Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective ...Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.展开更多
In the field of medical imaging,the traditional local binary pattern (LBP)and its improved algorithms are often sensitive to noise.Traditional LBPs are solely based on the signal information from local differences,and...In the field of medical imaging,the traditional local binary pattern (LBP)and its improved algorithms are often sensitive to noise.Traditional LBPs are solely based on the signal information from local differences,and the binary quantization method oversimplifies the local texture features while disregarding the imaging information from the concaveconvex regions between the high-order pixels and the neighboring sampling points.Therefore,we propose an improved Derived Mean Complete Local Binary Pattern (DM_CLBP) algorithm based on high-order derivatives.In the DM_CLBP method,the grey value of a single pixel is replaced by the mean grey value of the rectangular area block,and the difference between pixel values in the area is obtained using the second-order differentiation method.Based on the calculation concept of the complete local binary pattern (CLBP)algorithm,the cascade signs and magnitudes of the two components are encoded and recombined in DM_CLBP using a uniform pattern.The results from the experiments showed that the proposed DM_CLBP descriptors achieved a classification accuracy of 94.4%.Compared with LBP and other improved algorithms,the DM_CLBP algorithm presented in this study can effectively differentiate between lesion areas and normal areas in thyroid MR,(magnetic resonance)images and shows the improved accuracy of area classification.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.82104281,81922070,81973286,81801818 and 82273897)Shanghai Municipal Health Commission’s TCM research project(No.2022CX005)+1 种基金Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004)Three-year Action Plan for Shanghai TCM Development and Inheritance Program[No.ZY(2021–2023)-0401]。
文摘Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.
基金the National Natural Science Foundation of China under Grant Nos_61728205,61772242,61402204, and 61572239the Natural Science Foundation of Jiangsu Province of China under Grant No.BK20130529+3 种基金the Research Fund for Advanced Talents of Jiangsu University of China under Grant No.14JDG141the Science and Technology Project of Zhenjiang City of China under Grant No.SH20140110the Special Software Development Foundation of Zhenjiang City of China under Grant No.201322the Science and Technology Support Foundation of Zhenjiang City (Industrial)under Grant No.GY2014013.
文摘In the field of medical imaging,the traditional local binary pattern (LBP)and its improved algorithms are often sensitive to noise.Traditional LBPs are solely based on the signal information from local differences,and the binary quantization method oversimplifies the local texture features while disregarding the imaging information from the concaveconvex regions between the high-order pixels and the neighboring sampling points.Therefore,we propose an improved Derived Mean Complete Local Binary Pattern (DM_CLBP) algorithm based on high-order derivatives.In the DM_CLBP method,the grey value of a single pixel is replaced by the mean grey value of the rectangular area block,and the difference between pixel values in the area is obtained using the second-order differentiation method.Based on the calculation concept of the complete local binary pattern (CLBP)algorithm,the cascade signs and magnitudes of the two components are encoded and recombined in DM_CLBP using a uniform pattern.The results from the experiments showed that the proposed DM_CLBP descriptors achieved a classification accuracy of 94.4%.Compared with LBP and other improved algorithms,the DM_CLBP algorithm presented in this study can effectively differentiate between lesion areas and normal areas in thyroid MR,(magnetic resonance)images and shows the improved accuracy of area classification.
