This commentary delves into the evolving landscape of cancer incidence and mortality in Costa Rica, presenting a comprehensive analysis of the data. Key findings reveal a concerning upward trajectory in cancer inciden...This commentary delves into the evolving landscape of cancer incidence and mortality in Costa Rica, presenting a comprehensive analysis of the data. Key findings reveal a concerning upward trajectory in cancer incidence rates, placing Costa Rica at the forefront within Central America. While prostate cancer and breast cancer dominate, disparities emerge when scrutinizing gender-specific trends. Notably, stomach and cervical cancers show declines, potentially attributed to targeted interventions. However, colorectal and liver cancers witness mortality increases, necessitating strategic responses. Geographical disparities persist across provinces, highlighting the need for equitable healthcare access. In conclusion, this commentary underscores the urgency of addressing the burgeoning cancer burden in Costa Rica, calling for evidence-based interventions and collaborative efforts on a global scale.展开更多
Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyo...Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.展开更多
More than a decade ago, when we first embarked on our joumey to delineate the biological function of vascular endothelial growth factor B （VEGF-B）, we had a hard time comprehending why VEGF-B was needed. In mice, ge...More than a decade ago, when we first embarked on our joumey to delineate the biological function of vascular endothelial growth factor B （VEGF-B）, we had a hard time comprehending why VEGF-B was needed. In mice, genetic deletion of VEGF-B seemed to be harmless, since the VEGF-B null mice, to a large extent, can still live a fairly normal life [1]. Moreover, overexpression of VEGF-B in different mouse tissues, such as the skin or skeletal muscle,展开更多
Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling...Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling molecules, play equally important tyrosine roles as protein tyrosine kinases in signal transduction. SHP-2, a cytoplajsmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.展开更多
A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs. Extensive structural and functional studies reveal atomic details of DNA repair protein and ...A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs. Extensive structural and functional studies reveal atomic details of DNA repair protein and nucleic acid interactions. This review summarizes seemingly diverse structural motifs used in lesion recognition and suggests a general mechanism to recognize DNA lesion by the poor base stacking. After initial recognition of this shared structural feature of lesions, different DNA repair pathways use unique verification mechanisms to ensure correct lesion identification and removal.展开更多
AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatoc...AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs)from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.展开更多
BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rif...BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rifampicin pre- and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson＇s disease. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus （China） from November 2006 to October 2008. MATERIALS： Rifampicin was purchased from MD, USA; rotenone was purchased from Sigma, USA; mouse anti-rat α-synuclein monoclonal antibody was purchased from B＆D, USA; and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon, USA. METHODS： A total of 72 male, Sprague Dawley rats, aged 8 weeks, were randomly assigned to 5 groups： blank control （n = 12）, rifampicin （n = 12）, rotenone （n = 16）, rifampicin pre-treatment （n = 16）, and rifampicin post-treatment （n = 16）. Parkinson＇s disease model rats were established via a subcutaneous injection of rotenone （1.5 mg/kg per day） in the three treatment groups, once a day for 3 successive weeks. Rifampicin （30 mg/kg per day） was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction. Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group, once a day for 3 successive weeks in total. MAIN OUTCOME MEASURES： Prior to treatment and in the end of the 3^rd week after treatment, the rats were evaluated using the modified neurological severity score. The substantia nigra from the rats was extracted for hematoxylin-eosin staining. Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression. RESULTS： Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group, in addition to neurodegradation, hypopigmentation, and pyknosis. In the rifampicin pre-treatment and post-treatment groups, the number of dopaminergic neurons was significantly increased compared with the rotenone group （P 〈 0.01）, with slight neuronal damage. Compared with the rotenone group, substantia nigral tyrosine hydroxylase expression was significantly increased in the rifampicin pre-treatment and post-treatment groups （P 〈 0.01）, but α-synuclein expression and modified neurological severity scores were significantly decreased （P 〈 0.01）. In addition, the effect of rifampicin in the pre-treatment group was superior to the post-treatment group. There was no significant difference in tyrosine hydroxylase and α-synuclein expression, or in the modified neurological severity scores, between the blank control and rifampicin groups （P 〉 0.05）. CONCLUSION： Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone. Moreover, rifampicin enhanced tyrosine hydroxylase expression, but inhibited α-synuclein expression. The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.展开更多
AIM:To investigate the biological features of hepatitis B virus(HBV)-transfected HepG2.2.15 cells. METHODS:The cell ultrastructure,cell cycle and apoptosis,and the abilities of proliferation and invasion of HBV-transf...AIM:To investigate the biological features of hepatitis B virus(HBV)-transfected HepG2.2.15 cells. METHODS:The cell ultrastructure,cell cycle and apoptosis,and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy,flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay.Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice,and the pathological analysis of tumor formation was performed.Two cytoskeletal proteins were detected by Western blotting. RESULTS:Compared with HepG2 cells,HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope.HepG2.2.15 cells proliferated and migrated slowly in vitro,and hardly formed tumor and lung metastasis in nude mice.Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase,and apoptosis was minor in both cell lines.Furthermore,the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION:HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection.展开更多
Objective: Tumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapie...Objective: Tumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapies and clinical outcomes. However, systematic analysis of immune-related genes in gastric cancer(GC) has not been reported.Methods: Expressions of a total of 718 immune-related genes were generated in 372 stomach adenocarcinoma(STAD) patients from The Cancer Genome Atlas(TCGA) database using RNA-sequencing data. Integrated bioinformatics analyses were performed to identify prognostic factors as well.Results: Survival analyses revealed 73 genes, which were significantly associated with patient’s overall survival(OS). Taken together with clinicopathological parameters, we established a predictive model, containing 10 immune-related genes, which were NRP1, C6, CXCR4, LBP, PNMA1, TLR5, ITGA6, MICB, PBK and TNFRSF18,with powerful efficiency in distinguishing satisfactory or poor survival of STAD patients. Moreover, the top 3 ranked prognostic genes, NRP1, TGFβ2 and MFGE8, were also significantly associated with patient’s OS by an independent validation achieved from Kaplan-Meier plotter database.Conclusions: We profiled prognostic immune signature and established prognostic predictive model for GC,which could reflect immune disorders within tumor microenvironment, and also may provide novel predictive and therapeutic targets for GC patients in the near future.展开更多
Grapevine(Vitis vinifera),one of the most economically important fruit crops in the world,suffers significant yield losses from powdery mildew,a major fungal disease caused by Erysiphe necator.In addition to suppressi...Grapevine(Vitis vinifera),one of the most economically important fruit crops in the world,suffers significant yield losses from powdery mildew,a major fungal disease caused by Erysiphe necator.In addition to suppressing host immunity,phytopathogens modulate host proteins termed susceptibility(S)factors to promote their proliferation in plants.In this study,CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated 9)technology was used to enable the targeted mutagenesis of MLO(mildew resistance Locus O)family genes that are thought to serve as S factors for powdery mildew fungi.Small deletions or insertions were induced in one or both alleles of two grapevine MLO genes,VvMLO3 and VvMLO4,in the transgenic plantlets of the powdery mildew-susceptible cultivar Thompson Seedless.The editing efficiency achieved with different CRISPR/Cas9 constructs varied from 0 to 38.5%.Among the 20 VvMLO3/4-edited lines obtained,one was homozygous for a single mutation,three harbored biallelic mutations,seven were heterozygous for the mutations,and nine were chimeric,as indicated by the presence of more than two mutated alleles in each line.Six of the 20 VvMLO3/4-edited grapevine lines showed normal growth,while the remaining lines exhibited senescence-like chlorosis and necrosis.Importantly,four VvMLO3-edited lines showed enhanced resistance to powdery mildew,which was associated with host cell death,cell wall apposition(CWA)and H2O2 accumulation.Taken together,our results demonstrate that CRISPR/Cas9 genome-editing technology can be successfully used to induce targeted mutations in genes of interest to improve traits of economic importance,such as disease resistance in grapevines.展开更多
文摘This commentary delves into the evolving landscape of cancer incidence and mortality in Costa Rica, presenting a comprehensive analysis of the data. Key findings reveal a concerning upward trajectory in cancer incidence rates, placing Costa Rica at the forefront within Central America. While prostate cancer and breast cancer dominate, disparities emerge when scrutinizing gender-specific trends. Notably, stomach and cervical cancers show declines, potentially attributed to targeted interventions. However, colorectal and liver cancers witness mortality increases, necessitating strategic responses. Geographical disparities persist across provinces, highlighting the need for equitable healthcare access. In conclusion, this commentary underscores the urgency of addressing the burgeoning cancer burden in Costa Rica, calling for evidence-based interventions and collaborative efforts on a global scale.
文摘Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition(DHC),which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies.Despite significant progress in reducing mortality rates from cardiovascular diseases(CVDs),heart failure remains a major cause of increased morbidity among diabetic patients.These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components,and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment.While a variety of conventional diagnostic and therapeutic strategies are available,DHC continues to present a significant challenge.Point-of-care diagnostics,supported by nanobiosensing techniques,offer a promising alternative for these complex scenarios.Although conventional medications have been widely used in DHC patients,they raise several concerns regarding various physiological aspects.Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC,offering a promising approach to deliver drugs beyond the limitations of traditional therapies.This article aims to explore the potential connections between autophagy,mitophagy and DHC,while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.
文摘More than a decade ago, when we first embarked on our joumey to delineate the biological function of vascular endothelial growth factor B （VEGF-B）, we had a hard time comprehending why VEGF-B was needed. In mice, genetic deletion of VEGF-B seemed to be harmless, since the VEGF-B null mice, to a large extent, can still live a fairly normal life [1]. Moreover, overexpression of VEGF-B in different mouse tissues, such as the skin or skeletal muscle,
文摘Cellular biological activities are tightly controlled by intracellular signaling processes initiated by extracellular signals. Protein tyrosine phosphatases, which remove phosphate groups from phosphorylated signaling molecules, play equally important tyrosine roles as protein tyrosine kinases in signal transduction. SHP-2, a cytoplajsmic SH2 domain containing protein tyrosine phosphatase, is involved in the signaling pathways of a variety of growth factors and cytokines. Recent studies have clearly demonstrated that this phosphatase plays an important role in transducing signal relay from the cell surface to the nucleus, and is a critical intracellular regulator in mediating cell proliferation and differentiation.
文摘A fundamental question in DNA repair is how a lesion is detected when embedded in millions to billions of normal base pairs. Extensive structural and functional studies reveal atomic details of DNA repair protein and nucleic acid interactions. This review summarizes seemingly diverse structural motifs used in lesion recognition and suggests a general mechanism to recognize DNA lesion by the poor base stacking. After initial recognition of this shared structural feature of lesions, different DNA repair pathways use unique verification mechanisms to ensure correct lesion identification and removal.
基金Supported by the National Natural Science Foundation of China,No. 30370645, by the Hundred Leading Scientists Program of the Public Health Sector of Shanghai, No, 98BR007
文摘AIM: Codon 72 exon 4 polymorphism (Arg72Pro) of the p53 gene has been implicated in cancer risk. Our objective was to investigate the possible association between p53Arg72Pro polymorphism and susceptibility to hepatocellular carcinoma (HCC) among Chinese population.METHODS: The p53 Arg72Pro genotypes were determined by PCR-based restriction fragment length polymorphism (RFLP) analysis in 507 HCC cases and 541 controls. Odds ratios (ORs) for HCC and 95% confidence intervals (CIs)from unconditional logistic regression models were used to evaluate relative risks. Potential risk factors were included in the logistic regression models as covariates in the multivariate analyses on genotype and HCC.RESULTS: The frequencies for Pro and Arg alleles were 44.5%, 55.5% in HCC cases, and 40.3% and 59.7% in controls, respectively. The Pro allele was significantly associated with the presence of HCC (P = 0.05) and had a higher risk for HCC (OR = 1.19, 95% CI 1.00-1.41) as compared with the Arg allele. After adjusted for potential risk factors, Arg/Pro heterozygotes had an 1.21-fold increased risk (95% CI 0.82-1.78, P = 0.34) of HCC compared with Arg homozygotes, whereas the risk for Pro homozygotes was 1.79 (95% CI 1.06-3.01, P = 0.03) times higher than that for Arg homozygotes. Pro-allele carriers had a higher relative risk of HCC than the Arg-only carriers (adjusted OR = 1.33, 95% CI 0.92-1.92, P = 0.13), although the difference was not statistically significant.CONCLUSION: Homozygosity for Pro of p53 Arg72Pro is potentially one of the genetic risk factors for HCC in Chinese population. The p53 Arg72Pro polymorphism may be used as a stratification marker in screening individuals at a high risk of HCC.
基金the Natural Science Foundation of Guangdong Province,No.04009355Science and Technology Planning Project of Guandong Province,China,05B33801003
文摘BACKGROUND： Rifampicin inhibits the formation of a-synuclein multimer and protects against 1-methyl-4-phenyl-1,2, 3, 6-tetrahydropyritine （MPTP）-induced PC12 cell apoptosis. OBJECTIVE： To compare the effect of rifampicin pre- and post-treatment on tyrosine hydroxylase and α-synuclein expression in substantia nigra pars compacta in a rat model of Parkinson＇s disease. DESIGN, TIME AND SE＇B＇ING： A randomized, controlled experiment was performed at the Experimental Animal Center of Sun Yat-sen University North Campus （China） from November 2006 to October 2008. MATERIALS： Rifampicin was purchased from MD, USA; rotenone was purchased from Sigma, USA; mouse anti-rat α-synuclein monoclonal antibody was purchased from B＆D, USA; and rabbit anti-rat tyrosine hydroxylase monoclonal antibody was purchased from Chemicon, USA. METHODS： A total of 72 male, Sprague Dawley rats, aged 8 weeks, were randomly assigned to 5 groups： blank control （n = 12）, rifampicin （n = 12）, rotenone （n = 16）, rifampicin pre-treatment （n = 16）, and rifampicin post-treatment （n = 16）. Parkinson＇s disease model rats were established via a subcutaneous injection of rotenone （1.5 mg/kg per day） in the three treatment groups, once a day for 3 successive weeks. Rifampicin （30 mg/kg per day） was intragastrically administered in the rifampicin pre-treatment group 3 days prior to rotenone induction and in the rifampicin post-treatment group 7 days after rotenone induction. Rats were treated with a subcutaneous injection of 1 mL/kg per day sunflower oil in the blank control group and an intragastric injection of 30 mg/kg per day rifampicin in the rifampicin group, once a day for 3 successive weeks in total. MAIN OUTCOME MEASURES： Prior to treatment and in the end of the 3^rd week after treatment, the rats were evaluated using the modified neurological severity score. The substantia nigra from the rats was extracted for hematoxylin-eosin staining. Western blot analysis was performed to determine tyrosine hydroxylase and α-synuclein expression. RESULTS： Hematoxylin-eosin staining revealed a significant reduction in the number of substantia nigral neurons in the rotenone group, in addition to neurodegradation, hypopigmentation, and pyknosis. In the rifampicin pre-treatment and post-treatment groups, the number of dopaminergic neurons was significantly increased compared with the rotenone group （P 〈 0.01）, with slight neuronal damage. Compared with the rotenone group, substantia nigral tyrosine hydroxylase expression was significantly increased in the rifampicin pre-treatment and post-treatment groups （P 〈 0.01）, but α-synuclein expression and modified neurological severity scores were significantly decreased （P 〈 0.01）. In addition, the effect of rifampicin in the pre-treatment group was superior to the post-treatment group. There was no significant difference in tyrosine hydroxylase and α-synuclein expression, or in the modified neurological severity scores, between the blank control and rifampicin groups （P 〉 0.05）. CONCLUSION： Rifampicin significantly attenuated neuropathological and behavioral motor deficits induced by rotenone. Moreover, rifampicin enhanced tyrosine hydroxylase expression, but inhibited α-synuclein expression. The effect of rifampicin pre-treatment was superior to rifampicin post-treatment.
基金Supported by Graduate Innovation Foundation of Harbin Medical University No.HCXB2010010Key Technology Project of Heilongjiang Science and Technology Department,No.ZJY04-0102
文摘AIM:To investigate the biological features of hepatitis B virus(HBV)-transfected HepG2.2.15 cells. METHODS:The cell ultrastructure,cell cycle and apoptosis,and the abilities of proliferation and invasion of HBV-transfected HepG2.2.15 and the parent HepG2 cells were examined by electron microscopy,flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trans-well assay.Oncogenicity of the two cell lines was compared via subcutaneous injection and orthotopic injection or implantation in nude mice,and the pathological analysis of tumor formation was performed.Two cytoskeletal proteins were detected by Western blotting. RESULTS:Compared with HepG2 cells,HepG2.2.15 cells showed organelle degeneration and filopodia disappearance under electron microscope.HepG2.2.15 cells proliferated and migrated slowly in vitro,and hardly formed tumor and lung metastasis in nude mice.Flow cytometry showed that the majority of HepG2.2.15 cells were arrested in G1 phase,and apoptosis was minor in both cell lines.Furthermore,the levels of cytoskeletal proteins F-actin and Ezrin were decreased in HepG2.2.15 cells. CONCLUSION:HepG2.2.15 cells demonstrated a lower proliferation and invasion ability than the HepG2 cells due to HBV transfection.
基金financially supported by the Scientific Research Foundation of Shanxi Province Healthy Commission (No. 2017068)the Doctor Scientific Research Foundation of Shanxi cancer hospital (No. 2017A03)the Natural Science Foundation of Shanxi Province (No. 201801D221259)
文摘Objective: Tumor microenvironment, especially the host immune system, plays a pivotal role in tumor initiation and progression. Profiling of immune signature within tumor might uncover biomarkers for targeted therapies and clinical outcomes. However, systematic analysis of immune-related genes in gastric cancer(GC) has not been reported.Methods: Expressions of a total of 718 immune-related genes were generated in 372 stomach adenocarcinoma(STAD) patients from The Cancer Genome Atlas(TCGA) database using RNA-sequencing data. Integrated bioinformatics analyses were performed to identify prognostic factors as well.Results: Survival analyses revealed 73 genes, which were significantly associated with patient’s overall survival(OS). Taken together with clinicopathological parameters, we established a predictive model, containing 10 immune-related genes, which were NRP1, C6, CXCR4, LBP, PNMA1, TLR5, ITGA6, MICB, PBK and TNFRSF18,with powerful efficiency in distinguishing satisfactory or poor survival of STAD patients. Moreover, the top 3 ranked prognostic genes, NRP1, TGFβ2 and MFGE8, were also significantly associated with patient’s OS by an independent validation achieved from Kaplan-Meier plotter database.Conclusions: We profiled prognostic immune signature and established prognostic predictive model for GC,which could reflect immune disorders within tumor microenvironment, and also may provide novel predictive and therapeutic targets for GC patients in the near future.
基金supported by the National Key Research and Development Program of China(2018YFD1000300)the National Natural Science Foundation of China(Grant No.31772264)to Y.-Q.W.,and NSF support(IOS-1901566)to S.X.
文摘Grapevine(Vitis vinifera),one of the most economically important fruit crops in the world,suffers significant yield losses from powdery mildew,a major fungal disease caused by Erysiphe necator.In addition to suppressing host immunity,phytopathogens modulate host proteins termed susceptibility(S)factors to promote their proliferation in plants.In this study,CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/CRISPR-associated 9)technology was used to enable the targeted mutagenesis of MLO(mildew resistance Locus O)family genes that are thought to serve as S factors for powdery mildew fungi.Small deletions or insertions were induced in one or both alleles of two grapevine MLO genes,VvMLO3 and VvMLO4,in the transgenic plantlets of the powdery mildew-susceptible cultivar Thompson Seedless.The editing efficiency achieved with different CRISPR/Cas9 constructs varied from 0 to 38.5%.Among the 20 VvMLO3/4-edited lines obtained,one was homozygous for a single mutation,three harbored biallelic mutations,seven were heterozygous for the mutations,and nine were chimeric,as indicated by the presence of more than two mutated alleles in each line.Six of the 20 VvMLO3/4-edited grapevine lines showed normal growth,while the remaining lines exhibited senescence-like chlorosis and necrosis.Importantly,four VvMLO3-edited lines showed enhanced resistance to powdery mildew,which was associated with host cell death,cell wall apposition(CWA)and H2O2 accumulation.Taken together,our results demonstrate that CRISPR/Cas9 genome-editing technology can be successfully used to induce targeted mutations in genes of interest to improve traits of economic importance,such as disease resistance in grapevines.
