Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising st...Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.展开更多
Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and mole...Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.展开更多
In recent years,the pursuit of high-efficiency electrochemical storage technology,the multivalent metalion batteries (MIBs) based on aqueous electrolytes have been widely explored by researchers because of their safet...In recent years,the pursuit of high-efficiency electrochemical storage technology,the multivalent metalion batteries (MIBs) based on aqueous electrolytes have been widely explored by researchers because of their safety,environmental friendliness,abundant reserves and low price,and especially the merits in energy and power densities.This review firstly expounds on the problems existing in the electrode materials of aqueous multivalent MIBs (Zn^(2+),Mg^(2+),Al^(3+),Ca^(2+)),from the classical inorganic materials to the emerging organic compounds,and then summarizes the design strategies in bulk and interface structure of electrodes with favorable kinetics and stable cycling performance,especially laying the emphasis on the charge storage mechanism of cathode materials and dendrite-free Zinc anode from the aspect of electrolyte optimization strategies,which can be extended to other aqueous multivalent MIBs.Ultimately,the possible development directions of the aqueous multivalent MIBs in the future are provided,anticipating to provide a meaningful guideline for researchers in this area.展开更多
The development of lithium(Li)metal batteries has been severely limited by the formation of lithium dendrites and the associated catastrophic failure and inferior Coulombic efficiency which caused by non-uniform or in...The development of lithium(Li)metal batteries has been severely limited by the formation of lithium dendrites and the associated catastrophic failure and inferior Coulombic efficiency which caused by non-uniform or insufficient Li^(+)supply across the electrode-electrolyte interface.Therefore,a rational strategy is to construct a robust electrolyte that can allow efficient and uniform Li^(+)transport to ensure sufficient Li^(+)supply and homogenize the Li plating/stripping.Herein,we report an ion-percolating electrolyte membrane that acts as a stable Li^(+)reservoir to ensure a near-single Li^(+)transference number(0.78)and homogenizes Li^(+)migration to eradicate dendrite growth,endowing Li//LFP cell with an ultrahigh average Coulombic efficiency(ca.99.97%)after cycling for nearly half of a year and superior cycling stability when pairing with LiCoO_(2) with limited Li amount and LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2).These estimable attributes demonstrate significant potential of utility value for the ion-percolating electrolyte.展开更多
基金supported by the National Natural Science Foundation of China (82021001,31825018)National Key Research and Development Program of China (2022YFF0710901)+3 种基金Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32060100)Biological Resources Program of Chinese Academy of Sciences (KFJ-BRP-005)National Science and Technology Innovation 2030 Major Program 2021ZD0200900。
文摘Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.
文摘Objective:Glucose-6-phosphate isomerase(GPI)deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants.This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics,often posing challenges for precise diagnoses using conventional methods.To this end,this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family.Methods:The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis.Novel compound heterozygous variants of the GPI gene,c.174C>A(p.Asn58Lys)and c.1538G>T(p.Trp513Leu),were identified using whole-exome and Sanger sequencing.The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure.Results:By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study,we found that most variants were located in exons 3,4,12,and 18,with a few localized in exons 8,9,and 14.This study identified novel compound heterozygous variants associated with GPI deficiency.These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids.Conclusion:Early family-based sequencing analyses,especially for patients with congenital anemia,can help increase diagnostic accuracy for GPI deficiency,improve child healthcare,and enable genetic counseling.
基金supported by the National Key R&D Program of China(2016YFA0202500)the Natural Science Foundation of China(51803054,51772093)+1 种基金the Natural Science Foundation of Hunan province(2020JJ3022,2019JJ50223,2019JJ20010)the foundation from Education Department of Hunan Province(19B270,SYL201802008)。
文摘In recent years,the pursuit of high-efficiency electrochemical storage technology,the multivalent metalion batteries (MIBs) based on aqueous electrolytes have been widely explored by researchers because of their safety,environmental friendliness,abundant reserves and low price,and especially the merits in energy and power densities.This review firstly expounds on the problems existing in the electrode materials of aqueous multivalent MIBs (Zn^(2+),Mg^(2+),Al^(3+),Ca^(2+)),from the classical inorganic materials to the emerging organic compounds,and then summarizes the design strategies in bulk and interface structure of electrodes with favorable kinetics and stable cycling performance,especially laying the emphasis on the charge storage mechanism of cathode materials and dendrite-free Zinc anode from the aspect of electrolyte optimization strategies,which can be extended to other aqueous multivalent MIBs.Ultimately,the possible development directions of the aqueous multivalent MIBs in the future are provided,anticipating to provide a meaningful guideline for researchers in this area.
基金National Natural Science Foundation of China,Grant/Award Number:51803054Basic Science Center Project of the National Key R&D Program of China,Grant/Award Number:2021YFB2400400+2 种基金Science and Technology Innovation Program of Hunan Province,Grant/Award Number:2023RC3154Natural Science Foundation of Hunan Province,Grant/Award Numbers:2019JJ50223,2020JJ3022Foundation from Education Department of Hunan Province,Grant/Award Number:19B270。
文摘The development of lithium(Li)metal batteries has been severely limited by the formation of lithium dendrites and the associated catastrophic failure and inferior Coulombic efficiency which caused by non-uniform or insufficient Li^(+)supply across the electrode-electrolyte interface.Therefore,a rational strategy is to construct a robust electrolyte that can allow efficient and uniform Li^(+)transport to ensure sufficient Li^(+)supply and homogenize the Li plating/stripping.Herein,we report an ion-percolating electrolyte membrane that acts as a stable Li^(+)reservoir to ensure a near-single Li^(+)transference number(0.78)and homogenizes Li^(+)migration to eradicate dendrite growth,endowing Li//LFP cell with an ultrahigh average Coulombic efficiency(ca.99.97%)after cycling for nearly half of a year and superior cycling stability when pairing with LiCoO_(2) with limited Li amount and LiNi_(0.8)Mn_(0.1)Co_(0.1)O_(2).These estimable attributes demonstrate significant potential of utility value for the ion-percolating electrolyte.
