Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma(PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution o...Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma(PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear.Methods: Spatial transcriptomics(STs), a new technique, was used to investigate the ST features of engrafted human PDAC in the ischemic hind limbs of nude mice. Transcriptomes from ST spots in the hypoxic tumor and the control were clustered using differentially-expressed genes. These data were compared to determine the spatial organization of hypoxia-induced heterogeneity in PDAC. Clinical relevance was validated using the Tumor Cancer Genome Atlas and KM-plotter databases. The CMAP website was used to identify molecules that may serve as therapeutic targets for PDAC.Results: ST showed that the tumor cell subgroups decreased to 7 subgroups in the hypoxia group, compared to 9 subgroups in the control group. Different subgroups showed positional characteristics and different gene signatures. Subgroup 6 located at the invasive front showed a higher proliferative ability under hypoxia. Subgroup 6 had active functions including cell proliferation, invasion, and response to stress. Expressions of hypoxia-related genes, LDHA, TPI1, and ENO1, induced changes. CMAP analysis indicated that ADZ-6482, a PI3 K inhibitor, was targeted by the invasive subgroup in hypoxic tumors.Conclusions: This study is the first to describe hypoxic microenvironment-induced spatial transcriptome changes in PDAC, and to identify potential treatment targets for PDAC. These data will provide the basis for further investigations of the prognoses and treatments of hypoxic tumors.展开更多
Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remai...Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remains unclear.Methods: The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl2-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated in vitro and in vivo. Hypoxia-and ENO1-induced gene expression was analyzed by transcriptomic sequencing.Results: The prognosis of PDAC with high ENO1 expression was poor(P < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases(P < 0.05). Hypoxia increased ENO1 expression in PDAC and promoted its migration and invasion. Apoptotic cells and the apoptosis marker caspase-3 in the CoCl_(2)-treated ENO1-sh group were significantly elevated(P < 0.05). Transcriptomic sequencing indicated that CoCl_(2)-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis(P < 0.05). Consistent results were also observed in a PDAC-bearing mouse hindlimb ischemia model.Conclusions: Hypoxia-induced ENO1 expression promotes ERK phosphorylation and inhibits apoptosis, thus leading to PDAC survival and invasion. These results suggest that ENO1 is a potential therapeutic target for PDAC.展开更多
Polyaluminum chloride modified clay(PAC-MC)is a safe and efficient red tide control agent that has been studied and applied worldwide.Although it is well known that the distribution of hydrolytic aluminum species in P...Polyaluminum chloride modified clay(PAC-MC)is a safe and efficient red tide control agent that has been studied and applied worldwide.Although it is well known that the distribution of hydrolytic aluminum species in PAC affects its flocculation,little is known about the influence of particulars aluminum species on the microalgae removal efficiency of PAC-MC;this lack of knowledge creates a bottleneck in the development of more efficient MCs based on aluminum salts.The ferron method was used in this study to quantitatively analyze the distributions of and variations in different hydrolytic aluminum species during the process of microalgae removal by PAC-MC.The results showed that Ala,which made up 5%–20%of the total aluminum,and Alp,which made up 15%–55%of the total aluminum,significantly affected microalgae removal,with Pearson’s correlation coefficients of 0.83 and 0.89,respectively.Most of the aluminum in the PAC-MC sank rapidly into the sediments,but the rate and velocity of settlement were affected by the dose of modified clay.The optimal dose of PAC-MC for precipitating microalgae was determined based on its aluminum profile.These results provide guidance for the precise application of PAC-MC in the control of harmful algal blooms.展开更多
基金supported by grants from the National Natural Science Key Foundation of China (Grants Nos. 82030092 and 81230050)。
文摘Objective: Hypoxia is a significant feature of solid tumors, including pancreatic ductal adenocarcinoma(PDAC). It is associated with tumor invasion, metastasis, and drug resistance. However, the spatial distribution of hypoxia-related heterogeneity in PDAC remains unclear.Methods: Spatial transcriptomics(STs), a new technique, was used to investigate the ST features of engrafted human PDAC in the ischemic hind limbs of nude mice. Transcriptomes from ST spots in the hypoxic tumor and the control were clustered using differentially-expressed genes. These data were compared to determine the spatial organization of hypoxia-induced heterogeneity in PDAC. Clinical relevance was validated using the Tumor Cancer Genome Atlas and KM-plotter databases. The CMAP website was used to identify molecules that may serve as therapeutic targets for PDAC.Results: ST showed that the tumor cell subgroups decreased to 7 subgroups in the hypoxia group, compared to 9 subgroups in the control group. Different subgroups showed positional characteristics and different gene signatures. Subgroup 6 located at the invasive front showed a higher proliferative ability under hypoxia. Subgroup 6 had active functions including cell proliferation, invasion, and response to stress. Expressions of hypoxia-related genes, LDHA, TPI1, and ENO1, induced changes. CMAP analysis indicated that ADZ-6482, a PI3 K inhibitor, was targeted by the invasive subgroup in hypoxic tumors.Conclusions: This study is the first to describe hypoxic microenvironment-induced spatial transcriptome changes in PDAC, and to identify potential treatment targets for PDAC. These data will provide the basis for further investigations of the prognoses and treatments of hypoxic tumors.
基金supported by grants from the National Natural Science Key Foundation of China(Grant No.82030092).
文摘Objective: Hypoxia is an important feature of pancreatic ductal adenocarcinoma(PDAC). Previously, we found that hypoxia promotes ENO1 expression and PDAC invasion. However, the underlying molecular mechanism was remains unclear.Methods: The relationship between ENO1 expression and clinicopathological characteristics was analyzed in 84 patients with PADC. The effects of CoCl2-induced hypoxia and ENO1 downregulation on the apoptosis, invasion, and proliferation of PDAC cells were evaluated in vitro and in vivo. Hypoxia-and ENO1-induced gene expression was analyzed by transcriptomic sequencing.Results: The prognosis of PDAC with high ENO1 expression was poor(P < 0.05). High ENO1 expression was closely associated with histological differentiation and tumor invasion in 84 PDAC cases(P < 0.05). Hypoxia increased ENO1 expression in PDAC and promoted its migration and invasion. Apoptotic cells and the apoptosis marker caspase-3 in the CoCl_(2)-treated ENO1-sh group were significantly elevated(P < 0.05). Transcriptomic sequencing indicated that CoCl_(2)-induced PDAC cells initiated MAPK signaling. Under hypoxic conditions, PDAC cells upregulated ENO1 expression, thereby accelerating ERK phosphorylation and inhibiting apoptosis(P < 0.05). Consistent results were also observed in a PDAC-bearing mouse hindlimb ischemia model.Conclusions: Hypoxia-induced ENO1 expression promotes ERK phosphorylation and inhibits apoptosis, thus leading to PDAC survival and invasion. These results suggest that ENO1 is a potential therapeutic target for PDAC.
基金supported by the National Natural Science Foundation of China(No.41976145)the Taishan Scholars Climbing Program of Shandong Province of 2019+1 种基金the Science and Technology Major Project of Guangxi(No.AA17202020-4)。
文摘Polyaluminum chloride modified clay(PAC-MC)is a safe and efficient red tide control agent that has been studied and applied worldwide.Although it is well known that the distribution of hydrolytic aluminum species in PAC affects its flocculation,little is known about the influence of particulars aluminum species on the microalgae removal efficiency of PAC-MC;this lack of knowledge creates a bottleneck in the development of more efficient MCs based on aluminum salts.The ferron method was used in this study to quantitatively analyze the distributions of and variations in different hydrolytic aluminum species during the process of microalgae removal by PAC-MC.The results showed that Ala,which made up 5%–20%of the total aluminum,and Alp,which made up 15%–55%of the total aluminum,significantly affected microalgae removal,with Pearson’s correlation coefficients of 0.83 and 0.89,respectively.Most of the aluminum in the PAC-MC sank rapidly into the sediments,but the rate and velocity of settlement were affected by the dose of modified clay.The optimal dose of PAC-MC for precipitating microalgae was determined based on its aluminum profile.These results provide guidance for the precise application of PAC-MC in the control of harmful algal blooms.
