This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,a...This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,and recent advancements in plant science applications.It highlights the method's groundbreaking applications in spatial mapping of plant metabolites,dynamic hormone monitoring,and functional studies of tissue microdomains,while offering critical insights into current technical limitations and future research directions.展开更多
Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ion...Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)could provide a more comprehensive understanding of their essential functions.Here,we evaluated 4-nitrocatechol(4-NC)as a novel positive-ion matrix for enhancing in situ detection and imaging of LMW compounds from the rat liver,brain,and germinating Chinese-yew seed by MALDI-MS.Our results showed that the 4-NC possessed remarkable features,including strong ultraviolet absorption,uniform matrix crystal,excellent chemical stability,and fewer matrix-related background peaks.The use of 4-NC led to the successful detection of 232,218,and193 LMW compounds from the three abovementioned tissue sections,respectively.Also,the use of 4-NC improved the imaging quality of LMW compounds in tissue sections through MALDI-MSI and has the potential as a matrix for MALDI tissue imaging of LMW compounds.展开更多
Salvia miltiorrhiza Bge(SMB)has long been used in traditional Chinese medicine to treat cardiovascular and cerebrovascular diseases.Growing clinical usage has led to a huge demand for artificial planting of SMB.Thus,c...Salvia miltiorrhiza Bge(SMB)has long been used in traditional Chinese medicine to treat cardiovascular and cerebrovascular diseases.Growing clinical usage has led to a huge demand for artificial planting of SMB.Thus,continuous cropping of SMB is an important challenge that needs to be addressed.Continuous cropping can alter the metabolic profile of plants,resulting in poor growth and low yield.In this study,we tried to image the spatial location and variation of endogenous metabolites in continuously cropped SMB using matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDIMSI).Spatially resolved expressions of tanshinones,salvianolic acids,polyamines,phenolic acids,amino acids,and oligosaccharides in normal and continuously cropped SMB roots were compared.The expressions of dihydrotanshinone Ⅰ,tanshinone Ⅱ A,dehydromiltirone,miltirone,dehydrotanshinone ⅡA,spermine,salvianolic acid B/E,tetrasaccharide,and pentasaccharide in continuously cropped SMB roots were much lower than those in normal roots.There was little difference in the expressions of caffeic acid and salvianolic acid A in normal and continuously cropped SMB roots.Ferulic acid was more widely distributed in xylem of normal SMB but strongly expressed in xylem,phloem,and cambium of continuously cropped SMB.The spatially resolved metabolite information enhances our understanding of the metabolic signature of continuously cropped SMB and also provides insights into the metabolic effects of continuous cropping in other plants.展开更多
Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorpt...Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial omics.In this work,4-aminoazobenzene(AAB)was successfully screened and optimized as a new negative ion(-)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using MALDIMSI.Obviously,AAB exhibited superior properties in terms of ultraviolet absorption,background ion interference,matrix morphology,and metabolite ionization efficiency.AAB was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections,where 264and 339 metabolite ion signals were successfully detected and imaged using(-)MALDI-MS,respectively.In addition,high-resolution imaging of mouse eyeball section using MALDI-tims TOF MSI with spatial resolution of up to 10μm was successfully carried out,showing that AAB is an efficient(-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.展开更多
为研究多次蒸晒西洋参中皂苷成分变化及其在组织中的空间分布特征,采用超高效液相色谱四极杆飞行时间串联质谱仪(ultra performance liquid chromatography quadrupole time⁃of⁃flight tandem mass spectrometry,UPLC⁃Q⁃TOF⁃MS/MS)对西...为研究多次蒸晒西洋参中皂苷成分变化及其在组织中的空间分布特征,采用超高效液相色谱四极杆飞行时间串联质谱仪(ultra performance liquid chromatography quadrupole time⁃of⁃flight tandem mass spectrometry,UPLC⁃Q⁃TOF⁃MS/MS)对西洋参提取液进行检测和鉴定。采用基质辅助激光解吸电离质谱成像(matrix⁃assisted laser desorption/ionization mass spectrometry imaging,MALDI⁃MSI)对西洋参中原型皂苷及其代谢产物的空间分布和时空变化进行可视化分析。UPLC结果显示从0~9次蒸制西洋参中共鉴定出90种主要人参皂苷,在西洋参的反复蒸晒过程中,极性人参皂苷转化成低极性或非极性人参皂苷,原型皂苷含量减少,稀有皂苷含量增加,主要为人参皂苷20(S/R)⁃Rg_(3)、20(S/R)⁃Rh_(2)、Rk_(1)、Rg_(5)、Rs_(5)、Rs_(4)等。MALDI⁃MSI组织分布结果表明生西洋参中皂苷主要分布于表皮及韧皮部,蒸晒过程导致皂苷成分发生转化,木质部和髓质中的分布增加。该研究为西洋参蒸制引起的生物活性和药理作用的变化提供了基础信息,为扩大西洋参的药用范围提供了参考。展开更多
目的 采用大气压基质辅助激光解吸电离-离子阱-飞行时间质谱(atmospheric pressure matrix assisted laser desorption combined with ion trap-time of flight mass spectrometry, AP-MALDI-IT-TOF/MS)和解吸电喷雾电离-四级杆-飞行时...目的 采用大气压基质辅助激光解吸电离-离子阱-飞行时间质谱(atmospheric pressure matrix assisted laser desorption combined with ion trap-time of flight mass spectrometry, AP-MALDI-IT-TOF/MS)和解吸电喷雾电离-四级杆-飞行时间质谱(desorption electrospray ionization combined with quadrupole-time of flight mass spectrometry, DESI-Q-TOF/MS)两种技术,实现板蓝根的全质谱成像分析,揭示多种成分的组织原位可视化分布,寻找品质特征相关指标群。方法 不同商品规格的板蓝根,分别喷涂2,5-二羟基苯乙酮(2,5-DHAP)和1,5-二氨基萘(1,5-DAN)基质,在正、负离子模式下进行AP-MALDI-IT-TOF/MS质谱成像、成分鉴定和偏最小二乘回归(partial least squares regression, PLSR)分析。不同品质特征的板蓝根,在正、负离子模式下进行DESI-Q-TOF/MS质谱成像、成分鉴定和正交偏最小二乘判别分析(orthogonal partial least squares discrimination analysis, OPLS-DA)分析。结果 板蓝根经质谱成像分析,初步鉴别得到多个类别约100余个化合物,AP-MALDI-IT-TOF/MS和DESI-Q-TOF/MS均可揭示板蓝根化合物的空间分布,并可区分不同规格、品质样品,3-醛基吲哚、前告依春/表前告依春、isatithioetherin C/isatithioetherin E、松柏苷、紫丁香酚苷、直铁线莲宁B、腺苷、腺嘌呤、尿苷、精氨酸、2-羟基丁二酸、顺丁烯二酸/富马酸、枸橼酸、大黄素-8-O-β-D-葡萄糖苷、异牡荆素在高商品规格/品质样品中特定空间分布信号更强,对分类影响显著,组成品质特征相关指标群。结论 质谱成像可将中药材的品质与化学信息建立连接,为其质量评价和进一步开发利用提供实验基础和新的手段。展开更多
Bisphenol A（BPA） plays an important role in metabolic disorders. As a major alternative to BPA, it is unclear whether the exposure of bisphenol S（BPS） may result in lipidome disturbance. Using a mouse model, we in...Bisphenol A（BPA） plays an important role in metabolic disorders. As a major alternative to BPA, it is unclear whether the exposure of bisphenol S（BPS） may result in lipidome disturbance. Using a mouse model, we investigated the effects of BPS exposure on metabolism and spatial distribution of lipids by using lipidomics analysis and matrix-assisted laser desorption/ionization（MALDI）-mass spectrometry imaging（MSI） in mouse liver tissues. Lipid metabolites displayed significant up-regulation in phosphatidylethanolamines（PE）, lysophosphatidylcholines（LPC）, lysophosphatidylethanolamines（LPE） and lysophosphatidylserine（LPS） as well as remarkable down-regulation in phosphatidylcholine（PC） and phosphatidylserine（PS） in mouse liver after the exposure at 100 m g BPS/kg body weight/day.The obtained results indicated that the lipidome of liver was perturbed significantly in glycerophospholipid（GP） fatty acid remodeling pathway upon the BPS exposure. We applied MSI and multivariate statistical analysis to evaluate the abundance variation of lipid markers in BPS-treated liver sections and to compare with the analytical results from olive oil-treated liver sections. Differential structural lipids with up-regulated PE（20：1/20：4）, LPC（20：4）, LPE（20：4）, LPS（33：4） and down-regulated PC（20：4/22：6）and PS（18：0/22：6）, which were related to GP fatty acid remodeling, changed and co-localized in the liver sections. To explore the cause of variation of lipid abundance, expression of enzymes that regulate biosynthesis and metabolism of fatty acid in liver tissues were analyzed. Consistent with the results of liver lipidome and spatial distribution, a decrease in hepatic expression of LPC acyltransferase 1（LPCAT1）,LPCAT2 and LPS acyltransferase and an increase expression of LPCAT3, LPCAT4, LPE acyltransferase 1（LPEAT1）, LPEAT2 and phospholipase A2 s were observed in GP fatty acid remodeling pathway. Our results demonstrated that exposure to BPS could induce the GP fatty acid remodeling, which might be useful in toxicity evaluation for bisphenols-induced hepatic diseases.展开更多
Application of matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatiotemporal alterations of lipids in biological tissues has brought many significant results.Howeve...Application of matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatiotemporal alterations of lipids in biological tissues has brought many significant results.However, the presence of structural isomers varying in C=C double bond(DB) locations makes isomerresolved MSI an urgent need. Herein, we introduce a new type of light-driven on-tissue [2 + 2] cycloaddition reaction coupled with MALDI-MS/MS imaging to identify lipid DB position isomers and their spatial signatures in biological tissues. 3-Benzoylpyridine was introduced as a novel derivatization reagent, and it exhibited great reactivity toward lipid C=C bond to form oxetanes under both ultraviolet light and visible light irradiation. With this approach, DB position isomers of lipids were imaged with highly differential levels in distinct regions of rat brain, providing an accurate and spatially resolved approach to study tissue lipidomics.展开更多
文摘This paper provides a systematic review of Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging(MALDI-MSI),encompassing its technical principles,experimental workflows,matrix optimization strategies,and recent advancements in plant science applications.It highlights the method's groundbreaking applications in spatial mapping of plant metabolites,dynamic hormone monitoring,and functional studies of tissue microdomains,while offering critical insights into current technical limitations and future research directions.
基金supported by the National Natural Science Foundation of China(Nos.31770384 and 21605164)the Youth Academic Team Project of MUC(No.10301-02200301)+1 种基金the Huayi Technology Innovation Center for Research Resources(No.HTIC P01RR2017001A)the Key Laboratory Construction Funds of State Ethnic Affairs Commission of China(No.10301-02200303)。
文摘Low-molecular-weight(LMW)compounds are ubiquitous in living organisms and play essential roles in biological processes.The direct analysis of LMW compounds in biological tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)could provide a more comprehensive understanding of their essential functions.Here,we evaluated 4-nitrocatechol(4-NC)as a novel positive-ion matrix for enhancing in situ detection and imaging of LMW compounds from the rat liver,brain,and germinating Chinese-yew seed by MALDI-MS.Our results showed that the 4-NC possessed remarkable features,including strong ultraviolet absorption,uniform matrix crystal,excellent chemical stability,and fewer matrix-related background peaks.The use of 4-NC led to the successful detection of 232,218,and193 LMW compounds from the three abovementioned tissue sections,respectively.Also,the use of 4-NC improved the imaging quality of LMW compounds in tissue sections through MALDI-MSI and has the potential as a matrix for MALDI tissue imaging of LMW compounds.
基金supported by the Taishan Scholars Program of Shandong Province(Grant No.:tsqn202103096 for C.Sun and Grant No.:ts201511068 for L.Guo)the National Natural Science Foundation of China(Grant No.:82003886)the National Key R&D Program of China(Grant Nos.:2017YFC1700703 and 2017YFC-1702701).
文摘Salvia miltiorrhiza Bge(SMB)has long been used in traditional Chinese medicine to treat cardiovascular and cerebrovascular diseases.Growing clinical usage has led to a huge demand for artificial planting of SMB.Thus,continuous cropping of SMB is an important challenge that needs to be addressed.Continuous cropping can alter the metabolic profile of plants,resulting in poor growth and low yield.In this study,we tried to image the spatial location and variation of endogenous metabolites in continuously cropped SMB using matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDIMSI).Spatially resolved expressions of tanshinones,salvianolic acids,polyamines,phenolic acids,amino acids,and oligosaccharides in normal and continuously cropped SMB roots were compared.The expressions of dihydrotanshinone Ⅰ,tanshinone Ⅱ A,dehydromiltirone,miltirone,dehydrotanshinone ⅡA,spermine,salvianolic acid B/E,tetrasaccharide,and pentasaccharide in continuously cropped SMB roots were much lower than those in normal roots.There was little difference in the expressions of caffeic acid and salvianolic acid A in normal and continuously cropped SMB roots.Ferulic acid was more widely distributed in xylem of normal SMB but strongly expressed in xylem,phloem,and cambium of continuously cropped SMB.The spatially resolved metabolite information enhances our understanding of the metabolic signature of continuously cropped SMB and also provides insights into the metabolic effects of continuous cropping in other plants.
基金supported by the National Natural Science Foundation of China(Nos.31770384 and 21605164)the Youth Academic Team Project of MUC(No.10301-02200301)+1 种基金the Huayi Technology Innovation Center for Research Resources(No.HTIC P01RR2017001A)the Key Laboratory Construction Funds of State Ethnic Affairs Commission of China(No.10301-02200303)。
文摘Endogenous metabolites play key functions in many important physiological and biochemical processes.The comprehensive in situ detection and direct imaging of metabolites in bio-tissues by matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI)is very important for understanding complex and diverse biological processes and has become an essential aspect of spatial omics.In this work,4-aminoazobenzene(AAB)was successfully screened and optimized as a new negative ion(-)MALDI matrix to enhance the in situ detection and imaging of metabolites in tissues using MALDIMSI.Obviously,AAB exhibited superior properties in terms of ultraviolet absorption,background ion interference,matrix morphology,and metabolite ionization efficiency.AAB was used for in situ detection and imaging of metabolites in rat brain and germinating Chinese yew seed tissue sections,where 264and 339 metabolite ion signals were successfully detected and imaged using(-)MALDI-MS,respectively.In addition,high-resolution imaging of mouse eyeball section using MALDI-tims TOF MSI with spatial resolution of up to 10μm was successfully carried out,showing that AAB is an efficient(-)MALDI matrix for capturing high-resolution images of metabolites in biological tissue sections.
文摘为研究多次蒸晒西洋参中皂苷成分变化及其在组织中的空间分布特征,采用超高效液相色谱四极杆飞行时间串联质谱仪(ultra performance liquid chromatography quadrupole time⁃of⁃flight tandem mass spectrometry,UPLC⁃Q⁃TOF⁃MS/MS)对西洋参提取液进行检测和鉴定。采用基质辅助激光解吸电离质谱成像(matrix⁃assisted laser desorption/ionization mass spectrometry imaging,MALDI⁃MSI)对西洋参中原型皂苷及其代谢产物的空间分布和时空变化进行可视化分析。UPLC结果显示从0~9次蒸制西洋参中共鉴定出90种主要人参皂苷,在西洋参的反复蒸晒过程中,极性人参皂苷转化成低极性或非极性人参皂苷,原型皂苷含量减少,稀有皂苷含量增加,主要为人参皂苷20(S/R)⁃Rg_(3)、20(S/R)⁃Rh_(2)、Rk_(1)、Rg_(5)、Rs_(5)、Rs_(4)等。MALDI⁃MSI组织分布结果表明生西洋参中皂苷主要分布于表皮及韧皮部,蒸晒过程导致皂苷成分发生转化,木质部和髓质中的分布增加。该研究为西洋参蒸制引起的生物活性和药理作用的变化提供了基础信息,为扩大西洋参的药用范围提供了参考。
文摘目的 采用大气压基质辅助激光解吸电离-离子阱-飞行时间质谱(atmospheric pressure matrix assisted laser desorption combined with ion trap-time of flight mass spectrometry, AP-MALDI-IT-TOF/MS)和解吸电喷雾电离-四级杆-飞行时间质谱(desorption electrospray ionization combined with quadrupole-time of flight mass spectrometry, DESI-Q-TOF/MS)两种技术,实现板蓝根的全质谱成像分析,揭示多种成分的组织原位可视化分布,寻找品质特征相关指标群。方法 不同商品规格的板蓝根,分别喷涂2,5-二羟基苯乙酮(2,5-DHAP)和1,5-二氨基萘(1,5-DAN)基质,在正、负离子模式下进行AP-MALDI-IT-TOF/MS质谱成像、成分鉴定和偏最小二乘回归(partial least squares regression, PLSR)分析。不同品质特征的板蓝根,在正、负离子模式下进行DESI-Q-TOF/MS质谱成像、成分鉴定和正交偏最小二乘判别分析(orthogonal partial least squares discrimination analysis, OPLS-DA)分析。结果 板蓝根经质谱成像分析,初步鉴别得到多个类别约100余个化合物,AP-MALDI-IT-TOF/MS和DESI-Q-TOF/MS均可揭示板蓝根化合物的空间分布,并可区分不同规格、品质样品,3-醛基吲哚、前告依春/表前告依春、isatithioetherin C/isatithioetherin E、松柏苷、紫丁香酚苷、直铁线莲宁B、腺苷、腺嘌呤、尿苷、精氨酸、2-羟基丁二酸、顺丁烯二酸/富马酸、枸橼酸、大黄素-8-O-β-D-葡萄糖苷、异牡荆素在高商品规格/品质样品中特定空间分布信号更强,对分类影响显著,组成品质特征相关指标群。结论 质谱成像可将中药材的品质与化学信息建立连接,为其质量评价和进一步开发利用提供实验基础和新的手段。
基金supported by the grants from the National Natural Science Foundation of China (Nos. 21507106, 91543202)Hong Kong Research Grants Council-General Research Fund (No. 1230195)Hong Kong Baptist University Strategic Development Fund(No.15-1012-P04)
文摘Bisphenol A（BPA） plays an important role in metabolic disorders. As a major alternative to BPA, it is unclear whether the exposure of bisphenol S（BPS） may result in lipidome disturbance. Using a mouse model, we investigated the effects of BPS exposure on metabolism and spatial distribution of lipids by using lipidomics analysis and matrix-assisted laser desorption/ionization（MALDI）-mass spectrometry imaging（MSI） in mouse liver tissues. Lipid metabolites displayed significant up-regulation in phosphatidylethanolamines（PE）, lysophosphatidylcholines（LPC）, lysophosphatidylethanolamines（LPE） and lysophosphatidylserine（LPS） as well as remarkable down-regulation in phosphatidylcholine（PC） and phosphatidylserine（PS） in mouse liver after the exposure at 100 m g BPS/kg body weight/day.The obtained results indicated that the lipidome of liver was perturbed significantly in glycerophospholipid（GP） fatty acid remodeling pathway upon the BPS exposure. We applied MSI and multivariate statistical analysis to evaluate the abundance variation of lipid markers in BPS-treated liver sections and to compare with the analytical results from olive oil-treated liver sections. Differential structural lipids with up-regulated PE（20：1/20：4）, LPC（20：4）, LPE（20：4）, LPS（33：4） and down-regulated PC（20：4/22：6）and PS（18：0/22：6）, which were related to GP fatty acid remodeling, changed and co-localized in the liver sections. To explore the cause of variation of lipid abundance, expression of enzymes that regulate biosynthesis and metabolism of fatty acid in liver tissues were analyzed. Consistent with the results of liver lipidome and spatial distribution, a decrease in hepatic expression of LPC acyltransferase 1（LPCAT1）,LPCAT2 and LPS acyltransferase and an increase expression of LPCAT3, LPCAT4, LPE acyltransferase 1（LPEAT1）, LPEAT2 and phospholipase A2 s were observed in GP fatty acid remodeling pathway. Our results demonstrated that exposure to BPS could induce the GP fatty acid remodeling, which might be useful in toxicity evaluation for bisphenols-induced hepatic diseases.
基金supported by the National Natural Science Foundation of China (Nos. 81903571, 21904080)the Taishan Scholars the Taishan Scholars Program (C. Sun, No. tsqn202103096)the Shandong Province “Double-Hundred Talent Plan” Program。
文摘Application of matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatiotemporal alterations of lipids in biological tissues has brought many significant results.However, the presence of structural isomers varying in C=C double bond(DB) locations makes isomerresolved MSI an urgent need. Herein, we introduce a new type of light-driven on-tissue [2 + 2] cycloaddition reaction coupled with MALDI-MS/MS imaging to identify lipid DB position isomers and their spatial signatures in biological tissues. 3-Benzoylpyridine was introduced as a novel derivatization reagent, and it exhibited great reactivity toward lipid C=C bond to form oxetanes under both ultraviolet light and visible light irradiation. With this approach, DB position isomers of lipids were imaged with highly differential levels in distinct regions of rat brain, providing an accurate and spatially resolved approach to study tissue lipidomics.
基金国家自然科学基金重点项目(No.81891012)国家重大新药创制专项(No.2018ZX09711001-009)+3 种基金国家重点研发计划(No.2017YFC1702504)中国医学科学院重点实验室课题(No.2018PT35030)国家重点研发项目(No.2018YFC1707408)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2016-I2M-1-012)。
