Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PR...Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PRC1 and PRC2.PRC1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019).PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).展开更多
BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its pre...BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its precise function and mecha-nisms in CRC remain unclear.AIM To investigate the role and mechanism of the MAZ/ubiquitin-like with PHD and RING finger domains 1(UHRF1)/esophageal cancer-related gene 4(ECRG4)axis in CRC metastasis.METHODS Western blot,quantitative reverse transcription polymerase chain reaction(PCR)and transwell were performed to evaluate the impact of MAZ knockdown on CRC cell migration and invasion.A xenograft tumor metastasis model was es-tablished by injecting MAZ-deficient CRC cells into nude mice to assess in vivo metastatic potential.Dual-luciferase reporter assay was performed to determine the role of MAZ and its downstream target,UHRF1.Chromatin immunoprecip-itation-quantitative PCR and methylation-specific PCR were used to analyze whether UHRF1 regulated ECRG4 through DNA methylation.RESULTS MAZ was highly upregulated in CRC cells and promoted CRC migration,inva-sion,epithelial-mesenchymal transition(EMT)and metastasis.Mechanistically,MAZ transcriptionally activated UHRF1,which in turn led to DNA methylation of ECRG4.Knockdown of MAZ suppressed CRC migration and invasion was reversed by overexpression of UHRF1.Loss of UHRF1 upregulated ECRG4,inhibited EMT,and reduced cell migration and invasion.However,simultaneous knockdown of ECRG4 partially reversed these effects.CONCLUSION MAZ promotes CRC cell migration,invasion,and EMT by transcriptionally activating UHRF1,which downreg-ulates ECRG4 through DNA methylation.展开更多
目的:观察RYBP(Ring1 and YY1-binding protein)在急性白血病中的表达情况,初步探索其在急性白血病中的临床意义。方法:应用蛋白质免疫印迹(western blot)技术分别检测急性单核细胞白血病细胞株SHI-1、急性早幼粒白血病细胞株HL-60、慢...目的:观察RYBP(Ring1 and YY1-binding protein)在急性白血病中的表达情况,初步探索其在急性白血病中的临床意义。方法:应用蛋白质免疫印迹(western blot)技术分别检测急性单核细胞白血病细胞株SHI-1、急性早幼粒白血病细胞株HL-60、慢性粒细胞白血病细胞株K562、51例初治急性白血病(AL)患者、23例急性白血病完全缓解(ALCR)患者和21例对照(非恶性血液病)患者骨髓单个核细胞中RYBP的表达情况。结果:SHI-1、HL-60及K562细胞株RYBP表达均为强阳性;21例阴性对照中RYBP表达均为阴性。AL组RYBP表达阳性率为73%,ALCR组阳性率为13%,AL组RYBP表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05)。结论:RYBP在急性白血病细胞中表达水平异常增高,提示RYBP可能与急性白血病密切相关。展开更多
目的:检测RYBP(ring1 and YY1 binding protein)在直肠癌的表达,分析与直肠癌的相关性。方法:用免疫组织化学方法检测107例直肠癌病人标本RYBP的表达,分析RYBP表达程度与直肠癌肿瘤体积、TNM分期及预后等的相关性。结果:107例标本中有45...目的:检测RYBP(ring1 and YY1 binding protein)在直肠癌的表达,分析与直肠癌的相关性。方法:用免疫组织化学方法检测107例直肠癌病人标本RYBP的表达,分析RYBP表达程度与直肠癌肿瘤体积、TNM分期及预后等的相关性。结果:107例标本中有45例RYBP低表达,62例RYBP高表达;肿瘤体积和RYBP的表达无相关性。RYBP表达程度高的病人TNM分期相对较早,有统计学意义。RYBP低表达病人的累积生存时间显著低于RYBP高表达病人,有统计学差异。结论:RYBP的表达程度与直肠癌的预后有关,可在直肠癌的诊断及预后评估中作为参考指标。展开更多
目的探讨BRCA1相关的RING结构域(BRCA1-associated RING domain,BARD1)蛋白在宫颈癌和癌前病变组织中的表达及临床意义。方法选取2016年1月至2018年9月在本院治疗的88名宫颈癌患者(收集癌组织及癌旁组织标本)以及子宫颈鳞状上皮内瘤变患...目的探讨BRCA1相关的RING结构域(BRCA1-associated RING domain,BARD1)蛋白在宫颈癌和癌前病变组织中的表达及临床意义。方法选取2016年1月至2018年9月在本院治疗的88名宫颈癌患者(收集癌组织及癌旁组织标本)以及子宫颈鳞状上皮内瘤变患者112例为癌前病变组[48例低级别上皮内病变(LSIL),64例高级别上皮内病变(HSIL)]为研究对象。应用免疫组化法测定宫颈癌和癌前病变组中BARD1蛋白表达水平。通过χ^(2)检验分析BARD1蛋白表达与宫颈癌患者临床病理特征的关系,多因素Cox回归模型探讨宫颈癌预后相关因素。结果LSIL组、HSIL组、宫颈癌组BARD1蛋白阳性率低于癌旁组[83.3%(40/48)、68.8%(44/64)、36.4%(32/88)vs 96.6%(85/88)](P<0.05);HSIL组、宫颈癌组BARD1蛋白表达阳性率低于LSIL组[68.8%(44/64)、36.4%(32/88)vs 83.3%(40/48)](P<0.05);宫颈癌组BARD1蛋白表达阳性率低于HSIL组[36.4%(32/88)vs 68.8%(44/64)](P<0.05)。肿瘤最大径≥2 cm、国际妇产科联盟(FIGO)分期越高、浸润深度越深、病理级别越低、有淋巴结转移、有复发的宫颈癌患者BARD1阳性表达率越低(P<0.05)。BARD1阳性和阴性患者3年总生存率分别为100.0%(32/32)和35.7%(20/56),BARD1阴性表达的宫颈癌患者3年生存率显著缩短(P<0.05)。多因素Cox回归分析显示:FIGO分期Ⅱ期、病理级别低、BARD1阴性是影响宫颈癌患者预后的独立危险因素(P<0.05)。结论宫颈癌及癌前病变患者组织中BARD1阳性表达降低,且宫颈癌患者癌组织中BARD1阳性表达更低,BARD1表达水平与宫颈癌患者病理特征有一定相关性,BARD1阴性是宫颈癌患者预后危险因素。展开更多
目的通过检测乳腺黏液癌（以M表述）及浸润性导管癌（符合基底细胞样癌分子分型诊断标准：以D-B表述）标本中乳腺癌阻抑蛋白1关联RING蛋白1（BRCA1-associated RING domain,BARD1）剪切变异体表达水平的差异,结合术后随访结果,探讨BARD...目的通过检测乳腺黏液癌（以M表述）及浸润性导管癌（符合基底细胞样癌分子分型诊断标准：以D-B表述）标本中乳腺癌阻抑蛋白1关联RING蛋白1（BRCA1-associated RING domain,BARD1）剪切变异体表达水平的差异,结合术后随访结果,探讨BARD1基因在乳腺癌中可能的临床意义。方法以本院乳腺中心标本库储存的43例M标本及39例D-B标本提取的目的基因进行RT-PCR,对相应病例石蜡包埋组织切片进行病理免疫组织化学检测;患者术后每半年随访1次,记录无病生存期（disease free survival,DFS）及总生存期（overall survival,OS）;分析BARD1基因的临床意义。结果在所有标本中共发现4种BARD1基因的转录产物：全长BARD1基因（full lenth,Fl）,剪切变异体γ、δ和ε,其中Fl在所有组织中均有表达,剪切变异体δ和ε在M中的阳性表达率低于D-B（P〈0.005）;免疫组织化学检测发现在D-B中BARD1蛋白阳性细胞比率显著高于M（P〈0.005）,两种癌组织中蛋白均异位表达于细胞质中;BARD1剪切变异体的阳性表达与乳腺癌预后差的因素有关（P〈0.05）。研究病例术后随访36~70个月,单因素分析发现,剪切变异体ε阳性表达与乳腺癌术后无病生存期及总生存期缩短均显著相关（P〈0.05）。结论 BARD1剪切变异体在不同类型乳腺癌中的表达存在差异;与正常组织细胞相比,BARD1剪切变异体异位表达在肿瘤细胞质中;剪切变异体δ和ε与乳腺癌预后差的因素相关,并且剪切变异体ε阳性表达的患者无病生存期及总生存期均显著缩短。因此BARD1剪切变异体的异常表达或许影响乳腺癌的生物学行为,进而影响乳腺癌的预后。展开更多
Polycomb group genes play crucial roles in the maintenance of the transcriptionally silenced state of genes for proper cell differentiation in animals and plants. While components of the polycomb repressive complex2 ...Polycomb group genes play crucial roles in the maintenance of the transcriptionally silenced state of genes for proper cell differentiation in animals and plants. While components of the polycomb repressive complex2 （PRC2） are evolutionarily conserved and their functions are extensively studied in plants, PRCI differs considerably between animals and plants, and its functions in plants are as yet not well described. Previous studies have identified the Arabidopsis AtRINGla and AtRINGlb as homologues of the animal PRC1 subunit RING1. Here, we show that the Atringla Atringlb double mutant exhibits derepression of embryonic traits during vegetative growth. Accordingly, several key regulatory genes involved in embryogenesis and stem cell activity are ectopically expressed in the mutant. Furthermore, we show that the mutant phenotypes and increased expression of regulatory genes are enhanced by the PRC2 mutant c/f. Finally, we show that three homologues of the animal PRCl-subunit ring-finger protein BMI1, AtBMIIa, AtBMIlb and AtBMIlc, can bind with AtRINGla or AtRINGIb, and in addition, AtBMIlc can bind with LHP1. The Atbmila Atbmilb double mutant shows derepression of embryonic traits similar to that of the Atringla Atringlb double mutant. Interestingly, expression levels of AtBMIla, AtBMIlb and AtBMIlc are elevated in the Atringla Atringlb mutant and those of AtBMIlc, AtRINGla and AtRINGlb are elevated in the Atbmila Atbmilb mu- tant, suggesting a self-regulatory feedback mechanism. Taken together, our results illuminate crucial functions of the PRCl-like ring-finger components in stable repression of embryonic traits and regulatory genes for proper somatic growth.展开更多
AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α...AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.展开更多
L-Arginine (L-Arg), the precursor of nitric oxide (NO), plays an important role in muscle function. Fasttwitchglycolytic fibres are more susceptible to age-related atrophy than slow-twitch oxidative fibres.The effect ...L-Arginine (L-Arg), the precursor of nitric oxide (NO), plays an important role in muscle function. Fasttwitchglycolytic fibres are more susceptible to age-related atrophy than slow-twitch oxidative fibres.The effect of L-Arg/NO on protein metabolism of fast- and slow-twitch muscle fibres was evaluated inchickens. In Exp. 1, 48 chicks at 1 day old were divided into 4 groups of 12 birds and subjected to 4treatments: basal diet without supplementation or supplemented with 1% L-Arg, and water supplementedwith or without L-nitro-arginine methyl ester (L-NAME, 18.5 mM). In Exp. 2, 48 chicks weredivided into 4 groups of 12 birds fed with the basal diet and subjected to the following treatments: tapwater (control), tap water supplemented with L-NAME (18.5 mM), or molsidomine (MS, 0.1 mM), or18.5 mM L-NAME t 0.1 mM MS (NAMS). The regulatory effect of L-Arg/NO was further investigatedin vitro with myoblasts obtained from chicken embryo pectoralis major (PM) and biceps femoris (BF).In vivo, dietary L-Arg supplementation increased breast (t14.94%, P < 0.05) and thigh muscle mass(t23.40%, P < 0.05);whereas, MS treatment had no detectable influence. However, L-NAME treatmentblocked the beneficial influence of L-Arg on muscle development. L-Arg decreased (P < 0.05) proteinsynthesis rate, phosphorylated mTOR and ribosomal protein S6 kinase beta-1 (p70S6K) levels in breastmuscle, which was recovered by L-NAME treatment. In vitro, L-Arg or sodium nitroprusside (SNP)reduced protein synthesis rate, suppressed phosphorylated mTOR/p70S6K and decreased atrogin-1 andmuscle RING finger 1 (MuRF1) in myoblasts from PM muscle (P < 0.05). L-NAME abolished the inhibitoryeffect of L-Arg on protein synthesis and the mTOR/p70S6K pathway. However, myoblasts from BF muscleshowed the weak influence. Moreover, blocking the mTOR/p70S6K pathway with rapamycin suppressedprotein synthesis of the 2 types of myoblasts;whereas, the protein expression of atrogin-1 and MuRF1levels were restricted only in myoblasts from PM muscle. In conclusion, L-Arg/NO/mTOR/p70S6Kpathway enhances protein accumulation and muscle development in fast-twitch glycolytic muscle inchickens. L-Arg/NO regulates protein turnover in a muscle fibre specific way, which highlights the potentialclinical application in fast-twitch glycolytic muscle fibres.展开更多
Leaves are the most important plant parts for photosynthesis and respiration. Many genes are involved in determining leaf shape;however, little is known about the effects of brassinosteroid (BR) signaling-pathway gene...Leaves are the most important plant parts for photosynthesis and respiration. Many genes are involved in determining leaf shape;however, little is known about the effects of brassinosteroid (BR) signaling-pathway genes on the development of leaf shape. Here, the brassinosteroid-responsive RING-H2 (BRH1) gene, which is suppressed by 24-epi-brassinolide treatment, was isolated from Arabidopsis thaliana. The amino acid sequence contained a highly conserved RING finger domain. In a phylogenetic analysis,BRH1 clustered closely with GLYMA11G02470.1. The leaves of brh1 mutant plants were not much different to those of the wild-type, while transgenic plants with high BRH1 expression levels had rounder rosette leaves. Mutants of the BR synthesis pathway also had a similar round leaf phenotype, and greater BRH1 expression levels. Moreover, the related marker genes KNAT1,AtHB13 and ROT4, which are known to control leaf shape, altered transcriptional levels in both transgenic BRH1 and BR-synthesis mutant lines. Thus, BRH1 may be involved in the BR signaling pathway and regulate the growth and development of rosette leaves. Research on BRH1 may prove valuable for understanding the regulatory mechanism of leaf shape and improving the leaf shapes of ornamental plants.展开更多
A three-dimensional model of GaAs/A1GaAs quantum double rings in the lateral static electric field is investigated theoretically. The eigenvalue problem with the effective-mass approximation is solved by means of the ...A three-dimensional model of GaAs/A1GaAs quantum double rings in the lateral static electric field is investigated theoretically. The eigenvalue problem with the effective-mass approximation is solved by means of the finite-element method. The energy levels and wave functions of quantum-confined electrons and heavy holes are obtained and show an agreement with our previous theoretical and experimental studies. It is shown in the approximation of neglecting the Coulomb attraction between the electron and heavy hole that a relatively large Stark shift of exciton emission of 4 meV is attainable with an applied electric field of 0.7 kV/cm.展开更多
基金supported by the National Natural Science Foundation of China(31925009,U21A20195)the National Key Research and Development Program of China(2021YFA1100300)。
文摘Dear Editor,Polycomb group(Pc G)proteins represent important roles in repressing gene expression throughout development.The Polycomb repressive complexes(PRCs)have been subdivided into two central protein complexes,PRC1 and PRC2.PRC1 catalyzes H2AK119ub and PRC2catalyzes H3K27me1/2/3(Fursova et al.,2019).PRC1 is further categorized as CBX-containing canonical PRC1(c PRC1)and RYBP/YAF2-containing variant PRC1(v PRC1)(Blackledge and Klose,2021).
基金Supported by Hangzhou Medical and Health Science and Technology Plan,No.B20210014.
文摘BACKGROUND Colorectal cancer(CRC)is one of the most common causes of cancer mortality worldwide.The transcription factor Myc-associated zinc finger protein(MAZ)has been implicated in cancer progression.However,its precise function and mecha-nisms in CRC remain unclear.AIM To investigate the role and mechanism of the MAZ/ubiquitin-like with PHD and RING finger domains 1(UHRF1)/esophageal cancer-related gene 4(ECRG4)axis in CRC metastasis.METHODS Western blot,quantitative reverse transcription polymerase chain reaction(PCR)and transwell were performed to evaluate the impact of MAZ knockdown on CRC cell migration and invasion.A xenograft tumor metastasis model was es-tablished by injecting MAZ-deficient CRC cells into nude mice to assess in vivo metastatic potential.Dual-luciferase reporter assay was performed to determine the role of MAZ and its downstream target,UHRF1.Chromatin immunoprecip-itation-quantitative PCR and methylation-specific PCR were used to analyze whether UHRF1 regulated ECRG4 through DNA methylation.RESULTS MAZ was highly upregulated in CRC cells and promoted CRC migration,inva-sion,epithelial-mesenchymal transition(EMT)and metastasis.Mechanistically,MAZ transcriptionally activated UHRF1,which in turn led to DNA methylation of ECRG4.Knockdown of MAZ suppressed CRC migration and invasion was reversed by overexpression of UHRF1.Loss of UHRF1 upregulated ECRG4,inhibited EMT,and reduced cell migration and invasion.However,simultaneous knockdown of ECRG4 partially reversed these effects.CONCLUSION MAZ promotes CRC cell migration,invasion,and EMT by transcriptionally activating UHRF1,which downreg-ulates ECRG4 through DNA methylation.
文摘目的:观察RYBP(Ring1 and YY1-binding protein)在急性白血病中的表达情况,初步探索其在急性白血病中的临床意义。方法:应用蛋白质免疫印迹(western blot)技术分别检测急性单核细胞白血病细胞株SHI-1、急性早幼粒白血病细胞株HL-60、慢性粒细胞白血病细胞株K562、51例初治急性白血病(AL)患者、23例急性白血病完全缓解(ALCR)患者和21例对照(非恶性血液病)患者骨髓单个核细胞中RYBP的表达情况。结果:SHI-1、HL-60及K562细胞株RYBP表达均为强阳性;21例阴性对照中RYBP表达均为阴性。AL组RYBP表达阳性率为73%,ALCR组阳性率为13%,AL组RYBP表达阳性率及表达量比ALCR组及对照组明显增高(P<0.05)。结论:RYBP在急性白血病细胞中表达水平异常增高,提示RYBP可能与急性白血病密切相关。
文摘目的:检测RYBP(ring1 and YY1 binding protein)在直肠癌的表达,分析与直肠癌的相关性。方法:用免疫组织化学方法检测107例直肠癌病人标本RYBP的表达,分析RYBP表达程度与直肠癌肿瘤体积、TNM分期及预后等的相关性。结果:107例标本中有45例RYBP低表达,62例RYBP高表达;肿瘤体积和RYBP的表达无相关性。RYBP表达程度高的病人TNM分期相对较早,有统计学意义。RYBP低表达病人的累积生存时间显著低于RYBP高表达病人,有统计学差异。结论:RYBP的表达程度与直肠癌的预后有关,可在直肠癌的诊断及预后评估中作为参考指标。
文摘Polycomb group genes play crucial roles in the maintenance of the transcriptionally silenced state of genes for proper cell differentiation in animals and plants. While components of the polycomb repressive complex2 （PRC2） are evolutionarily conserved and their functions are extensively studied in plants, PRCI differs considerably between animals and plants, and its functions in plants are as yet not well described. Previous studies have identified the Arabidopsis AtRINGla and AtRINGlb as homologues of the animal PRC1 subunit RING1. Here, we show that the Atringla Atringlb double mutant exhibits derepression of embryonic traits during vegetative growth. Accordingly, several key regulatory genes involved in embryogenesis and stem cell activity are ectopically expressed in the mutant. Furthermore, we show that the mutant phenotypes and increased expression of regulatory genes are enhanced by the PRC2 mutant c/f. Finally, we show that three homologues of the animal PRCl-subunit ring-finger protein BMI1, AtBMIIa, AtBMIlb and AtBMIlc, can bind with AtRINGla or AtRINGIb, and in addition, AtBMIlc can bind with LHP1. The Atbmila Atbmilb double mutant shows derepression of embryonic traits similar to that of the Atringla Atringlb double mutant. Interestingly, expression levels of AtBMIla, AtBMIlb and AtBMIlc are elevated in the Atringla Atringlb mutant and those of AtBMIlc, AtRINGla and AtRINGlb are elevated in the Atbmila Atbmilb mu- tant, suggesting a self-regulatory feedback mechanism. Taken together, our results illuminate crucial functions of the PRCl-like ring-finger components in stable repression of embryonic traits and regulatory genes for proper somatic growth.
基金Supported by Indian Council of Medical Research,New Delhi,India
文摘AIM: To investigate the role of [breast and ovarian cancer susceptibility 1（BRCA1）-associated RING domain 1（BARD1）]/BRCA1 E3-ubiquitin ligase complex in governing the stability of mutant liver X receptor-（LXR-α） protein in coronary heart disease（CHD） subjects.METHODS: The expression analysis of various genes was carried out by quantitative real time polymerase chain reaction and western blotting within blood mononuclear cells of human CHD subjects at various stages of coronary occlusion and their corresponding normal healthy counterparts.Immunoprecipitation experiments were performed to establish protein interactions between LXR-αand BARD1.Peripheral blood mononuclear cells were cultured and exposed to Vitamin D3 and Cisplatin to validate the degradation of mutant LXR-αprotein in CHD subjects by BARD1/BRCA1 complex.RESULTS: The expression of mutant LXR-αprotein in CHD subjects was found to decrease gradually with the severity of coronary occlusion exhibiting a strong negative correlation,r =-0.975 at P 【 0.001.Further,the expression of BARD1 and BRCA1 also increased with the disease severity,r = 0.895 and 0.873 respectively（P 【 0.001）.Immunoprecipitation studies established that BARD1/BRCA1 complex degrades mutant LXR-αvia ubiquitination.The absence of functional LXR-αprotein resulted in increased expression of inflammatory cytokines such as interleukin（IL）-6,IL-8 and interferon-and decreased expression of ABCA1（ATP-binding cassette A1）（r = 0.932,0.949,0.918 and-0.902 with respect to Gensini score;P 【 0.001）.Additionally,cell culture experiments proved that Vitamin D3 could prevent the degradation of mutant LXR-αand restore its functional activity to some extent.CONCLUSION: Mutant LXR-αprotein in CHD subjects is degraded by BARD1/BRCA1 complex and Vitamin D3 can rescue and restore its function.
基金the Key Technologies Research and Development Programof China(2021YFD1300405)the Earmarked Fund for China Agriculture Research System(CARS-40-K09)+1 种基金National Natural Science Foundation of China(31772619)Key Technology Research and Development Program of Shandong Province(2019JZZY020602).
文摘L-Arginine (L-Arg), the precursor of nitric oxide (NO), plays an important role in muscle function. Fasttwitchglycolytic fibres are more susceptible to age-related atrophy than slow-twitch oxidative fibres.The effect of L-Arg/NO on protein metabolism of fast- and slow-twitch muscle fibres was evaluated inchickens. In Exp. 1, 48 chicks at 1 day old were divided into 4 groups of 12 birds and subjected to 4treatments: basal diet without supplementation or supplemented with 1% L-Arg, and water supplementedwith or without L-nitro-arginine methyl ester (L-NAME, 18.5 mM). In Exp. 2, 48 chicks weredivided into 4 groups of 12 birds fed with the basal diet and subjected to the following treatments: tapwater (control), tap water supplemented with L-NAME (18.5 mM), or molsidomine (MS, 0.1 mM), or18.5 mM L-NAME t 0.1 mM MS (NAMS). The regulatory effect of L-Arg/NO was further investigatedin vitro with myoblasts obtained from chicken embryo pectoralis major (PM) and biceps femoris (BF).In vivo, dietary L-Arg supplementation increased breast (t14.94%, P < 0.05) and thigh muscle mass(t23.40%, P < 0.05);whereas, MS treatment had no detectable influence. However, L-NAME treatmentblocked the beneficial influence of L-Arg on muscle development. L-Arg decreased (P < 0.05) proteinsynthesis rate, phosphorylated mTOR and ribosomal protein S6 kinase beta-1 (p70S6K) levels in breastmuscle, which was recovered by L-NAME treatment. In vitro, L-Arg or sodium nitroprusside (SNP)reduced protein synthesis rate, suppressed phosphorylated mTOR/p70S6K and decreased atrogin-1 andmuscle RING finger 1 (MuRF1) in myoblasts from PM muscle (P < 0.05). L-NAME abolished the inhibitoryeffect of L-Arg on protein synthesis and the mTOR/p70S6K pathway. However, myoblasts from BF muscleshowed the weak influence. Moreover, blocking the mTOR/p70S6K pathway with rapamycin suppressedprotein synthesis of the 2 types of myoblasts;whereas, the protein expression of atrogin-1 and MuRF1levels were restricted only in myoblasts from PM muscle. In conclusion, L-Arg/NO/mTOR/p70S6Kpathway enhances protein accumulation and muscle development in fast-twitch glycolytic muscle inchickens. L-Arg/NO regulates protein turnover in a muscle fibre specific way, which highlights the potentialclinical application in fast-twitch glycolytic muscle fibres.
基金supported by the Major Program of Joint Funds (Sinkiang) of the National Natural Science Foundation of China(U1303282)
文摘Leaves are the most important plant parts for photosynthesis and respiration. Many genes are involved in determining leaf shape;however, little is known about the effects of brassinosteroid (BR) signaling-pathway genes on the development of leaf shape. Here, the brassinosteroid-responsive RING-H2 (BRH1) gene, which is suppressed by 24-epi-brassinolide treatment, was isolated from Arabidopsis thaliana. The amino acid sequence contained a highly conserved RING finger domain. In a phylogenetic analysis,BRH1 clustered closely with GLYMA11G02470.1. The leaves of brh1 mutant plants were not much different to those of the wild-type, while transgenic plants with high BRH1 expression levels had rounder rosette leaves. Mutants of the BR synthesis pathway also had a similar round leaf phenotype, and greater BRH1 expression levels. Moreover, the related marker genes KNAT1,AtHB13 and ROT4, which are known to control leaf shape, altered transcriptional levels in both transgenic BRH1 and BR-synthesis mutant lines. Thus, BRH1 may be involved in the BR signaling pathway and regulate the growth and development of rosette leaves. Research on BRH1 may prove valuable for understanding the regulatory mechanism of leaf shape and improving the leaf shapes of ornamental plants.
基金supported by a Grant-in-Aid for Scientific Research from the Ministry of Education,Science,Sports,and Culture of Japan (No.20340080).
文摘A three-dimensional model of GaAs/A1GaAs quantum double rings in the lateral static electric field is investigated theoretically. The eigenvalue problem with the effective-mass approximation is solved by means of the finite-element method. The energy levels and wave functions of quantum-confined electrons and heavy holes are obtained and show an agreement with our previous theoretical and experimental studies. It is shown in the approximation of neglecting the Coulomb attraction between the electron and heavy hole that a relatively large Stark shift of exciton emission of 4 meV is attainable with an applied electric field of 0.7 kV/cm.
