Inversion techniques are conducted based on the tangential x-ray crystal spectroscopy(TXCS)geometry on EAST to obtain the local profiles of ion temperature(Ti)and toroidal rotation velocity(vt).Firstly,local emissivit...Inversion techniques are conducted based on the tangential x-ray crystal spectroscopy(TXCS)geometry on EAST to obtain the local profiles of ion temperature(Ti)and toroidal rotation velocity(vt).Firstly,local emissivity profiles of the impurity argon are obtained using the asymmetrical Abel inversion.Then,the local vt and Ti profiles are calculated by considering the local emissivity profiles and the TXCS detailed geometry.In addition,how the changes in the vt profiles affect the accuracy in the Ti profiles is discussed in detail.It is also found that the lineintegrated Ti profiles are becoming less accurate with the increase in the radial gradient in the local vt profiles.Nonetheless,accurate Ti radial profiles are reconstructed after considering the effects of the emissivity and velocity,which are verified by comparing the inverted vt and Ti profiles with those local profile measurements from the Charge eXchange Recombination Spectroscopy(CXRS)on EAST.展开更多
A new multi-channel motional Stark effect(MSE)diagnostic system has been developed on the upgraded EAST tokamak,which was installed on the port C to observe a tangential neutral beam.A telecentric imaging lens was dep...A new multi-channel motional Stark effect(MSE)diagnostic system has been developed on the upgraded EAST tokamak,which was installed on the port C to observe a tangential neutral beam.A telecentric imaging lens was deployed to ensure uniform illumination from the core to the boundary.A square fiber head which contained 23 fiber bundles was mounted to this imaging lens;each fiber bundle contained 19 fibers and two of them were assigned to CXRS and BES spectrometer,respectively.The angle tuning method was used for matching the Doppler shift of theσcomponent’s wavelength which was caused by the beam voltage.At the present stage,the MSE system only contains ten channels that would be extended to 23 channels in the future,covering a measurement range from R=1.8 to R=2.27 m with a temporal resolution of 10 ms and a spatial resolution of3 cm.The polarization angle-constrained q profiles and current density profiles were reconstructed with EFIT equilibrium reconstructions.In the sawtooth discharges,the q=1 surface position was validated by the ECE signals,which further verified the rationality of the MSE measurement.展开更多
Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of ca...Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.展开更多
The Songpan-Ganze orogenic belt on the northeastern margin of the Tibetan Plateau extends westward from the Songpan-Ganze terrain in western Sichuan to the Tianshuihai region in West Kunlun,Xinjiang.It hosts numerous ...The Songpan-Ganze orogenic belt on the northeastern margin of the Tibetan Plateau extends westward from the Songpan-Ganze terrain in western Sichuan to the Tianshuihai region in West Kunlun,Xinjiang.It hosts numerous giant spodumene pegmatite deposits and ore fields,including Jiajika and Ke’eryin in western Sichuan Province,Zhawulong on the border between the Sichuan and Qinghai Provinces,and Dahongliutan in Xinjiang Region.These form the Songpan-Ganze-West Kunlun(SP-GZ-WK) pegmatite-type rare-metal metallogenic belt.The pegmatite type rare-metal deposits in this belt are hosted in the metamorphic thermal domes in the metamorphosed flysh of the Triassic Xikang and Bayankalashan Groups.The mineralized pegmatites are intimately related to the Li-and volatile-rich two-mica granites that are peraluminous and have high(Li+Na+K)/(Mn+Fe+Mg+Ca+Ti) ratios.Pegmatites and granites in individual ore field throughout the belt typically form a cogenetic granite-pegmatite system,in which pegmatite dikes commonly surround granites.Spodumene is the predominant ore mineral in most pegmatites with limited hydrothermal alteration.In the granite-pegmatite systems,granitic magmas were emplaced under P-T conditions of 800–850°C and ~550 MPa,while spodumene crystallized in an alkaline environment.The granite-pegmatite systems share similar Sr-Nd-Hf-Li isotopic compositions to the metasediments of the Xikang and Bayankalashan Groups.The δ7Li values tend to increase from the granites to the Li-poor pegmatites,whereas the reverse is observed between the Li-poor and Li-rich pegmatites.These geochronological data suggest that the granite-pegmatite systems formed in the Late Triassic and tend to be progressively younger from the outer to the inner zones of the metallogenic belt.These characteristics show that the granitic-pegmatitic melts were derived from the anatexis of the Xikang and Bayankalashan Groups during the Paleo-Tethyan orogeny in the Late Triassic.The separation of pegmatitic melts from granitic magmas can be best explained using the Jiajika-style “melt-melt immiscibility” or the Ke’eryin-style “fractional crystallization+melt-melt immiscibility” model.High-maturity terrestrial sediments are of key importance for the anatexis that results in the granitepegmatite melts.The bidirectional tectonic stresses in the Songpan-Ganze orogenic belt may have caused the mineralization difference between the Jiajika deposit and the Ke’eryin ore field.These features indicate the controls of the combination of orogenic deformation,metapelites anatexis,and magmatic differentiation on the rare-metal mineralization of pegmatites.We suggest that pegmatites,pegmatite–parental granite,and their protoliths are important indicators for rare-metal mineralization in the SP-GZ-WK pegmatite type rare-metal metallogenic belt.Based on the widespread presence of fertile metasediments and well development of metamorphic thermal dome,highly differentiated granites,and regional zonation of pegmatites,the Zhawulong ore field is the most prospective area for rare metals and thus should be the priority for future exploration.展开更多
This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry(LC–MS/MS)and its application to a pharmacokinetic study involving single and multi...This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry(LC–MS/MS)and its application to a pharmacokinetic study involving single and multiple intravenous infusions to healthy Chinese volunteers.After sample preparation of plasma by liquid–liquid extraction with ethyl acetate,the analyte and internal standard,urapidil,were separated by reversed phase chromatography in a run time of 4 min and detected by positive ion electrospray ionization followed by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 326.2-308.1 for ifenprodil and m/z 388.4-205.3 for IS.The assay was linear in the concentration range 0.2–50.0 ng/mL with recovery 476.4%.In the pharmacokinetic study of single intravenous infusions of 5,10 and 15 mg ifenprodil,peak plasma concentrations and areas under the plasma concentration–time curve were both linearly related to dose.In the pharmacokinetic study of multiple once daily intravenous infusions of 10 mg ifenprodil for 7 days,pharmacokinetic parameters were similar to those after the single dose showing that ifenprodil does not accumulate on repeated administration.展开更多
Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular hete...Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.展开更多
Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell t...Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.展开更多
基金supported by National Natural Science Foundation of China(Nos.12175278 and 12205072)the Comprehensive Research Facility for Fusion Technology Program of China(No.2018-000052-73-01-001228)+3 种基金Major Science and Technology Infrastructure Maintenance and Reconstruction Projects of the Chinese Academy of Sciences(2021),the University Synergy Innovation Program of Anhui Province(No.GXXT-2021-029)Anhui Provincial Key Research and Development Project(No.202104a06020021)Open Fund of the Magnetic Confinement Fusion Laboratory of Anhui Province(No.2021AMF01002)the National Magnetic Confinement Fusion Science Program of China(Nos.2019YFE03040000 and 2018YFE0303103).
文摘Inversion techniques are conducted based on the tangential x-ray crystal spectroscopy(TXCS)geometry on EAST to obtain the local profiles of ion temperature(Ti)and toroidal rotation velocity(vt).Firstly,local emissivity profiles of the impurity argon are obtained using the asymmetrical Abel inversion.Then,the local vt and Ti profiles are calculated by considering the local emissivity profiles and the TXCS detailed geometry.In addition,how the changes in the vt profiles affect the accuracy in the Ti profiles is discussed in detail.It is also found that the lineintegrated Ti profiles are becoming less accurate with the increase in the radial gradient in the local vt profiles.Nonetheless,accurate Ti radial profiles are reconstructed after considering the effects of the emissivity and velocity,which are verified by comparing the inverted vt and Ti profiles with those local profile measurements from the Charge eXchange Recombination Spectroscopy(CXRS)on EAST.
基金supported by the National MCF Energy R&D Program of China(No.2019YFE03040000)National Natural Science Foundation of China(Nos.12075280 and 11805236)+2 种基金Anhui Provincial Natural Science Foundation(No.1908085J01)CAS President’s International Fellowship Initiative(No.2022VMB0007)Comprehensive Research Facility for Fusion Technology Program of China(No.2018-000052-73-01-001228)。
文摘A new multi-channel motional Stark effect(MSE)diagnostic system has been developed on the upgraded EAST tokamak,which was installed on the port C to observe a tangential neutral beam.A telecentric imaging lens was deployed to ensure uniform illumination from the core to the boundary.A square fiber head which contained 23 fiber bundles was mounted to this imaging lens;each fiber bundle contained 19 fibers and two of them were assigned to CXRS and BES spectrometer,respectively.The angle tuning method was used for matching the Doppler shift of theσcomponent’s wavelength which was caused by the beam voltage.At the present stage,the MSE system only contains ten channels that would be extended to 23 channels in the future,covering a measurement range from R=1.8 to R=2.27 m with a temporal resolution of 10 ms and a spatial resolution of3 cm.The polarization angle-constrained q profiles and current density profiles were reconstructed with EFIT equilibrium reconstructions.In the sawtooth discharges,the q=1 surface position was validated by the ECE signals,which further verified the rationality of the MSE measurement.
基金supported by the National Natural Science Foundation of China(No.82072811).
文摘Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.
基金supported by the Chinese National Key R&D Program (Grant No. 2019YFC0605200)the National Natural Science Foundation of China (Grant Nos. 41872096 and 42002109)the China Geological Survey Project (Grant Nos. DD20221684 and DD20230289)。
文摘The Songpan-Ganze orogenic belt on the northeastern margin of the Tibetan Plateau extends westward from the Songpan-Ganze terrain in western Sichuan to the Tianshuihai region in West Kunlun,Xinjiang.It hosts numerous giant spodumene pegmatite deposits and ore fields,including Jiajika and Ke’eryin in western Sichuan Province,Zhawulong on the border between the Sichuan and Qinghai Provinces,and Dahongliutan in Xinjiang Region.These form the Songpan-Ganze-West Kunlun(SP-GZ-WK) pegmatite-type rare-metal metallogenic belt.The pegmatite type rare-metal deposits in this belt are hosted in the metamorphic thermal domes in the metamorphosed flysh of the Triassic Xikang and Bayankalashan Groups.The mineralized pegmatites are intimately related to the Li-and volatile-rich two-mica granites that are peraluminous and have high(Li+Na+K)/(Mn+Fe+Mg+Ca+Ti) ratios.Pegmatites and granites in individual ore field throughout the belt typically form a cogenetic granite-pegmatite system,in which pegmatite dikes commonly surround granites.Spodumene is the predominant ore mineral in most pegmatites with limited hydrothermal alteration.In the granite-pegmatite systems,granitic magmas were emplaced under P-T conditions of 800–850°C and ~550 MPa,while spodumene crystallized in an alkaline environment.The granite-pegmatite systems share similar Sr-Nd-Hf-Li isotopic compositions to the metasediments of the Xikang and Bayankalashan Groups.The δ7Li values tend to increase from the granites to the Li-poor pegmatites,whereas the reverse is observed between the Li-poor and Li-rich pegmatites.These geochronological data suggest that the granite-pegmatite systems formed in the Late Triassic and tend to be progressively younger from the outer to the inner zones of the metallogenic belt.These characteristics show that the granitic-pegmatitic melts were derived from the anatexis of the Xikang and Bayankalashan Groups during the Paleo-Tethyan orogeny in the Late Triassic.The separation of pegmatitic melts from granitic magmas can be best explained using the Jiajika-style “melt-melt immiscibility” or the Ke’eryin-style “fractional crystallization+melt-melt immiscibility” model.High-maturity terrestrial sediments are of key importance for the anatexis that results in the granitepegmatite melts.The bidirectional tectonic stresses in the Songpan-Ganze orogenic belt may have caused the mineralization difference between the Jiajika deposit and the Ke’eryin ore field.These features indicate the controls of the combination of orogenic deformation,metapelites anatexis,and magmatic differentiation on the rare-metal mineralization of pegmatites.We suggest that pegmatites,pegmatite–parental granite,and their protoliths are important indicators for rare-metal mineralization in the SP-GZ-WK pegmatite type rare-metal metallogenic belt.Based on the widespread presence of fertile metasediments and well development of metamorphic thermal dome,highly differentiated granites,and regional zonation of pegmatites,the Zhawulong ore field is the most prospective area for rare metals and thus should be the priority for future exploration.
文摘This paper reports the development and validation of an assay for ifenprodil based on liquid chromatography–tandem mass spectrometry(LC–MS/MS)and its application to a pharmacokinetic study involving single and multiple intravenous infusions to healthy Chinese volunteers.After sample preparation of plasma by liquid–liquid extraction with ethyl acetate,the analyte and internal standard,urapidil,were separated by reversed phase chromatography in a run time of 4 min and detected by positive ion electrospray ionization followed by multiple reaction monitoring of the precursor-to-product ion transitions at m/z 326.2-308.1 for ifenprodil and m/z 388.4-205.3 for IS.The assay was linear in the concentration range 0.2–50.0 ng/mL with recovery 476.4%.In the pharmacokinetic study of single intravenous infusions of 5,10 and 15 mg ifenprodil,peak plasma concentrations and areas under the plasma concentration–time curve were both linearly related to dose.In the pharmacokinetic study of multiple once daily intravenous infusions of 10 mg ifenprodil for 7 days,pharmacokinetic parameters were similar to those after the single dose showing that ifenprodil does not accumulate on repeated administration.
基金supported by Shenzhen Sanming Engineering Project(SZSM202011012)Shenzhen Innovation Science and Technology Committee(JCYJ20180228175358223)National Natural Science Foundation of China(31670742)。
文摘Olfaction,the sense of smell,is a fundamental trait crucial to many species.The olfactory bulb(OB)plays pivotal roles in processing and transmitting odor information from the environment to the brain.The cellular heterogeneity of the mouse OB has been studied using single-cell RNA sequencing.However,the epigenetic landscape of the m OB remains mostly unexplored.Herein,we apply single-cell assay for transposaseaccessible chromatin sequencing to profile the genome-wide chromatin accessibility of 9,549 single cells from the m OB.Based on single-cell epigenetic signatures,m OB cells are classified into 21 clusters corresponding to 11 cell types.We identify distinct sets of putative regulatory elements specific to each cell cluster from which putative target genes and enriched potential functions are inferred.In addition,the transcription factor motifs enriched in each cell cluster are determined to indicate the developmental fate of each cell lineage.Our study provides a valuable epigenetic data set for the m OB at single-cell resolution,and the results can enhance our understanding of regulatory circuits and the therapeutic capacity of the OB at the single-cell level.
基金supported by the National Natural Science Foundation of China(31702074 and 31872309)Sanming Project of Medicine in Shenzhen(SZSM202011012)Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20170412153100794)。
文摘Parkinson's disease(PD)is a neurodegenerative disease,leading to the impairment of movement execution.PD pathogenesis has been largely investigated,either limited to bulk transcriptomic levels or at certain cell types,which failed to capture the cellular heterogeneity and intrinsic interplays among distinct cell types.Here,we report the application of single-nucleus RNA-seq on midbrain,striatum,and cerebellum of theα-syn-A53 T mouse,a well-established PD mouse model,and matched controls,generating the first single cell transcriptomic atlas for the PD model mouse brain composed of 46,174 individual cells.Additionally,we comprehensively depicte the dysfunctions in PD pathology,covering the elevation of NF-k B activity,the alteration of ion channel components,the perturbation of protein homeostasis network,and the dysregulation of glutamatergic signaling.Notably,we identify a variety of cell types closely associated with PD risk genes.Taken together,our study provides valuable resources to systematically dissect the molecular mechanism of PD pathogenesis at the single-cell resolution,which facilitates the development of novel approaches for diagnosis and therapies against PD.
基金the China Postdoctoral Science Foundation(2017M622795)the Science,Technology and Innovation Commission of Shenzhen Municipality(JCYJ20180507183628543)the Fundamental Research Funds for the Central Universities(2662018PY025 and 2662017PY105)。