The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem ...The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.展开更多
Here we report that the presence of MgCO_(3) stimulates the extracellular polymeric substance (EPS) secretion of Microcystis Aeruginosa (M. Aeruginosa). This stimulation led to a significant reduction in the total con...Here we report that the presence of MgCO_(3) stimulates the extracellular polymeric substance (EPS) secretion of Microcystis Aeruginosa (M. Aeruginosa). This stimulation led to a significant reduction in the total concentration of NH_(4)^(+)‒N by more than 86%, and effective recovery of PO_(4)^(3-)‒P within three days from concentrated wastewater (WW), although the secreted EPS inhibited the conversion of MgCO_(3) to specific crystal forms (MgNH4PO4.6H2O or MgHPO4.7H2O). Moreover, with an increase in PO_(4)^(3-) concentration in WW, these crystals appeared, thus the removal of NH_(4)^(+)‒N and PO_(4)^(3-)‒P nutrients can be attributed to the combined effect of M. Aeruginosa and MgCO_(3). We used Surface-Enhanced Raman Spectroscopy (SERS) combined with X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (FESEM-EDS), and X-ray Photoelectron Spectroscopy (XPS) to investigate the mechanism for competitive interactions between M. Aeruginosa and MgCO_(3) in removing NH_(4)^(+)‒N and PO_(4)^(3-)‒P. We identified that the bound EPS accumulated amorphous Mg–P–O dense particles on M. Aeruginosa, while soluble EPS, containing –COOH groups of humic-like substances decreased the pH of the solution and coordinated with Mg^(2+) ions. Therefore, both secreted bound and soluble EPS play a vital role in hindering the transformation of Mg^(2+) ions or MgCO_(3) to MgNH4PO4.6H2O or MgHPO4.7H2O crystals within WW, and they enhanced M. Aeruginosa 's ability in absorbing nutrients of NH_(4)^(+)‒N and PO_(4)^(3-)‒P. This mechanism plays a crucial role in the efficient recovery of NH_(4)^(+)‒N and PO_(4)^(3-)‒P from concentrated wastewater sources such as aerobically or anaerobically digested effluent from various sources like agriculture, livestock, and domestic wastewaters.展开更多
基金funded by the NIH Office of Research Infrastructure Programs(P40 OD010440)supported by the National Natural Science Foundation of China(82471893 and 82070913)+2 种基金Key discipline project of Hongkou District Health Commission(HKLCFC202403)Tongji Hospital Start-up Funding for Scientific Research(RCQD2301)Research fund from Shanghai Fourth People's Hospital(sykyqd01801,SYXKZT-2021-1001).
文摘The mitochondrial 3243A>G mutation(m.3243A>G)is associated with diverse clinical phenotypes.To elucidate the underlying mechanisms and explore intervention strategies in m.3243A>G patients,urine-derived stem cells(USCs)and a mitochondrial leucyl-tRNA synthetase gene(lars-2)deficient Caenorhabditis elegans(C.elegans)model are used to assess mitochondrial homeostasis and neuromuscular dysfunction.Patient-derived USCs with high levels of m.3243A>G heteroplasmy exhibit impaired mitochondrial function,disrupted mitochondrial dynamics,and inhibited mitophagy,which are reversed by MitoQ through suppression of OMA1 zinc metallopeptidase(OMA1)-induced mitochondrial phosphatase and tensin(PTEN)induced kinase 1(PINK1)degradation.Furthermore,lars-2 knockdown in C.elegans induces mitochondrial stress and mimics the loss of neural and muscle functions observed in patients with the m.3243A>G mutation.MitoQ treatment partially improves neurobehavioral function by promoting the PINK1 pathway.These findings suggest that MitoQ has therapeutic potential in the context of the m.3243A>G mutation.
基金supported by Cultivating Fund Project of Hubei Hongshan Laboratory(2022hspy002).
文摘Here we report that the presence of MgCO_(3) stimulates the extracellular polymeric substance (EPS) secretion of Microcystis Aeruginosa (M. Aeruginosa). This stimulation led to a significant reduction in the total concentration of NH_(4)^(+)‒N by more than 86%, and effective recovery of PO_(4)^(3-)‒P within three days from concentrated wastewater (WW), although the secreted EPS inhibited the conversion of MgCO_(3) to specific crystal forms (MgNH4PO4.6H2O or MgHPO4.7H2O). Moreover, with an increase in PO_(4)^(3-) concentration in WW, these crystals appeared, thus the removal of NH_(4)^(+)‒N and PO_(4)^(3-)‒P nutrients can be attributed to the combined effect of M. Aeruginosa and MgCO_(3). We used Surface-Enhanced Raman Spectroscopy (SERS) combined with X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy (FESEM-EDS), and X-ray Photoelectron Spectroscopy (XPS) to investigate the mechanism for competitive interactions between M. Aeruginosa and MgCO_(3) in removing NH_(4)^(+)‒N and PO_(4)^(3-)‒P. We identified that the bound EPS accumulated amorphous Mg–P–O dense particles on M. Aeruginosa, while soluble EPS, containing –COOH groups of humic-like substances decreased the pH of the solution and coordinated with Mg^(2+) ions. Therefore, both secreted bound and soluble EPS play a vital role in hindering the transformation of Mg^(2+) ions or MgCO_(3) to MgNH4PO4.6H2O or MgHPO4.7H2O crystals within WW, and they enhanced M. Aeruginosa 's ability in absorbing nutrients of NH_(4)^(+)‒N and PO_(4)^(3-)‒P. This mechanism plays a crucial role in the efficient recovery of NH_(4)^(+)‒N and PO_(4)^(3-)‒P from concentrated wastewater sources such as aerobically or anaerobically digested effluent from various sources like agriculture, livestock, and domestic wastewaters.
