To address the current issues of low reconfigurability,low integration,and high dynamic power consumption in programmable units,this study proposes a novel programmable photonic unit cell,termed MZI-cascaded-ring unit...To address the current issues of low reconfigurability,low integration,and high dynamic power consumption in programmable units,this study proposes a novel programmable photonic unit cell,termed MZI-cascaded-ring unit(MCR).The unit functions analogously to an MZI,enabling broadband routing when operating within the free spectral range(FSR)of the embedded resonator,and it transitions into a wavelength-selective mode,leveraging the micro-ring’s resonance to achieve precise amplitude and phase control for narrowband signals while outside the FSR,featuring dual operational regimes.With the implementation of spiral waveguide structures,the design achieves higher integration density and lower dynamic power consumption.Based on the hexagonal mesh extension of such a unit,the programmable photonic processor successfully demonstrates a reconfiguration of large amounts of fundamental functions with tunable performance metrics,including broadband linear operations like optical router and wavelength-selective functionalities like wavelength division multiplexing.This work establishes a new paradigm for programmable photonic integrated circuit design.展开更多
Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored.Here,we deter...Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored.Here,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 patients.BHMT was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC.Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite effect.We combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models.In contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis.Additionally,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of G6PD.Protein sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246.Furthermore,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed hepatocarcinogenesis.Taken together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.展开更多
基金National Natural Science Foundation of China(62075038)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX24_0401).
文摘To address the current issues of low reconfigurability,low integration,and high dynamic power consumption in programmable units,this study proposes a novel programmable photonic unit cell,termed MZI-cascaded-ring unit(MCR).The unit functions analogously to an MZI,enabling broadband routing when operating within the free spectral range(FSR)of the embedded resonator,and it transitions into a wavelength-selective mode,leveraging the micro-ring’s resonance to achieve precise amplitude and phase control for narrowband signals while outside the FSR,featuring dual operational regimes.With the implementation of spiral waveguide structures,the design achieves higher integration density and lower dynamic power consumption.Based on the hexagonal mesh extension of such a unit,the programmable photonic processor successfully demonstrates a reconfiguration of large amounts of fundamental functions with tunable performance metrics,including broadband linear operations like optical router and wavelength-selective functionalities like wavelength division multiplexing.This work establishes a new paradigm for programmable photonic integrated circuit design.
基金supported by the National Natural Science Foundation of China(82103282)Higher Education Disciplinary Innovation Program(D20036)+2 种基金Henan Province Medical Science and Technology Research Plan(SBGJ202103061,LHGJ20190135)“Science and Technology to create Central Plains”Young Talent Lifting Project(2023HYTP041)Henan Charity General Federation of Hepatobiliary Care Fund(GDXZ2023002).
文摘Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored.Here,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 patients.BHMT was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC.Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite effect.We combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models.In contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis.Additionally,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of G6PD.Protein sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246.Furthermore,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed hepatocarcinogenesis.Taken together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.
