This paper examines the effect of the microstructure and electrical conductivity(EC)on the swelling ratio and pressure in red-bed mudstone sampled from arid areas in the Xining region in the northeastern Tibetan Plate...This paper examines the effect of the microstructure and electrical conductivity(EC)on the swelling ratio and pressure in red-bed mudstone sampled from arid areas in the Xining region in the northeastern Tibetan Plateau.A series of laboratory tests,including swelling experiments,X-ray diffraction(XRD),and scanning electron microscope(SEM),was carried out for mechanical and microstructural analysis.The coupled influence of the EC and microstructural parameters on the expansion ratio and pressure was investigated,and the weight coefficients were discussed by the entropy weight method.The results revealed an increasing exponential trend in EC,and the maximum swelling speed occurred at an EC of approximately 10 μS/cm.In addition,a method for predicting the expansion potential is proposed based on the microstructure,and its reliability is verified by comparing with swelling experimental results.In addition,according to the image analysis results,the ranges of the change in the clay minerals content(CMC),the fractal dimension(FD),the average diameter(AD)of pores,and the plane porosity(PP)are 23.75%-53%,1.08-1.17,7.53-22.45 mm,and 0.62%-1.25%,respectively.Moreover,mudstone swelling is negatively correlated with the plane porosity,fractal dimension and average diameter and is linearly correlated with the clay mineral content.Furthermore,the weight values prove that the microstructural characteristics,including FD,AD,and PP,are the main factors influencing the expansion properties of red-bed mudstones in the Xining region.Based on the combination of macro and micro-analyses,a quantitative analysis of the swelling process of mudstones can provide a better reference for understanding the mechanism of expansion behavior.展开更多
目的通过对重组结核杆菌融合蛋白(EC)[该制品名称是国家药典委员会确定的药品中文通用名称,"EC"为重组融合蛋白"结核分枝杆菌早期分泌性抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)"](简称"EC")的免疫特性...目的通过对重组结核杆菌融合蛋白(EC)[该制品名称是国家药典委员会确定的药品中文通用名称,"EC"为重组融合蛋白"结核分枝杆菌早期分泌性抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)"](简称"EC")的免疫特性和临床前安全性研究,探讨其临床应用前景。方法(1)免疫特性研究:取6只雌性豚鼠,使用结核分枝杆菌H37Ra活菌菌液致敏,5周后,皮内注射2.5μg/ml EC原液0.2ml;取4只雌性豚鼠,使用卡介菌活菌菌液致敏,5周后,皮内注射20μg/ml EC原液0.2ml;观察注射部位平均硬结或红晕反应直径[(纵径+横径)/2],≥5mm判为阳性,<5mm判为阴性。(2)急性毒性试验:取80只ICR[(美国)Institute of Cancer Research]小鼠,分为单次肌内和皮内注射组,每组40只,雌雄各半;每组再分为4组,每组10只,雌雄各半。高剂量组(注射EC53.61μg/0.1ml)、低剂量组(注射EC 0.2μg/0.1ml)、溶剂对照组(注射EC稀释液0.1ml)、空白对照组(不给予任何受试物),观察小鼠的外观、运动功能、体质量、各脏器和药物注射部位皮肤等是否有异常。(3)豚鼠全身主动过敏试验:取豚鼠24只,分为4组,每组6只,雌雄各半,各组豚鼠分别隔日腹腔注射高剂量(5μg/kg)EC、低剂量(0.5μg/kg)EC、牛血清白蛋白(60mg)和0.9%NaCl(质量分数为0.9%的NaCl溶液)注射液(2ml),连续3次。致敏结束,末次致敏后第12天静脉快速注射2倍致敏剂量对以上相应的各组致敏豚鼠进行激发。致敏期间,每天观察豚鼠的症状,并于初次和最后一次致敏及激发当日测定每只豚鼠的体质量。(4)皮内刺激试验:取6只新西兰兔,单次皮内注射EC 10μg(0.2ml)/点,每侧5个点,观察皮内注射后的刺激反应情况。结果(1)免疫特性研究结果:EC原液对卡介菌活菌菌液致敏的4只豚鼠的皮肤试验,阳性为0只;EC原液对结核分枝杆菌H37Ra活菌菌液致敏的6只豚鼠的皮肤试验,阳性为6只。(2)急性毒性试验结果:所有小鼠未出现明显的急性中毒反应和显示急性中毒靶器官。小鼠皮内注射EC前、注射EC后1d、3d、5d、7d、8d、10d、12d、14d高剂量组、低剂量组小鼠平均体质量分别为(20.6±1.3)g^(24.9±2.1)g、(20.5±1.6)g^(26.0±3.1)g;注射后不同观察时间各组平均体质量与空白对照组[(21.0±1.1)g^(25.3±2.3)g]比较差异均无统计学意义(t值分别为0.571~0.392,0.695~0.615;P值分别为0.575~0.700,0.496~0.546);小鼠肌内注射EC前、注射EC后1d、3d、5d、7d、8d、10d、12d、14d高剂量组、低剂量组小鼠平均体质量分别为(21.0±1.5)g^(26.2±1.9)g、(20.5±2.1)g^(25.8±3.8)g;注射后不同观察时间各组平均体质量与空白对照组[(21.2±1.7)g^(25.8±3.1)g]比较差异均无统计学意义(t值分别为0.360~0.318,0.900~0.006;P值分别为0.723~0.754,0.380~0.995)。(3)豚鼠全身主动过敏试验结果:豚鼠无过敏反应。高剂量组、低剂量组豚鼠首次致敏、末次致敏、激发的平均体质量分别为(327.5±24.3)g、(347.2±32.7)g、(402.2±34.9)g;(331.3±26.7)g、(346.2±32.0)g、(411.3±38.9)g,与相应观察时间注射0.9%NaCl的阴性对照组[(329.5±27.4)g、(348.3±27.0)g、(399.4±25.4)g]比较,差异均无统计学意义(t值分别为0.328、0.181、0.284,0.474、0.366、0.875;P值分别为0.757、0.864、0.788,0.656、0.730、0.422)。(4)兔皮内刺激试验结果:单次皮内注射10μg(0.2ml)/点EC,无明显刺激反应。结论EC能够鉴别结核感染与卡介苗免疫,临床前动物试验安全性好,有望应用于人群结核感染的诊断与鉴别诊断。展开更多
21世纪互联网技术在促进电子商务迅猛发展的同时,在供应链管理中的应用也越来越普遍。Bto B是电子商务的主体,因此,B to B模式的电子商务面向企业整个供应链管理,并带来供应链的变革,使企业降低交易成本、缩短订货周期,改善信息管理和...21世纪互联网技术在促进电子商务迅猛发展的同时,在供应链管理中的应用也越来越普遍。Bto B是电子商务的主体,因此,B to B模式的电子商务面向企业整个供应链管理,并带来供应链的变革,使企业降低交易成本、缩短订货周期,改善信息管理和提高决策水平,从质量、成本和响应速度三方面改进企业经营,增强企业竞争能力。在当今信息爆炸的时代,企业能不能以及如何采用先进的IT,将直接关系到企业的生存与发展,特别是如何在采用SCM的同时应用先进的IT,更是企业以及理论需要结合起来共同探索的供应链管理之路。展开更多
Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we i...Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.展开更多
基金the funding support from National Natural Science Foundation of China(Grant No.42077271)Sichuan Science and Technology Program,China(Grant No.2023YFS0364)Chengdu Science and Technology Program(Grant No.2022-YF05-00340-SN).
文摘This paper examines the effect of the microstructure and electrical conductivity(EC)on the swelling ratio and pressure in red-bed mudstone sampled from arid areas in the Xining region in the northeastern Tibetan Plateau.A series of laboratory tests,including swelling experiments,X-ray diffraction(XRD),and scanning electron microscope(SEM),was carried out for mechanical and microstructural analysis.The coupled influence of the EC and microstructural parameters on the expansion ratio and pressure was investigated,and the weight coefficients were discussed by the entropy weight method.The results revealed an increasing exponential trend in EC,and the maximum swelling speed occurred at an EC of approximately 10 μS/cm.In addition,a method for predicting the expansion potential is proposed based on the microstructure,and its reliability is verified by comparing with swelling experimental results.In addition,according to the image analysis results,the ranges of the change in the clay minerals content(CMC),the fractal dimension(FD),the average diameter(AD)of pores,and the plane porosity(PP)are 23.75%-53%,1.08-1.17,7.53-22.45 mm,and 0.62%-1.25%,respectively.Moreover,mudstone swelling is negatively correlated with the plane porosity,fractal dimension and average diameter and is linearly correlated with the clay mineral content.Furthermore,the weight values prove that the microstructural characteristics,including FD,AD,and PP,are the main factors influencing the expansion properties of red-bed mudstones in the Xining region.Based on the combination of macro and micro-analyses,a quantitative analysis of the swelling process of mudstones can provide a better reference for understanding the mechanism of expansion behavior.
文摘目的通过对重组结核杆菌融合蛋白(EC)[该制品名称是国家药典委员会确定的药品中文通用名称,"EC"为重组融合蛋白"结核分枝杆菌早期分泌性抗原靶6(ESAT-6)和培养滤液蛋白10(CFP-10)"](简称"EC")的免疫特性和临床前安全性研究,探讨其临床应用前景。方法(1)免疫特性研究:取6只雌性豚鼠,使用结核分枝杆菌H37Ra活菌菌液致敏,5周后,皮内注射2.5μg/ml EC原液0.2ml;取4只雌性豚鼠,使用卡介菌活菌菌液致敏,5周后,皮内注射20μg/ml EC原液0.2ml;观察注射部位平均硬结或红晕反应直径[(纵径+横径)/2],≥5mm判为阳性,<5mm判为阴性。(2)急性毒性试验:取80只ICR[(美国)Institute of Cancer Research]小鼠,分为单次肌内和皮内注射组,每组40只,雌雄各半;每组再分为4组,每组10只,雌雄各半。高剂量组(注射EC53.61μg/0.1ml)、低剂量组(注射EC 0.2μg/0.1ml)、溶剂对照组(注射EC稀释液0.1ml)、空白对照组(不给予任何受试物),观察小鼠的外观、运动功能、体质量、各脏器和药物注射部位皮肤等是否有异常。(3)豚鼠全身主动过敏试验:取豚鼠24只,分为4组,每组6只,雌雄各半,各组豚鼠分别隔日腹腔注射高剂量(5μg/kg)EC、低剂量(0.5μg/kg)EC、牛血清白蛋白(60mg)和0.9%NaCl(质量分数为0.9%的NaCl溶液)注射液(2ml),连续3次。致敏结束,末次致敏后第12天静脉快速注射2倍致敏剂量对以上相应的各组致敏豚鼠进行激发。致敏期间,每天观察豚鼠的症状,并于初次和最后一次致敏及激发当日测定每只豚鼠的体质量。(4)皮内刺激试验:取6只新西兰兔,单次皮内注射EC 10μg(0.2ml)/点,每侧5个点,观察皮内注射后的刺激反应情况。结果(1)免疫特性研究结果:EC原液对卡介菌活菌菌液致敏的4只豚鼠的皮肤试验,阳性为0只;EC原液对结核分枝杆菌H37Ra活菌菌液致敏的6只豚鼠的皮肤试验,阳性为6只。(2)急性毒性试验结果:所有小鼠未出现明显的急性中毒反应和显示急性中毒靶器官。小鼠皮内注射EC前、注射EC后1d、3d、5d、7d、8d、10d、12d、14d高剂量组、低剂量组小鼠平均体质量分别为(20.6±1.3)g^(24.9±2.1)g、(20.5±1.6)g^(26.0±3.1)g;注射后不同观察时间各组平均体质量与空白对照组[(21.0±1.1)g^(25.3±2.3)g]比较差异均无统计学意义(t值分别为0.571~0.392,0.695~0.615;P值分别为0.575~0.700,0.496~0.546);小鼠肌内注射EC前、注射EC后1d、3d、5d、7d、8d、10d、12d、14d高剂量组、低剂量组小鼠平均体质量分别为(21.0±1.5)g^(26.2±1.9)g、(20.5±2.1)g^(25.8±3.8)g;注射后不同观察时间各组平均体质量与空白对照组[(21.2±1.7)g^(25.8±3.1)g]比较差异均无统计学意义(t值分别为0.360~0.318,0.900~0.006;P值分别为0.723~0.754,0.380~0.995)。(3)豚鼠全身主动过敏试验结果:豚鼠无过敏反应。高剂量组、低剂量组豚鼠首次致敏、末次致敏、激发的平均体质量分别为(327.5±24.3)g、(347.2±32.7)g、(402.2±34.9)g;(331.3±26.7)g、(346.2±32.0)g、(411.3±38.9)g,与相应观察时间注射0.9%NaCl的阴性对照组[(329.5±27.4)g、(348.3±27.0)g、(399.4±25.4)g]比较,差异均无统计学意义(t值分别为0.328、0.181、0.284,0.474、0.366、0.875;P值分别为0.757、0.864、0.788,0.656、0.730、0.422)。(4)兔皮内刺激试验结果:单次皮内注射10μg(0.2ml)/点EC,无明显刺激反应。结论EC能够鉴别结核感染与卡介苗免疫,临床前动物试验安全性好,有望应用于人群结核感染的诊断与鉴别诊断。
文摘21世纪互联网技术在促进电子商务迅猛发展的同时,在供应链管理中的应用也越来越普遍。Bto B是电子商务的主体,因此,B to B模式的电子商务面向企业整个供应链管理,并带来供应链的变革,使企业降低交易成本、缩短订货周期,改善信息管理和提高决策水平,从质量、成本和响应速度三方面改进企业经营,增强企业竞争能力。在当今信息爆炸的时代,企业能不能以及如何采用先进的IT,将直接关系到企业的生存与发展,特别是如何在采用SCM的同时应用先进的IT,更是企业以及理论需要结合起来共同探索的供应链管理之路。
基金supported by grants from the National Natural Science Foundation of China (Grant No. 30772316 and 81572568)
文摘Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.
