The p60 subunit of the chromatin assembly factor-1 complex,that is,chromatin assembly factor-1 subunit B(CHAF1B),is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self...The p60 subunit of the chromatin assembly factor-1 complex,that is,chromatin assembly factor-1 subunit B(CHAF1B),is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal.CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy.However,its expression and clinical significance in lung squamous-cell carcinoma(LUSC)remain unclear.In this study,we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates.Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes.Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo.Furthermore,bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7(SETD7)as a significant CHAF1B target gene.In addition,CHAF1B competitively binds to the SETD7 promoter region and represses its transcription.Altogether,these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.展开更多
In arid and semi-arid zones,water is the most vulnerable resource to climate change.In fact,various techniques such as artificial recharge are adopted to restore aquifers and to ensure aquifer sustainability in relati...In arid and semi-arid zones,water is the most vulnerable resource to climate change.In fact,various techniques such as artificial recharge are adopted to restore aquifers and to ensure aquifer sustainability in relation to the accelerated pace of exploitation.Morocco is a Mediterranean country highly vulnerable to climate change,many of its main aquifers are subjected to excessive drawdowns.This technique is practiced to increase potentiality of these aquifers.In the Northwestern area of Morocco,the significant development experienced by Tangier City in the industrial,tourism,and commercial sectors will lead to increased water requirements-up to 5 067 L/s(159.8 mm^3)by 2030.However,the Charf El Akab aquifer system,subject to artificial recharge,is the only groundwater resource of Tangier region;hence,a rational management context is needed to ensure aquifer sustainability,and optimized exploitation under the background of differing constraints,such as increased water requirements,and climate change impacts.This work aims to respond,for the first time,to the Charf El Akab aquifer overexploitation problem,and to evaluate the future scenarios of its exploitation in the event of failure of one of the superficial resources.This work also presents a synthesized hydrodynamic modeling based on the results of the numerical simulations carried out using Feflow software for 2004(date of cessation of injections)and 2011(date of resumption of these facilities),making it possible to evaluate the impact of the artificial recharge on the piezometric level of the aquifer on a spatiotemporal scale.Finally,the exploitation scenarios have shown that the aquifer of Charf El Akab will not adequatly provide for the region's water requirements on the future horizon,entailing an optimal management of water resources in the region and an intentionally increased recharge rate.展开更多
基金supported by the National Key Research and Development Program of China(Nos.2022YFA1103900 and 2020YFA0803300)CAMS Initiative for Innovative Medicine(Nos.2021-1-I2M-012,2021-I2M-1-014,2022-I2M-2-001,2021-I2M-1-021,and 2022-I2M-1-009)+1 种基金the Non-Profit Central Research Institute Fund of CAMS(Nos.2022-RC310-05 and 2021-RC310-003)the National Natural Science Foundation of China(Nos.82372944,82073092,and 82273076).
文摘The p60 subunit of the chromatin assembly factor-1 complex,that is,chromatin assembly factor-1 subunit B(CHAF1B),is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal.CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy.However,its expression and clinical significance in lung squamous-cell carcinoma(LUSC)remain unclear.In this study,we performed weighted gene correlation network analysis to analyze the Gene Expression Omnibus GSE68793 LUSC dataset and identified CHAF1B as one of the most important driver gene candidates.Immunohistochemical analysis of 126 LUSC tumor samples and 80 adjacent normal lung tissues showed the marked upregulation of CHAF1B in tumor tissues and the negative association of its expression level with patient survival outcomes.Silencing of CHAF1B suppressed LUSC proliferation in vitro and LUSC tumor growth in vivo.Furthermore,bulk RNA sequencing of CHAF1B knockdown cells indicated SET domain containing 7(SETD7)as a significant CHAF1B target gene.In addition,CHAF1B competitively binds to the SETD7 promoter region and represses its transcription.Altogether,these results imply that CHAF1B plays a vital role in LUSC tumorigenesis and may represent a potential molecular target for this deadly disease.
文摘In arid and semi-arid zones,water is the most vulnerable resource to climate change.In fact,various techniques such as artificial recharge are adopted to restore aquifers and to ensure aquifer sustainability in relation to the accelerated pace of exploitation.Morocco is a Mediterranean country highly vulnerable to climate change,many of its main aquifers are subjected to excessive drawdowns.This technique is practiced to increase potentiality of these aquifers.In the Northwestern area of Morocco,the significant development experienced by Tangier City in the industrial,tourism,and commercial sectors will lead to increased water requirements-up to 5 067 L/s(159.8 mm^3)by 2030.However,the Charf El Akab aquifer system,subject to artificial recharge,is the only groundwater resource of Tangier region;hence,a rational management context is needed to ensure aquifer sustainability,and optimized exploitation under the background of differing constraints,such as increased water requirements,and climate change impacts.This work aims to respond,for the first time,to the Charf El Akab aquifer overexploitation problem,and to evaluate the future scenarios of its exploitation in the event of failure of one of the superficial resources.This work also presents a synthesized hydrodynamic modeling based on the results of the numerical simulations carried out using Feflow software for 2004(date of cessation of injections)and 2011(date of resumption of these facilities),making it possible to evaluate the impact of the artificial recharge on the piezometric level of the aquifer on a spatiotemporal scale.Finally,the exploitation scenarios have shown that the aquifer of Charf El Akab will not adequatly provide for the region's water requirements on the future horizon,entailing an optimal management of water resources in the region and an intentionally increased recharge rate.
