In the process of collating the raw data,the authors noticed an inadvertent mistake occurred in Fig.3b that needs to be corrected after online publication of the article.In Fig.3b,as a result of an error in the graphi...In the process of collating the raw data,the authors noticed an inadvertent mistake occurred in Fig.3b that needs to be corrected after online publication of the article.In Fig.3b,as a result of an error in the graphics panel arrangement process,the band of NEMO was repeatedly inserted asβ-actin by mistake.The correct band is shown as below and in the updated Fig.3b.The correction did not affect any of our results or discussion as present in the original publication.We regret any inconvenience this has caused.展开更多
NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic target.Herein,using a combined strategy of molecular pharmacological phenotypin...NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic target.Herein,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO complex.It destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo.In addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβcomplex.Our study provides some new insights for the development of potent small-molecule PPI inhibitors.展开更多
The Yellow River Estuary(YRE)alternatively experienced channel aggradation and degradation during the period 1990-2016.To study the variation in flood discharge capacity during the process of river bed evolution,bankf...The Yellow River Estuary(YRE)alternatively experienced channel aggradation and degradation during the period 1990-2016.To study the variation in flood discharge capacity during the process of river bed evolution,bankfull characteristic parameters were investigated on the basis of measured hydrological data and surveyed cross-sectional profiles,which was crucial for comprehending the processes and the key factors to cause these rapid changes.A reach-averaged method was presented in this study in order to calculate the characteristic bankfull parameters in the YRE,and this method integrated the geometric mean using the logarithmic transformation with a weighted mean based on the distance between the two successive sections.The reach-averaged bankfull parameters in the tail reach of the Yellow River Estuary(the Lijin-Xihekou reach)during the period 1990-2016 were then calculated.Calculated results indicated that the adoption of a concept of reach-averaged bankfull discharge was much more representative than the cross-sectional bankfull discharge,and the results also indicated that bankfull discharges decreased during the process of channel aggradation,and increased during the process of channel degradation.Finally,an empirical formula and a delayed response function were established between the reach-averaged bankfull discharge and the previous 4-year average fluvial erosion intensity during flood seasons,and both of them were adopted to reproduce the reach-averaged bankfull discharges,and calculated results showed high correlations(R^(2)>0.8)of these two methods.展开更多
文摘In the process of collating the raw data,the authors noticed an inadvertent mistake occurred in Fig.3b that needs to be corrected after online publication of the article.In Fig.3b,as a result of an error in the graphics panel arrangement process,the band of NEMO was repeatedly inserted asβ-actin by mistake.The correct band is shown as below and in the updated Fig.3b.The correction did not affect any of our results or discussion as present in the original publication.We regret any inconvenience this has caused.
基金the National Natural Science Foundation of China(81930112 and 82004089)National Key Research and Development Program of China(No.2018YFC1705900 and 2020YFE0202200)+1 种基金Distinguished professor of Liaoning Province(XLYC2002008)Dalian Science and Technology Leading Talents Project(2019RD15)for financial support.
文摘NEMO/IKKβcomplex is a central regulator of NF-κB signaling pathway,its dissociation has been considered to be an attractive therapeutic target.Herein,using a combined strategy of molecular pharmacological phenotyping,proteomics and bioinformatics analysis,Shikonin(SHK)is identified as a potential inhibitor of the IKKβ/NEMO complex.It destabilizes IKKβ/NEMO complex with IC_(50) of 174 nM,thereby significantly impairing the proliferation of colorectal cancer cells by suppressing the NF-κB pathway in vitro and in vivo.In addition,we also elucidated the potential target sites of SHK in the NEMO/IKKβcomplex.Our study provides some new insights for the development of potent small-molecule PPI inhibitors.
基金supported by the Program of the National Key Research and Development Plan(No.2017YFC0405501)supported partly by the National Natural Science Foundation of China(Grant Nos.51725902,51579186,51809196).
文摘The Yellow River Estuary(YRE)alternatively experienced channel aggradation and degradation during the period 1990-2016.To study the variation in flood discharge capacity during the process of river bed evolution,bankfull characteristic parameters were investigated on the basis of measured hydrological data and surveyed cross-sectional profiles,which was crucial for comprehending the processes and the key factors to cause these rapid changes.A reach-averaged method was presented in this study in order to calculate the characteristic bankfull parameters in the YRE,and this method integrated the geometric mean using the logarithmic transformation with a weighted mean based on the distance between the two successive sections.The reach-averaged bankfull parameters in the tail reach of the Yellow River Estuary(the Lijin-Xihekou reach)during the period 1990-2016 were then calculated.Calculated results indicated that the adoption of a concept of reach-averaged bankfull discharge was much more representative than the cross-sectional bankfull discharge,and the results also indicated that bankfull discharges decreased during the process of channel aggradation,and increased during the process of channel degradation.Finally,an empirical formula and a delayed response function were established between the reach-averaged bankfull discharge and the previous 4-year average fluvial erosion intensity during flood seasons,and both of them were adopted to reproduce the reach-averaged bankfull discharges,and calculated results showed high correlations(R^(2)>0.8)of these two methods.
