In addition to well-defined DNA repair pathways, all living organisms have evolved mechanisms to avoid cell death caused by replication fork collapse at a site where replication is blocked due to disruptive covalent m...In addition to well-defined DNA repair pathways, all living organisms have evolved mechanisms to avoid cell death caused by replication fork collapse at a site where replication is blocked due to disruptive covalent modifications of DNA. The term DNA damage tolerance （DDT） has been employed loosely to include a collection of mechanisms by which cells survive replication-blocking lesions with or without associated genomic instability. Recent genetic analyses indicate that DDT in eukaryotes, from yeast to human, consists of two parallel pathways with one being error-free and another highly mutagenic. Interestingly, in budding yeast, these two pathways are mediated by sequential modifications of the proliferating cell nuclear antigen （PCNA） by two ubiquitination complexes Rad6-Rad18 and Mms2-Ubc13-Rad5. Damage-induced monoubiquitination of PCNA by Rad6-Rad18 promotes translesion synthesis （TLS） with increased mutagenesis, while subsequent polyubiquitination of PCNA at the same K164 residue by Mms2-Ubc13-Rad5 promotes error-free lesion bypass. Data obtained from recent studies suggest that the above mechanisms are conserved in higher eukaryotes. In particular, mammals contain multiple specialized TLS polymerases. Defects in one of the TLS polymerases have been linked to genomic instability and cancer.展开更多
AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes. METHODS: We used 6-wk-old male gerbils ora...AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes. METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2×108 CFU/mL). Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylori-eradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected & H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level. RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group. Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups. CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.展开更多
In contrast to astrocytes in mammals, fish astrocytes promote axon regeneration after brain injury and actively participate in the regeneration process. Neurolin, a regeneration-associated, Zn8-1abeled protein, is inv...In contrast to astrocytes in mammals, fish astrocytes promote axon regeneration after brain injury and actively participate in the regeneration process. Neurolin, a regeneration-associated, Zn8-1abeled protein, is involved in the repair of damaged optic nerve in goldfish. At 1 week after unilateral eye injury, the ex- pression of neurolin in the optic nerve and chiasm, and the expression of Pax6 that influences nervous system development in various brain regions in the rainbow trout （Oncorhynchus mykiss） were detected. Immunohistochemical staining revealed that the number of Zn8~ cells in the optic nerve head and intraor- bital segment was obviously increased, and the increase in Zn8~ cells was also observed in the proximal and distal parts of injured optic nerve. This suggests that Zn8＊ astrocytes participate in optic nerve regeneration. ELISA results revealed that Pax6 protein increased obviously at 1 week post-injury. Immunohistochemi- cal staining revealed the appearance of Pax6＋ neurogenic niches and a larger number of neural precursor cells, which are mainly from Pax6＋ radial glia cells, in the nuclei of the diencephalon and optic tectum of rainbow trout （Oncorhynchus mykiss）. Taken together, unilateral eye injury can cause optic nerve reaction, and the formation of neurogenic niches is likely a compensation phenomenon during the repair process of optic nerve injury in rainbow trout （Oncorhynchus mykiss）.展开更多
The concern on formation damage control of high permeability sandstone reservoir has been growing in oil industry in recent years. The invasion of particles and the filtrate of drilling fluid are proven as one of the ...The concern on formation damage control of high permeability sandstone reservoir has been growing in oil industry in recent years. The invasion of particles and the filtrate of drilling fluid are proven as one of the key factors accounting for reservoir damage. Based on the ideal packing theory, the practical software has been developed to optimize the blending proportion of several bridging agents, and the core flooding tests were conducted to evaluate return permeability of core samples contaminated with different drilling fluids. Experimental results show that the ideal packing approach can reduce the dynamic filtration rate, improve the return permeability and drawdown the breakthrough pressure, indicating that this kind of drilling fluids can meet the demands of formation damage control for high permeability sandstone reservoirs. Some applying procedures for formation damage control are also proposed in this paper.展开更多
Structural health monitoring （SHM） has become a hot and intensively researched field in civil engineering. Thereinto, damage identification play an important role in maintaining structural integrity and safety. Many...Structural health monitoring （SHM） has become a hot and intensively researched field in civil engineering. Thereinto, damage identification play an important role in maintaining structural integrity and safety. Many effective methods have been proposed for damage identification. However, accurate global identification of large real-world structures is not easy due to their com- plex and often unknown boundary conditions, nonlinear components, insensitivity of glohal response to localized damages, etc. Furthermore, global identification often requires lots of sensors and involves large number of unknowns. This is costly, rarely feasible in practice, and usually yields severely ill-conditioned identification problems. Substructuring approach is a possible solution： substructuring methods can focus on local small substructures; they need only a few sensors placed on the substruc- ture and yield smaller and numerically much more feasible identification problems. This paper proposed an improved sub- structure method using local free response for substructure damage identification. The virtual supports are constructed by Sub- structure Isolation Method （SIM） using the linear combination of the substructural responses. The influence of the global errors is isolated by adding the virtual supports on the main degree of freedoms （DOFs） of the substructure. Through the correlation analysis, the substructural modes are selected and used for damage identification of the substructure. A plain model of cable stayed bridge is used for the verification of the proposed method.展开更多
Liver injury remains a significant global health problem and has a variety of causes,including oxidative stress(OS),inflammation,and apoptosis of liver cells.There is currently no curative therapy for this disorder.Sa...Liver injury remains a significant global health problem and has a variety of causes,including oxidative stress(OS),inflammation,and apoptosis of liver cells.There is currently no curative therapy for this disorder.Sanwei Ganjiang Prescription(SWGJP),derived from traditional Chinese medicine(TCM),has shown its effectiveness in long-term liver damage therapy,although the underlying molecular mechanisms are still not fully understood.To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view,in the present study,a systems pharmacology approach was developed,which involved drug target identification and multilevel data integration analysis.Using a comprehensive systems approach,we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets.We further deciphered the mechanisms of SWGJP in treating liver injury,including compound-target network analysis,target-function network analysis,and integrated pathways analysis.We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway,such as Nrf2-dependent anti-oxidative stress module.Notably,systems pharmacology provides an alternative way to investigate the complex action mode of TCM.展开更多
基金Acknowledgments The authors wish to thank Landon Pastushok, Michelle Hanna and other members from the Xiao laboratory for helpful discussion. This work was supported by the Canadian Institutes of Health Research operating grants MOP-38104 and MOP-53240 to W Xiao, and the National Natural Science Foundation of China（Grant no. 30560132） to F Xu.
文摘In addition to well-defined DNA repair pathways, all living organisms have evolved mechanisms to avoid cell death caused by replication fork collapse at a site where replication is blocked due to disruptive covalent modifications of DNA. The term DNA damage tolerance （DDT） has been employed loosely to include a collection of mechanisms by which cells survive replication-blocking lesions with or without associated genomic instability. Recent genetic analyses indicate that DDT in eukaryotes, from yeast to human, consists of two parallel pathways with one being error-free and another highly mutagenic. Interestingly, in budding yeast, these two pathways are mediated by sequential modifications of the proliferating cell nuclear antigen （PCNA） by two ubiquitination complexes Rad6-Rad18 and Mms2-Ubc13-Rad5. Damage-induced monoubiquitination of PCNA by Rad6-Rad18 promotes translesion synthesis （TLS） with increased mutagenesis, while subsequent polyubiquitination of PCNA at the same K164 residue by Mms2-Ubc13-Rad5 promotes error-free lesion bypass. Data obtained from recent studies suggest that the above mechanisms are conserved in higher eukaryotes. In particular, mammals contain multiple specialized TLS polymerases. Defects in one of the TLS polymerases have been linked to genomic instability and cancer.
文摘AIM: To investigate the effectiveness of 4 d' anti-Helicobacter pylori therapy on the H pylori-infected Mongolian gerbils based on physiological and pathological changes. METHODS: We used 6-wk-old male gerbils orally inoculated with H pylori (ATCC43504, 2×108 CFU/mL). Seven weeks after H pylori inoculation, the animals of study group received 4 d' anti-H pylori triple therapy (H pylori-eradicated group). Seven days later, all animals of the H pylori-eradicated and control groups (H pylori-infected & H pylori-uninfected groups) were sacrificed. We examined gastric mucosal lesions macroscopically, studied gastritis microscopically and determined the stomach weight ratio, myeloperoxidase (MPO) activity and prostaglandin (PG) E2 level. RESULTS: The results showed that both macroscopic and histological gastric damages were significantly less in H pylori-eradicated group than H pylori-infected group. Stomach weight ratio, MPO activity and PGE2 levels were significantly higher in H pylori-infected group than those in the other two groups. CONCLUSION: Four days' anti-H pylori therapy was effective in the improvement of H pylori-induced gastric lesions in Mongolian gerbils.
基金supported by the President of the Russian Federation(grant No.MD-4318.2015.4 to EVP)+2 种基金by the Far East Branch of the Russian Academy of Sciences within the Program for Basic Research for 2015–2017(grant No.15-I-6-116 section Ⅲ to AAV and EVP)
文摘In contrast to astrocytes in mammals, fish astrocytes promote axon regeneration after brain injury and actively participate in the regeneration process. Neurolin, a regeneration-associated, Zn8-1abeled protein, is involved in the repair of damaged optic nerve in goldfish. At 1 week after unilateral eye injury, the ex- pression of neurolin in the optic nerve and chiasm, and the expression of Pax6 that influences nervous system development in various brain regions in the rainbow trout （Oncorhynchus mykiss） were detected. Immunohistochemical staining revealed that the number of Zn8~ cells in the optic nerve head and intraor- bital segment was obviously increased, and the increase in Zn8~ cells was also observed in the proximal and distal parts of injured optic nerve. This suggests that Zn8＊ astrocytes participate in optic nerve regeneration. ELISA results revealed that Pax6 protein increased obviously at 1 week post-injury. Immunohistochemi- cal staining revealed the appearance of Pax6＋ neurogenic niches and a larger number of neural precursor cells, which are mainly from Pax6＋ radial glia cells, in the nuclei of the diencephalon and optic tectum of rainbow trout （Oncorhynchus mykiss）. Taken together, unilateral eye injury can cause optic nerve reaction, and the formation of neurogenic niches is likely a compensation phenomenon during the repair process of optic nerve injury in rainbow trout （Oncorhynchus mykiss）.
文摘The concern on formation damage control of high permeability sandstone reservoir has been growing in oil industry in recent years. The invasion of particles and the filtrate of drilling fluid are proven as one of the key factors accounting for reservoir damage. Based on the ideal packing theory, the practical software has been developed to optimize the blending proportion of several bridging agents, and the core flooding tests were conducted to evaluate return permeability of core samples contaminated with different drilling fluids. Experimental results show that the ideal packing approach can reduce the dynamic filtration rate, improve the return permeability and drawdown the breakthrough pressure, indicating that this kind of drilling fluids can meet the demands of formation damage control for high permeability sandstone reservoirs. Some applying procedures for formation damage control are also proposed in this paper.
基金support by the National Natural Science Foundation of China(NSFC)(Grand No.51108057)the National Basic Research Program of China(973 Program)(Grand No.2013CB036305)+4 种基金the Fundamental Research Funds for the Central Universities(China)(Grand No.DUT13LK13)Special Financial Grant from the China Postdoctoral Science Foundation(Grand No.2012T50255)the Project of National Key Technology R&D Program(China)(Grand Nos.2011BAK02B01,2011BAK02B03,2006BAJ03B05)the Polish National Science Centre Project"AIA"(Grand No.DEC-2012/05/B/ST8/02971)the FP7 EU project Smart-Nest(Grand No.PIAPP-GA-2011-28499)
文摘Structural health monitoring （SHM） has become a hot and intensively researched field in civil engineering. Thereinto, damage identification play an important role in maintaining structural integrity and safety. Many effective methods have been proposed for damage identification. However, accurate global identification of large real-world structures is not easy due to their com- plex and often unknown boundary conditions, nonlinear components, insensitivity of glohal response to localized damages, etc. Furthermore, global identification often requires lots of sensors and involves large number of unknowns. This is costly, rarely feasible in practice, and usually yields severely ill-conditioned identification problems. Substructuring approach is a possible solution： substructuring methods can focus on local small substructures; they need only a few sensors placed on the substruc- ture and yield smaller and numerically much more feasible identification problems. This paper proposed an improved sub- structure method using local free response for substructure damage identification. The virtual supports are constructed by Sub- structure Isolation Method （SIM） using the linear combination of the substructural responses. The influence of the global errors is isolated by adding the virtual supports on the main degree of freedoms （DOFs） of the substructure. Through the correlation analysis, the substructural modes are selected and used for damage identification of the substructure. A plain model of cable stayed bridge is used for the verification of the proposed method.
基金supported by the National Natural Science Foundation of China(Nos.81603318,81473740,and 81673627)Guangdong Provincial Major Science and Technology for Special Program of China(No.2015A030302072)+2 种基金Guangdong Provincial Major Science and Technology for Special Program of China(No.2015A030302071)the Guangzhou Science Technology and Innovation Commission Technology Research Projects(No.201805010005)the Guangzhou Science Technology and Innovation Commission Technology Research Projects(No.201607010333)
文摘Liver injury remains a significant global health problem and has a variety of causes,including oxidative stress(OS),inflammation,and apoptosis of liver cells.There is currently no curative therapy for this disorder.Sanwei Ganjiang Prescription(SWGJP),derived from traditional Chinese medicine(TCM),has shown its effectiveness in long-term liver damage therapy,although the underlying molecular mechanisms are still not fully understood.To explore the underlining mechanisms of action for SWGJP in liver injury from a holistic view,in the present study,a systems pharmacology approach was developed,which involved drug target identification and multilevel data integration analysis.Using a comprehensive systems approach,we identified 43 candidate compounds in SWGJP and 408 corresponding potential targets.We further deciphered the mechanisms of SWGJP in treating liver injury,including compound-target network analysis,target-function network analysis,and integrated pathways analysis.We deduced that SWGJP may protect hepatocytes through several functional modules involved in liver injury integrated-pathway,such as Nrf2-dependent anti-oxidative stress module.Notably,systems pharmacology provides an alternative way to investigate the complex action mode of TCM.
