Hippo signaling pathway in liver tissue homeostasis

肝脏是人体最重要的器官之一,乙肝等病毒性与酒精等非病毒性因素诱发的肝损伤引起肝脏功能衰竭、再生重塑障碍、肝癌等疾病是我国重大社会健康问题,因此,; 研究肝脏稳态的调控机制对肝病的预防和临床治疗至关重要。Hippo信号通路参与了哺乳动物多种细胞和器官的稳态调控。最近研究表明,Hippo信号通路; 在肝脏发育、肝细胞命运决定、肝脏再生和癌症发生发展等过程中都发挥了非常重要的作用。因此,Hippo信号通路可成为肝脏相关疾病的治疗提供了新的靶点; 。本文综述了Hippo信号通路与肝脏稳态调控的相关研究及最新进展,以期为研究肝脏发育和肝脏相关疾病的治疗提供新的思路和策略。Liver cancer and diseases have become the leading cause of deaths in; China. Liver diseases including liver failure and liver cancer can be; genetic or caused by a variety of factors that damage the liver, such as; viruses and alcohol overdose. However, the underlying mechanisms that; maintain liver homeostasis remain unclear. Recent studies show that the; Hippo signaling pathway plays a critical role in maintaining liver; tissue homeostasis. Dysregulation of the Hippo signaling pathway impairs; liver regeneration and remarkly enhances liver overgrowth and; tumorigenesis. In this review, we summarize recent progresses on the; roles and regulation mechanisms of the Hippo signaling pathway in liver; development and diseases.国家自然科学基金项

Influence of Particle Damper Configurations on the Dynamic Characteristic for Gear Transmission System

齿轮传动正朝着高速、重载和高精度方向发展,对其动态性能要求越来越高。颗粒阻尼通过颗粒间、颗粒与阻尼器壁间的非弹性碰撞和摩擦作用耗能,具有减振效果; 显著、耐高温、各向同性、对原结构改动小等优点。利用有限元法对齿轮进行了有预应力的模态分析,通过齿轮系统动力学分析,研究单双齿啮合激励对齿轮传动的; 影响;同时建立齿轮传动离心场中颗粒系统耗能模型,将离散元法计算颗粒系统耗能和试验测试对比,分析阻尼器配置对齿轮传动系统动特性的影响。结果显示,阻; 尼器配置方案是影响齿轮传动系统动特性的一个重要因素,在阻尼孔中填充一定数量的颗粒,当阻尼器总体积相同且齿轮结构静刚度相差不大时,阻尼器个数越多颗; 粒系统能耗越大;当阻尼孔直径相同时,阻尼孔个数越多颗粒系统总能耗越小;当阻尼孔个数相同时,阻尼孔直径越大颗粒系统能耗越小。通过试验和仿真对比验证; 了模型的正确性,为颗粒阻尼在离心场中的应用提供重要的理论依据。The gear transmission is advancing towards high speed, heavy load and; high precision. The requirements for the dynamic performance of gear; system are urgently proposed. The particle damping dissipates mechanical; system energy through inelastic collisions and friction between; particles. It is an effective and simple measure for vibration; reduction. It has many advantages, such as isotropy, high temperature; resistance and less modification to the original structure. This paper; has conducted the prestressed modal analysis of gear system by the; finite element method. Based on the dynamics analysis of gear system,; the effect of single tooth and double teeth meshing incentive on gear; transmission has been analyzed. The energy dissipation model of particle; damping for gear transmission in centrifugal field has been established.; By contrasting theoretical analysis and the test, the effect of damper; configuration on dynamic characteristic of gear transmission system is; analyzed. The results show that damper configuration is an important; factor of the dynamic characteristic for gear transmission system.; Filling a certain number of particles, when the gears static stiffness; are similar and the total dampers volume are equal, the more damping; hole, the greater the total energy loss. When the damping holes diameter; are the same, the more number of damping hole, the smaller the total; energy loss. When the damping hole number is the same, the bigger the; diameter, the less the total energy loss. Experimental results are; consistency with the theoretical analysis. These results can provide; guidelines for the application of particle damping in centrifugal field.国家自然科学基金; 福建省重点科技专项; 中央高校基本科研业务费专项资金; 福建省高端装备制造协同创新中心资助项

Separation of terpenes and oxygenated compounds from citrus oil by supercritical CO_2 extraction

以冷榨柑橘精油为原料,采用gC/MS对柑橘精油原料进行定性及定量分析,确定了柑橘精油中的7种萜烯类化合物成分作为分离考察对象。实验探讨了超临界萃取压力、萃取温度、萃取时间和CO2流量等因素对含氧化合物分离效果的影响。实验结果表明,萃取相中萜烯类化合物的回收率总体上随着萃取压力、温度、时间和CO2流量的增大而增大。当萃取压力为12MPA,萃取温度为45℃,萃取时间为4H以及CO2流量为1.0l/MIn时,分离效果最佳,其萃取相中萜烯类化合物的回收率高达90.03%。Supercritical CO2 extraction was employed to separate terpenes and oxygenated compounds from citrus oil.The raw oil,the extract,and the raffinate were qualitatively and quantitatively analyzed by GC/MS,respectively,with the terpenes being represented by seven typical compounds.The influences of several experimental factors including extration pressure,extraction temperature,extraction time and CO2 flow rate on the separation of the oxygenated compounds were studied.The results indicate that the recovery rate of terpenes in the extract generally increases with the increasing of extraction pressure,temperature,time and CO2 flow rate.The optimum conditions for extracting terpenes are as follows: pressure 12 MPa,temperature 45 ℃,extraction time 4 h,and CO2 flow rate 1.0 L/min.Under these optimum conditions,the recovery rate of terpenes in the extract is 90.03%.福建省新世纪人才支持项目(0000-X04157

Extraction of insecticidal toosendanin from meliaceae by supercritical CO_2

王宏涛(1968-),男,博士,副教授,主要研究方向为天然产物的提取分离等, E-mail: [email protected]。[中文文摘]苦楝素是楝科植物中制备植物源农药的主要杀虫成分。针对不同种源楝树的皮、叶及果实,采用溶剂浸提法提取筛选苦楝素含量较高的种源作为实验原料,采用乙醇提取,考察液固质量比、提取时间和提取次数等参数对苦楝素提取率的影响。当液固质量比为25∶1、提取时间为4 h、提取次数为3次时,苦楝素的提取率达18%。进一步采用超临界CO2萃取考察压力、温度、萃取时间、原料粒径和夹带剂等参数对苦楝素萃取率的影响,当温度为40℃、压力为20 MPa、时间为2.0 h、原料粒径为40目、夹带剂乙醇质量为CO2质量的12.5%时,苦楝素的萃取率达43.5%。在对萃取液结晶纯化中成功分离得到质量分数达98%的苦楝素。[英文文摘]Toosendanin is the main insecticidal component of meliaceae plants for producing botanical insecticides.The extraction of toosendanin from the parks,leaves and fruits of the various meliaceae plants was studied by using ethanol,and the part of the meliaceae plants with the maximal mass fraction of toosendanin was selected as experimental materials.The effects of the mass ratio of liquid to solid,extraction time,and extraction times on the yield of toosendan were investigated by using ethanol extraction method. The yield of toosendanin is up to 18% at them ass ratio of liquid to so lid of 25:1, extraction time of 4h and extract ing 3 times. The effects of pressure, temperature, extraction time, and the partic le size of materials and the dosage of mod if iers on the yield of toosendanin w ere investigated bym eans of supercritical CO2 extraction. The yield of toosendan in is up to 43.5% when ethanol is used as mod ifier with its mass 12.5% of CO2 mass at temperature 40,pressure 20 MPa,extraction time 2h and material particle size 40 mesh. The toosendanin crystal with mass fraction 98% was separated from the extracts by using crystalliza tionm ethod.福建省新世纪人才支持计划项

Expression of Fusion Protein of Parathyroid Hormone and Transferrin N-terminal Half-molecule in Pichia pastoris

利用重叠PCR技术将PTH(parathyroidhormone,甲状旁腺激素)基因与TFN(transferrinN_terminalhalf_molecule,转铁蛋白N端半分子)基因在体外融合,融合基因克隆至真核表达载体pPIC9中,转化毕赤酵母GS115。转化子经甲醇诱导后,融合蛋白得到了表达并分泌到发酵上清液中。经SPSepharoseFF阳离子交换层析、PhenylSepharoseFastFlow疏水层析纯化获得了纯度大于95%的PTH_TFN样品。Westernblot分析及腺苷酸环化酶实验证明融合蛋白中的PTH具有与抗PTH抗体结合能力及刺激腺苷酸环化酶的活性,铁饱和实验证明融合蛋白中的TFN和单独的TFN具有相同铁结合能力。因而TFN可望作为PTH的天然运输载体。The fused gene (PTH_TFN) of parathyroid hormone (PTH) gene and transferring N_terminal half_molecule (TFN) gene was amplified by multiple PCR and inserted into pPIC9 vector. The recombinant plasmid pPIC9_PTH_TFN was transformed into Pichia pastoris GS115 by PEG. After methanol induction, the target protein was expressed in fermentation supernatant at high level.The fused protein PTH_TFN with purity being higher than 95% was finally obtained after purification through two_step chromatography : SP Sepharose Fast Flow and Phenyl Sepharose Fast Flow.Western blot analysis and adenylate cyclase assay proved that the fused protein exhibited the bioactivity to stimulate cAMP synthesis and the ability to bind Fe ~3+ in the Fe ~3+ saturation study as the recombinant TFN did indicating that TFN could be used as the transcellar carrier of PTH.国家高技术研究与发展项目基金资助(No.2004AA215172)。~

Composite microparticles of ibuprofen/lipid generated by supercritical fluids from their melts

采用CO2及N2辅助的气体饱和溶液微粒形成技术制备布洛芬/肉豆蔻酸、布洛芬/三棕榈酸甘油酯复合微粒,考察它们的形态、颗粒分布以及复合微粒中药物的溶出情况。N2辅助过程制得的布洛芬(质量分数5%)/肉豆蔻酸复合微粒与用该过程得到的纯肉豆蔻酸大小及粒径分布大致相同,而CO2辅助过程制得的布洛芬/肉豆蔻酸复合微粒却要比该过程得到的纯肉豆蔻酸的粒径要大,分布也较宽;CO2及N2辅助形成的布洛芬/肉豆蔻酸复合微粒无缓释效果。用N2辅助制备得到的含20%布洛芬(质量分数)的复合微粒保持了三棕榈酸甘油酯微粒化后的颗粒形貌,粒径更大;用CO2辅助制备得到的含20%布洛芬的复合微粒其粒径比三棕榈酸甘油酯微粒化后的颗粒粒径要小,粒径分布更窄;布洛芬/三棕榈酸甘油酯复合微粒具有缓释效果,而且用N2辅助制备的布洛芬含量为5%的复合微粒比布洛芬含量为20%的复合微粒溶出慢。Using the CO2-assisted and N2-assisted atomization processes,ibuprofen/lipid composite microparticles can be produced;the lipid includes myristic acid(MA) and tripalmitin(TP).The ibuprofen(5% in mass ratie)/MA composite microparticles show similar particle sizes to that of pure MA from the N2-assisted process,while the composite microparticles have a large particle size and particle size distribution,compared to that of pure MA from the CO2-assisted process.The dissolution reveals no controlled release of ibuprofen for the ibuprofen/MA composite microparticles either from the N2-assisted process or from the CO2-assisted process.For the ibuprofen/TP system,the obtained composite microparticles containing 20%(in mass) ibuprofen show similar particle morphology,while has a larger particle size(PS) than that of the pure myristic acid particles in the case of N2-assisted process.Nevertheless,the microparticles from the CO2-assisted process has a small PS and narrow PSD,compared to that of the pure myristic acid particles.The obtained ibuprofen/TP composite microparticles containing 5% or 20% ibuprofen show an evidently controlled drug release.For example,the drug release is only 20% in 500 min for the ibuprofen/TP microparticles containing 20% ibuprofen,prepared by the CO2-assisted process.国家自然科学基金资助项目(20406015);; 福建省新世纪优秀人才支持计划;; 福建省自然科学基金资助项目(2007J0167

Preparation of Tripalmitin Micronization by Supercritical Fluids Technique

利用气体饱和溶液微粒形成技术实验装置,分别用超临界n2和超临界CO2制备三棕榈酸甘油酯微粒,探讨压力、温度以及喷嘴大小等工艺参数对微粒(粒径、粒径分布和形貌)的影响。结果表明:n2辅助过程得到的微粒基本为球状;预膨胀压力越高,粒径越小,粒径分布越窄;100μM喷嘴下制得的微粒粒径最小,且分布较均匀。CO2辅助过程得到的微粒部分为球状,部分为针状和片状;预膨胀压力越高,粒径越小,粒径分布越窄;喷嘴直径大小对微粒平均粒径及粒径分布影响不大;预膨胀温度升高,颗粒的粒径稍微增大。CO2辅助过程得到的微粒粒径比n2辅助过程得到的微粒粒径稍大,但两者的粒径分布相差不大。Generation of tripalmitin microparticles from its melts was investigated by using both supercritical CO2 and supercritical N2.The effects of various operating conditions,such as the pre-expansion pressure,pre-expansion temperature,and nozzle size on the particle morphology,particle size and particle size distribution(PSD) were investigated.Results showed that microspheres were obtained from the N2-assisted process,the particle size decreased and PSD narrowed with the increasing of the pre-expansion pressure,nozzle size showed no obvious effect on the microparticles,and pre-expansion temperature should be less than 72 ℃ to obtain solid particles.From the CO2-assited process,spherical,lamellate and needle-like particles were obtained,the particle size decreased,PSD narrowed with the increasing of the pre-expansion pressure,nozzle size showed no obvious effect on the particles and the pre-expansion temperature slightly increased the average size of particles.Particles' PSD from supercritical CO2 was close to that from supercritical N2

The Effects of Physical and Chemical Conditions on Forming Mycelial Pellet of Phanerochaete chrysosporium and Biosorption of Lead

[中文文摘]为了探讨影响微生物菌丝球生长的物理化学因素和控制菌丝球大小的规律以及微生物吸附重金属的效果，对黄孢展齿革菌（Ｐｈａｎｅｒｏｃｈａｅｔｅｃｈｒｙｓｏｓｐｏｒｉｕｍ）呈球状体生长和用此菌丝球吸附水溶液中的Ｐｂ２＋进行了研究．实验结果表明，在培养液ｐＨ值为４．５，孢子悬液浓度为１０６个／ｍｌ，表面活性剂吐温８０的浓度为０．１％，高碳氮和摇床转速为１５０ｒ／ｍｉｎ的条件下，于３９℃下培养３ｄ，形成直径在１．５—１．７ｍｍ范围内的菌丝球，光滑均匀，具有一定机械强度，对Ｐｂ２＋的吸附能力最强．用０．２ｍｏｌ／Ｌ的ＮａＯＨ溶液处理该菌丝球，对２５ｍｇ／Ｌ的铅溶液的吸附率达到了９５％以上，表明用该菌丝球吸附水溶液中的Ｐｂ２＋是可行的．[英文文摘]The research on the growth of Phanerochaete chrysosporium in the form of pellet was made in this paper to examine the effects of physical and chemical conditions on the formation of mycelial pellets.The experimental results showed that the microorganism pellets of smooth surface,even size(diameter)and good mechanical properties could be obtained at the follwoing culture conditions:pH4 5,10 6 spores/ml in inoculum,01% Tween 80 in medium,high C/N and on the shaker of 150r/min for 3d.Using P. ch ry sosp orium m ycelial pellet s in the bio sorption of Pb2+ from aqueou s solution, the up take reached the maximum when the diam eter of pellet w as in the range of 115—117mm. W hen the pellet s w ere p ret reated by bo iling in 012mo löL N aOH fo r 40m in, the Pb2+ up take w as far h igher than the pellets without pret reatm en t, and the removal efficiency could reach above 95%. The research results showed that the removal of Pb2+ from aqueous solution by P. chrysosp oriumm ycelial pellets was practical.国家教委留学回国人员科研启动基

Separation and identification of auraptene from grapefruit peel oil

橙油素是广泛存在于柑橘类果实中的天然抗癌活性成分。选用SP70大孔吸附树脂分离纯化葡萄柚精油中的橙油素,该树脂对于橙油素的吸附容量和解吸率分别达到14.53 Mg/g和83.32%,并成功地从树脂床层的洗脱液中结晶分离出橙油素晶体。对所得晶体分别采用差示扫描量热仪(dSC)、紫外吸收光谱(uV)、红外吸收光谱(Ir)、电喷雾质谱(ESI-MS)进行定性分析,分析结果与橙油素标准品相符合。进一步采用高效液相色谱(HPlC)对所得晶体进行定量分析,结果表明所得晶体中橙油素的质量分数可达85%。Auraptene exists widely in the peels and juice sacs of citrus species and is reported to be an effective inhibitor of chemical carcinogenesis in some rodent models.The separation and purification of auraptene from the grapefruit peel oil was performed by SP70 macroporous resin adsorption.The amount adsorbed and the recovery of auraptene were 14.53 mg/g and 83.32% respectively.Auraptene was crystallized out from the concentrated eluate of macroporous resin bed successfully.Differential scanning calorimetric(DSC),ultraviolet spectrum(UV),infrared spectroscopy(IR) and electrospray ionization mass spectroscopy(ESI-MS) were all used to analyze the obtained crystals qualitatively.The analytical results are in accordance with that of auraptene standard.Furthermore,high performance liquid chromatography(HPLC) was utilized to quantify auraptene of the crystals obtained.The mass fraction of auraptene in the obtained crystals can reach 85%.福建省新世纪人才支持项目(0000-X04157

Mechanism of geniposide in improving free fatty acid metabolism in rats with non-alcoholic fatty liver disease

观察栀子苷改善非酒精性脂肪性肝病的效果,从游离脂肪酸探讨栀子苷调节非酒精性脂肪性肝病的作用机制。健康雄性Wistar大鼠40只,随机分为4组:正常组、模型组、栀子苷组和血脂康组,每组大鼠10只,正常组大鼠给予正常大鼠饲料喂养,其余3组大鼠均采用高脂饲料喂养以诱导非酒精性脂肪性肝病,造模时间为8周,从第5周起至第8周末,栀子苷组和血脂康组分别灌服相应的药物。记录大鼠体重、肝湿重、脂肪质量;用相应方法检测肝组织TG,FFA,FAS,AMPK,ACCase及Malonyl-Co A含量,血清CHO,LDL-C的含量,血清AST,ALT的活性;观察肝脏组织肉眼及病理变化(HE染色法)。结果显示,与正常组相比,模型组大鼠的体重;肝湿重;脂肪重;血清CHO,LDL-C,ALT,AST;肝组织TG,FFA,FAS,ACCase及Malonyl-Co A含量皆显著升高(P<0.01);肝组织AMPK活性显著降低(P<0.01),肝组织肉眼外观及病理切片脂肪变性明显,并出现炎症损伤;与模型组相比,栀子苷组大鼠体重、脂肪质量、肝组织FFA含量、血清ALT,AST活性均显著降低(P<0.01),肝湿重,肝组织TG,FAS,ACCase及Malonyl-Co A含量明显降低(P<0.05),肝组织AMPK活性明显增多(P<0.05),肝脏肉眼外观及病理学表现均有所改善;与模型组相比,血脂康组大鼠的肝湿重、脂肪质量、肝组织TG,FFA和血清LDL-C水平明显降低(P<0.05);与血脂康组相比,栀子苷组大鼠的体重、脂肪质量、肝组织FFA含量均显著降低(P<0.01),其他方面无明显差异。结果表明,栀子苷具有显著的改善高脂饮食诱导的大鼠非酒精性脂肪性肝病的药理效应;其改善大鼠非酒精性脂肪性肝病的游离脂肪酸代谢是通过调节"AMPK-ACCase-Malonyl-Co A-FFA"轴来实现的。To observe the effect of geniposide on non-alcoholic fatty liver disease( NAFLD),and discuss the mechanism of geniposide for NAFLD from the aspect of free fatty acid,forty healthy Wistar male rats were randomly divided into normal group,model group,geniposide and Xuezhikang group. The rats in normal group were fed with normal diets,and the rats in other 3 groups were given with high-fat diet for 8 weeks to induce the NAFLD models. From the week 5 to end of week 8,the rats in geniposide and Xuezhikang group were intervened with corresponding medicines. The body weight,liver wet weight,and fat weight of the rats were recorded.Visual and pathological changes in hepatic tissues were observed with HE staining. The contents of TG,FFA,FAS,AMPK,ACCase and Malonyl-Co A in hepatic tissue,contents of CHO and LDL-C in serum and activities of AST and ALT in serum were detected by using corresponding methods. The results showed that the body weight,liver wet weight,and fat weight of the rats,CHO,LDL-C,ALT and AST levels in serum,TG,FFA,FAS,ACCase and Malonyl-Co A levels in hepatic tissues of the rats in model group were significantly higher than those in normal group( P < 0. 01),while AMPK activity was significantly lower than that of the normal group( P < 0. 01),with obvious visual and pathological steatosis in hepatic tissues,and inflammatory injury occurred in model group. Compared with the model group,body weight of the rat,fat weight,levels of FFA in hepatic tissues,ALT and AST activities in serum,liver wet weight,TG,FAS,ACCase and Malonyl-Co A levels were significantly decreased in geniposide group( P < 0. 01),while the AMPK activity in hepatic tissues was significantly increased( P < 0. 05),with improvement in visual and pathological performance.Compared with the model group,liver wet weight,fat weight,TG and FFA levels in hepatic tissues,and LDL-C level in serum were significantly decreased in Xuezhikang group( P < 0. 05). Compared with Xuezhikang group,the body weight of rat,fat weight and FFA level in hepatic tissues were significantly lower in geniposide group( P < 0. 01),but with no significant difference in other aspects. These findings indicated that geniposide was highly effective in improving the pharmacological effect of NAFLD induced by highfat diet,and the mechanism was achieved through AMPK-ACCase-Malonyl-Co A-FFA axis.国家自然科学基金项目(81274155;81503529);; 福建省自然科学基金项目(2014J01374);; 福建省高等学校新世纪人才计划项目;; 厦门市科技计划项目(3502Z20134020);; 福建省中医药科研项目(WZPW201308