Objective:To study the expression of ALDHI in colon cancer and its clinical significance. Methods:The expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues ...Objective:To study the expression of ALDHI in colon cancer and its clinical significance. Methods:The expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues with immunohistochemistry method.The correlations of the expression with clinicopathological parameters and prognosis of colon cancer were analyzed. Results:The positive rate of expression of ALDH1 was 76.5%(75/98) in the cancer tissues and 13.3%(2/15) in normal colon tissues.There were an obvious statistical difference(P【0.05) between the two groups,The ALDH1 expression was significantly correlated with the histological grade. TNM stages and lymph node metastasis in colon cancer(P【0.05).It was also related with patients’ survival time,those with positive expressions had a poor prognosis(P【0.05).Conclusions:The results suggeste that the overexpression of ALDHl plays important roles in proliferation and progression in colon cancer,the ALDHl may be a valuable marker to predict the biological behavior and trend of metastasis of colon cancer.展开更多
MYH9 has dual functions in tumors.However,its role in inducing tumor stemness in hepatocellular carcinoma(HCC)is not yet determined.Here,we found that MYH9 is an effective promoter of tumor stemness that facilitates h...MYH9 has dual functions in tumors.However,its role in inducing tumor stemness in hepatocellular carcinoma(HCC)is not yet determined.Here,we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma pathogenesis.Importantly,targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in vivo.Mechanistic analysis suggested that MYH9 interacted with GSK3βand reduced its protein expression by ubiquitin-mediated degradation,which therefore dysregulated theβ-catenin destruction complex and induced the downstream tumor stemness phenotype,epithelial–mesenchymal transition,and c-Jun signaling in HCC.C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop.X protein is a hepatitis B virus(HBV)-encoded key oncogenic protein that promotes HCC pathogenesis.Interestingly,we observed that HBV X protein(HBX)interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun signaling.Targeting MYH9 blocked HBX-induced GSK3βubiquitination to activate theβ-catenin destruction complex and suppressed cancer stemness and EMT.Based on TCGA database analysis,MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma patients.In clinical samples,high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma patients.These findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration,invasion,growth,and sorafenib resistance in HCC patients.Our study demonstrated that MYH9 is a crucial therapeutic target in HCC.展开更多
Subgrade construction is frequently interrupted due to precipitation,soil shortage,and environmental protection.Therefore,increasing the thickness layer is required to reduce construction costs and to allow highways t...Subgrade construction is frequently interrupted due to precipitation,soil shortage,and environmental protection.Therefore,increasing the thickness layer is required to reduce construction costs and to allow highways to be placed into service earlier.This paper presents a series of full-scale field experiments evaluating the compaction quality of gravel subgrade with large-thickness layers of 65 cm and 80 cm using heavy vibratory rollers.An improved sand cone method was first proposed and calibrated to investigate the distribution of soil compaction degree across the full subgrade depth.Results showed that dynamic soil stresses caused by the heavy vibratory rollers were 2.4–5.9 times larger than those of traditional rollers,especially at deeper depths,which were large enough to densify the soils to the full depth.A unified empirical formula was proposed to determine the vertical distribution of dynamic soil stresses caused by roller excitation.It was demonstrated that soils were effectively compacted in a uniform fashion with respect to the full depth to 96.0%–97.2%and 94.1%–95.4%for the large-thickness layers of 65 cm and 80 cm within 6 or 7 passes,respectively.Empirically,linear formulae were finally established between soil compaction degree and the subgrade reaction modulus,dynamic modulus of deformation,dynamic deflection,and relative difference of settlement to conveniently evaluate the compaction qualities.It is demonstrated that increasing the thickness layer by means of heavy rollers can significantly reduce the cost and time burdens involved in construction while ensuring overall subgrade quality.展开更多
文摘Objective:To study the expression of ALDHI in colon cancer and its clinical significance. Methods:The expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues with immunohistochemistry method.The correlations of the expression with clinicopathological parameters and prognosis of colon cancer were analyzed. Results:The positive rate of expression of ALDH1 was 76.5%(75/98) in the cancer tissues and 13.3%(2/15) in normal colon tissues.There were an obvious statistical difference(P【0.05) between the two groups,The ALDH1 expression was significantly correlated with the histological grade. TNM stages and lymph node metastasis in colon cancer(P【0.05).It was also related with patients’ survival time,those with positive expressions had a poor prognosis(P【0.05).Conclusions:The results suggeste that the overexpression of ALDHl plays important roles in proliferation and progression in colon cancer,the ALDHl may be a valuable marker to predict the biological behavior and trend of metastasis of colon cancer.
基金funded by the Natural Science Foundation of China(NSFC)(no.81773151)The Supporting Plan for Special Talents in Guangdong Province(no.2016TQ03R466)+3 种基金the Guangzhou Science and Technology Funding Projects(no.201604020009)the Nature Science Foundation of Guizhou Province(no.[2018]1127)the Hunan Provincial Science and Technology Department Project(no.2017SK50504)the Hunan Provincial Health and Family Planning Commission Project(no.B20180875).
文摘MYH9 has dual functions in tumors.However,its role in inducing tumor stemness in hepatocellular carcinoma(HCC)is not yet determined.Here,we found that MYH9 is an effective promoter of tumor stemness that facilitates hepatocellular carcinoma pathogenesis.Importantly,targeting MYH9 remarkably improved the survival of hepatocellular carcinoma-bearing mice and promoted sorafenib sensitivity of hepatocellular carcinoma cells in vivo.Mechanistic analysis suggested that MYH9 interacted with GSK3βand reduced its protein expression by ubiquitin-mediated degradation,which therefore dysregulated theβ-catenin destruction complex and induced the downstream tumor stemness phenotype,epithelial–mesenchymal transition,and c-Jun signaling in HCC.C-Jun transcriptionally stimulated MYH9 expression and formed an MYH9/GSK3β/β-catenin/c-Jun feedback loop.X protein is a hepatitis B virus(HBV)-encoded key oncogenic protein that promotes HCC pathogenesis.Interestingly,we observed that HBV X protein(HBX)interacted with MYH9 and induced its expression by modulating GSK3β/β-catenin/c-Jun signaling.Targeting MYH9 blocked HBX-induced GSK3βubiquitination to activate theβ-catenin destruction complex and suppressed cancer stemness and EMT.Based on TCGA database analysis,MYH9 was found to be elevated and conferred poor prognosis for hepatocellular carcinoma patients.In clinical samples,high MYH9 expression levels predicted poor prognosis of hepatocellular carcinoma patients.These findings identify the suppression of MYH9 as an alternative approach for the effective eradication of CSC properties to inhibit cancer migration,invasion,growth,and sorafenib resistance in HCC patients.Our study demonstrated that MYH9 is a crucial therapeutic target in HCC.
基金the National Natural Science Foundation for Young Scientists of China(No.51608306)the Shandong Provincial Natural Science Foundation of China(Nos.ZR2021ME103 and ZR2021QE254)+1 种基金the Shandong Transportation Science and Technology Foundation(Nos.2020-MS1-044,2021B63,and 202060804178)the Young Scholar Future Plan Funds of Shandong University,China。
文摘Subgrade construction is frequently interrupted due to precipitation,soil shortage,and environmental protection.Therefore,increasing the thickness layer is required to reduce construction costs and to allow highways to be placed into service earlier.This paper presents a series of full-scale field experiments evaluating the compaction quality of gravel subgrade with large-thickness layers of 65 cm and 80 cm using heavy vibratory rollers.An improved sand cone method was first proposed and calibrated to investigate the distribution of soil compaction degree across the full subgrade depth.Results showed that dynamic soil stresses caused by the heavy vibratory rollers were 2.4–5.9 times larger than those of traditional rollers,especially at deeper depths,which were large enough to densify the soils to the full depth.A unified empirical formula was proposed to determine the vertical distribution of dynamic soil stresses caused by roller excitation.It was demonstrated that soils were effectively compacted in a uniform fashion with respect to the full depth to 96.0%–97.2%and 94.1%–95.4%for the large-thickness layers of 65 cm and 80 cm within 6 or 7 passes,respectively.Empirically,linear formulae were finally established between soil compaction degree and the subgrade reaction modulus,dynamic modulus of deformation,dynamic deflection,and relative difference of settlement to conveniently evaluate the compaction qualities.It is demonstrated that increasing the thickness layer by means of heavy rollers can significantly reduce the cost and time burdens involved in construction while ensuring overall subgrade quality.
