Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two g...Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.展开更多
Small ubiquitin-like modifier (SUMO) conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and...Small ubiquitin-like modifier (SUMO) conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.展开更多
Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression...Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression.We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.Methods A SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells.VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR).Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues.Inhibition of SENP1 by siRNA was associated with decreased VEGF expression.SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%,38.2%,and 58.2% in high,moderate and low differentiated tumors,respectively,P=0.046),higher T stage (10.9% in T1,and 89.1% in T2 and T3 tumor samples,P <0.001)and TNM stage (10.9% in stage Ⅰ,and 89.1% in stages Ⅱ and Ⅲ tumor samples,P <0.001).The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%,P <0.001).Sixty three patients received postoperative chemotherapy,including 34 with SENP1 over-expression and 29 with SENP1 low expression.Among the 34 patients with SENP1 over-expression,22 (64.7%) patients developed recurrence or metastasis,significantly higher than those in the low expression group 27.6% (8/29) (P=0.005).Multivariate Cox regression analysis showed that lymph node metastasis (P=0.015),TNM stage (P=-0.001),and SENP1 expression level (P=0.002) were independent prognostic factors for the survival of NSCLC patients.Conclusions SENP1 may be a promising predictor of survival,a predictive factor of chemo-sensitivity for NSCLC patients,and potentially a desirable drug target for lung carcinoma target therapy.展开更多
AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and ...AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation.Flow cytometry was used for cell cycle analysis.Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion.Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.RESULTS Uba2 expression was higher in GC than in normal tissues.Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.CONCLUSION Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.展开更多
High frequency surface wave radar (HFSWR) is well proved to have over the horizon (OTH) detection capability to weak aerial targets, such as concealed airplanes or cruise missiles. The most important problem of detect...High frequency surface wave radar (HFSWR) is well proved to have over the horizon (OTH) detection capability to weak aerial targets, such as concealed airplanes or cruise missiles. The most important problem of detection of fast and small targets using HFSWR is earlier warning, i.e. enlargement of detection range oftargets. Therefore, the detection threshold should be decreased as low as possible, but numerous false alarms are brought about at the same time. On this condition, conventional track initiation techniques, which normally require the probability of false alarm to be at the level of 10-6, will initiate enormous false tracks and lead to abnormal operation of tracking system. An adaptive modified hough transform (AMHT) track initiator is proposed accordingly and the relation of detection range to the performance of track initiator is analyzed in this paper. Simulations are performed to confirm the capability of track initiation to fast and small targets in dense clutter by AMHT track initiator. The tolerable probability of false alarm of detector can reach the level of 10 -3 . And it performs better than track initiator based on modified hough transform (MHT).展开更多
Two kinds of regression equations are used to reproduce the sediment flux of the 26 small coastal watersheds in southeastern China.The first kind is the global equations suggested by Milliman and Syvitski(1992),Mulder...Two kinds of regression equations are used to reproduce the sediment flux of the 26 small coastal watersheds in southeastern China.The first kind is the global equations suggested by Milliman and Syvitski(1992),Mulder and Syvitski(1996),Syvitski et al.(2003),and Syvitski and Milliman(2007).The second kind is the modified equations revised by the characteristics of the coastal watersheds,including the drainage area,mean water discharge,and mean sediment discharge.Compared with the observations of the hydrometric stations,the global equations overestimate the sediment flux by 1–2 orders of magnitude.By using the modified equations,the accuracy of the estimated sediment flux is significantly improved,with the relative error in the range of 7%–24%.The reason for the overestimation mainly caused by different parameters’domain and regression coefficients between global rivers and study coastal watersheds.This study demonstrates that modification needs to be considered when using global regression equations to reproduce the sediment flux of the small coastal watersheds in southeastern China.展开更多
基金Acknowledgments This study was funded by the National Natural Science Foundation of China (81570323, 30972709, 81061120527, 81241082) and the 12th Five-Year National Program of the Ministry of Scientific Technology (2012BAI10B01). We thank Liu M and Zhou L from Beijing Hospital for providing experimental data, the nurses from Beijing Anzhen Hospital for collecting specimens, and the study volunteers.
文摘Background The genes encoding adiponectin receptor 1 (ADIPOR1) and small ubiquitin-like modifier 4 (SUM04) have been linked to anti-atherogenic effects, but little is known about whether polymorphisms in the two genes, acting separately or interacting, affect risk of coronary artery disease (CAD) without diabetes. Methods We genotyped 200 CAD patients without diabetes and 200 controls without CAD or diabetes at three single-nucleotide polymorphisms (SNPs) in ADIPOR1 and one SNP in SUM04, which were chosen based on previous studies. Potential associations were also explored between these SNPs and clinical characteristics of CAD without diabetes. Results Risk alleles at three SNPs inADIPOR1 (rs7539542-G, rs7514221-C and rs3737884-G) and the G allele at SNP rs237025 in SUM04 significantly increased risk of CAD without diabetes, with ORs ranging from 1.79 to 4.44. Carriers of any of these four risk alleles showed similar adverse clinical characteristics. Compared with individuals with a CC or GC genotype, those with a GG genotype at rs3737884 were at significantly higher risk of CAD that affected the left anterior descending coronary artery (OR: 6.77, P = 0.009), the right coronary artery (OR: 4.81, P = 0.028) or a relatively large number of vessels (P = 0.04). Individuals carrying a risk allele at one or more of the three SNPs in ADIPOR1 as well as a risk allele at the SNP in SUM04 were at significantly higher risk of CAD without diabetes than individuals not carrying any risk alleles (OR: 5.82, 95% CI: 1.23-27.7, P= 0.013). Conelusions SNPs in ADIPORl and SUMO4 are associated with elevated risk of CAD without diabetes, and SNPs in the two genes may interact to jointly affect disease risk.
基金supported by the Max Planck Societythe German Research Foundation DFG (SFB 635 to G.C., and SPP 1365 and grant BA1158/3–1 to A.B.)+1 种基金the Austrian Research Foundation FWF (grant P 21215 to A.B.)pre-doctoral fellowships from the International Max Planck Research School to R.B. and R.H
文摘Small ubiquitin-like modifier (SUMO) conjugation affects a broad range of processes in plants, including growth, flower initiation, pathogen defense, and responses to abiotic stress. Here, we investigate in vivo and in vitro a SUMO conjugating enzyme with a Cys to Ser change in the active site, and show that it has a dominant negative effect. In planta expression significantly perturbs normal development, leading to growth retardation, early flowering and gene expression changes. We suggest that the mutant protein can serve as a probe to investigate sumoylation, also in plants for which poor genetic infrastructure precludes analysis via loss-of-function mutants.
文摘Background Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors.Despite the advances in therapy over the years,its mortality remains high.The aim of this study was to evaluate the expression of small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) in NSCLC tissues and its role in the regulation of vascular endothelial growth factor (VEGF) expression.We also investigated the association between the expression level of SENP1 and the clinicopathological features and survival of the patients.Methods A SENP1 small interfering RNA (siRNA) was constructed and transfected into the NSCLC cells.VEGF gene expression was analyzed by real-time polymerase chain reaction (RT-PCR).Immunohistochemistry staining was used to assess the expression of SENP1 in 100 NSCLC patients and its association with the clinicopathological features and survival was analyzed.Results VEGF expression was significantly higher in NSCLC tissues than in normal lung tissues.Inhibition of SENP1 by siRNA was associated with decreased VEGF expression.SENP1 was over-expressed in 55 of the 100 NSCLC samples (55%) and was associated with a moderate and low histological tumor grade (3.6%,38.2%,and 58.2% in high,moderate and low differentiated tumors,respectively,P=0.046),higher T stage (10.9% in T1,and 89.1% in T2 and T3 tumor samples,P <0.001)and TNM stage (10.9% in stage Ⅰ,and 89.1% in stages Ⅱ and Ⅲ tumor samples,P <0.001).The rate of lymph node metastasis was significantly higher in the SENP1 over-expression group (76.4%) than that in the SENP1 low expression group (33.3%,P <0.001).Sixty three patients received postoperative chemotherapy,including 34 with SENP1 over-expression and 29 with SENP1 low expression.Among the 34 patients with SENP1 over-expression,22 (64.7%) patients developed recurrence or metastasis,significantly higher than those in the low expression group 27.6% (8/29) (P=0.005).Multivariate Cox regression analysis showed that lymph node metastasis (P=0.015),TNM stage (P=-0.001),and SENP1 expression level (P=0.002) were independent prognostic factors for the survival of NSCLC patients.Conclusions SENP1 may be a promising predictor of survival,a predictive factor of chemo-sensitivity for NSCLC patients,and potentially a desirable drug target for lung carcinoma target therapy.
基金the Science and Technology Department of Jilin Province(No.20150204006YY)
文摘AIM To investigate the function and mechanism of ubiquitinlike modifier activating enzyme 2(Uba2) in progression of gastric cancer(GC) cells.METHODS Uba2 level in patients with GC was analyzed by Western blotting and immunohistochemistry. MTT and colony formation assays were performed to examine cell proliferation.Flow cytometry was used for cell cycle analysis.Wound healing and Transwell assays were conducted to examine the effects of Uba2 on migration and invasion.Expression levels of cell cycle-related proteins, epithelial-mesenchymal transition(EMT) biomarkers, and involvement of the Wnt/β-catenin pathway was assessed by Western blotting. Activation of the Wnt/β-catenin pathway was confirmed by luciferase assay.RESULTS Uba2 expression was higher in GC than in normal tissues.Increased Uba2 expression was correlated with tissue differentiation, Lauren's classification, vascular invasion,and TNM stage, as determined by the analysis of 100 GC cases(P < 0.05). Knock-down of Uba2 inhibited GC cell proliferation, induced cell cycle arrest, and altered expression of cyclin D1, P21, P27, and Bcl-2, while upregulation of Uba2 showed the opposite effects. The wound healing and Transwell assays showed that Uba2 promoted GC cell migration and invasion. Western blotting revealed alterations in EMT biomarkers, suggesting the role of Uba2 in EMT. Furthermore, the luciferase reporter assay indicated the involvement of the Wnt/β-catenin signaling pathway as a possible modulator of Uba2 oncogenic functions.CONCLUSION Uba2 plays a vital role in GC cell migration and invasion,possibly by regulating the Wnt/β-catenin signaling pathway and EMT.
文摘High frequency surface wave radar (HFSWR) is well proved to have over the horizon (OTH) detection capability to weak aerial targets, such as concealed airplanes or cruise missiles. The most important problem of detection of fast and small targets using HFSWR is earlier warning, i.e. enlargement of detection range oftargets. Therefore, the detection threshold should be decreased as low as possible, but numerous false alarms are brought about at the same time. On this condition, conventional track initiation techniques, which normally require the probability of false alarm to be at the level of 10-6, will initiate enormous false tracks and lead to abnormal operation of tracking system. An adaptive modified hough transform (AMHT) track initiator is proposed accordingly and the relation of detection range to the performance of track initiator is analyzed in this paper. Simulations are performed to confirm the capability of track initiation to fast and small targets in dense clutter by AMHT track initiator. The tolerable probability of false alarm of detector can reach the level of 10 -3 . And it performs better than track initiator based on modified hough transform (MHT).
基金The National Natural Science Foundation of China under contract Nos 41625021,41676079 and 41906021the Project of Enhancing School with Innovation of Guangdong Ocean University under contract No.Q18307the Program for Scientific Research Start-up Funds of Guangdong Ocean University under contract No.060302112010
文摘Two kinds of regression equations are used to reproduce the sediment flux of the 26 small coastal watersheds in southeastern China.The first kind is the global equations suggested by Milliman and Syvitski(1992),Mulder and Syvitski(1996),Syvitski et al.(2003),and Syvitski and Milliman(2007).The second kind is the modified equations revised by the characteristics of the coastal watersheds,including the drainage area,mean water discharge,and mean sediment discharge.Compared with the observations of the hydrometric stations,the global equations overestimate the sediment flux by 1–2 orders of magnitude.By using the modified equations,the accuracy of the estimated sediment flux is significantly improved,with the relative error in the range of 7%–24%.The reason for the overestimation mainly caused by different parameters’domain and regression coefficients between global rivers and study coastal watersheds.This study demonstrates that modification needs to be considered when using global regression equations to reproduce the sediment flux of the small coastal watersheds in southeastern China.
文摘目的 探讨加减清金化痰汤联合头孢唑肟治疗进展期非小细胞肺癌(non-small-cell lung cancer, NSCLC)化疗后肺部感染的效果及对血清中性粒细胞与淋巴细胞比值(Neutrophils lymphocytes ratio, NLR)、降钙素原(Procalcitonin, PCT)、高迁移率族蛋白B1(High mobility group box 1,HMGB1)水平、免疫状态的影响。方法 选取2018年3月—2021年3月我院进展期NSCLC化疗后肺部感染患者102例,以随机数字表法分为治疗组、对照组,各51例。对照组给予头孢唑肟治疗,治疗组在对照组基础上给予加减清金化痰汤治疗,均治疗2 w。比较两组肺部感染疗效、感染症状改善情况、不良反应以及治疗前、治疗2 w后血清血清中性粒细胞与淋巴细胞比值(Neutrophil to Lymphocyte Ratio, NLR)、降钙素原(Procalcitonin, PCT)、高迁移率族蛋白B1(High mobility group box 1,HMGB1)、免疫功能指标(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、肺功能指标[用力肺活量(Forced vital capacity, FVC)、每分钟最大通气量占预计值百分比(Maximum ventilation volume per minute as a percentage of expected value, MVV)、第1 s用力呼气容积占预计值百分比(percentage of forced expiratory volume in first second to predicted value, FEV1)]水平。结果 治疗组治疗2 w后总有效率为92.16%,高于对照组的76.47%(P<0.05);经治疗,治疗组退热、咳嗽消失、肺部啰音消失时间较对照组短(P<0.05);治疗组治疗2 w后血清NLR、PCT、HMGB1、CD8^(+)水平均低于对照组,血清CD4^(+)、CD4^(+)/CD8^(+)水平均高于对照组(P<0.05);治疗组治疗2 w后FVC、MVV、FEV1水平均高于对照组(P<0.05);两组治疗期间不良反应发生率相比,差异无统计学意义(P>0.05)。结论 应用加减清金化痰汤联合头孢唑肟治疗进展期NSCLC化疗后肺部感染可减轻感染症状,降低血清NLR、PCT、HMGB1表达,提升免疫功能与肺功能,安全有效。