Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treat...Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.展开更多
Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,res...Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.展开更多
Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity...Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.展开更多
A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS...A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS scheme is used to implement the wavelength-multi- plexed-profile fitting method. Second harmonic （2f） signal of eight H20 transitions features near 7,170 cm^-1 are measured in one period using a single tunable diode laser. Spatial resolved temperature distribution upon a CH4/air premixed flat flame burner is obtained. The result validates the feasibility of strategy for non-uniform flow field diagnostics by means of WMS-2f TDLAS.展开更多
We developed a novel method for real-time monitoring of alteration of the local epithelium vessel/capillary and blood oxygenation spatial pattern in epithelium exploiting a compact fibre sensor system based on spatial...We developed a novel method for real-time monitoring of alteration of the local epithelium vessel/capillary and blood oxygenation spatial pattern in epithelium exploiting a compact fibre sensor system based on spatially and spectrally resolved diffuse reflectance.The method is based on collection of spatially resolved diffuse reflectance Re(λ)by fiber sensors.The spatial resolution is provided as a dependence of Re(λ)on a set of distancesρbetween the source and detector(attenuation curve).It is expected that the new method can reasonably extract the minor spatial deviations of oxygenation and local blood volume fraction-parameters,directly related to the local vessel density and capillary spatial patterns in the epithelium.Light scattering in visible range is naturally taken into account in the proposed method.展开更多
Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein...Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine Nmethyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.展开更多
Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for...Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for spatial domain identification tasks.Currently,most methods define adjacency relation between cells or spots by their spatial distance in SRT data,which overlooks key biological interactions like gene expression similarities,and leads to inaccuracies in spatial domain identification.To tackle this challenge,we propose a novel method,SpaGRA(https://github.com/sunxue-yy/SpaGRA),for automatic multi-relationship construction based on graph augmentation.SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks(GATs).This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning.Additionally,SpaGRA uses these multi-view relationships to construct negative samples,addressing sampling bias posed by random selection.Experimental results show that SpaGRA presents superior domain identification performance on multiple datasets generated from different protocols.Using SpaGRA,we analyze the functional regions in the mouse hypothalamus,identify key genes related to heart development in mouse embryos,and observe cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data.Overall,SpaGRA can effectively characterize spatial structures across diverse SRT datasets.展开更多
The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology,from the invention of the microscope 350 years ago to the recent emergence of single-cell sequencing,by which the s...The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology,from the invention of the microscope 350 years ago to the recent emergence of single-cell sequencing,by which the scientific community has been able to visualize life at an unprecedented resolution.Most recently,the Spatially Resolved Transcriptomics(SRT)technologies have filled the gap in probing the spatial or even three-dimensional organization of the molecular foundation behind the molecular mysteries of life,including the origin of different cellular populations developed from totipotent cells and human diseases.In this review,we introduce recent progresses and challenges on SRT from the perspectives of technologies and bioinformatic tools,as well as the representative SRT applications.With the currently fast-moving progress of the SRT technologies and promising results from early adopted research projects,we can foresee the bright future of such new tools in understanding life at the most profound analytical level.展开更多
Spatial transcriptomics,which is capable of both measuring all gene activity in a tissue sample and mapping where this activity occurs,is vastly improving our understanding of biological processes and disease.The fiel...Spatial transcriptomics,which is capable of both measuring all gene activity in a tissue sample and mapping where this activity occurs,is vastly improving our understanding of biological processes and disease.The field has expanded rapidly in recent years,and the development of several new technologies has resulted in spatially resolved transcriptomics(SRT)becoming highly multiplexed,high-resolution,and high-throughput.Here,we summarize and compare the major methods of SRT,including imagingbased methods,sequencing-based methods,and in situ sequencing methods.We also highlight some typical applications of SRT in neuroscience,cancer biology,developmental biology,and hematology.Finally,we discuss future possibilities for improving spatially resolved transcriptomic methods and the expected applications of such methods,especially in the adult bone marrow,anticipating that new developments will unlock the full potential of spatially resolved multi-omics in both biological research and the clinic.展开更多
As for the emerging and cut edge spatially resolved metabolomics,mass spectrometry imaging(MSI)is a powerful tool that can map thousands of metabolites from bio-tissue sections without chemical labels.However,the stab...As for the emerging and cut edge spatially resolved metabolomics,mass spectrometry imaging(MSI)is a powerful tool that can map thousands of metabolites from bio-tissue sections without chemical labels.However,the stability,sensitivity and spatial resolution of MSI are always limited by the performance of its ionization probe.Herein,two types of probes(fine probe(P-100)and large probe(P-200))were designed and characterized to perform air-flow assisted desorption electrospray ionization(AFA-DESI)MSI analysis for spatially resolved metabolomics.It was determined that the spray introduced by P-100 was homogenous and stable under the spray solvent at a flow rate of 5-10μL/min,while P-200 can endure a high flow rate of up to 10-30μL/min.Moreover,the MSI images were acquired by AFA-DESI-MSI with P-100 from rat brain tissue section and with P-200 from whole-body tissue section of mouse,and these results presented unambiguous tissue structure with the distribution information of numerous metabolites.Furthermore,the spatially resolved metabolomic analysis of tumor tissue was successfully realized to discover the tumor associated biomarkers.As the key parts of AFA-DESI-MSI system,it has been demonstrated that the designed probs have excellent performance for spatially resolved metabolomics,and it will further promote its application in life science,and drug research and development.展开更多
Magnetic topological quantum materials(TQMs) provide a fertile ground for the emergence of fascinating topological magneto-electric effects. Recently, the discovery of intrinsic antiferromagnetic(AFM) topological insu...Magnetic topological quantum materials(TQMs) provide a fertile ground for the emergence of fascinating topological magneto-electric effects. Recently, the discovery of intrinsic antiferromagnetic(AFM) topological insulator MnBi_(2)Te_(4) that could realize quantized anomalous Hall effect and axion insulator phase ignited intensive study on this family of TQM compounds. Here, we investigated the AFM compound Mn Bi4 Te7 where Bi_(2)Te_(3) and MnBi_(2)Te_(4) layers alternate to form a superlattice. Using spatial-and angleresolved photoemission spectroscopy, we identified ubiquitous(albeit termination dependent) topological electronic structures from both Bi_(2)Te_(3) and MnBi_(2)Te_(4) terminations. Unexpectedly, while the bulk bands show strong temperature dependence correlated with the AFM transition, the topological surface states with a diminishing gap show negligible temperature dependence across the AFM transition.Together with the results of its sister compound MnBi_(2)Te_(4), we illustrate important aspects of electronic structures and the effect of magnetic ordering in this family of magnetic TQMs.展开更多
Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq(scRNA-seq)data.Compared with the commonly used variance-based methods,by mimicking the human maker selection in the ...Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq(scRNA-seq)data.Compared with the commonly used variance-based methods,by mimicking the human maker selection in the 2D visualization of cells,a new feature selection method called HRG(Highly Regional Genes)is proposed to find the informative genes,which show regional expression patterns in the cell-cell similarity network.We mathematically find the optimal expression patterns that can maximize the proposed scoring function.In comparison with several unsupervised methods,HRG shows high accuracy and robustness,and can increase the performance of downstream cell clustering and gene correlation analysis.Also,it is applicable for selecting informative genes of sequencing-based spatial transcriptomic data.展开更多
Over the past decade,systems biology and plant-omics have increasingly become the main stream in plant biology research.New developments in mass spectrometry and bioinformatics tools,and methodological schema to inte-...Over the past decade,systems biology and plant-omics have increasingly become the main stream in plant biology research.New developments in mass spectrometry and bioinformatics tools,and methodological schema to inte-grate multi-omics data have leveraged recent advances in proteomics and metabolomics.These progresses are driv-ing a rapid evolution in the field of plant research,greatly facilitating our understanding of the mechanistic aspects of plant metabolisms and the interactions of plants with their external environment.Here,we review the recent progresses in MS-based proteomics and metabolomics tools and workflows with a special focus on their applications to plant biology research using several case studies related to mechanistic understanding of stress response,gene/protein function characterization,metabolic and signaling pathways exploration,and natural product discovery.We also present a projection concerning future perspectives in MS-based proteomics and metabolomics development including their applications to and challenges for system biology.This review is intended to provide readers with an overview of how advanced MS technology,and integrated application of proteomics and metabolomics can be used to advance plant system biology research.展开更多
Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and h...Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and high-dimensional data have rapidly emerged as a powerful tool to unravel spatial gene expression patterns and cell type distribution in biological samples,revolutionizing the understanding of gene regulatory interactions and cell niches.However,limited accessible tools for data visualization impede the potential impact and application of this technology.Here we introduce VT3D,a visualization toolbox that allows users to explore 3D transcriptomic data,enabling gene expression projection to any 2D plane of interest,2D virtual slice creation and visualization,and interactive 3D data browsing with surface model plots.In addition,it can either work on personal devices in standalone mode or be hosted as a web-based server.We apply VT3D to multiple datasets produced by the most popular techniques,including both sequencing-based approaches(Stereo-seq,spatial transcriptomics,and Slide-seq)and imaging-based approaches(MERFISH and STARMap),and successfully build a 3D atlas database that allows interactive data browsing.We demonstrate that VT3D bridges the gap between researchers and spatially resolved transcriptomics,thus accelerating related studies such as embryogenesis and organogenesis processes.The source code of VT3D is available at https://github.com/BGI-Qingdao/VT3D,and the modeled atlas database is available at http://www.bgiocean.com/vt3d_example.展开更多
There are significant differences in the extent of impurity incorporation on different crystallographic directions of GaN microstructures,and the impurity-related deep energy level behavior will have a significant imp...There are significant differences in the extent of impurity incorporation on different crystallographic directions of GaN microstructures,and the impurity-related deep energy level behavior will have a significant impact on device performance.However,a comprehensive understanding of the effect of lateral growth on device performance has not been achieved due to the lack of comprehensive spatial distribution characterization of the optical behavior and impurity incorporation in GaN microstructures.We present a comprehensive study of the optical behavior and growth mechanism of self-assembled GaN microdisks using nanoscale spatially resolved cathodoluminescence(CL)mapping.We have found a clear growth orientation-dependent optical behavior of the lateral and vertical growth sectors of self-assembled GaN microcrystals.The lateral growth sector,i.e.,the{101¯1}-growth sector,forms six side facets of the microdisk and shows significant near-bandgap emission(NBE)and weak deep energy level luminescence.Cavity effect enhanced emission was found for the first time in such a truncated hexagonal Na-flux GaN microdisk system with an ultra-smooth surface(Ra<0.7 nm)and low stress.The self-assembled microdisk shows significant ultraviolet(UV)lasing action(main lasing peak wavelength 370.9 nm,quality factor 1278,threshold 6×10^(4)μJ/cm^(2))under pulsed optical pumping.We believe that the appearance of UV lasing action may be related to the light limitation on the six side facets of the lateral growth of the GaN microdisk,the high structural quality,the low content of deep energy level defects,the low surface roughness,and the low stress.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.:82074104)the Research Project of Clinical Toxicology Transformation from the Chinese Society of Toxicology,China(Grant No.:CST2021CT101)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences,China(Grant Nos.:2017-I2M-1-011 and 2022-I2M-2-002).
文摘Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.
基金supported by the National Natural Science Foundation of China(Grant No.:81974500)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences,China(Grant No.:2022-I2M-2-001).
文摘Tumors are spatially heterogeneous tissues that comprise numerous cell types with intricate structures.By interacting with the microenvironment,tumor cells undergo dynamic changes in gene expression and metabolism,resulting in spatiotemporal variations in their capacity for proliferation and metastasis.In recent years,the rapid development of histological techniques has enabled efficient and high-throughput biomolecule analysis.By preserving location information while obtaining a large number of gene and molecular data,spatially resolved metabolomics(SRM)and spatially resolved transcriptomics(SRT)approaches can offer new ideas and reliable tools for the in-depth study of tumors.This review provides a comprehensive introduction and summary of the fundamental principles and research methods used for SRM and SRT techniques,as well as a review of their applications in cancer-related fields.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81974500,81773678)the CAMS Innovation Fund for Medical Sciences(Grant No.:2022-I2M-2-001).
文摘Against tumor-dependent metabolic vulnerability is an attractive strategy for tumor-targeted therapy.However,metabolic inhibitors are limited by the drug resistance of cancerous cells due to their metabolic plasticity and heterogeneity.Herein,choline metabolism was discovered by spatially resolved metabolomics analysis as metabolic vulnerability which is highly active in different cancer types,and a choline-modified strategy for small molecule-drug conjugates(SMDCs)design was developed to fool tumor cells into indiscriminately taking in choline-modified chemotherapy drugs for targeted cancer therapy,instead of directly inhibiting choline metabolism.As a proof-of-concept,choline-modified SMDCs were designed,screened,and investigated for their druggability in vitro and in vivo.This strategy improved tumor targeting,preserved tumor inhibition and reduced toxicity of paclitaxel,through targeted drug delivery to tumor by highly expressed choline transporters,and site-specific release by carboxylesterase.This study expands the strategy of targeting metabolic vulnerability and provides new ideas of developing SMDCs for precise cancer therapy.
基金supported by the National Natural Science Foundation of China(10772188)
文摘A novel method based on wavelength-multiplexed line-of-sight absorption and profile fitting for nonuniform flow field measurement is reported. A wavelength scanning combing laser temperature and current modulation WMS scheme is used to implement the wavelength-multi- plexed-profile fitting method. Second harmonic （2f） signal of eight H20 transitions features near 7,170 cm^-1 are measured in one period using a single tunable diode laser. Spatial resolved temperature distribution upon a CH4/air premixed flat flame burner is obtained. The result validates the feasibility of strategy for non-uniform flow field diagnostics by means of WMS-2f TDLAS.
基金The authors gratefully acknowledge funding of the Erlangen Graduate School in Advanced Optical Technologies(SAOT)by the German National Science Foundation(DFG)in the framework of the excellence initiative for support of this study.
文摘We developed a novel method for real-time monitoring of alteration of the local epithelium vessel/capillary and blood oxygenation spatial pattern in epithelium exploiting a compact fibre sensor system based on spatially and spectrally resolved diffuse reflectance.The method is based on collection of spatially resolved diffuse reflectance Re(λ)by fiber sensors.The spatial resolution is provided as a dependence of Re(λ)on a set of distancesρbetween the source and detector(attenuation curve).It is expected that the new method can reasonably extract the minor spatial deviations of oxygenation and local blood volume fraction-parameters,directly related to the local vessel density and capillary spatial patterns in the epithelium.Light scattering in visible range is naturally taken into account in the proposed method.
基金support from the National Key R&D Program of China(Grant No:2022YFC3401003)the National Natural Science Foundation of China(Grant No:21927808)+2 种基金the National Natural Science Foundation of China(Grant No:22104160)the National Key Research and Development Program of China(Grant No:2017YFC1704006)the Innovation Team of Ethnomedicine of National Ethnic Affairs Commission,China.We thank all the research staff who contributed to the study.
文摘Polygala tenuifolia,commonly known as Yuanzhi(YZ)in Chinese,has been shown to possess antiinsomnia properties.However,the material basis and the mechanism underlying its sedative-hypnotic effects remain unclear.Herein,we investigated the active components and neurochemical mechanism of YZ extracts using liquid chromatography tandem mass spectrometry(LC-MS/MS)-based pharmacometabolomics and mass spectrometry imaging(MSI)-based spatial resolved metabolomics.According to the results,17 prototypes out of 101 ingredients in the YZ extract were detected in both the plasma and brain,which might be the major components contributing to the sedative-hypnotic effects.Network pharmacology analysis revealed that these prototypes may exert their effects through neuroactive ligand-receptor interaction,serotonergic synapse,dopaminergic synapse,and dopaminergic synapse,among other pathways.LC-MS/MS-based targeted metabolomics and Western blot(WB)revealed that tryptophan-serotonin-melatonin(Trp-5-HT-Mel)and tyrosine-norepinephrine-adrenaline(Tyr-Ne-Ad)are the key regulated pathways.Dopa decarboxylase(DDC)upregulation and phenylethanolamine Nmethyltransferase(PNMT)downregulation further confirmed these pathways.Furthermore,MSI-based spatially resolved metabolomics revealed notable alterations in 5-HT in the pineal gland(PG),and Ad in the brainstem,including the middle brain(MB),pons(PN),and hypothalamus(HY).In summary,this study illustrates the efficacy of an integrated multidimensional metabolomics approach in unraveling the sedative-hypnotic effects and neurochemical mechanisms of a Chinese herbal medicine,YZ.
基金supported by the National Natural Science Foundation of China(Nos.62303271,U1806202,62103397)the Natural Science Foundation of Shandong Province(ZR2023QF081)Funding for open access charge:the National Natural Science Foundation of China(Nos.62303271,U1806202).
文摘Recent advances in spatially resolved transcriptomics(SRT)have provided new opportunities for characterizing spatial structures of various tissues.Graph-based geometric deep learning has gained widespread adoption for spatial domain identification tasks.Currently,most methods define adjacency relation between cells or spots by their spatial distance in SRT data,which overlooks key biological interactions like gene expression similarities,and leads to inaccuracies in spatial domain identification.To tackle this challenge,we propose a novel method,SpaGRA(https://github.com/sunxue-yy/SpaGRA),for automatic multi-relationship construction based on graph augmentation.SpaGRA uses spatial distance as prior knowledge and dynamically adjusts edge weights with multi-head graph attention networks(GATs).This helps SpaGRA to uncover diverse node relationships and enhance message passing in geometric contrastive learning.Additionally,SpaGRA uses these multi-view relationships to construct negative samples,addressing sampling bias posed by random selection.Experimental results show that SpaGRA presents superior domain identification performance on multiple datasets generated from different protocols.Using SpaGRA,we analyze the functional regions in the mouse hypothalamus,identify key genes related to heart development in mouse embryos,and observe cancer-associated fibroblasts enveloping cancer cells in the latest Visium HD data.Overall,SpaGRA can effectively characterize spatial structures across diverse SRT datasets.
基金supported by the Shenzhen Key Laboratory of Single-Cell Omics(ZDSYS20190902093613831)the Guangdong Provincial Key Laboratory of Genome Read and Write(2017B030301011)Longqi Liu was supported by the National Natural Science Foundation of China(31900466).
文摘The ability to explore life kingdoms is largely driven by innovations and breakthroughs in technology,from the invention of the microscope 350 years ago to the recent emergence of single-cell sequencing,by which the scientific community has been able to visualize life at an unprecedented resolution.Most recently,the Spatially Resolved Transcriptomics(SRT)technologies have filled the gap in probing the spatial or even three-dimensional organization of the molecular foundation behind the molecular mysteries of life,including the origin of different cellular populations developed from totipotent cells and human diseases.In this review,we introduce recent progresses and challenges on SRT from the perspectives of technologies and bioinformatic tools,as well as the representative SRT applications.With the currently fast-moving progress of the SRT technologies and promising results from early adopted research projects,we can foresee the bright future of such new tools in understanding life at the most profound analytical level.
基金the Ministry of Science and Technology of China(2021YFA1100900 and 2020YFE0203000)the National Natural Science Foundation of China(81730006,81922002,81861148029,and 81870086)+2 种基金CAMS Innovation Fund for Medical Sciences(2021-I2M-1-040 and 2021-I2M-1-019)Haihe Laboratory of Cell Ecosystem Innovation Fund(HH22KYZX0016)Distinguished Young Scholars of Tianjin(19JCJQJC63400).
文摘Spatial transcriptomics,which is capable of both measuring all gene activity in a tissue sample and mapping where this activity occurs,is vastly improving our understanding of biological processes and disease.The field has expanded rapidly in recent years,and the development of several new technologies has resulted in spatially resolved transcriptomics(SRT)becoming highly multiplexed,high-resolution,and high-throughput.Here,we summarize and compare the major methods of SRT,including imagingbased methods,sequencing-based methods,and in situ sequencing methods.We also highlight some typical applications of SRT in neuroscience,cancer biology,developmental biology,and hematology.Finally,we discuss future possibilities for improving spatially resolved transcriptomic methods and the expected applications of such methods,especially in the adult bone marrow,anticipating that new developments will unlock the full potential of spatially resolved multi-omics in both biological research and the clinic.
基金financial support from the National Natural Science Foundation of China(Nos.81974500 and 81773678)the CAMS Innovation Fund for Medical Sciences(No.2022-I2M-2-001)。
文摘As for the emerging and cut edge spatially resolved metabolomics,mass spectrometry imaging(MSI)is a powerful tool that can map thousands of metabolites from bio-tissue sections without chemical labels.However,the stability,sensitivity and spatial resolution of MSI are always limited by the performance of its ionization probe.Herein,two types of probes(fine probe(P-100)and large probe(P-200))were designed and characterized to perform air-flow assisted desorption electrospray ionization(AFA-DESI)MSI analysis for spatially resolved metabolomics.It was determined that the spray introduced by P-100 was homogenous and stable under the spray solvent at a flow rate of 5-10μL/min,while P-200 can endure a high flow rate of up to 10-30μL/min.Moreover,the MSI images were acquired by AFA-DESI-MSI with P-100 from rat brain tissue section and with P-200 from whole-body tissue section of mouse,and these results presented unambiguous tissue structure with the distribution information of numerous metabolites.Furthermore,the spatially resolved metabolomic analysis of tumor tissue was successfully realized to discover the tumor associated biomarkers.As the key parts of AFA-DESI-MSI system,it has been demonstrated that the designed probs have excellent performance for spatially resolved metabolomics,and it will further promote its application in life science,and drug research and development.
基金supported by the National Key Research and Development Program of China (2017YFA0305400, 2017YFA0304600, 2018YFA0307100, and 2018YFA0305603)the National Natural Science Foundation of China (11774190, 11674229, 11634009, 11774427, 51788104, and 11874035)+1 种基金EPSRC Platform Grant (EP/M020517/1)the support from the Shanghai Pujiang Program (17PJ1406200)。
文摘Magnetic topological quantum materials(TQMs) provide a fertile ground for the emergence of fascinating topological magneto-electric effects. Recently, the discovery of intrinsic antiferromagnetic(AFM) topological insulator MnBi_(2)Te_(4) that could realize quantized anomalous Hall effect and axion insulator phase ignited intensive study on this family of TQM compounds. Here, we investigated the AFM compound Mn Bi4 Te7 where Bi_(2)Te_(3) and MnBi_(2)Te_(4) layers alternate to form a superlattice. Using spatial-and angleresolved photoemission spectroscopy, we identified ubiquitous(albeit termination dependent) topological electronic structures from both Bi_(2)Te_(3) and MnBi_(2)Te_(4) terminations. Unexpectedly, while the bulk bands show strong temperature dependence correlated with the AFM transition, the topological surface states with a diminishing gap show negligible temperature dependence across the AFM transition.Together with the results of its sister compound MnBi_(2)Te_(4), we illustrate important aspects of electronic structures and the effect of magnetic ordering in this family of magnetic TQMs.
基金supported by the National Key Research and Development Program(2020YFA0712403,2020YFA0906900)National Natural Science Foundation of China(61922047,81890993,61721003,62133006)BNRIST Young Innovation Fund(BNR2020RC01009)。
文摘Gene selection is an indispensable step for analyzing noisy and high-dimensional single-cell RNA-seq(scRNA-seq)data.Compared with the commonly used variance-based methods,by mimicking the human maker selection in the 2D visualization of cells,a new feature selection method called HRG(Highly Regional Genes)is proposed to find the informative genes,which show regional expression patterns in the cell-cell similarity network.We mathematically find the optimal expression patterns that can maximize the proposed scoring function.In comparison with several unsupervised methods,HRG shows high accuracy and robustness,and can increase the performance of downstream cell clustering and gene correlation analysis.Also,it is applicable for selecting informative genes of sequencing-based spatial transcriptomic data.
基金This research was supported by the Key Realm R&D Program of Guangdong Province(No.2020B0202090005)the Science and Technology Program of Guangdong Province(2021A0505030050)+2 种基金the Project of Collaborative Innovation Center of Guangdong Academy of Agricultural Sciences(XTXM202203)the Special Fund for Scientific Innovation Strategy-construction of High-Level Academy of Agriculture Science(No.R2020PY-JX019,R2021YJ-QG004)two USDA grants(No.8062-21000-046-00D and No.8062-21000-047-00D)。
文摘Over the past decade,systems biology and plant-omics have increasingly become the main stream in plant biology research.New developments in mass spectrometry and bioinformatics tools,and methodological schema to inte-grate multi-omics data have leveraged recent advances in proteomics and metabolomics.These progresses are driv-ing a rapid evolution in the field of plant research,greatly facilitating our understanding of the mechanistic aspects of plant metabolisms and the interactions of plants with their external environment.Here,we review the recent progresses in MS-based proteomics and metabolomics tools and workflows with a special focus on their applications to plant biology research using several case studies related to mechanistic understanding of stress response,gene/protein function characterization,metabolic and signaling pathways exploration,and natural product discovery.We also present a projection concerning future perspectives in MS-based proteomics and metabolomics development including their applications to and challenges for system biology.This review is intended to provide readers with an overview of how advanced MS technology,and integrated application of proteomics and metabolomics can be used to advance plant system biology research.
基金supported by the General Program(Key Program,Major Research Plan)of National Natural Science Foundation of China(No.32170439).
文摘Data visualization empowers researchers to communicate their results that support scientific reasoning in an intuitive way.Three-dimension(3D)spatially resolved transcriptomic atlases constructed from multi-view and high-dimensional data have rapidly emerged as a powerful tool to unravel spatial gene expression patterns and cell type distribution in biological samples,revolutionizing the understanding of gene regulatory interactions and cell niches.However,limited accessible tools for data visualization impede the potential impact and application of this technology.Here we introduce VT3D,a visualization toolbox that allows users to explore 3D transcriptomic data,enabling gene expression projection to any 2D plane of interest,2D virtual slice creation and visualization,and interactive 3D data browsing with surface model plots.In addition,it can either work on personal devices in standalone mode or be hosted as a web-based server.We apply VT3D to multiple datasets produced by the most popular techniques,including both sequencing-based approaches(Stereo-seq,spatial transcriptomics,and Slide-seq)and imaging-based approaches(MERFISH and STARMap),and successfully build a 3D atlas database that allows interactive data browsing.We demonstrate that VT3D bridges the gap between researchers and spatially resolved transcriptomics,thus accelerating related studies such as embryogenesis and organogenesis processes.The source code of VT3D is available at https://github.com/BGI-Qingdao/VT3D,and the modeled atlas database is available at http://www.bgiocean.com/vt3d_example.
基金This work was supported by the National Key R&D Program of China(No.2021YFB3602000)the Fundamental Research Funds for the Central Universities(No.WK5290000003).
文摘There are significant differences in the extent of impurity incorporation on different crystallographic directions of GaN microstructures,and the impurity-related deep energy level behavior will have a significant impact on device performance.However,a comprehensive understanding of the effect of lateral growth on device performance has not been achieved due to the lack of comprehensive spatial distribution characterization of the optical behavior and impurity incorporation in GaN microstructures.We present a comprehensive study of the optical behavior and growth mechanism of self-assembled GaN microdisks using nanoscale spatially resolved cathodoluminescence(CL)mapping.We have found a clear growth orientation-dependent optical behavior of the lateral and vertical growth sectors of self-assembled GaN microcrystals.The lateral growth sector,i.e.,the{101¯1}-growth sector,forms six side facets of the microdisk and shows significant near-bandgap emission(NBE)and weak deep energy level luminescence.Cavity effect enhanced emission was found for the first time in such a truncated hexagonal Na-flux GaN microdisk system with an ultra-smooth surface(Ra<0.7 nm)and low stress.The self-assembled microdisk shows significant ultraviolet(UV)lasing action(main lasing peak wavelength 370.9 nm,quality factor 1278,threshold 6×10^(4)μJ/cm^(2))under pulsed optical pumping.We believe that the appearance of UV lasing action may be related to the light limitation on the six side facets of the lateral growth of the GaN microdisk,the high structural quality,the low content of deep energy level defects,the low surface roughness,and the low stress.
