The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibit...The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.展开更多
Present monitoring and prediction of schistosomiasis’s intermediate parasite, snail, are based on re-mote sensing image’s spectral signatures, and the calculation result is in fact an incom-plete-constraints solutio...Present monitoring and prediction of schistosomiasis’s intermediate parasite, snail, are based on re-mote sensing image’s spectral signatures, and the calculation result is in fact an incom-plete-constraints solution. TM image of the Poyang Lake region on October 31, 2005 was combined with GIS thematic data (DEM, boundary of the Poyang Lake, vegetation, soil and land use) to make a prediction on snail spatial distribution in the region by remote sensing, geo-informatics and knowl-edge-driven modeling according to mechanism of snail occurrence. Result shows that with change of overall fuzzy membership of snail occurrence from high to low, snail occurrence of the snail samples of validation group goes up to 81% within 10% high fuzzy membership range, denoting high efficiency of the model in predicting snail occurrence.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82125036,82273964,81973363,82304538,81973188)the State Key Laboratory of Natural Medicines of CPU(No.SKLNMZZ202207)+3 种基金the“Double-First Class”Program of CPU,the National Key Research and Development Program of China(No.2017YFA0503900)the Jiangsu Provincial Natural Science Fund for Distinguished Young Scholar(No.BK20230042)the Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2023ZB171)the Shenzhen Fundamental Research Program(No.JCYJ20200109114225087).
文摘The tumor suppressor protein p53 is central to cancer biology,with its pathway reactivation emerging as a promising therapeutic strategy in oncology.This study introduced LZ22,a novel compound that selectively inhibits the growth,migration,and metastasis of tumor cells expressing wild-type p53,demonstrating ineffectiveness in cells devoid of p53 or those expressing mutant p53.LZ22’s mechanism of action involves a high-affinity interaction with the histidine-96 pocket of the MDM2 protein.This interaction disrupted the MDM2-p53 binding,consequently stabilizing p53 by shielding it from proteasomal degradation.LZ22 impeded cell cycle progression and diminished cell proliferation by reinstating the p53-dependent suppression of the CDK2/Rb signaling pathway.Moreover,LZ22 alleviated the p53-dependent repression of Snail transcription factor expression and its consequent EMT,effectively reducing tumor cell migration and distal metastasis.Importantly,LZ22 administration in tumor-bearing mice did not manifest notable side effects.The findings position LZ22 as a structurally unique reactivator of p53,offering therapeutic promise for the management of human cancers with wild-type TP53.
基金the research project of Jiangxi Provincial Educational Bureau in 2007 (No. 137[2007])the National Natural Science Foundation of China (Grant No. 30590370)
文摘Present monitoring and prediction of schistosomiasis’s intermediate parasite, snail, are based on re-mote sensing image’s spectral signatures, and the calculation result is in fact an incom-plete-constraints solution. TM image of the Poyang Lake region on October 31, 2005 was combined with GIS thematic data (DEM, boundary of the Poyang Lake, vegetation, soil and land use) to make a prediction on snail spatial distribution in the region by remote sensing, geo-informatics and knowl-edge-driven modeling according to mechanism of snail occurrence. Result shows that with change of overall fuzzy membership of snail occurrence from high to low, snail occurrence of the snail samples of validation group goes up to 81% within 10% high fuzzy membership range, denoting high efficiency of the model in predicting snail occurrence.
