。
旁系同源(paralogs): 同源的基因是由于基因复制产生的。用于分子进化分析中的序列必须是直系同源的，才能真实
反映进化过程。
旁系同源
直系同源
系统进化树的种类
Eukaryote 4
系统进化树的种类
——物种树、基因树
物种树：代表一个物种或群体进化历史的系统进化树，两个物种分歧的时间为两个物种发生生殖隔离的时间
基因树：由来自各个物种的一个基因构建的系统进化树（不完全等同于物种树），表示基因分离的时间。
基因分裂
基因分裂基因分裂物种分裂
关于分子钟的讨论和争议
1、对长期进化而言，不存在以恒定速率替换的生物大分子一级结构；（基因功能的改变、基因数目的增加）
2、不存在通用的分子钟；
3、争议：分子钟的准确性中性理论（分子钟成立的基础）
第一节生物进化的分子机制
分子途经研究生物进化的可行性分子进化的模式分子进化的特点研究分子进化的作用
末端节点：代表最终分类，可以是物种，群体，或者蛋白质、DNA、RNA分子等
A
B
C
D 祖先节点/树根
内部节点/分歧点，该
E
分支可能的祖先节点
系统进化树的概念
进化树分支的图像称为进化的拓扑结构理论上，一个DNA序列在物种形成或基因复制时，
分裂成两个子序列，因此系统进化树一般是二歧的。
A BC D F G E†
氨基酸
例：血红蛋白分子的外区的功能要次于内区的功能，外区的进化速率是内区进化速率的10倍。
核苷酸
例：DNA密码子的同义替代频率高于非同义替代频率；内含子上的核苷酸替代频率较高。

2024年中考英语仿真模拟预测卷(三)试卷精选全文

精选全文完整版（可编辑修改）九年级英语综合模拟卷（满分：100分）听说部分（25分）Ⅰ. 听说题（25分）ⅰ）听下面短文，短文播放一遍。

你有50秒钟的时间准备，然后模仿朗读。

当听到”开始录音”的信号后，立即在50秒钟内模仿朗读短文；当听到要求”停止录音”的信号时，停止模仿朗读。

（4分）1. ________________________________________________________________________________________ ___________________________________________________________________________________________ ___________________________________________________________________________________________ⅱ）听选信息（6分）听三段对话，每段播放两遍。

请根据所听到的内容，选择正确信息。

听第一段对话，回答2—3两个问题。

( ) 2. What is the main reason John is worried about his rabbit?A. The rabbit is sick.B. The rabbit is missing.C. John is going on a business trip.( ) 3. How does Helen plan to help John with his rabbit?A. By introducing a pet store.B. By offering to take care of the rabbit.C. By suggesting John’s son to take care of the rabbit.听第二段对话，回答4—5两个问题。

结肠癌NCCN指南123.ppt

• 肝或肺转移瘤的术后复发再次手术可以在严格筛选的患者中施行（43例接收反复肝转移瘤切除术患者，5年OS和PFS分别为73%、22%）
1. BMC Surg 2010;10:27. 2. Ann Surg Oncol 2011;18:1380-1388
• 肝转移瘤的可切除性
• 保留足够正常肝储备功能的基础上能否获得阴性的手术切缘
• 一些研究发现：V600E突变者一线化疗加入爱必妥仍然可以获益
• 但是：
• COIN：对BRAF突变患者爱必妥加入FOLFOX或 XELOX不仅没益甚至有害
• 中位OS:BRAF突变者为8.8个月，KRAS突变者为 14.4个月，KRAS野生型者为20.1个月
1. N Engl J Med 2009;361:98-99. 2. J Clin Oncol 2010;28 (May 20 suppl):3570 3. Eur J Cancer 2012;48:1466-1475. 4. J Clin Oncol 2011 5. Lancet 2011;377:2103-2114
3. JAMA 2011;305:487-494
同时性转移不可切除
晚期或转移性结肠癌化疗
晚期或转移性结肠癌化疗
晚期或转移性结肠癌化疗
晚期或转移性结肠癌化疗
晚期或转移性结肠癌化疗
• FOLFOXIRI vs FOLFIRI
• GONO:R0切除率15%vs6%，所有患者5年OS为 15%vs8%，中位OS为23.4个月vs16.7个月
• NRAS和其他KRAS突变
• PRIME:对具有任何一个KRAS或者NRAS突变的患者,帕尼单抗加入FOLFOX会使患者PFS和OS缩短
• FIRE-3：爱必妥加入FOLFIRI会使KRAS或NRAS 突变的患者治疗受损

不同来源诱导剂建立的卵巢早衰动物模型的比较

不同来源诱导剂建立的卵巢早衰动物模型的比较目的比较不同来源的诱导剂建立的卵巢早衰动物模型。

方法选取97只雌性SD大鼠分别给予120 mg/kg的环磷酰胺、白消安、35%半乳糖食物丸，制备卵巢早衰动物模型。

通过观察体重变化，激素血清浓度水平，卵巢病理切片等分析数据。

结果单次给药环磷酰胺后，大鼠体重增加非常缓慢，卵巢受损；随着血清LH浓度上升趋势，血清E2浓度下降趋势和受损的卵巢，35%半乳糖食物颗粒饲喂的大鼠体重增加缓慢，其中白蛋白和总蛋白以及受损的卵巢的血清浓度显著升高（P＜0.05）。

结论不同诱导物可产生不同特征POF模型，为进一步研究提供有效的实验依据。

标签：大鼠；卵巢早衰；动物模型卵巢早衰（POF）是指40岁以前卵巢早衰或卵巢功能衰退，主要发生在平均绝经年龄前两年的标准偏差人口，其原因可能与内源性基因，异常自身免疫，感染，医疗疗法等影响有关。

POF具有明显异质性及显着遗传性。

染色体异常被一直被认为是POF的常见原因。

基于POF基因组学致突变大鼠模型在探索，且不同模型之间存在较大差异，因此在探索POF治疗方法时很难选择合适的动物模型。

本文通过比较不同方法致大鼠卵巢早衰动物模型之间的差异，为POF治疗进一步研究提供实验依据。

1 材料和方法1.1 一般材料环磷酰胺由上海金穗生物有限公司提供。

35%半乳糖食品颗粒由南通营养饲料有限公司提供。

1.2 研究方法雌性大鼠在室温（22±2）℃和相对湿度（50±10）%的标准实验室条件下培养12 h光暗周期，水和食物随意提供。

每只大鼠的平均食物消耗为28g。

所有手术均在戊巴比妥钠麻醉下进行。

将体重约为（180～200）g的56只SD大鼠分成A、B、C组，A组大鼠用120 mg/kg的溶于0.9%盐水溶液中的单次腹膜内注射环磷酰胺处理，B组大鼠用单一的用0.9%盐水溶液以12 mg/kg的剂量自发注射白消安注射液，C组大鼠为对照组，用0.9%盐水溶液腹膜内处理。

妇产科之性传播疾病ppt课件

Incubation period about 6 d with first episodes lasting for 10 ~ 12 d.
Location: Vulva, vagina, cervix, perineal and perianal skin, often extending to the buttocks.
[D] Intracelluar inclusion, immunology with monoclonal antibody.
[T] Azithromycin 1g oral, single dose Doxycycline 100mg bid for 7 d, Minocine?
Ofloxacin 100 mg tid for 7 d Erythromycin 500 mg qid for 7 d. for
Among neonates with encephalitis > 50% of survivors are left with severe neurologic impairment.
App. 85 % of early neonatal herpes infections are aquired during delivery from virion contaminated maternal vaginal secretions, therefore C-section for women with active genital lesions at time of labor. 40 ~70% of all neonates with herpes are born to asymptomatic mothers.
60 ~ 90 % of patients with recurrence of herpetic lesions in the first 6 m. after initial infection.

疟原虫(疟疾)

2.1雄配子形成（exflagellation）
♂配子体几分钟内核分裂为48块，胞质亦向外伸出4-8条细丝，核分别进入细丝内，称出丝现象，即♂配子形成细丝脱离母体，在蚊胃腔中游动，即♂配子（male gamete）或小配子（microgamete）

2.1 动合子（ookinete）
三、致病
发作周期和红内期裂体增殖周期一致。疟原虫代谢产物(外源性热原质) 裂殖子、残余和变性血约蛋白、红细胞碎片被吞噬细胞吞食 —产生内源性热原质。非典型发作：混合感染；同种不同批感染；机体免疫力下降

原因
疟疾初发作停止后，在无再感染的情况下，由于体内残存的红内期疟原虫，在一定条件下又大量增殖又引起疟疾发作，称为再燃（recrudescence）。疟疾初发后，红细胞内期疟原虫已被消灭，未经蚊媒传播感染，但经过一段时间的潜隐期，又出现疟疾发作，称为复发（relapse）。恶性疟原虫和三日疟原虫都不引起复发，只有再燃；而间日疟和卵形疟则既有再燃，又有复发。
♀♂ 配子受精，形成圆球形的合子（zygote）。合子数小时后变为长形的香蕉状的能活动的动合子(ookinete)。

2-1卵囊（oocyst）

动合子穿过蚊胃壁，在胃弹性纤维膜下，虫体变圆并分泌囊壁形成球形的卵囊 (oocyst)，卵囊也称囊合子。
2.2 孢子增殖
2 恶性疟原虫—大滋养体
一般不出现在外周血体小结实，圆形，不活动疟色素集中一团，黑褐色原虫此时开始集中在内脏毛细血管

3 恶性疟原虫成熟裂殖体
裂殖子8～36个，通常 18～24个，排列不规则疟色素集中成一团虫体占红细胞体积的 2/3至3/4

果蝇的发育和成虫盘解剖

实验一果蝇的发育和成虫盘解剖1、果蝇胚胎发育和成虫盘自1910年遗传学鼻祖Morgan发现第一个突变体白眼果蝇以来，生物学家将果蝇作为遗传学研究的模式动物已经近百年，并广泛应用于现代遗传学和发育生物学研究的模型。

果蝇生命周期如图1。

果蝇胚胎发育速度快，前13次卵裂每次只间隔9min，细胞核成倍增加成为一个合胞体（syncytim），发育过程中的胚胎为观察分析卵裂、早期胚胎发生和躯体模式形成等发育调控机制的提供了很好的材料。

果蝇胚胎发育的梯度假说被证实，在1997年和1998年连续两年被《Science》杂志评为当年十大突破成就之一。

现已鉴定出在一些卵子中形成梯度、调节细胞定位和分化并决定胚胎发育方式的形态发生素（morphogen）。

果蝇存在变态过程，由幼虫（larval）经蛹（pupal）转变为成虫。

成虫盘（imaginal discs）是果蝇早期胚胎发育期间保留下来的而在幼虫期开始分化的。

变态期间，幼虫表皮转成蛹壳而成虫盘则发育成为成虫外层。

成虫盘首先出现在20~40细胞群的胚胎中，由胚胎上皮内陷形成，最初通过各种标记基因的表达而被确认。

每一个成虫盘都由单层上皮构成片状或囊状，并有一个细茎与胚胎和幼虫的上皮连接。

最终每一个液囊展平，液囊的两端具有不同的特征，并执行不同的发育任务。

一端形成较厚而高度折叠的成虫盘上皮，另一端形成较薄而展开的周膜。

大部分成虫外胚层结构由成虫盘上皮演化而来。

成虫盘在一、二、三龄幼虫期都有不同程度的细胞增殖，在晚期三龄幼虫后，即变态之前，每个成虫盘形成了数万个细胞。

在变态之前，大约产卵后108h(AEL)，25℃放置，三龄幼虫即蠕动——“爬”出培养基，生活在培养瓶的瓶壁上，这个阶段约12h，在这个阶段末期，果蝇幼虫前端的呼吸孔外翻，幼虫停止蠕动并开始蛹化。

上皮形成蛹的桶状体壁——蛹壳，此时为白色的蛹前期阶段（WPP）。

大约1h后，蛹壳变为深褐色。

蛹化开始的第一个5-6h后，果蝇仍然处于蛹前期阶段，成虫细胞仍然分泌形成蛹的表皮。

米诺环素对人类胶质瘤U87和LN229细胞体外增殖及凋亡的影响

米诺环素对人类胶质瘤U87和LN229细胞体外增殖及凋亡的影响赵海龙;严婉约;李巧巧;李科;刘丽;李丽娟【摘要】目的探讨米诺环素对人类胶质瘤U87和LN229细胞体外增殖及凋亡的影响,为米诺环素治疗临床胶质瘤提供基础.方法采用MTT法和BrdU标记法检测不同浓度米诺环素(0、50、100、200 μmol/L)对人类胶质瘤细胞株U87和LN229细胞增殖水平的影响;软琼脂克隆形成实验检测米诺环素对胶质瘤细胞自我更新能力的影响;通过免疫荧光标记自噬相关蛋白LC3B和Annexin V-FITC/PI双染细胞凋亡法分别检测米诺环素处理胶质瘤细胞中自噬水平和凋亡水平;使用3-甲基腺嘌呤(3-MA)阻断细胞自噬通路后,分别观察米诺环素对胶质瘤细胞自噬水平和凋亡水平的影响;qRT-PCR法和Western blot法检测米诺环素作用下促凋亡蛋白Bax、抑凋亡蛋白Bcl-2的基因和蛋白表达水平.结果米诺环素对人类胶质瘤细胞的增殖和自我更新能力有明显抑制作用,并呈剂量依赖性;米诺环素可诱导人类胶质瘤细胞发生广泛的细胞自噬与凋亡,但凋亡水平呈现剂量依赖性,而不同浓度处理下的自噬水平无显著性差异;使用3-MA阻断自噬通路对细胞凋亡水平、细胞增殖水平和自我更新能力无显著性影响;米诺环素处理后的胶质瘤细胞中Bax蛋白表达上调,Bcl-2蛋白表达下调.结论米诺环素可以诱导细胞发生自噬和凋亡,进而抑制人类胶质瘤细胞的增殖和自我更新能力,其中主要依赖于细胞凋亡通路的激活.因此,米诺环素可能成为潜在的胶质瘤治疗药物.【期刊名称】《遵义医学院学报》【年(卷),期】2017(040)005【总页数】8页(P496-503)【关键词】米诺环素;胶质瘤;增殖;凋亡;Bax;Bcl-2【作者】赵海龙;严婉约;李巧巧;李科;刘丽;李丽娟【作者单位】遵义医学院基础医学院病理生理学教研室,贵州遵义563099;遵义医学院基础医学院2014级卓越医生班,贵州遵义563099;遵义医学院基础医学院2014级卓越医生班,贵州遵义563099;遵义医学院基础医学院2014级卓越医生班,贵州遵义563099;遵义医学院基础医学院2014级卓越医生班,贵州遵义563099;遵义医学院基础医学院病理生理学教研室,贵州遵义563099【正文语种】中文【中图分类】R739.41人类神经胶质瘤是最常见的原发性中枢神经系统肿瘤，约占所有颅内原发肿瘤的44.7%，发病率高达48%，其恶性度高，病死率高，严重威胁着人类的生命和健康[1]。

浓缩生长因子联合Bio-oss骨粉促进骨缺损愈合的实验研究

浓缩生长因子联合Bio-oss骨粉促进骨缺损愈合的实验研究牛临生;解军军【摘要】目的：探究浓缩生长因子（concentrated growth factors，CGF）联合Bio-oss骨粉是否能促进骨缺损的愈合。

方法选择新西兰白兔16只，在它们的颅盖骨上分别制备2个直径为3 mm圆形骨缺损。

实验组：在制备的骨缺损处植入CGF+Bio-oss骨粉，对照组只植入Bio-oss骨粉，于术后4、8周，取标本，并从大体、X线、组织学等方面观察骨缺损的愈合情况。

采用SPSS17.0软件对数据进行统计学分析。

结果实验组骨缺损愈合的效果明显高于对照组，两组相比差异有统计学意义（P＜0.05）。

结论浓缩生长因子联合Bio-oss骨粉能明显促进骨缺损的愈合，缩短愈合时间。

%Objective To investigate the concentrated growth factors and Bio-oss bone meal on promoting the healing of bone defect. Methods Selecting sixteen New Zealand white rabbits, each of whose cranium bones were performed two round, 3 mm diameter, bone defects. The experimental group:the concentrated growth factors (CGF) and Bio-oss bone meal were implanted around the prepared bone defect. Control group:only implant Bio-oss bone meal. At the 4, 8 weeks, to observe the healing of bone defect by the shape, histology and X-Ray. Statistical analysis was conducted for the data by SPSS17.0 software. Results The experimental group was better than the control group. There were statistical significance between the experimental group and control group (P<0.05). Conclusion CGF and Bio-oss bone meal can facilitate the healing of bone tissue defect and Shorten the healing time.【期刊名称】《中国医药指南》【年(卷),期】2016(014)016【总页数】2页(P17-17,18)【关键词】浓缩生长因子(CGF);骨缺损;骨愈合【作者】牛临生;解军军【作者单位】临汾市人民医院口腔科，山西临汾041000;临汾市人民医院口腔科，山西临汾041000【正文语种】中文【中图分类】R683浓缩生长因子（CGF）是自体血液经过特殊离心后所获得的血小板浓缩物，含有多种生长因子以及纤维蛋白［1］。

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Synchronous Generator Emulation Control Strategy for V oltage Source Converter(VSC)Stations Minyuan Guan,Member,IEEE,Wulue Pan,Jing Zhang,Member,IEEE,Quanrui Hao,Member,IEEE,Jingzhou Cheng,and Xiang ZhengAbstract—The voltage source converter(VSC)station is playing a more important role in modern power systems,but the dynamic behavior of the VSC station is quite different from that of the synchronous generator.This paper presents the synchronous generator emulation control(SGEC)strategy for the VSC-HVDC station.The SGEC strategy is divided into the inner control loop and the outer control loop.The inner controller is developed for fast current and voltage regulations.An inertia element is introduced into the frequency-power droop to determine the command reference of the frequency,and the inertia response and the primary frequency regulation are emulated.In addition,the secondary frequency regulation can be achieved by modulating the scheduled power in the SGEC strategy.The time-domain simulation results demonstrate the VSC station with the proposed control strategy can provide desired frequency support to a low-inertia grid.Therefore,the SGEC strategy provides a simple and practical solution for the VSC station to emulate the behavior of a synchronous generator.Index Terms—High-voltage direct-current(HVDC)trans-mission,modular multilevel converter(MMC),synchronous generator(SG)emulation,vector control,virtual synchronous generator,voltage source converter(VSC)station,VSC-HVDC.I.I NTRODUCTIONW ITH the continuous progress of the high-voltage high-power voltage source converter(VSC)technolo-gies,more and more VSC based devices like VSC-HVDC transmission systems,ﬂexible AC transmission systems (FACTS)and energy storage systems(ESS)have been in-stalled,and the VSC station is playing a more important role in modern power systems[1],[2].The transmission rating up to several hundred MW has been reached in recent VSC-HVDC projects[3],[4].The conventional synchronous generator has inherent fea-tures beneﬁcial to power system stability,such as the increaseManuscript received March23,2014;revised June25,2014and September 30,2014;accepted November19,2014.Date of publication January14,2015; date of current version August03,2015.This work was supported in part by the Key Science and Technology Program of State Grid Zhejiang Electric Power Company under Project5211011306Z4.Paper no.TPWRS-00404-2014.M.Guan is with Huzhou Power Supply Company of State Grid Zhejiang Electric Power Company,Huzhou313000,China(e-mail: guanminyuan@;hanren@).W.Pan,J.Zhang,J.Cheng,and X.Zheng are with the State Grid Zhejiang Electric Power Company,Hangzhou310007,China(e-mail:panwulue@163. com;eejzhang@;10910035@;zﬂying08@). Q.Hao is with the School of Electrical Engineering,Shandong University, Jinan250061,China(e-mail:haoquanrui@).Color versions of one or more of theﬁgures in this paper are available online at .Digital Object Identiﬁer10.1109/TPWRS.2014.2384498in system inertia,the synchronizing power and the damping power.The synchronous generator is not only able to work in parallel with other generators,but is also able to supply a pas-sive network.The vector current control has been widely used in the control of the VSC-HVDC system for the fast current reg-ulation abilities.With the constant power control,the delivered power of the VSC-HVDC system could be precisely controlled at the scheduled value,irrespective of the frequency variations of the two grids.Thus,the dynamic behavior of the VSC sta-tion is quite different from that of the synchronous generator. The frequency oscillations in one grid could be isolated from the other grid to some extent,which improves the security of the grid operation.One typical application of VSC-HVDC transmission systems is to supply a weak or passive grid(i.e.,an island grid)far away from the main grid.With the constant power control,the output power from the VSC station is controlled as a constant, and no frequency support is provided to the weak grid.When a signiﬁcant part of the power in a local gird is supplied by the VSC station,the system inertia becomes lower,and changes in generation or load may cause large frequency deviations pos-sibly leading to system instability.The frequency problem will be more serious,when the local grid becomes a passive net-work supplied by the VSC station.It becomes beneﬁcial to the frequency stability that the VSC station can provide frequency support to the local grid.Recently,novel control techniques are presented,by which the VSC station is able to provide the in-ertial response[5]–[8],the frequency regulation[2],[9],and/or the power system damping[10],[11].Power-synchronization control is presented for the VSC station to realize very useful features of the synchronous generator,such as the power supply and voltage support to a weak grid[12]–[14].On the other hand,a new concept of virtual synchronous gen-erator,which represents a VSC operated in the similar way as the synchronous generator,has been proposed in[15].Some novel virtual synchronous generator models have been devel-oped for VSCs in[16]–[18],in which additional control loops are specially designed to model the swing equation of the syn-chronous generator.For instance,the angular frequency refer-ence of the converter output voltage is determined by the virtual generator control loop[17],[18]:(1) where is the grid angular frequency,is the virtual mechan-ical power,and is electrical output power from the con-verter.Thus,the measurement of the grid frequency is required.0885-8950©2015IEEE.Personal use is permitted,but republication/redistribution requires IEEE permission.See /publications_standards/publications/rights/index.html for more information.Fig.1.Schematic diagram of a VSC-HVDC transmission system supplying a small local grid.The inertia coefﬁcient and the damping power coefﬁcient,de-noted byand ,are two different control parameters.To re-alize the primary frequency regulation,the virtual mechanical input power is determined by the virtual governor control loop [17],[18](2)where is the reference value of the output power and is the nominal angular frequency.The time delay and the differ-ence coefﬁcient,denoted by and ,are two different control parameters.The additional control loops,the measurement of the grid frequency as well as the selection of control parameters make the control scheme complicated.To enable the continuous operation irrespective of the net-work conditions,the conventional droop control (CDC)strategy is widely used for the VSC station supplying a weak or passive grid [19]–[21].In the CDC strategy,the frequency of the VSC output voltage is automatically regulated according to the devi-ation of the real power from its scheduled value.The proposed synchronous generator emulation control (SGEC)strategy includes an inner control loop and an outer control loop.Due to the fast current limiting of the inner current controller,the over-current blocking of the converter valves could be avoided.Only a ﬁrst-order inertia element is added to the CDC strategy to determine the frequency command reference,without any additional control loop.The proposed SGEC strategy is considered as a simple and practical solution for the VSC station to imitate the behavior of a synchronous generator.The rest of this paper is organized as follows.Section II introduces the mathematical model and the SGEC strategy of the VSC-HVDC station.The performance of the SGEC strategy is analyzed in Section III,by which the swing equation,the primary frequency regulation and the secondary frequency regulation of synchronous generators are obtained.To evaluate the performance of the SGEC strategy,time-domain simulation studies in the PSCAD/EMTDC software environment are presented in Section IV.Section V concludes this paper.II.C ONTROL S CHEMEIt is depicted in Fig.1that the power is delivered from the main grid to the local grid by a VSC-HVDCtransmissionFig.2.AC-side of a VSC station.system.The two VSC stations,denoted by VSC1and VSC2,are linked by a pair of DC cables.Each VSC station is connected to the AC system through an interfacing reactor and a converter transformer.The converter reactor blocks the high-frequency harmonic currents generated by the VSC station from entering into the power system,while a high-pass (HP)ﬁlter is installed at the PCC to provide a low-impendence path to ground for the high-frequency harmonic currents.The converter reactor and the HP ﬁlter constitute a low-pass ﬁlter system.Because a large portion of power is supplied by the VSC sta-tion,the inertia of the local grid is signiﬁcantly reduced.It be-comes especially beneﬁcial to the frequency stability of the local grid that the VSC station can provide frequency support.A.VSC ModelThe AC-side of different VSCs can be generally represented by a three-phase AC voltage source [22]–[25].In conventional VSCs like the two-level converter and the neutral point clamped (NPC)converter,and are the inductance and resistance of the interfacing reactor [22].In modular multilevel converter (MMC),and are half of the inductance and resistance of the arm reactor [25],[26].The HP ﬁlter is considered purely capac-itive at the fundamental frequency [27],and its equivalent ca-pacitance is represented by .According to Fig.2,the AC-side dynamics of different VSCs are generally expressed as(3)(4)whereand are the column vectors of the three-phase output voltages and currents from the VSC,and andare the column vectors of the three-phase output voltages and currents at the PCC.GUAN et al.:SYNCHRONOUS GENERATOR EMULATION CONTROL STRATEGY FOR VSC STATIONS 3095The balanced three-phase voltages and currents can be trans-formed to the synchronous dq -axis voltage and current compo-nents via the following Park transformation [23]:(5a)(5b)The AC-side dynamics of the VSC station,in term of the dq -axis components,are expressed as [22]–[25](6a)(6b)(7a)(7b)If the -axis is ﬁxed to the grid voltage vector,the -axis component of the PCC voltage is equal to the amplitude of the voltage vector,and the -axis component of the PCC voltage is zero in steady-state.As shown in Fig.2,the real power output at the PCC is given by [22](8)B.Inner Control LoopThe inner control loop is a vector control scheme including a current controller and a voltage controller.Because the vector control scheme has been widely used in the control of VSC [22]–[25],only a brief description is given here.The inner cur-rent controller is given by (9)[22]–[24]:(9a)(9b)where is the frequency reference of the outer control loop,and represent the proportional and integral gains,respec-tively.Since the VSC has very little over-current capability,a large transient current due to disturbances will stress or damage the valves [2].If the value of the dq -axis current command refer-ences and are limited,the fast-response current controller is effective in preventing the VSC from over-current blocking.The voltage control mode is designed to control the AC volt-ages at the PCC,which can be regulated by the charging of the capacitive ﬁlter.Thus,the current command references and of the inner current control are given by(10a)(10b)The tuning of PI gains in (9)and (10)has been given in [28].The command references of the dq -axis voltage components are given by(11)Fig.3.Overall control scheme of the SGEC strategy.where is the nominal amplitude of the PCC voltage.The inner control scheme is illustrated in Fig.3.C.Outer Control LoopThe inductive component of the line impedances in high voltage (HV)networks is typically much higher than the resistive one,and the value of the real power delivered to the grid can be regulated by controlling the frequency of the voltages at the PCC [29].The outer control loop is developed to regulate the angular frequency of the PCC voltages,in which the synchronizing signal for the Park transformation is(12)whereis the command reference of the angular frequency of the PCC voltages.The three-phase voltages at the PCC are derived by the inverse Park transformation in (14):(13)(14)Thus,the phase-a voltage is expressed as(15)The differentiation of the phase angle in (15)is the angular frequency(16)Because the differentiations of the dq -axis voltage compo-nents at the PCC in steady state are both zero,the second term in (16)is a transient component.Thus,the angular frequency of the PCC voltages could track its command reference in steady state with the outer control loop.3096IEEE TRANSACTIONS ON POWER SYSTEMS,VOL.30,NO.6,NOVEMBER2015D.Synchronous Generator Emulation ControlTo emulate the swing equation,the command reference of the angular frequency of the PCC voltages can be determined as(17) In the swing equation,and are the mechanical input power and the electrical output power,and are the inertia coefﬁcient and the damping power coefﬁcient,and is the nominal angular frequency.Applying the Laplace transform,(17)can be rewritten as(18) In the SGEC strategy,the command reference of the angular frequency can be derived from(18)as(19) in which the lag time of theﬁrst order inertia element is de-ﬁned as(20) If the lag time is0,(20)is simpliﬁed as(21) which represents the CDC strategy.In the CDC strategy,is the droop coefﬁcient.and are the actual and sched-uled real power outputs from the PCC to the grid,respectively. Comparing(19)and(21),the SGEC strategy is realized only by adding aﬁrst-order inertia element to the widely used CDC strategy,without any additional control loops.Only one addi-tional control parameter(i.e.,the lag time in theﬁrst-order in-ertia element)is required,so the SGEC strategy is considered much simpler than the previous strategies.As a matter of fact,a time lag is always implied in(21)be-cause the control system is not ideal.In conventional control schemes,a short lag time is required to ensure the fast response of the controller.However,the situation becomes different when the inertia response is taken into consideration.In the CDC strategy,the lag time is usually too short(i.e.,several millisec-onds)to inﬂuence the electromechanical transients as well as the system inertia.In the SGEC strategy,aﬁrst-order inertia el-ement with a larger lag time(i.e.,several hundred milliseconds) is intentionally added to the CDC strategy.As a result,the VSC station is able to imitate the behavior of a synchronous gener-ator,and increases the system inertia obviously.The overall SGEC scheme is illustrated in Fig.3,by which the command reference for the angular frequency of the three-phase output voltages is determined.To prevent excessive frequency deviations,the amplitude of the command reference of the an-gular frequency is limited.The SGEC strategy is considered as a simple and practical control strategy for synchronous generator emulation,since it is based on a small modiﬁcation of the CDC strategy and no ad-ditional control loop is required.The vector current controller included in the SGEC scheme is effective in preventing the VSC from over-current blocking during system disturbances.It is considered highly important for the practical VSC control,as the VSC station usually have very little over-current capabili-ties[12]–[14].III.A NALYSISA.Swing EquationThe SGEC strategy of(19)can be rewritten as(22)Theﬁrst term in(22)is a constant.In the SGEC strategy,the scheduled and actual powers areﬁltered by theﬁrst-order iner-tial element.As a result,the frequency reference in(22)could be smoothed and the expected inertial response is introduced into the frequency regulation.Equation(17)is rewritten as(23)When the scheduled output power is greater than the ac-tual output power,the frequency reference will be gradually increased.On the contrary,the frequency reference will be gradually decreased,when the scheduled power is lower than the actual value.The damping power is proportional to the de-viation of the frequency reference from the nominal frequency. It should be noted that an increase in the inertia decreases the oscillation damping like that in a synchronous generator[30]. Taking the single-machine inﬁnite bus system as an example, the damping ratio of the characteristic equation is represented by[31](24) where is the synchronizing power coefﬁcient.Substituting (20)into(24),we obtain(25) The inertia is increased,but the oscillation damping is re-duced for the larger lag time in the SGEC strategy.B.Primary Frequency RegulationAccording to(16)and(22),the frequency deviation in steady state is given by(26)Thus,there is a droop relationship between the frequency and the output power,which is the same as that of the primary frequency regulation of a synchronous generator.Thus,the fre-quency of the VSC station is adjustable,which can coordinate with other generators or supply a passive network[19]–[21]. When the converter output power is equal to the scheduledGUAN et al.:SYNCHRONOUS GENERATOR EMULATION CONTROL STRATEGY FOR VSC STATIONS3097Fig.4.Frequency-power characteristics in steady state.power,the frequency of the PCC voltage will settle down at the nominal value.Otherwise,the frequency of the PCC voltage is changed in proportional to the deviation of the real power from the scheduled value.In consequence,the VSC station is able to provide primary frequency regulation to the local grid.Moreover,the amplitude of frequency deviation can be limited by using the saturation limits as shown in Fig.3.The steady-state frequency characteristics of the SGEC controlled VSC station is illustrated in Fig.4.C.Secondary Frequency RegulationIn an isolated power system,the secondary frequency con-trol is adopted in certain synchronous generator to restore the system frequency to the nominal value,which is accomplished by adding a slow-response integral term acting on the mechan-ical power reference of the speed governor[30].As shown in Fig.3,the secondary frequency regulation could be realized by adding a slow-response integral term to modulate the scheduled power of the converter:(27) where is the initial scheduled power set by the system op-erator.Therefore,the SGEC strategy provides the VSC stations with a simple and practical solution for the emulation of syn-chronous generators.IV.C ASE S TUDYA.Study SystemThe MMC is an emerging and attractive VSC topology for HVDC applications[3],[25].The schematic diagram of the study system is illustrated in Fig.1,and the power is delivered from the main grid to the local grid by an MMC-HVDC trans-mission system.Detailed model of the MMC-HVDC system is implemented in the PSCAD/EMTDC software environment, and the parameters are listed in Table I.The control parame-ters of the CDC and SGEC strategies are given in Table II.A modiﬁed3-machine9-bus system is adopted as a typical case of the local grid,in which a large synchronous generator is replaced by the inverter station.The parameters of the other two synchronous generators are listed in Table III.The perfor-mances of the local grid with the CDC and SGEC strategiesTABLE IP ARAMETERS OF MMC-HVDC SYSTEMTABLE IIC ONTROL PARAMETERSunder different operation cases are investigated and compared by PSCAD/EMTDC simulations.The main object of this study is the AC-side dynamics of the converter station,not the internal characteristics of the converter itself.Thus,an adequate small number of sub-modules(i.e.,20 sub-modules)per arm is implemented in the MMC station to simplify the converter modeling and speed up the simulation. The parameters of the sub-module are not practical values.The nearest level modulation(NLM)algorithm in[32],[33]and the straightforward voltage balancing strategy in[3]are adopted.B.Case1:Steady-State OperationThe steady-state operation is considered in theﬁrst case.The output powers to the local grid from the VSC station,the gen-erator G1and the generator G2are350MW,150MW,and100 MW,respectively.The control strategy of the VSC station is changed from the CDC strategy to the SGEC strategy ats.Because there is no real rotating component in the converter,3098IEEE TRANSACTIONS ON POWER SYSTEMS,VOL.30,NO.6,NOVEMBER 2015TABLE IIIP ARAMETERS OF S YNCHRONOUS GENERATORSthe frequency reference given by the controller is considered as the frequency of the VSC station.The frequency curve and the output power of the VSC are il-lustrated in Fig.5(a)and (b),while voltages and currents at the PCC are shown in Fig.5(c)and (d).The frequency reference of the VSC station with the SGEC strategy is smoother than that with the CDC strategy due to the larger lag time.Small steady-state frequency variations always exist because an ac-tual power system is not ideal.But the frequency variations are reduced under larger system inertia.Since the frequency regu-lation of the inner controller is not achieved instantaneously,the small ripples in the frequency reference have very little impact on the power system.As a result,there is no obvious difference in the output power,the PCC voltages and currents under the two control strategies.Therefore,the steady-state performances of the CDC and SGEC strategies are similar to each other.C.Case 2:Load ChangesThe most common disturbance in a power system is the load change.Due to the lack of inertia,an unbalance in the power generation and consumption will result in a large system fre-quency excursion.As shown in Fig.1,an additional load of 50MW is connected to bus 6at s,which represents 8.3%of the total pre-disturbance load in the local grid.If the secondary frequency regulation is provided by the generator G1,the corresponding responses of the study system with the two control strategies are illustrated in Fig.6.As shown in Fig.6,the frequency drop of the VSC station under the SGEC strategy is slower and smoother than that under the CDC strategy.As a result,the frequency drops of two syn-chronous generators under the SGEC strategy are also slower than that under the CDC strategy.Due to the inertial charac-teristics,the maximum frequency drops of the VSC station,G1and G2are reduced by the SGEC strategy.After a shortperiodFig.5.Simulation waveforms of the converter station during steady-state op-eration:(a)frequency curve of the VSC,(b)output power at the PCC,(c)the PCC voltages,and (d)the PCCcurrents.Fig.6.Simulation waveforms of the converter station with the SGEC and CDC strategies under load change (secondary frequency regulation from G1):(a)fre-quency curves of the VSC,(b)output powers at the PCC,(c)frequency curves of G1,and (d)frequency curves of G2.of transient,the frequency of the local grid can be restored to the nominal value by the secondary frequency regulation from G1.Thus,the system inertia could be increased by the SGEC strategy.If the secondary frequency regulation is provided by the VSC station,the corresponding responses of the study system withGUAN et al.:SYNCHRONOUS GENERATOR EMULATION CONTROL STRATEGY FOR VSC STATIONS3099Fig.7.Simulation waveforms of the converter station with the SGEC and CDC strategies under load change(secondary frequency regulation from the VSC station):(a)frequency curves of the VSC,(b)output powers at the PCC,(c) frequency curves of G1,and(d)frequency curves of G2.the two control strategies are illustrated in Fig.7.After a short period of transient,the frequency of the local grid can be also restored to the nominal value by the secondary frequency regu-lation from the VSC station.The output power of the VSC sta-tion is increased by50MW to supply the additional load.Thus, the VSC station is able to provide second frequency regulation to a low-inertia grid.However,the electromechanical oscillations under the SGEC strategy are damped out more slowly than that under the CDC strategy.This is due to the feature of synchronous generator that the oscillation damping would be decreased by an increase in the inertia[30].D.Case3:AC FaultThe disturbance in this case is a three-phase grounding fault occurring in the middle of line6–9,which is near the VSC station.The fault is cleared inﬁve cycles(0.1s)by opening line6–9.The dynamic performances of the study systems in re-sponse to this three-phase fault are illustrated in Fig.8. When the three-phase fault happens at s,the output powers of the VSC station with the two control strategies are decreased almost to zero.As a result,the frequency of the VSC station with the CDC strategy is suddenly changed to the upper limit,and the frequencies of G1and G2are both accelerated to about51.3Hz.In contrast,the frequency of the VSC station with the SGEC strategy is gradually changed,and the frequen-cies of G1and G2are accelerated to about50.5Hz and50.7Hz. After the fault is cleared,the output powers of the VSC stations are gradually restored,and the VSC station and the generators settle down to new steady-state conditions.During thetransient Fig.8.Simulation waveforms of the converter station with the SGEC and CDCstrategies under AC fault at line6–9:(a)frequency curves of the VSC,(b)output powers at the PCC,(c)frequency curves of G1,and(d)frequency curves ofG2. Fig.9.Simulation waveforms of the converter station with the SGEC and CDC strategies under AC fault at line8–9:(a)frequency curves of the VSC,(b)outputpowers at the PCC,(c)frequency curves of G1,and(d)frequency curves of G2. period,the frequency deviations of the VSC station and the gen-erators with the SGEC strategy are much smaller than that with the CDC strategy.The other disturbance is a three-phase grounding fault occur-ring in the middle of line8–9,which is far away from the VSC station.The fault is cleared inﬁve cycles(0.1s)by opening3100IEEE TRANSACTIONS ON POWER SYSTEMS,VOL.30,NO.6,NOVEMBER2015line8–9.The dynamic performances of the study systems in re-sponse to this three-phase fault are illustrated in Fig.9.During the transient period,the frequency deviations of the VSC sta-tion and the generators with the SGEC strategy are also much smaller than that with the CDC strategy.Therefore,the SGEC strategy is effective in increasing the system inertia and reducing frequency deviations of a low-in-ertia grid.V.C ONCLUSIONThe synchronous generator emulation control strategy is proposed for the VSC station,by which the behavior of a synchronous generator can be emulated.The control scheme is divided into two separate loops:an inner control loop and an outer control loop.The inner controller is a conventional vector controller developed for the fast current control and the PCC voltage regulation.In the outer controller,the conventional droop control is modiﬁed by introducing aﬁrst-order inertia element.The lag time of the inertia element is intentionally increased to provide the inertia response.As a result,the frequency regulation of the SGEC strategy is found to be a nice analogy to the swing equation of a synchronous generator. Moreover,the primary and secondary frequency regulations are also realized by the SGEC strategy.Therefore,the frequency support can be provided by the VSC station with the SGEC strategy,which is especially desired to a low-inertia gird. 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