The stability and high productivity of heterogeneous terpenoid production in Escherichia coli expression system is one of the most key issues for its large scale industrialization.In the current study on taking lycope...The stability and high productivity of heterogeneous terpenoid production in Escherichia coli expression system is one of the most key issues for its large scale industrialization.In the current study on taking lycopene biosynthesis as an example,an integrated Escherichia coli system has been generated successfully,which resulted into stable and high lycopene production.In this process,two modules of mevalonate(MVA)pathway and one module of lycopene expression pathway were completely integrated in the chromosome.Firstly,the copy number and integrated position of three modules of heterologous pathways were rationally optimized.Later,a strain DH416 equipped with heterogeneous expression pathways through chromosomal integration was efficiently derived from parental strain DH411.The evolving DH416 strain efficiently produced the lycopene level of 1.22 g/L(49.9 mg/g DCW)in a 5 L fermenter with mean productivity of 61.0 mg/L/h.Additionally,the integrated strain showed more genetic stability than the plasmid systems after successive 21st passage.展开更多
The hedgehog （Hh） signaling pathway plays an essential role in the embryonic development and homeostasis of diverse adult tissues, and its deregulation has been implicated in the tumorigenesis and metastasis of vari...The hedgehog （Hh） signaling pathway plays an essential role in the embryonic development and homeostasis of diverse adult tissues, and its deregulation has been implicated in the tumorigenesis and metastasis of various malignancies including breast cancer. Aberrant activation of the Hh pathway includes the following mechanisms： （I） Hh ligand-independent mechanism - Loss of function mutations in the Hh receptor Patched 1 （PTCH1） or gain of function mutations in the Smoothened （SMO） lead to constitutive activation of this pathway; （II） Autocrine signaling- Ith ligand produced by tumor cells stimulates the Hh signaling in tumor cells; （III） Paracrine signaling - tumor cell produced-Hh ligand activates stromal and endothelial cells that produce growth factors in microenvironment for supporting tumor growth and survival; and （IV） Reverse paracrine signaling - Hh ligand produced by stromal cells support tumor growth and survival. Upon the pathway activation, the Gli transcription factors, effectors of the Hh signaling, activate or inhibit transcription by binding to their responsive genes and interacting with the transcriptional complex. The Gli transcription factor family includes Glil, Gli2, and Gli3 （1）. Glil is a transcriptional activator whose expression has been recognized as an activation state of the Hh signaling pathway, Gli2 is either an activator or repressor, and Gli3 is a strong repressor of transcriptional activities. To date, a ligand-dependent autocrine model of activating the Hh signaling has been described in breast cancer, and both an autocrine and paracrine mechanisms in colorectal cancer, pancreatic cancer and prostate cancer （2,3）. Notably, a ligand-independent mechanism （mutationsin PTCHI and SMO） of the signaling has been well demonstrated in basal cell carcinoma and medulloblastoma （4,5）.展开更多
Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
BACKGROUND： Liver regeneration is a complex process. micro RNAs（mi RNAs） are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that mi RN...BACKGROUND： Liver regeneration is a complex process. micro RNAs（mi RNAs） are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that mi RNAs are closely linked to liver regeneration.DATA SOURCES： All included studies were obtained from Pub Med, Embase, the Science Direct databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.RESULTS： We grouped studies that involved mi RNA and liver regeneration into two groups： mi RNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant mi RNAs separately from the related pathways.CONCLUSIONS： Blocking or stimulating the pathways of mi RNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of mi RNA.展开更多
Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Xiao Zhixiong(肖智雄)from the College of Life Science,Sichuan University de...Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Xiao Zhixiong(肖智雄)from the College of Life Science,Sichuan University demonstrates thatΔNp63αis a common inhibitory target in oncogenic PI3K/Ras/Her2-induced展开更多
基金supported by grants from the National Key Research and Development Program of China(2018YFA0900300 and 2019YFA090141)the National Science and Technology Major Project(2017ZX07402003).
文摘The stability and high productivity of heterogeneous terpenoid production in Escherichia coli expression system is one of the most key issues for its large scale industrialization.In the current study on taking lycopene biosynthesis as an example,an integrated Escherichia coli system has been generated successfully,which resulted into stable and high lycopene production.In this process,two modules of mevalonate(MVA)pathway and one module of lycopene expression pathway were completely integrated in the chromosome.Firstly,the copy number and integrated position of three modules of heterologous pathways were rationally optimized.Later,a strain DH416 equipped with heterogeneous expression pathways through chromosomal integration was efficiently derived from parental strain DH411.The evolving DH416 strain efficiently produced the lycopene level of 1.22 g/L(49.9 mg/g DCW)in a 5 L fermenter with mean productivity of 61.0 mg/L/h.Additionally,the integrated strain showed more genetic stability than the plasmid systems after successive 21st passage.
文摘The hedgehog （Hh） signaling pathway plays an essential role in the embryonic development and homeostasis of diverse adult tissues, and its deregulation has been implicated in the tumorigenesis and metastasis of various malignancies including breast cancer. Aberrant activation of the Hh pathway includes the following mechanisms： （I） Hh ligand-independent mechanism - Loss of function mutations in the Hh receptor Patched 1 （PTCH1） or gain of function mutations in the Smoothened （SMO） lead to constitutive activation of this pathway; （II） Autocrine signaling- Ith ligand produced by tumor cells stimulates the Hh signaling in tumor cells; （III） Paracrine signaling - tumor cell produced-Hh ligand activates stromal and endothelial cells that produce growth factors in microenvironment for supporting tumor growth and survival; and （IV） Reverse paracrine signaling - Hh ligand produced by stromal cells support tumor growth and survival. Upon the pathway activation, the Gli transcription factors, effectors of the Hh signaling, activate or inhibit transcription by binding to their responsive genes and interacting with the transcriptional complex. The Gli transcription factor family includes Glil, Gli2, and Gli3 （1）. Glil is a transcriptional activator whose expression has been recognized as an activation state of the Hh signaling pathway, Gli2 is either an activator or repressor, and Gli3 is a strong repressor of transcriptional activities. To date, a ligand-dependent autocrine model of activating the Hh signaling has been described in breast cancer, and both an autocrine and paracrine mechanisms in colorectal cancer, pancreatic cancer and prostate cancer （2,3）. Notably, a ligand-independent mechanism （mutationsin PTCHI and SMO） of the signaling has been well demonstrated in basal cell carcinoma and medulloblastoma （4,5）.
基金This work was supported by the National Natural Science Foundation of China (No 30370904and No 30671258)the National High Technology Research and Development Program(863 project)of China (No 2006AA10Z121)the Program for New Century Excellent Talents in University(No NCET-07-0712)
文摘Cotton(Gossypium hirsutum L.) is the leading fiber crop and one of the mainstays of the economy in the world.Cotton fibers,as the main product of cotton plants,are unicellular,linear
文摘BACKGROUND： Liver regeneration is a complex process. micro RNAs（mi RNAs） are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that mi RNAs are closely linked to liver regeneration.DATA SOURCES： All included studies were obtained from Pub Med, Embase, the Science Direct databases and Web of Science, with no limitation on publication year. Only studies published in English were considered.RESULTS： We grouped studies that involved mi RNA and liver regeneration into two groups： mi RNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant mi RNAs separately from the related pathways.CONCLUSIONS： Blocking or stimulating the pathways of mi RNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of mi RNA.
文摘Subject Code:H16With the support by the National Natural Science Foundation of China,a collaborative study by the research groups led by Prof.Xiao Zhixiong(肖智雄)from the College of Life Science,Sichuan University demonstrates thatΔNp63αis a common inhibitory target in oncogenic PI3K/Ras/Her2-induced
