m6A甲基转移酶METTL3通过β‐arrestin 1/p65调控结肠癌细胞增殖

目的探讨m6A甲基转移酶METTL3通过β-arrestin 1/p65在结肠癌细胞中的作用机制。方法使用结肠癌细胞系HCT116,应用荧光定量PCR、Western blot测定结肠癌细胞中METTL3、β-arrestin 1及增值蛋白PCNA、Cyclin D1及Cyclin E的表达水平;利用细胞转染及细胞克隆实验,观察METTL3、β-arres-tin1和p65在结肠癌细胞增殖中的作用。结果METTL3和β-arrestin 1在结肠癌细胞中表达升高(以actin作为内参基因,与正常对照组比较,P<0.05)。结肠癌细胞转染METTL3-shRNA后,转染组灰度(0.36±0.046)较对照组(1.27±0.14)明显减少(P=0.0004);与对照组克隆数(465±42)比较,转染组细胞增殖(85±37)明显减少(P<0.05);细胞增殖蛋白PCNA、Cyclin D1及Cyclin E的表达也明显减少(分别为P<0.01、0.05、0.01);结肠癌细胞中METTL3、β-arrestin 1和p-p65蛋白表达均增高(均为P<0.05)。随后HCT116细胞沉默MET-TL3的表达,发现细胞中β-arrestin 1、p-p65蛋白的表达明显下降(均为P<0.05)。结论METTL3影响结肠癌细胞的增殖可能通过β-arrestin 1/p65调控参与肿瘤的发生发展。

固定化脂肪酶ANL-MARE催化酸解合成1-油酸-2-棕榈酸-3-亚油酸甘油三酯

1-油酸-2-棕榈酸-3-亚油酸甘油三酯(OPL)是人乳中主要的脂质组成,为满足婴幼儿配方食品母乳化需求,该试验探究了新型固定化脂肪酶ANL-MARE催化制备OPL的方法。试验成功制备和表征了固定化酶ANLMARE,并以ANL-MARE为生物催化剂,建立了一种用三棕榈酸甘油三酯(PPP)、油酸(OA)和亚油酸(LA)高效酶催化制备富含OPL结构脂的方法。经单因素和响应面试验优化,获得OPL最优合成工艺为:PPP与总脂肪酸的摩尔比1:14.27,OA与LA摩尔比为1:0.76,脂肪酶添加量12.70%,反应温度50℃,反应4 h,此条件下产物中OPL相对含量为47.93%,2位棕榈酸(sn-2 PA)占总棕榈酸(PA)的质量分数(sn-2 PA相对含量)为71.69%。此外,固定化酶ANL-MARE与商业脂肪酶相比,表现出较好的催化合成OPL的活性。综上所述,固定化酶ANL-MARE具有催化制备OPL结构脂的重大潜力,为人乳脂替代脂的高效制备提供了新策略和理论基础。

Improved LS+MAR hybrid method to UT1-UTC ultra-short-term prediction by using first-order-difference UT1-UTC

Accurate ultra-short-term prediction of the Earth rotation parameters(ERP)holds paramount impor-tance for real-time applications,particularly in reference frame conversion.Among them,diurnal rota-tion(UT1-UTC)which cannot be directly estimated through Global Navigation Satellite System(GNSS)techniques,significantly affects the rapid and ultra-rapid orbit determination of GNsS satellites.Pres-ently,the traditional LS(least squares)+AR(autoregressive)and LS+MAR(multivariate autoregressive)hybrid methods stand as primary approaches for UT1-UTC ultra-short-term predictions(1-10 days).The LS+MAR hybrid method relies on the UT1-UTC and LOD(length of day)series.However,the correlation between LOD and first-order-difference UT1-UTC is stronger than that between LOD and UT1-UTC.In light of this,and with the aid of the first-order-difference UT1-UTC,we propose an enhanced LS+MAR hybrid method to UT1-UTC ultra-short-term prediction.By using the UT1-UTC and LOD data series of the IERS(International Earth Rotation and Reference Systems Service)EOP 14 C04 product,we conducted a thorough analysis and evaluation of the improved method's prediction performance compared to the traditional LS+AR and LS+MAR hybrid methods.According to the numerical results over more than 210 days,they demonstrate that,when considering the correlation information between the LoD and the first-order-difference UT1-UTC,the mean absolute errors(MAEs)of the improved LS+MAR hybrid method range from 21 to 934μs in 1-10 days predictions.In comparison to the traditional LS+AR hybrid method,the MAEs show a reduction of 7-53μs in 1-10 days predictions,with corresponding improvement percentages ranging from 1 to 28%.Similarly,when compared to the traditional LS+MAR hybrid method,the MAEs have a reduction of 5-42μs in 1-10 days predictions,with corresponding improvement percentages ranging from 4-20%.Additionally,when aided by GNSS-derived LOD data series,the MAEs of improved LS+MAR hybrid method experience further reduction.

SIL1 improves cognitive impairment in APP23/PS45 mice by regulating amyloid precursor protein processing and Aβ generation

SIL1,an endoplasmic reticulum(ER)-resident protein,is reported to play a protective role in Alzheimer’s disease(AD).However,the effect of SIL1 on amyloid precursor protein(APP)processing remains unclear.In this study,the role of SIL1 in APP processing was explored both in vitro and in vivo.In the in vitro experiment,SIL1 was either overexpressed or knocked down in cells stably expressing the human Swedish mutant APP695.In the in vivo experiment,AAV-SIL1-EGFP or AAV-EGFP was microinjected into APP23/PS45 mice and their wild-type littermates.Western blotting(WB),immunohistochemistry,RNA sequencing(RNA-seq),and behavioral experiments were performed to evaluate the relevant parameters.Results indicated that SIL1 expression decreased in APP23/PS45 mice.Overexpression of SIL1 significantly decreased the protein levels of APP,presenilin-1(PS1),and C-terminal fragments(CTFs)of APP in vivo and in vitro.Conversely,knockdown of SIL1 increased the protein levels of APP,β-site APP cleavage enzyme 1(BACE1),PS1,and CTFs,as well as APP mRNA expression in 2EB2 cells.Furthermore,SIL1 overexpression reduced the number of senile plaques in APP23/PS45 mice.Importantly,Y-maze and Morris Water maze tests demonstrated that SIL1 overexpression improved cognitive impairment in APP23/PS45 mice.These findings indicate that SIL1 improves cognitive impairment in APP23/PS45 mice by inhibiting APP amyloidogenic processing and suggest that SIL1 is a potential therapeutic target for AD by modulating APP processing.

TLC Identification and Extraction Process of Rubiasin-1-methyl Ether from Yao Medicine Chuanlianzhu

[Objectives]To establish a thin-layer chromatography(TLC)method for the determination of rubiadin-1-methyl ether in Yao Medicine Chuanlianzhu(Damnacanthus giganteus).[Methods]A silica gel G thin-layer plate was adopted for TLC.Petroleum ether(60-90℃)-chloroform-methanol-water(7:15:3:1)was used as the developing solvent and inspected under ultraviolet lamp(365 nm).The content was determined by Inertsil ODS-3 C 18 column(4.60 mm×250 mm,5μm),mobile phase:acetonitrile-0.2%phosphoric acid gradient elution,detection wavelength 277 nm,flow rate 1.0 mL/min,column temperature 30℃,injection volume 10μL.[Results]The spots of 10 Chuanlianzhu samples from different origins showed the same color at the same position as the control,and the spots were clear and specific.The injection volume of rubiadin-1-methyl ether showed a good linear relationship in the range of 2.90-145μg(R=0.9996).The average recovery rate of rubiadin-1-methyl ether in the low,medium and high dose groups of Yao Medicine Chuanlianzhu was 98.72%,and RSD=1.78%.[Conclusions]This method can effectively identify Yao Medicine Chuanlianzhu medicinal materials and accurately determine the content of rubiadin-1-methyl ether in the medicinal materials.It provides a scientific basis for the development and utilization of Yao Medicine Chuanlianzhu medicinal resources.

Optimization of processing parameters for preparation of Al-3Ti-1B grain refiner

Al-3Ti-1B master alloys were prepared at different processing parameters by the reaction of halide salts,and the grain refining response of Al-7Si alloy was investigated with Al-3Ti-B master alloy.The microstructure of master alloy and its grain refining effect on Al-7Si alloy were investigated by means of OM,XRD and SEM.Experimental results show that,the size of Al3Ti particles presented in Al-3Ti-1B master alloys increases with the increase of reaction temperature and decreases with the increase of cooling rate.The grain refining efficiency of Al-3Ti-1B master alloy on Al-7Si alloy is mainly attributed to heterogeneous nucleation of Al3Ti particles,and the morphology ofα(Al)changes from coarse dendritic to fine equiaxed.As a result,Al-3Ti-1B master alloy is prepared by permanent mold,and holding at 800 ℃for 30min,which has better grain refining performance on Al-7Si alloy.

Influence of Angiotensin II on α1-Adrenergic Receptors Function in Rat Aorta and Expression in Vascular Smooth Muscle Cells

Angiotensin II (Ang II) is the main mediator of the Renin-Angiotensin-System acting on AT1 and other AT receptors. It is regarded as a pleiotropic agent that induces many actions, including functioning as a growth factor, and as a contractile hormone, among others. The aim of this work was to examine the impact of Ang II on the expression and function of α1-adrenergic receptors (α1-ARs) in cultured rat aorta, and aorta-derived smooth muscle cells. Isolated Wistar rat aorta was incubated for 24 h in DMEM at 37˚C, then subjected to isometric tension and to the action of added norepinephrine, in concentration-response curves. Ang II was added (1 × 10−5 M), and in some experiments, 5-Methylurapidil (α1A-AR antagonist), AH11110A (α1B-AR antagonist), or BMY-7378 (α1D-AR antagonist), were used to identify the α1-AR involved in the response. Desensitization of the contractile response to norepinephrine was observed due to incubation time, and by the Ang II action. α1D-AR was protected from desensitization by BMY-7378;while RS-100329 and prazosin partially mitigated desensitization. In another set of experiments, isolated aorta-derived smooth muscle cells were exposed to Ang II and α1-ARs proteins were evaluated. α1D-AR increased at 30 and 60 min post Ang II exposure, the α1A-AR diminished from 1 to 4 h, while α1B-AR remained unchanged over 24 h of Ang II exposure. Ang II induced an increase of α1D-AR at short times, and BMY-7378 protected α1D-AR from desensitization.

血清c5ar1、ALP及25(OH)D3的表达规律对股骨颈骨折术后骨折愈合情况的预测价值

目的:探讨血清补体成分5a受体1(Complement component 5a receptor,c5ar1)、碱性磷酸酶(Alkaline phosphatase,ALP)及25羟基维生素D(Vitamin D325-hydroxy monohydrate,25(OH)D3)的表达规律对股骨颈骨折术后骨折愈合情况的预测价值.方法:选取2019年1月至2022年12月本院治疗的股骨颈发生骨折且实施全髋关节置换术的98例患者作为研究对象.依据其术后6 m的影像学方面检查结果评估患者的骨折愈合情况,并将患者分成骨折愈合组(77例)和未愈合组(21例).于入院及术后42 d分别对两组的血清c5ar1、ALP、25(OH)D3水平进行测定,采用Pearson相关性分析c5ar1、ALP、25(OH)D3的相关性.采用受试者工作(Receiver operating characteristic,ROC)曲线分析血清c5ar1、ALP及25(OH)D3对股骨颈骨折术后骨折的愈合情况的预测价值.结果:骨折愈合组术后血清c5ar1、ALP及25(OH)D3的表达水平均高于术前(P<0.05),未愈合组术后血清c5ar1、ALP及25(OH)D3的表达水平均低于术前(P<0.05);Pearson相关性分析结果显示,c5ar1与25(OH)D3呈正相关关系(P<0.05);c5ar1、ALP、25(OH)D3诊断股骨颈骨折术后骨折愈合情况的敏感度分别为92.20%、62.30%、76.60%,特异度分别为90.50%、47.60%、52.40%,ROC曲线分析显示,c5ar1、ALP、25(OH)D3诊断股骨颈骨折术后骨折愈合情况的曲线下面积(area under curve,AUC)分别为0.953、0.515、0.765.结论:血清c5ar1、ALP及25(OH)D3的表达水平升高可促进股骨颈骨折术后骨折愈合,c5ar1与25(OH)D3呈正相关关系,c5ar1、25(OH)D3诊断股骨颈骨折术后骨折愈合情况具有较高的准确性,而ALP预测股骨颈骨折术后骨折愈合情况的准确性较低.

A New Vector Markov Process for M/G/1 Queue

In this paper, by considering the stochastic proces s of the busy period and the idle period, and introducing the unfinished work as a supplementary variable, a new vector Markov process was presented to study th e M/G/1 queue again. Through establishing and solving the density evolution equa tions, the busy-period distribution, and the stationary distributions of waitin g time and queue length were obtained. In addition, the stability condition of th is queue system was given by means of an imbedded renewal process.

Formation Process of Magnetized Fusion Target on the YingGuang 1 Device

Magnetized target fusion is an alternative method to fulfill the goal of controlled fusion, which combines advan- tages of both magnetic confinement fusion and inertial confinement fusion since its parameter space lies between the two traditional ways. Field reversed configuration （FFtC） is a good candidate of magnetized targets due to its translatable, compressible, high /3 and high energy density properties. Dynamic formation process of high density FFtC is observed on the YingGuang 1 device for the first time in China. The evolution of a magnetic field is detected with magnetic probes, and the compression process can be clearly seen from images taken with a high-speed multi-frame CCD camera. The process is also studied with two-dimensional magneto hydrodynamic code MPF-2D theoretically, and the results agree well with the experiment. Combining the experimental data and the theoretical analysis, the length of the formed FRC is about 39 cm, the diameter is about 2-2. 7cm, the average density is 1.3× 1016 cm-3, and the average temperature is 137eV.

Preliminary Announcement for the 1st Pacific Rim International Conference on Advanced Materials and Processing(PRICM-1)

The Joint Conference Organizing Committee of The Chinese Society of Metals(CSM),The Japan Insti-tute of Metals(JIM),The Korean Institute of Metals(KIM)and The Minerals,Metals & Materials Society(TMS)announces The First Pacific Rim International Conference on Advanced Materials and Processing(PRICM-1)which will be held in Hangzhou,China,in the last week of June,1992 lasting about four days.It is agreed that the PRICM-1 will be organized by The Chinese Society of Metals.

A new sol-gel process for preparing Ba(Mg_(1/3)Nb_(2/3))O_3 nanopowders

Commercially available niobium (V) oxide [Nb2O5], with barium acetate [Ba(CH3COO)2] and magnesium acetate [Mg(CH3COO)2-4H2O] was used as the starting material in the sol-gel process for preparing Ba(Mg1/3Nb2/3)O3 (BMN) nanopowders. At first, Nb2O5 reacted with melting sodium hydroxide and transformed into dispersible oxide. The resulting glassy substance after cooling was dispersed and washed several times in distilled water to remove the Na+ ions. The as-prepared colloidal Nb2O5-nH2O was subsequently mixed with acetic solution of barium acetate and magnesium acetate according to the required molar proportions and followed by gelation. The ultrafine BMN powders were finally obtained after heat-treating the gel at 820℃for 1 h, and the as-sintered nanoceramics revealed a high relative density of 98.2%, and a high microwave Q-factor, of 10397 at 1.45GHz.

WT-1、AR和Ki-67在睾丸穿刺活检组织病理诊断中的应用

目的探讨睾丸穿刺活检标本中Sertoli细胞和生精细胞的特异性标志物。方法选取3例经病理诊断为前列腺腺癌行去势治疗的正常睾丸组织及15例临床诊断为无精症的睾丸穿刺活检组织,采用免疫组化En Vision两步法检测WT-1、AR和Ki-67的表达。结果免疫组化染色显示WT-1和AR在3例正常睾丸组织和15例睾丸穿刺活检组织曲细精管内的Sertoli细胞胞核均呈棕黄色,阳性率均为100%,生精细胞胞核的阳性率为0。15例睾丸活检组织中生精细胞的Ki-67阳性率为100%。结论 WT-1、AR和Ki-67可做为睾丸穿刺活检组织中Sertoli细胞和生精细胞的特异性标志物,为睾丸穿刺活检的病理诊断提供依据。

AR(1)型自相关过程的过程能力分析方法研究

传统上进行过程能力分析是基于过程观测数据统计独立这一基本假设,而实际工作中,过程数据并不是总能满足彼此统计独立的假设前提。介绍了过程观测值符合AR(1)型自相关模型时,计算过程能力指数的方法。用一个具体案例进行分析,结果表明:数据间存在正相关时,传统方法高估了过程能力指数,而利用笔者介绍的方法可以得到正确的结论。

低氧和运动经AR-IGF-1对骨骼肌蛋白质合成的作用

目的:探讨低氧、运动对骨骼肌蛋白质合成的作用。方法:2月龄雄性SD大鼠40只随机分为对照组、低氧组、运动组、低氧运动组,实验28天后取材测试。结果:(1)运动组AR蛋白表达量、AR活性与骨骼肌总蛋白质含量比对照组显著升高;(2)低氧组骨骼肌睾酮含量、AR蛋白表达量、IGF-1mRNA含量以及肌纤维横截面积较对照组显著降低;AR活性、骨骼肌蛋白质含量较对照组显著升高;(3)低氧运动组AR蛋白表达量、AR活性和骨骼肌总蛋白含量比运动组显著下降。结论:(1)运动后进行低氧暴露比单纯运动更能通过AR含量-AR活性水平抑制蛋白质合成;(2)低氧、运动或低氧运动通过睾酮调节AR数量及活性,最终影响骨骼肌蛋白含量;(3)低氧、运动或低氧运动可通过调节AR转录活性影响IGF-1mRNA表达,最终调节骨骼肌蛋白质合成。

AR(1)误差的非线性随机效应模型的参数估计

介绍一类具有AR(1)误差的非线性随机效应模型估计的EM算法,这种算法能一次性的估计出模型中的所有参数,并用随机模拟数据和实际例子说明了EM算法的有效性.

DJ-1下调PTEN诱导AR表达促进非激素依赖性乳腺癌转移的研究

目的探讨癌症和帕金森病相关蛋白DJ-1(parkinson disease protein 7,oncogene DJ-1,DJ-1)下调磷酸酯酶与张力蛋白同源物(phosphatase and tensin homolog,PTEN)诱导雄激素受体(androgen receptor,AR)表达促进非激素依赖性乳腺癌转移的机制。方法构建人绿色荧光蛋白表达载体pEGFP/DJ-1;Western blotting对比分析过表达DJ-1基因后MDA-MB-231细胞DJ-1、PTEN、雄激素受体(androgen receptor,AR)的表达;体外迁移与侵袭实验检测过表达DJ-1基因后对MDA-MB-231细胞的迁移与侵袭的影响。收集转移的非激素依赖性乳腺癌和未出现转移的非激素依赖性乳腺癌手术切除标本各40例,采用免疫组织化学检测DJ-1蛋白的表达。结果 Western blotting发现经过转染人DJ-1基因的绿色荧光蛋白表达载体pEGFP/DJ-1后,MDA-MB-231细胞DJ-1的表达水平升高,PTEN的表达水平下降,AR水平升高。体外迁移与侵袭实验发现,转染pEGFP/DJ-1促进SWO-38细胞的迁移和侵袭,与转染空白对照组比较,差异有统计学意义(P<0.05)。发生转移非激素依赖性乳腺癌组织中DJ-1阳性表达率(85.0%)明显高于未发生转移乳腺癌组织(55.0%)(P<0.05)。结论 DJ-1能促进非激素依赖性乳腺癌的迁移与侵袭。这可能与DJ-1抑制PTEN表达,提高AR水平从而促进肿瘤细胞的迁移侵袭能力有关。

三阴型乳腺癌中AR、SOX10、EGFR和PD-L1的表达及临床意义

目的探讨三阴型乳腺癌(triple negative breast cancer,TNBC)中AR、SOX10、EGFR及PD-L1的表达及与预后的关系。方法收集557例TNBC患者的临床病理资料,采用免疫组化法检测TNBC中AR、SOX10、EGFR及PD-L1的表达,并复习相关文献。结果557例TNBC中AR、SOX10和EGFR的阳性率分别为16.0%、63.6%和74.7%,AR阳性患者肿瘤直径较小且不易发生转移(P均<0.005),SOX10与EGFR表达与Ki-67增殖指数、组织学类型、分级相关(P均<0.005)。PD-L1阳性率为37.9%,PD-L1表达与肿瘤大小和Ki-67增殖指数相关(P均<0.005),且阳性者多不表达AR,多伴SOX10和EGFR阳性。PD-L1阴性者的无进展生存期(progression-free survival,PFS)比阳性者长,AR和SOX10的表达与患者生存期相关。结论TNBC中AR通常阴性,SOX10和EGFR阳性,PD-L1表达与AR、SOX10、EGFR相关,PD-L1、AR和SOX10的表达和TNBC的PFS相关,有望成为治疗TNBC的新靶点。

黄精皂苷对慢性应激抑郁大鼠海马5-HT1AR/cAMP/PKA信号通路的影响

目的探讨黄精皂苷(SRP)对慢性应激抑郁模型大鼠行为学的影响及部分机制。方法 SD大鼠60只随机分为6组:正常组、模型组、SRP(100、200、400 mg/kg)组和氟西汀(2 mg/kg)组。采用不同应激方法建立大鼠慢性应激抑郁模型,观察大鼠行为学指标变化,放射免疫法测定海马环腺苷酸(cAMP)含量,免疫组化法测定海马5-羟色胺受体(5-HT1AR)、蛋白激酶A(PKA)、反应元件结合蛋白(CREB)蛋白表达水平。结果应激刺激后,与正常组相比,模型组大鼠自主活动次数减少,体重降低,糖水消耗减少,处于抑郁状态。免疫组化结果显示,与正常组比较,模型组海马5-HT1AR、cAMP、PKA、CREB表达显著降低,SRP组5-HT1AR、cAMP、PKA、CREB表达显著上调(P<0.01)。结论 SRP对慢性应激抑郁大鼠的行为学有改善作用,可能是通过调节5-HT1AR/cAMP/PKA/CREB信号通路发挥抗抑郁作用。

加味四逆散对青少期应激结合成年后诱导抑郁大鼠行为学、海马CA1区5-HT1AR表达的影响

目的：观察青少期应激结合成年后诱导抑郁大鼠行为学、海马CA1区5-HT_（1A）R表达的变化及加味四逆散干预作用。方法：Wistar大鼠随机分成空白组、模型组、加味四逆散组、氟西汀组4组,每组33只;组内随机再分为青少期、成年期、成年后3小组,每小组11只。选取44、56、78 d3个时间点作为青少期、成年期、成年后3个阶段的取材时间点。采取慢性不可预知应激模型,第21-44天、第57-78天造模及给药; 44~55天正常喂养不予造模及给药。观察大鼠的一般情况与旷场实验情况,采用免疫组织化学染色法观察海马CA1区5-HT1A R阳性细胞的分布变化。结果：各时期模型组大鼠一般状况较差,加味四逆散组及氟西汀组有明显改善。旷场实验活跃度上,青少期与成年后模型组显著降低（P 〈0. 05）,加味四逆散组与氟西汀组活跃程度显著升高（P 〈0. 01、P 〈0. 05）。总区路程变化结果中,成年期模型组大鼠有显著降低（P 〈0. 05）,成年期及成年后加味四逆散组有显著提升（P 〈0. 05、P 〈0. 01）;且在成年后与氟西汀组对比有显著差异（P 〈0. 01）。各组大鼠海马CA1区5-HT_（1A）R平均光密度值组内比较,青少期与成年后组模型组有显著降低（P 〈0. 05,P 〈0. 01）;组间比较,成年后模型组、氟西汀组呈显著上升（P 〈0. 01,P 〈0. 05）;加味四逆散组有上升趋势。结论：在青少期受到慢性不可预知应激的大鼠可产生抑郁样行为,成年后继续施加刺激则会进一步加重抑郁状态,海马内5-HT1AR改变可能是加味四逆散改善应激大鼠抑郁样行为的重要通路。