Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
A chemo-mechanical model is developed to investigate the effects on the stress development of the coating of polycrystalline Ni-rich LiNixMnyCo_(z)O_(2)(x≥0.8)(NMC)particles with poly(3,4-ethylenedioxythiophene)(PEDO...A chemo-mechanical model is developed to investigate the effects on the stress development of the coating of polycrystalline Ni-rich LiNixMnyCo_(z)O_(2)(x≥0.8)(NMC)particles with poly(3,4-ethylenedioxythiophene)(PEDOT).The simulation results show that the coating of primary NMC particles significantly reduces the stress generation by efficiently accommodating the volume change associated with the lithium diffusion,and the coating layer plays roles both as a cushion against the volume change and a channel for the lithium transport,promoting the lithium distribution across the secondary particles more homogeneously.Besides,the lower stiffness,higher ionic conductivity,and larger thickness of the coating layer improve the stress mitigation.This paper provides a mathematical framework for calculating the chemo-mechanical responses of anisotropic electrode materials and fundamental insights into how the coating of NMC active particles mitigates stress levels.展开更多
Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,an...Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,and 0.20)materials are successfully prepared by using solid-state method at 925℃for 4 h with 2.5-wt%Bi_(2)O_(3)sintering aids.The content of Gd^(3+)ion can affect micromorphology,grain size,bulk density,and magneto-dielectric properties of the ferrite.With Gd^(3+)ion content increasing,saturation magnetization(Ms)first increases and then decreases.The maximum value of Ms is 44.86 emu/g at x=0.15.Additionally,sites occupied by Gd^(3+)ions can change magnetic anisotropy constant of the ferrite.Magnetocrystalline anisotropy constant(K_1)is derived from initial magnetization curve,and found to be related to spin-orbit coupling and intersublattice interactions between metal ions.The real part of magnetic permeability(μ′)and real part of dielectric permittivity(ε′)are measured in a frequency range of 10 MHz-1 GHz.When x=0.15,material has excellent magneto-dielectric properties(μ′≈12.2 andε′≈17.61),low magnetic loss(tanδμ≈0.03 at 500 MHz),and dielectric loss(tanδε≈0.04 at 500 MHz).The results show that Gd-doped Co_(2)Z ferrite has broad application prospects in multilayer filters and high-frequency antennas.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金the National Research Foundation of Korea(Nos.2018R1A5A7023490 and 2022R1A2C1003003)。
文摘A chemo-mechanical model is developed to investigate the effects on the stress development of the coating of polycrystalline Ni-rich LiNixMnyCo_(z)O_(2)(x≥0.8)(NMC)particles with poly(3,4-ethylenedioxythiophene)(PEDOT).The simulation results show that the coating of primary NMC particles significantly reduces the stress generation by efficiently accommodating the volume change associated with the lithium diffusion,and the coating layer plays roles both as a cushion against the volume change and a channel for the lithium transport,promoting the lithium distribution across the secondary particles more homogeneously.Besides,the lower stiffness,higher ionic conductivity,and larger thickness of the coating layer improve the stress mitigation.This paper provides a mathematical framework for calculating the chemo-mechanical responses of anisotropic electrode materials and fundamental insights into how the coating of NMC active particles mitigates stress levels.
基金the National Key Research and Development Program of China(Grant No.2022YFB3504800)the National Natural Science Foundation of China(Grant Nos.61901142,52003256,and 51902037)the Natural Science Foundation of Shanxi Province,China(Grant No.201901D211259)。
文摘Magneto-dielectric properties of Co_(2)Z ferrite materials are tuned via Gd doping for applications in high-frequency antennas and filters in the present work.Ba_(3)Co_(2)Fe_(24-x)Gd_(x)O_(41)(x=0.00,0.05,0.10,0.15,and 0.20)materials are successfully prepared by using solid-state method at 925℃for 4 h with 2.5-wt%Bi_(2)O_(3)sintering aids.The content of Gd^(3+)ion can affect micromorphology,grain size,bulk density,and magneto-dielectric properties of the ferrite.With Gd^(3+)ion content increasing,saturation magnetization(Ms)first increases and then decreases.The maximum value of Ms is 44.86 emu/g at x=0.15.Additionally,sites occupied by Gd^(3+)ions can change magnetic anisotropy constant of the ferrite.Magnetocrystalline anisotropy constant(K_1)is derived from initial magnetization curve,and found to be related to spin-orbit coupling and intersublattice interactions between metal ions.The real part of magnetic permeability(μ′)and real part of dielectric permittivity(ε′)are measured in a frequency range of 10 MHz-1 GHz.When x=0.15,material has excellent magneto-dielectric properties(μ′≈12.2 andε′≈17.61),low magnetic loss(tanδμ≈0.03 at 500 MHz),and dielectric loss(tanδε≈0.04 at 500 MHz).The results show that Gd-doped Co_(2)Z ferrite has broad application prospects in multilayer filters and high-frequency antennas.
