During the Sino\|American Expedition to Mt. Qomolangma in May 1997, a 41m ice core was recovered from an elevation of 6500m from the northern branch firn basin of the Far East Rongbuk Glacier in Mt. Everest. The ice c...During the Sino\|American Expedition to Mt. Qomolangma in May 1997, a 41m ice core was recovered from an elevation of 6500m from the northern branch firn basin of the Far East Rongbuk Glacier in Mt. Everest. The ice core was dated down to 1814 by counting δ 18 O peaks and referring to the variations of β activity and major ion concentrations. The average annual accumulation is 224mm (ice equivalent). Five cold periods and five warm periods have been reconstructed from the ice core for the last 200 years and the general tendency of climatic change is warming, which is agree with the temperature change in the Northern Hemisphere. Also the climatic records in Far East Rongbuk ice core has good agreement with that in the Guliya ice core. This indicates that the climatic changes are consistent in the northwestern and southern Qinghai—Tibetan Plateau, and the ranges of climatic changes are larger in southern Plateau than that in northwestern Plateau. Though the δ 18 O variations has some negatively correlation with precipitation amount for short time scale, these do not effect δ 18 O changes reflecting temperature for long time scale.展开更多
Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o ...Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.展开更多
文摘During the Sino\|American Expedition to Mt. Qomolangma in May 1997, a 41m ice core was recovered from an elevation of 6500m from the northern branch firn basin of the Far East Rongbuk Glacier in Mt. Everest. The ice core was dated down to 1814 by counting δ 18 O peaks and referring to the variations of β activity and major ion concentrations. The average annual accumulation is 224mm (ice equivalent). Five cold periods and five warm periods have been reconstructed from the ice core for the last 200 years and the general tendency of climatic change is warming, which is agree with the temperature change in the Northern Hemisphere. Also the climatic records in Far East Rongbuk ice core has good agreement with that in the Guliya ice core. This indicates that the climatic changes are consistent in the northwestern and southern Qinghai—Tibetan Plateau, and the ranges of climatic changes are larger in southern Plateau than that in northwestern Plateau. Though the δ 18 O variations has some negatively correlation with precipitation amount for short time scale, these do not effect δ 18 O changes reflecting temperature for long time scale.
文摘Industrial activities such as smelting emissions,mineral combustion and industrial wastewater discharge might lead to copper pollution in the environment.This kind of copper pollution has harmful effects on aquatic o rganisms,plants and animals through direct or indirect exposure.However,the current understanding of the toxicity of copper is rather limited.Copper overload can perturb intracellular homeostasis and induce oxidative stress and e ven cell death.Recently,cuproptosis has been identified as a copper-dependent form of cell death induced by o xidative stress in mitochondria.We uncover here that zinc transporter 1(ZNT1)is an important regulator involved in cuproptosis.Firstly,we established the copper overload-induced cell death model with the overexpression of copper importer SLC31A1 in HeLa cells.Using this model,we conducted unbiased genome-wide CRISPR-Cas9 screens in cells treated with copper.Our results revealed a significant enrichment of ZNT1 gene in both library A and library B plasmids.Knocking out of ZNT1 in HeLa cells notably prevented cuproptosis.Subsequent knockout of metal transcription factor 1(MTF1)in ZNT1-deficient cells nearly abolished their ability to resist copper-induced cell death.However,overexpression of metallothionein 1X(MT1X)in the double-knockout cells could p artially restored the resistance to cuproptosis by loss of MTF1.Mechanistically,knockout of ZNT1 could promote MT1X expression by activating MTF1.As a consequence,the interaction between MT1X and copper was e nhanced,reducing the flow of copper into mitochondria and eliminating mitochondria damage.Taken together,this study reveals the important role of ZNT1 in cuproptosis and shows MTF1-MT1X axis mediated resistance to c uproptosis.Moreover,our study will help to understand the regulatory mechanism of cellular and systemic copper homeostasis under copper overload,and present insights into novel treatments for damages caused by both genetic copper overload diseases and environmental copper contamination.
