Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We use...Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.展开更多
This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and im...This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and immunohis to chemically detected to evaluate the correlation of EMP-1 expression to the clinical features of NSCLC. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling. Moreover, tumor xeno-grafts were established by subcutaneous injection of PC9 cell suspension (about 5×107/mL in 100 μL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in NSCLC patients as compared with those with benign lung diseases. Over-expression of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of NSCLC by activating PI3K/AKT pathway.展开更多
Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and gr...Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and growth factors for lymphangiogenesis. Importantly, lymphatic endothelial receptor tyrosine kinase VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype. It demonstrates the plasticity of endothelial cells and offers the possibility of transcriptional reprogramming of vascular endothelial cells as future putative therapeutic applications.展开更多
The objective of this study was to determine the genotype effects of the bovine insulin-like growth factor Ⅰ （IGF-Ⅰ） and its binding protein 3 （IGFBP3） genes on growth and development traits in beef cows, includ...The objective of this study was to determine the genotype effects of the bovine insulin-like growth factor Ⅰ （IGF-Ⅰ） and its binding protein 3 （IGFBP3） genes on growth and development traits in beef cows, including 130 Chinese Simmental, 42 Nanyang, and 47 Luxi Yellow cattle. Sequence variations in the bovine IGF-Ⅰ and IGFBP3 genes were investigated by single strand conformation polymorphism （SSCP）. SSCPs were detected in 6 fragments, which is the 5＇-flanking region, the 2nd exon, the 5th exon, and the 5th intron of the IGF-1 gene, and the 2nd exon, the 3rd exon of the 1GFBP3 gene. Two polymorphisms, an A-to-G transition in the 2rid exon of the IGF-Ⅰ gene and a T-to-C transition in the 2rid exon of IGFBP3 gene were detected in 3 breeds. The allele frequencies of 2 polymorphisms were 0.0411 （A）, 0.9589 （B）, and 0.7237 （A）, 0.2763 （B）, respectively. These 2 loci were analyzed to associate with body weight, height at withers, body length, heart girth, rump width, and beef production index （BPI） at 0, 6, 12, 24, and 36-month old. The IGFBP3 locus was shown to be associated with rump width, heart girth at 24-month and 36-month. Animals with BB genotype had higher rump width （24.86 ± 0.47） cm at 24-month and （27.50 ± 0.63） em at 36-month. The heart girth was highest for the individuals with BB genotype （171.33 ± 1.84） cm and higher than those with AB genotype （166.68 ± 1.13） cm （P〈 0.05） at 36-month.展开更多
Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epi...Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months.During the course of the disease,there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body.Genetic testing showed that both patients carried heterozygous missense mutations in the ATP1A3 gene(OMIM:614820):c.3025(exon 22)A>G(p.K1009E)and c.2443(exon 18)G>A(p.E815K).Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.展开更多
Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was download...Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN.展开更多
Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown th...Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.展开更多
High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies o...High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors,especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species(ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition,SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster.Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.展开更多
基金supported by the National Key Research and Development Program of China(2016YFC0501203)the National Genetically Modified Organism Project(2016ZX08010005-9)。
文摘Plant mitochondrial phosphate transporters regulate phosphate transport and ATP synthesis. Determining whether they function in abiotic stress response process would shed light on their response to salt stress. We used the CRISPR/Cas9 gene-editing system to mutagenize two mitochondrial phosphate transporters, OsMPT3;1 and OsMPT3;2, to investigate their regulatory roles under salt stress. Two cas9(CRISPR-associated protein9)-free homozygous mutants, mpt33 and mpt30, were confirmed to be stable. Both OsMPT3;1 and OsMPT3;2 were markedly induced by salt stress, and their mutagenesis strongly inhibited growth and development, especially under salt stress. Mutagenesis sharply reduced the accumulation of ATP, phosphate, calcium, soluble sugar, and proline and increased osmotic potential, malondialdehyde, and Na^+ /K^+ ratio under salt stress. Both mutants demonstrate normal growth and development in the presence of ATP, revealing high sensitivity to exogenous ATP under salt stress. The mutants showed lowered rates of Na^+ efflux but also of K^+ and Ca^(2+) influx under salt stress. Mutagenesis of OsMPT3;2 altered the enrichment profiles of differentially expressed genes involved mainly in synthesis of secondary metabolites, metabolism of glycolysis, pyruvate, tricarboxylic acid cycle, in response to salt stress. The mutant displayed significant accumulation differences in 14 metabolites involved in 17 metabolic pathways, and strongly up-regulated the accumulation of glutamine, a precursor in proline synthesis, under salt stress. These findings suggest that the OsMPT3 gene modulates phosphate transport and energy supply for ATP synthesis and triggers changes in accumulation of ions and metabolites participating in osmotic regulation in rice under salt stress, thus increasing rice salt tolerance. This study demonstrates the effective application of CRISPR/Cas9 gene-editing to the investigation of plant functional genes.
基金supported by grants from the National Natural Science Foundation of China (Nos.81072431,30872472,30973496 and 30800569)the Innovative Foundation of Huazhong University of Science and Technology (No.2010MS027)+1 种基金the Foundation of "973" Program (No.2009CB521802)by Special Fund for Central University Basic Scientific Research (Nos.2011JC062,2011JC063)
文摘This study examined the role of EMP-1 in tumorigenesis of non-small cell lung carcinoma (NSCLC) and the possible mechanism. Specimens were collected from 28 patients with benign lung diseases and 28 with NSCLC, and immunohis to chemically detected to evaluate the correlation of EMP-1 expression to the clinical features of NSCLC. Recombinant adenovirus was constructed to over-express EMP-1 and then infect PC9 cells. Cell proliferation was measured by Ki67 staining. Western blotting was performed to examine the effect of EMP-1 on the PI3K/AKT signaling. Moreover, tumor xeno-grafts were established by subcutaneous injection of PC9 cell suspension (about 5×107/mL in 100 μL of PBS) into the right hind limbs of athymic nude mice. The results showed EMP-1 was significantly up-regulated in NSCLC patients as compared with those with benign lung diseases. Over-expression of EMP-1 promoted proliferation of PC9 cells, which coincided with the activation of the PI3K/AKT pathway. EMP-1 promoted the growth of xenografts of PC9 cells in athymic nude mice. It was concluded that EMP-1 expression may contribute to the development and progress of NSCLC by activating PI3K/AKT pathway.
文摘Lymphangiogenesis, the growth of new lymphatic vessels, has long been regarded as a putative efficient pathway to neoplastic metastization. Recent results have shown the necessity of lymphatic molecular markers and growth factors for lymphangiogenesis. Importantly, lymphatic endothelial receptor tyrosine kinase VEGFR-3 and its ligands VEGF-C and VEGF-D play crucial roles in promoting lymphatic vascular growth both during development and in pathological conditions. Isolation of pure cultures of lymphatic and blood vascular endothelial cells and systematic characterization of their transcriptomes provide useful cell culture models and novel potential vascular markers and offer further insights into the lymphatic vascular biology. Ectopic expression of the lymphatic endothelial specific homeobox transcription factor Prox1 in blood endothelial cells results in a shift in the gene expression profile towards the lymphatic endothelial phenotype. It demonstrates the plasticity of endothelial cells and offers the possibility of transcriptional reprogramming of vascular endothelial cells as future putative therapeutic applications.
基金funded by the National Key Technology R&D Program of the China (2006BAD01A10,2006BAD14B07, 2006BAD04A16)the National High Technology Research and Development Program of China (2006AA10Z197)
文摘The objective of this study was to determine the genotype effects of the bovine insulin-like growth factor Ⅰ （IGF-Ⅰ） and its binding protein 3 （IGFBP3） genes on growth and development traits in beef cows, including 130 Chinese Simmental, 42 Nanyang, and 47 Luxi Yellow cattle. Sequence variations in the bovine IGF-Ⅰ and IGFBP3 genes were investigated by single strand conformation polymorphism （SSCP）. SSCPs were detected in 6 fragments, which is the 5＇-flanking region, the 2nd exon, the 5th exon, and the 5th intron of the IGF-1 gene, and the 2nd exon, the 3rd exon of the 1GFBP3 gene. Two polymorphisms, an A-to-G transition in the 2rid exon of the IGF-Ⅰ gene and a T-to-C transition in the 2rid exon of IGFBP3 gene were detected in 3 breeds. The allele frequencies of 2 polymorphisms were 0.0411 （A）, 0.9589 （B）, and 0.7237 （A）, 0.2763 （B）, respectively. These 2 loci were analyzed to associate with body weight, height at withers, body length, heart girth, rump width, and beef production index （BPI） at 0, 6, 12, 24, and 36-month old. The IGFBP3 locus was shown to be associated with rump width, heart girth at 24-month and 36-month. Animals with BB genotype had higher rump width （24.86 ± 0.47） cm at 24-month and （27.50 ± 0.63） em at 36-month. The heart girth was highest for the individuals with BB genotype （171.33 ± 1.84） cm and higher than those with AB genotype （166.68 ± 1.13） cm （P〈 0.05） at 36-month.
基金Research Fund of Anhui Medical University(Grant Number:2019xkj176).
文摘Alternating hemiplegia of childhood is a rare neurodevelopmental disorder.Most cases are reported as sporadic disorder due to de novo variants,and few with family members involved.Two boys were hospitalized due to epileptic seizures occurred initially at age of six to seven months.During the course of the disease,there were repeated episodes of paroxysmal weakness or paralysis affecting one side of the body.Genetic testing showed that both patients carried heterozygous missense mutations in the ATP1A3 gene(OMIM:614820):c.3025(exon 22)A>G(p.K1009E)and c.2443(exon 18)G>A(p.E815K).Flunarizine can significantly improve the paroxysmal motor symptoms of pediatric patients with alternating hemiplegia.
文摘Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN.
基金Yunnan Provincial Department of Science and Technology Project(202101AY070001-224).
文摘Schizophrenia(SCZ)is the most common serious mental illness with a high disability rate and heavy social and family burdens.At present,there is no clear etiology and pathogenesis of schizophrenia.Studies have shown that the occurrence of schizophrenia may be related to the abnormality of the hypothalamic-pituitary-adrenal(HPA)axis.The LIM-homeobox gene 3(LHXS)and early growth response 1(EGR1)can affect pituitary function.Because the synapsin 2(SYN2)gene polymorphism regulates the activity of LHX3 and EGR1,it may cause the occurrence of schizophrenia.This article will review the possible involvement of SYN2 gene polymorphism in the pathogenesis of schizophrenia via regulating the activity of LHX3 and EGR1,then to afiect the HPA axis.
基金supported by grants from the National Key Research&Development Plan,China (Grant Nos.2021YFD1200201,2022YFD1200502)National Natural Science Foundation of China(31972426,31991182)+3 种基金Key Project of Hubei Hongshan Laboratory(Grant No.2021hszd007)Wuhan Major Project of Key Technologies in Biological Breeding (Grant No.2022021302024852)Fundamental Research Funds for the Central Universities,China (Grant No.2662022YLPY001)International Cooperation Promotion Plan of Shihezi University (Grant No.GJHZ202104)。
文摘High temperature stress is one of the major environmental factors that affect the growth and development of plants. Although WRKY transcription factors play a critical role in stress responses, there are few studies on the regulation of heat stress by WRKY transcription factors,especially in tomato. Here, we identified a group I WRKY transcription factor, SlWRKY3, involved in thermotolerance in tomato. First, SlWRKY3 was induced and upregulated under heat stress. Accordingly, overexpression of SlWRKY3 led to an increase, whereas knock-out of SlWRKY3 resulted in decreased tolerance to heat stress. Overexpression of SlWRKY3 accumulated less reactive oxygen species(ROS), whereas knock-out of SlWRKY3 accumulated more ROS under heat stress. This indicated that SlWRKY3 positively regulates heat stress in tomato. In addition,SlWRKY3 activated the expression of a range of abiotic stress-responsive genes involved in ROS scavenging, such as a SlGRXS1 gene cluster.Further analysis showed that SlWRKY3 can bind to the promoters of the SlGRXS1 gene cluster and activate their expression. Collectively, these results imply that SlWRKY3 is a positive regulator of thermotolerance through direct binding to the promoters of the SlGRXS1 gene cluster and activating their expression and ROS scavenging.
