Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as ...Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.展开更多
The 200 Gbit/s passive optical network(PON)is most likely to be the next-generation scheme following 50G PON.The costeffective direct detection(DD)system is the economical choice.However,larger-capacity DD systems wil...The 200 Gbit/s passive optical network(PON)is most likely to be the next-generation scheme following 50G PON.The costeffective direct detection(DD)system is the economical choice.However,larger-capacity DD systems will face much more serious power fading caused by chromatic dispersion(CD)combined with square-law DD and thereby significantly increases the complexity of equalization algorithms.In this paper,a 200 Gbit/s Nyquist 4-level pulse amplitude modulation(PAM4)single side-band(SSB)modulation-DD downlink scheme is designed,and a low complexity quadratic-nonlinear equalizer is proposed for this system.The computational complexity of the quadratic nonlinear equalizer is about 28%of that of the conventional Volterra nonlinear equalizer,while still exhibiting excellent nonlinear equalization ability.Simulation results for the 200 Gbit/s system with 20 km fiber transmission show that it can achieve a power budget of 29 dB,while a 30.4 dB power budget is obtained in the 50 Gbit/s experimental transmission.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82372277(to ZW),82272361(to XS),82271395(to GL)Guangdong Province Basic and Applied Basic Research Fund Project,No.2024A1515010615(to XS)+1 种基金Guangdong Province Natural Youth Promotion Project,No.2314070000241(to GL)Guangzhou Science and Technology Project,No.2025A04J4740(to GL).
文摘Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.
基金ZTE Industry-University-Institute Cooperation Funds under Grant No.HC-CN-20230105001National Natural Science Foundation of China under Grant No.62001045。
文摘The 200 Gbit/s passive optical network(PON)is most likely to be the next-generation scheme following 50G PON.The costeffective direct detection(DD)system is the economical choice.However,larger-capacity DD systems will face much more serious power fading caused by chromatic dispersion(CD)combined with square-law DD and thereby significantly increases the complexity of equalization algorithms.In this paper,a 200 Gbit/s Nyquist 4-level pulse amplitude modulation(PAM4)single side-band(SSB)modulation-DD downlink scheme is designed,and a low complexity quadratic-nonlinear equalizer is proposed for this system.The computational complexity of the quadratic nonlinear equalizer is about 28%of that of the conventional Volterra nonlinear equalizer,while still exhibiting excellent nonlinear equalization ability.Simulation results for the 200 Gbit/s system with 20 km fiber transmission show that it can achieve a power budget of 29 dB,while a 30.4 dB power budget is obtained in the 50 Gbit/s experimental transmission.
