Rho/ROCK信号通路是细胞内一条重要的信号转导通路,其中Rho蛋白和ROCK(Rho-associated protein kinase)是其关键组成部分。Rho蛋白是一类小型GTP酶,参与调控细胞骨架的关键过程。ROCK作为Rho蛋白的下游效应蛋白激酶,能够调节细胞的形态...Rho/ROCK信号通路是细胞内一条重要的信号转导通路,其中Rho蛋白和ROCK(Rho-associated protein kinase)是其关键组成部分。Rho蛋白是一类小型GTP酶,参与调控细胞骨架的关键过程。ROCK作为Rho蛋白的下游效应蛋白激酶,能够调节细胞的形态、迁移和增殖等多种生物学过程。近年来,Rho/ROCK信号通路在各种病毒复制中的作用逐渐受到重视,研究发现一些病毒通过Rho/ROCK通路干扰细胞的收缩、黏附和迁移,参与调节病毒感染引发的免疫反应,并影响细胞间的紧密连接。现主要综述Rho/ROCK信号通路及其关键信号分子Rho和ROCK的活化与调控在病毒复制及细胞间紧密连接蛋白研究中的进展。展开更多
目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ra...目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。展开更多
Rockbursts, which mainly affect mining roadways, are dynamic disasters arising from the surrounding rock under high stress. Understanding the interaction between supports and the surrounding rock is necessary for effe...Rockbursts, which mainly affect mining roadways, are dynamic disasters arising from the surrounding rock under high stress. Understanding the interaction between supports and the surrounding rock is necessary for effective rockburst control. In this study, the squeezing behavior of the surrounding rock is analyzed in rockburst roadways, and a mechanical model of rockbursts is established considering the dynamic support stress, thus deriving formulas and providing characteristic curves for describing the interaction between the support and surrounding rock. Design principles and parameters of supports for rockburst control are proposed. The results show that only when the geostress magnitude exceeds a critical value can it drive the formation of rockburst conditions. The main factors influencing the convergence response and rockburst occurrence around roadways are geostress, rock brittleness, uniaxial compressive strength, and roadway excavation size. Roadway support devices can play a role in controlling rockburst by suppressing the squeezing evolution of the surrounding rock towards instability points of rockburst. Further, the higher the strength and the longer the impact stroke of support devices with constant resistance, the more easily multiple balance points can be formed with the surrounding rock to control rockburst occurrence. Supports with long impact stroke allow adaptation to varying geostress levels around the roadway, aiding in rockburst control. The results offer a quantitative method for designing support systems for rockburst-prone roadways. The design criterion of supports is determined by the intersection between the convergence curve of the surrounding rock and the squeezing deformation curve of the support devices.展开更多
Rock fragmentation is an important indicator for assessing the quality of blasting operations.However,accurate prediction of rock fragmentation after blasting is challenging due to the complicated blasting parameters ...Rock fragmentation is an important indicator for assessing the quality of blasting operations.However,accurate prediction of rock fragmentation after blasting is challenging due to the complicated blasting parameters and rock properties.For this reason,optimized by the Bayesian optimization algorithm(BOA),four hybrid machine learning models,including random forest,adaptive boosting,gradient boosting,and extremely randomized trees,were developed in this study.A total of 102 data sets with seven input parameters(spacing-to-burden ratio,hole depth-to-burden ratio,burden-to-hole diameter ratio,stemming length-to-burden ratio,powder factor,in situ block size,and elastic modulus)and one output parameter(rock fragment mean size,X_(50))were adopted to train and validate the predictive models.The root mean square error(RMSE),the mean absolute error(MAE),and the coefficient of determination(R^(2))were used as the evaluation metrics.The evaluation results demonstrated that the hybrid models showed superior performance than the standalone models.The hybrid model consisting of gradient boosting and BOA(GBoost-BOA)achieved the best prediction results compared with the other hybrid models,with the highest R^(2)value of 0.96 and the smallest values of RMSE and MAE of 0.03 and 0.02,respectively.Furthermore,sensitivity analysis was carried out to study the effects of input variables on rock fragmentation.In situ block size(XB),elastic modulus(E),and stemming length-to-burden ratio(T/B)were set as the main influencing factors.The proposed hybrid model provided a reliable prediction result and thus could be considered an alternative approach for rock fragment prediction in mining engineering.展开更多
Backfill is often employed in mining operations for ground support,with its positive impact on ground stability acknowledged in many underground mines.However,existing studies have predominantly focused only on the st...Backfill is often employed in mining operations for ground support,with its positive impact on ground stability acknowledged in many underground mines.However,existing studies have predominantly focused only on the stress development within the backfill material,leaving the influence of stope backfilling on stress distribution in surrounding rock mass and ground stability largely unexplored.Therefore,this paper presents numerical models in FLAC3D to investigate,for the first time,the time-dependent stress redistribution around a vertical backfilled stope and its implications on ground stability,considering the creep of surrounding rock mass.Using the Soft Soil constitutive model,the compressibility of backfill under large pressure was captured.It is found that the creep deformation of rock mass exercises compression on backfill and results in a less void ratio and increased modulus for fill material.The compacted backfill conversely influenced the stress distribution and ground stability of rock mass which was a combined effect of wall creep and compressibility of backfill.With the increase of time or/and creep deformation,the minimum principal stress in the rocks surrounding the backfilled stope increased towards the pre-mining stress state,while the deviatoric stress reduces leading to an increased factor of safety and improved ground stability.This improvement effect of backfill on ground stability increased with the increase of mine depth and stope height,while it is also more pronounced for the narrow stope,the backfill with a smaller compression index,and the soft rocks with a smaller viscosity coefficient.Furthermore,the results emphasize the importance of minimizing empty time and backfilling extracted stope as soon as possible for ground control.Reduction of filling gap height enhances the local stability around the roof of stope.展开更多
文摘Rho/ROCK信号通路是细胞内一条重要的信号转导通路,其中Rho蛋白和ROCK(Rho-associated protein kinase)是其关键组成部分。Rho蛋白是一类小型GTP酶,参与调控细胞骨架的关键过程。ROCK作为Rho蛋白的下游效应蛋白激酶,能够调节细胞的形态、迁移和增殖等多种生物学过程。近年来,Rho/ROCK信号通路在各种病毒复制中的作用逐渐受到重视,研究发现一些病毒通过Rho/ROCK通路干扰细胞的收缩、黏附和迁移,参与调节病毒感染引发的免疫反应,并影响细胞间的紧密连接。现主要综述Rho/ROCK信号通路及其关键信号分子Rho和ROCK的活化与调控在病毒复制及细胞间紧密连接蛋白研究中的进展。
文摘目的探究毛兰素(Erianin)在特应性皮炎(atopic dermatitis,AD)中的作用及其在高迁移率族蛋白1(high mobility group box-1,HMGB1)/晚期糖基化终末产物受体(receptor for advanced glycation end products,RAGE)-Ras同源基因家族成员A(Ras homolog gene family member A,RhoA)/Rho关联含卷曲螺旋结合蛋白激酶1(recombinant Rho associated coiled coil containing protein kinase 1,ROCK1)信号通路中的调控机制。方法1-氯-2,4-二硝基苯(1-Chloro-2,4-dinitrobenzene,DNCB)诱导BALB/c小鼠作为AD的模型,测量小鼠的皮肤厚度、脾和淋巴结的重量。甲苯胺蓝和HE染色检测小鼠的背部皮肤和耳朵的病理改变;ELISA检测炎症因子水平;肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)刺激HaCaT细胞建立AD体外模型;采用流式细胞术检测细胞活性氧(reactive oxygen species,ROS);免疫荧光法检测线粒体活性氧(mitochondrion reactive oxygen species,mtROS);TUNEL检测细胞凋亡情况;免疫蛋白印迹法检测HMGB1、RAGE、RhoA、ROCK1蛋白表达情况。结果在体内实验中毛兰素抑制皮肤厚度的增加,减轻脾和淋巴结重量,改善炎症细胞的浸润和肥大细胞脱颗粒,降低炎症因子水平(P<0.05)。在体外实验中,毛兰素减少TNF-α诱导的HaCaT细胞ROS、mtROS的产生(P<0.01)。毛兰素治疗后HMGB1、RAGE、RhoA及ROCK1的蛋白表达量下降(P<0.01);使用RAGE特异性阻断剂(TFA)处理r-HMGB1刺激的HaCaT细胞后,HMGB1的表达没有发生变化,RAGE、RhoA及ROCK1表达减少(P<0.01);在Rho激酶抑制剂Y-27632+r-HMGB1组中,除RAGE的表达没有降低,其余结果与TFA+r-HMGB1组相近。结论毛兰素可能通过调节HMGB1/RAGE-RhoA/ROCK1信号通路缓解特应性皮炎。
基金funded by the National Natural Science Foundation of China (No. 52304133)the National Key R&D Program of China (No. 2022YFC3004605)the Department of Science and Technology of Liaoning Province (No. 2023-BS-083)。
文摘Rockbursts, which mainly affect mining roadways, are dynamic disasters arising from the surrounding rock under high stress. Understanding the interaction between supports and the surrounding rock is necessary for effective rockburst control. In this study, the squeezing behavior of the surrounding rock is analyzed in rockburst roadways, and a mechanical model of rockbursts is established considering the dynamic support stress, thus deriving formulas and providing characteristic curves for describing the interaction between the support and surrounding rock. Design principles and parameters of supports for rockburst control are proposed. The results show that only when the geostress magnitude exceeds a critical value can it drive the formation of rockburst conditions. The main factors influencing the convergence response and rockburst occurrence around roadways are geostress, rock brittleness, uniaxial compressive strength, and roadway excavation size. Roadway support devices can play a role in controlling rockburst by suppressing the squeezing evolution of the surrounding rock towards instability points of rockburst. Further, the higher the strength and the longer the impact stroke of support devices with constant resistance, the more easily multiple balance points can be formed with the surrounding rock to control rockburst occurrence. Supports with long impact stroke allow adaptation to varying geostress levels around the roadway, aiding in rockburst control. The results offer a quantitative method for designing support systems for rockburst-prone roadways. The design criterion of supports is determined by the intersection between the convergence curve of the surrounding rock and the squeezing deformation curve of the support devices.
基金National Natural Science Foundation of China,Grant/Award Number:52374153。
文摘Rock fragmentation is an important indicator for assessing the quality of blasting operations.However,accurate prediction of rock fragmentation after blasting is challenging due to the complicated blasting parameters and rock properties.For this reason,optimized by the Bayesian optimization algorithm(BOA),four hybrid machine learning models,including random forest,adaptive boosting,gradient boosting,and extremely randomized trees,were developed in this study.A total of 102 data sets with seven input parameters(spacing-to-burden ratio,hole depth-to-burden ratio,burden-to-hole diameter ratio,stemming length-to-burden ratio,powder factor,in situ block size,and elastic modulus)and one output parameter(rock fragment mean size,X_(50))were adopted to train and validate the predictive models.The root mean square error(RMSE),the mean absolute error(MAE),and the coefficient of determination(R^(2))were used as the evaluation metrics.The evaluation results demonstrated that the hybrid models showed superior performance than the standalone models.The hybrid model consisting of gradient boosting and BOA(GBoost-BOA)achieved the best prediction results compared with the other hybrid models,with the highest R^(2)value of 0.96 and the smallest values of RMSE and MAE of 0.03 and 0.02,respectively.Furthermore,sensitivity analysis was carried out to study the effects of input variables on rock fragmentation.In situ block size(XB),elastic modulus(E),and stemming length-to-burden ratio(T/B)were set as the main influencing factors.The proposed hybrid model provided a reliable prediction result and thus could be considered an alternative approach for rock fragment prediction in mining engineering.
基金the funding support from the National Natural Science Foundation of China(Grant Nos.52304101 and 52004206)the China Postdoctoral Science Foundation(Grant No.2023MD734215)。
文摘Backfill is often employed in mining operations for ground support,with its positive impact on ground stability acknowledged in many underground mines.However,existing studies have predominantly focused only on the stress development within the backfill material,leaving the influence of stope backfilling on stress distribution in surrounding rock mass and ground stability largely unexplored.Therefore,this paper presents numerical models in FLAC3D to investigate,for the first time,the time-dependent stress redistribution around a vertical backfilled stope and its implications on ground stability,considering the creep of surrounding rock mass.Using the Soft Soil constitutive model,the compressibility of backfill under large pressure was captured.It is found that the creep deformation of rock mass exercises compression on backfill and results in a less void ratio and increased modulus for fill material.The compacted backfill conversely influenced the stress distribution and ground stability of rock mass which was a combined effect of wall creep and compressibility of backfill.With the increase of time or/and creep deformation,the minimum principal stress in the rocks surrounding the backfilled stope increased towards the pre-mining stress state,while the deviatoric stress reduces leading to an increased factor of safety and improved ground stability.This improvement effect of backfill on ground stability increased with the increase of mine depth and stope height,while it is also more pronounced for the narrow stope,the backfill with a smaller compression index,and the soft rocks with a smaller viscosity coefficient.Furthermore,the results emphasize the importance of minimizing empty time and backfilling extracted stope as soon as possible for ground control.Reduction of filling gap height enhances the local stability around the roof of stope.
