选取150份干扰物和浓度不同的葡萄糖样本数据,按照全干扰、缺失胆固醇、缺失乳酸、缺失白蛋白和缺失尿素将数据划分5个子集。每个子集进行卷积平滑滤波法(Savitzky-Golay smoothing,SG)处理后,建立偏最小二乘回归(Partial Least Squares...选取150份干扰物和浓度不同的葡萄糖样本数据,按照全干扰、缺失胆固醇、缺失乳酸、缺失白蛋白和缺失尿素将数据划分5个子集。每个子集进行卷积平滑滤波法(Savitzky-Golay smoothing,SG)处理后,建立偏最小二乘回归(Partial Least Squares Regression,PLSR)模型。利用克拉克误差网格(Clarke Error Grid,CEG)及t检验分析4种干扰物对葡萄糖预测影响。结果表明,子集1~5对应模型预测集相关系数(Correlation Coefficient of Prediction,R p)分别为0.9131、0.7115、0.7624、0.8578和0.8658,预测集均方根误差(Root Mean Square Error of Prediction,RMSEP)分别为54.8993、239.5512、162.3715、133.9682和106.0521 mg/dL。5个子集位于CEG的A+B区分别为100%、71.43%、66.66%、85.71%和88.89%。t检验中每1 mg/dL的胆固醇、乳酸和白蛋白分别使葡萄糖预测值降低5.288 mg/dL、增高2.214 mg/dL和增高0.031 mg/dL。故胆固醇和乳酸的影响相当显著,其次是白蛋白,而尿素的影响则相对较弱。因此,在中红外血糖定量分析中必须考虑胆固醇、乳酸和白蛋白对血糖检测的影响。展开更多
Urban expansion, which has affected ecosystem functioning and services at local to global scale, is projected to have aggravating impacts on landscape in the future. A detailed study on spatiotemporal patterns of Hong...Urban expansion, which has affected ecosystem functioning and services at local to global scale, is projected to have aggravating impacts on landscape in the future. A detailed study on spatiotemporal patterns of Hongta District in Yuxi City over a relatively long timeframe was conducted using multi-temporal Landsat TM, ETM+ and OLI data of 1987-2017 associated with Geographic Information System techniques and landscape analysis approaches. Results showed that sealed surfaces (urban area) have expanded from 1.4% to 11.8%, with an annually increasing rate of 7.63%. Trees, farm areas and barren lands all underwent a slight reduction during this time period, whereby 23.8% of farms and 9.8% of bare lands transferred into sealed surfaces. Focusing on the urban expansion pattern, it presents a uninuclear polarizing polygon mode illustrating the urbanization sprawl over time to all directions. The greatest expansions are seen in NNE and SSE direction, mainly because of the topographic constraints. A trade-off between urbanization and sustainable development is under investigation by reclaiming barren soil at the mountain range to transfer farming areas from low altitude plains to make way for urban growth.展开更多
Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiti...Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.展开更多
Feed-forward loops(FFLs)are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases.Enhancers are cis-regulatory elements that positively regulate prot...Feed-forward loops(FFLs)are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases.Enhancers are cis-regulatory elements that positively regulate protein-coding genes or microRNAs(miRNAs)by recruiting DNA-binding transcription factors(TFs).However,a comprehensive resource to identify,store,and analyze the FFLs of typical enhancer and super-enhancer FFLs is not currently available.Here,we present EnhFFL,an online database to provide a data resource for users to browse and search typical enhancer and super-enhancer FFLs.The current database covers 46280/7000 TFenhancer-miRNA FFLs,9997/236 enhancer-miRNA-gene FFLs,3561164/3193182 TF-enhancer-gene FFLs,and 1259/235 TF-enhancer feed-back loops(FBLs)across 91 tissues/cell lines of human and mouse,respectively.Users can browse loops by selecting species,types of tissue/cell line,and types of FFLs.EnhFFL supports searching elements including name/ID,genomic location,and the conservation of miRNA target genes.We also developed tools for users to screen customized FFLs using the threshold of q value as well as the confidence score of miRNA target genes.Disease and functional enrichment analysis showed that master miRNAs that are widely engaged in FFLs including TF-enhancer-miRNAs and enhancer-miRNA-genes are significantly involved in tumorigenesis.Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.展开更多
文摘Urban expansion, which has affected ecosystem functioning and services at local to global scale, is projected to have aggravating impacts on landscape in the future. A detailed study on spatiotemporal patterns of Hongta District in Yuxi City over a relatively long timeframe was conducted using multi-temporal Landsat TM, ETM+ and OLI data of 1987-2017 associated with Geographic Information System techniques and landscape analysis approaches. Results showed that sealed surfaces (urban area) have expanded from 1.4% to 11.8%, with an annually increasing rate of 7.63%. Trees, farm areas and barren lands all underwent a slight reduction during this time period, whereby 23.8% of farms and 9.8% of bare lands transferred into sealed surfaces. Focusing on the urban expansion pattern, it presents a uninuclear polarizing polygon mode illustrating the urbanization sprawl over time to all directions. The greatest expansions are seen in NNE and SSE direction, mainly because of the topographic constraints. A trade-off between urbanization and sustainable development is under investigation by reclaiming barren soil at the mountain range to transfer farming areas from low altitude plains to make way for urban growth.
基金supported by the National Natural Science Foundation of China (Grants 31771549 to Y.C.,82103251 to J.Z.,82203153 to K.Z.,and 82203574 to S.W.)the 1.3.5 Project for Disciplines of Excellence (Grants ZYGD18021,ZYJC18009,ZYJC21002,and ZYJC21015)+1 种基金the China Postdoctoral Science Foundation (Grants 2020TQ0210 and 2021M692268 to J.Z.)Natural Science Foundation of Sichuan Province (Grant 2022NSFSC1438 to J.Z.).
文摘Despite epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors(TKl)have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer(NSCLC),acquired resistance inevitably develops,limiting clinical efficacy.We found that TET2 was poly-ubiquitinated by E3 ligase CUL7^(FBXW11) and degraded in EGFR-TKI resistant NSCLC ells.Genetic perturbationof TET2 rendered parental cells more tolerant to TKI treatment.TET2 was stabilized by MEK1 phosphorylation at Ser 1107,while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7^(FBXW11),Loss of TET2 resulted in the upregulation of TNF/NF-kB signaling that confers the EGFR-TKI resistance.Genetic or pharmacological inhibition of NF-kB attenuate the TKI resistance both in vitro and in vivo.Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2,and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency.Therefore,combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.
基金The research was supported by the Basic Research Cultivation Support Programof Fundamental Research Funds for the Central Universities,the National Natural Science Foundation of China(Grant No.32071343)the Sichuan Science and Technology Program(Grant No.2021YJ0048).
文摘Feed-forward loops(FFLs)are thought to be one of the most common and important classes of transcriptional network motifs involved in various diseases.Enhancers are cis-regulatory elements that positively regulate protein-coding genes or microRNAs(miRNAs)by recruiting DNA-binding transcription factors(TFs).However,a comprehensive resource to identify,store,and analyze the FFLs of typical enhancer and super-enhancer FFLs is not currently available.Here,we present EnhFFL,an online database to provide a data resource for users to browse and search typical enhancer and super-enhancer FFLs.The current database covers 46280/7000 TFenhancer-miRNA FFLs,9997/236 enhancer-miRNA-gene FFLs,3561164/3193182 TF-enhancer-gene FFLs,and 1259/235 TF-enhancer feed-back loops(FBLs)across 91 tissues/cell lines of human and mouse,respectively.Users can browse loops by selecting species,types of tissue/cell line,and types of FFLs.EnhFFL supports searching elements including name/ID,genomic location,and the conservation of miRNA target genes.We also developed tools for users to screen customized FFLs using the threshold of q value as well as the confidence score of miRNA target genes.Disease and functional enrichment analysis showed that master miRNAs that are widely engaged in FFLs including TF-enhancer-miRNAs and enhancer-miRNA-genes are significantly involved in tumorigenesis.Database URL:http://lcbb.swjtu.edu.cn/EnhFFL/.
