Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and is...Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging.This strategy can map various substances including exogenous drugs,isotopically labeled metabolites,and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways.The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts,and can increase glutamate decarboxylase activity to elevateγ-aminobutyric acid(GABA)levels in the hypothalamus,agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation.These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.展开更多
We review the technique and research of the ultrahigh spatiotemporal resolved spectroscopy and its applications in the field of the ultrafast dynamics of mesoscopic systems and nanomaterials. Combining femtosecond tim...We review the technique and research of the ultrahigh spatiotemporal resolved spectroscopy and its applications in the field of the ultrafast dynamics of mesoscopic systems and nanomaterials. Combining femtosecond time-resolved spectroscopy and scanning near-field optical microscopy (SNOM),we can obtain the spectra with ultrahigh temporal and spatial resolutions simultaneously. Some problems in doing so are discussed. Then we show the important applications of the ultrahigh spatiotemporal resolved spectroscopy with a few typical examples.展开更多
Two-dimensional(2D)materials hold great potential for the development of next-generation integrated circuits(ICs)at the atomic limit.However,it is still very challenging to build high performance devices.One of the ma...Two-dimensional(2D)materials hold great potential for the development of next-generation integrated circuits(ICs)at the atomic limit.However,it is still very challenging to build high performance devices.One of the main factors that limit the incorporation of 2D materials into IC technology is their relatively low carrier mobility.Thus,the engineering strategies that focus on optimizing performance continue to emerge.Herein,using a spatiotemporal resolved pump-probe setup,the carrier transport performance and relaxation process of few-layer and bulk MoSe_(2) under pressure were investigated nondestructively and simultaneously.Our results show that pressure can tune the transport performance effectively.In particular,under pressure regulation,the carrier mobility of the bulk MoSe_(2) increases by~4 times;meanwhile,the carrier lifetimes of the samples become shorter.Although the processes almost return to their initial state after the pressure release,it is still surprising to see that the carrier mobilities of fewlayer and bulk MoSe2 are still~1.5 and 2 times enhanced,and carrier lifetimes are still shorter than the initial state.Combined with the Raman spectra under pressure,we consider that it is caused by the enhanced layer coupling and lattice compression.The combination of enhanced mobility and shortened lifetime in MoSe_(2) under pressure holds great potential for optoelectronic applications under the deep ocean and deep earth.展开更多
基金supported by the National Natural Science Foundation of China(No.21927808 and No.81974500)Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(CIFMS,No.2022-I2M-2-002 and 2021-1I2M-028,China)。
文摘Deconvolution of potential drug targets of the central nervous system(CNS)is particularly challenging because of the complicated structure and function of the brain.Here,a spatiotemporally resolved metabolomics and isotope tracing strategy was proposed and demonstrated to be powerful for deconvoluting and localizing potential targets of CNS drugs by using ambient mass spectrometry imaging.This strategy can map various substances including exogenous drugs,isotopically labeled metabolites,and various types of endogenous metabolites in the brain tissue sections to illustrate their microregional distribution pattern in the brain and locate drug action-related metabolic nodes and pathways.The strategy revealed that the sedative-hypnotic drug candidate YZG-331 was prominently distributed in the pineal gland and entered the thalamus and hypothalamus in relatively small amounts,and can increase glutamate decarboxylase activity to elevateγ-aminobutyric acid(GABA)levels in the hypothalamus,agonize organic cation transporter 3 to release extracellular histamine into peripheral circulation.These findings emphasize the promising capability of spatiotemporally resolved metabolomics and isotope tracing to help elucidate the multiple targets and the mechanisms of action of CNS drugs.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 10434020, 90501007 and 10521002)the National Basic Research Program of China (Grant No. 2007CB307001)
文摘We review the technique and research of the ultrahigh spatiotemporal resolved spectroscopy and its applications in the field of the ultrafast dynamics of mesoscopic systems and nanomaterials. Combining femtosecond time-resolved spectroscopy and scanning near-field optical microscopy (SNOM),we can obtain the spectra with ultrahigh temporal and spatial resolutions simultaneously. Some problems in doing so are discussed. Then we show the important applications of the ultrahigh spatiotemporal resolved spectroscopy with a few typical examples.
基金supported by the Fundamental Research Funds for the Central Universities+2021RC203the National Natural Science Foundation of China(Nos.11974088,61875236,and 61975007)+2 种基金the Beijing Natural Science Foundation(Nos.Z190006 and 4222073)the National Key R&D Program of China(Nos.2021YFA1400300 and 2020YFA0711502)the Synergetic Extreme Condition User Facility(SECUF),Chinese Academy of Sciences,for the Diamond anvil cell.
文摘Two-dimensional(2D)materials hold great potential for the development of next-generation integrated circuits(ICs)at the atomic limit.However,it is still very challenging to build high performance devices.One of the main factors that limit the incorporation of 2D materials into IC technology is their relatively low carrier mobility.Thus,the engineering strategies that focus on optimizing performance continue to emerge.Herein,using a spatiotemporal resolved pump-probe setup,the carrier transport performance and relaxation process of few-layer and bulk MoSe_(2) under pressure were investigated nondestructively and simultaneously.Our results show that pressure can tune the transport performance effectively.In particular,under pressure regulation,the carrier mobility of the bulk MoSe_(2) increases by~4 times;meanwhile,the carrier lifetimes of the samples become shorter.Although the processes almost return to their initial state after the pressure release,it is still surprising to see that the carrier mobilities of fewlayer and bulk MoSe2 are still~1.5 and 2 times enhanced,and carrier lifetimes are still shorter than the initial state.Combined with the Raman spectra under pressure,we consider that it is caused by the enhanced layer coupling and lattice compression.The combination of enhanced mobility and shortened lifetime in MoSe_(2) under pressure holds great potential for optoelectronic applications under the deep ocean and deep earth.
