From the point of view of design requirements, influence of the width of the output image of an imaging subsystem in a tomographic imaging spectrometer, namely width of the slit, the grating and the size of the CCD pi...From the point of view of design requirements, influence of the width of the output image of an imaging subsystem in a tomographic imaging spectrometer, namely width of the slit, the grating and the size of the CCD pixel are analyzed. For the tomographic imaging spectrometry, if the amplification ratio of the imaging subsystem is not high enough to make the whole object to be compressed within the slit, then either the slit width should be increased or the slit width kept unchanged but scanned to receive information of the object. While the width-increase method reduces the spectral resolving power and the SNR; the scanning method reduces the SNR. Analysis of the two cases and computer simulation results are given.展开更多
Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Her...Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.展开更多
Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity ...Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.展开更多
Canopy foliar Nitrogen Concentration （CNC） is one of the most important parameters influencing vegetation productivity in forest ecosystems. In this study, we explored the potential of imaging spectrometry （hypersp...Canopy foliar Nitrogen Concentration （CNC） is one of the most important parameters influencing vegetation productivity in forest ecosystems. In this study, we explored the potential of imaging spectrometry （hyperspectral） remote sensing of CNC in conifer plantations in China’s subtropical red soil hilly region. Our analysis included data from 57 field plots scattered across two transects covered by Hyperion images. Single regression and partial least squares regression （PLSR） were used to explore the relationships between CNC and hyperspectral data. The correlations between CNC and nearinfrared relfectance （NIR） were consistent in three data subsets （subsets A-C）. For all subsets, CNC was signiifcantly positively correlated with NIR in the two transects （R2=0.29, 0.33 and 0.36, P＆lt;0.05 or P＆lt;0.01, respectively）. It suggested that the NIR-CNC relationship exist despite a weak one, and the relationship may be weakened by the single canopy structure. Besides, we also applied a shortwave infrared （SWIR） index - Normalized Difference Nitrogen Index （NDNI） to estimate CNC variation. NDNI presented a signiifcant positive correlation with CNC in different subsets, but like NIR, it was also with low coefifcient of determination （R2=0.38, 0.20 and 0.17, P＆lt;0.01, respectively）. Also, the correlations between CNC and the entire spectrum reflectance （or its derivative and logarithmic transformation） by PLSR owned different signiifcance in various subsets. We did not ifnd the very robust relationship like previous literatures, so the data we used were checked again. The paired T-test was applied to estimate the inlfuence of inter-annual variability of FNC on the relationships between CNC and Hyperion data. The inter-annual mismatch between period of ifeldwork and Hyperion acquisition had no inlfuence on the correlations of CNC-Hyperion data. Meanwhile, we pointed out that the lack of the canopy structure variation in conifer plantation area may lead to these weak relationships.展开更多
A novel method for enhanced resolution,termed expansion mass spectrometry imaging,has been developed for lipid mass spectrometry imaging,utilizing existing commercially available mass spectrometers without necessitati...A novel method for enhanced resolution,termed expansion mass spectrometry imaging,has been developed for lipid mass spectrometry imaging,utilizing existing commercially available mass spectrometers without necessitating modifications.This approach involves embedding tissue sections in a swellable polyelectrolyte gel,with the target biomolecules indirectly anchored to the gel network.By employing matrix-assisted laser desorption ionization mass spectrometry imaging,the method has realized an enhanced spatial resolution that surpasses the conventional resolution limits of commercial instruments by approximately 4.5 fold.This enhancement permits the detailed visualization of intricate structures within the mouse brain at a subcellular level,with a lateral resolution nearing 1μm.As a physical technique for achieving resolution beyond standard capabilities,this readily adaptable approach presents a powerful tool for high-definition imaging in biological research.展开更多
Differentialiy expressed polypeptides in the brain of a BALB/c mouse model infected with scrapie strain 22L were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results sh...Differentialiy expressed polypeptides in the brain of a BALB/c mouse model infected with scrapie strain 22L were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that 21 peptides were down-regulated, with peptides of mass-to-charge ratio 758.772 5 and mass-to-charge ratio 5 432.206 9, demonstrating the most significant decreases. These finding suggest that these peptides are candidate biomarkers and may play an important role in the pathogenesis of prion disease.展开更多
Overlapping latent fingermarks constitute a serious challenge to database related recognition and matching algorithms in biometry, forensic and crime scene investigations. Mass spectrometry imaging (MSI) is a powerful...Overlapping latent fingermarks constitute a serious challenge to database related recognition and matching algorithms in biometry, forensic and crime scene investigations. Mass spectrometry imaging (MSI) is a powerful tool for deciphering and analyzing overlapping fingermarks based on the individual chemical information of each deposit. Fingermark MSI in practice still requires a subjective judgment of an MSI expert, such that rapid analysis, automation, standardization, and a quantitative evaluation of the complete detection and separation process of overlapped fingermarks from MSI data sets is the ultimate goal and will be necessary to become an accepted process in criminal investigations and law enforcement. Here we investigated the feasibility and efficiency of different statistical approaches for the separation of overlapped latent fingermarks based on MSI data. Entropy analysis of generated m/z-images was used to evaluate the results obtained from the statistical analysis. Furthermore, we demonstrate and discuss the opportunity to reconstitute and separate overlapping fingermarks by discrete scanning at selected x,y-positions defined from a previous image analysis using a more simple schema based on visible and therefore optical distinguishable overlapped ink-based fingermarks. The overlapped latent fingermarks were developed by rapid gold sputter coating and analyzed by laser based MSI, without (organic) matrix preparation. Latent finger marks can be transferred from the substrate/surface with and conserved on a soft gold sputtered soft membrane at low temperatures.展开更多
On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI)...On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.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
Background:Cowpea(Vigna unguiculata L.Walp.)is an economically important crop.It is nutritious and popular with consumers.However,it has been listed as one of the agricultural products of critical concern about safety...Background:Cowpea(Vigna unguiculata L.Walp.)is an economically important crop.It is nutritious and popular with consumers.However,it has been listed as one of the agricultural products of critical concern about safety in China and cyromazine is the major risk factor.Objectives:This study analyzed the dissipation and permeation kinetics of cyromazine residue in cowpea,to offer a scientific basis for the rational use of pesticide and ensure the safety of agricultural products.Materials and methods:The dissipation and residue level of the systemic insecticide cyromazine on cowpea under field and stored conditions were investigated.Subsequently,the spatial distribution of cyromazine was studied using mass spectrometry imaging to visualize the dynamic processes of permeation and migration in the tissues post pesticide application.Results:The dissipation processing of cyromazine in cowpea was shown to follow the first-order kinetics and half-life was 7.76 d in the field.In cowpea,the permeation and migration rate of cyromazine was faster than that in kidney beans and accumulation was mainly in the pulp.It is not safe to apply cyromazine to cowpeas with reference to the application method on kidney beans.Conclusions:These findings present vital data for the determination of risks linked with cowpea consumption and pesticide intake.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
Mass spectrometry imaging(MSI)has made the spatio-chemical characterization of a broad range of small-molecule metabolites within biological tissues possible.However,available matrix-assisted laser desorption/ionizati...Mass spectrometry imaging(MSI)has made the spatio-chemical characterization of a broad range of small-molecule metabolites within biological tissues possible.However,available matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)suffers from severe background interferences in low-mass ranges and inhomogeneous matrix deposition.Thus,surface-assisted LDI-MS(SALDI-MS)has been an attractive alternative for high-sensitivity detection and imaging of small biomolecules.In this study,we construct a new composite substrate,hydrophobic polydopamine(hPDA)-modified TiO_(2)nanotube(TDNT)coated with plasmonic gold nanoparticle(AuNP-hPDA-TDNT),as a dual-polarity SALDI substrate using an easy and cost-effective fabrication approach.Benefitting from the synergistic effects of TDNT semiconductor and plasmonic PDA modification,this SALDI substrate exhibits superior performance for dual-polarity detection of a vast diversity of small molecules.Highly reduced background interferences,lower detection limits,and spot-to-spot repeatability can be achieved using AuNP-hPDA-TDNT substrates.Due to its unique imprinting performance,various metabolites and lipids can be visualized within jatropha integerrima petals,ginkgo leaves,strawberry fruits,and latent fingerprints.More valuably,the universality of this matrix-free substrate is demonstrated for mapping spatial distribution of lipids within mouse brain tissue sections.Considered together,this AuNP-hPDA-TDNT material is expected to be a promising SALDI substrate in various fields,especially in nanomaterial development and life sciences.展开更多
Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser des...Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatial distribution of endogenous compounds(e.g., lipids) in CCS. However, only limited lipid species can be detected owing to a low ion yield by using MALDI. Besides, it is still challenging to fully characterize the structural diversity of lipids due to the existence of isomeric/isobaric species. Here, we carried out the initial application of MALDI coupled with laser-postionization(MALDI-2) and trapped ion mobility spectrometry(TIMS) imaging in HCT116 colon CCS to address these challenges. We demonstrated that MALDI-2 is capable of detecting more number and classes of lipids in HCT116 colon CCS with higher signal intensities than MALDI. TIMS could successfully separate numerous isobaric/isomeric species of lipids in CCS. Interestingly, we found that some isomeric/isobaric species have totally different spatial distributions in colon CCS. Further MS/MS imaging analysis was employed to determine the compositions of fatty acid chains for isomeric species by examining disparities in signal intensities and spatial distributions of product ions. This work stresses the robust ability of TIMS and MALDI-2 imaging in analyzing endogenous lipids in CCS, which could potentially become powerful tools for future cancer studies.展开更多
Imaging mass spectrometry (IMS) methodology for biological tissue component distribution map using MALDI-TOF MS and MALDI-TOF/TOF MS was established.Peak density distribution was probed to be quite useful for MS image...Imaging mass spectrometry (IMS) methodology for biological tissue component distribution map using MALDI-TOF MS and MALDI-TOF/TOF MS was established.Peak density distribution was probed to be quite useful for MS image classification.More than 40 000 spectra from 200 tissue sections were acquired and reproducibility between various of species groups was great than 80%.Tens of differentiately expressed components were detected by t-test (P<0.01).Classification modeling was created based on the differentiate components,blind species were analyzed for model validation,accuracy was above 90%.展开更多
Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development.Herein,an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectr...Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development.Herein,an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)was established for direct analysis of metabolites in renal tissue sections.This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I,a known nephrotoxic drug,aimed to discover metabolites associated with nephrotoxicity.As a result,38 metabolites related to the arginine-creatinine metabolic pathway,the urea cycle,the serine synthesis pathway,metabolism of lipids,choline,histamine,lysine,and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I.These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions.This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.展开更多
Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy(DN)is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies.In the...Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy(DN)is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies.In the present study,a spatial-resolved metabolomics approach based on air flowassisted desorption electrospray ionization(AFADESI)and matrix-assisted laser desorption ionization(MALDI)integrated mass spectrometry imaging(MSI)was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin(STZ)-treated DN rats and the therapeutic effect of astragalosideⅣ,a potential anti-diabetic drug,against DN.As a result,a wide range of functional metabolites including sugars,amino acids,nucleotides and their derivatives,fatty acids,phospholipids,sphingolipids,glycerides,carnitine and its derivatives,vitamins,peptides,and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution.These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside Ⅳ(100 mg/kg)for 12 weeks.This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats.These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.展开更多
Design and discovery of carrier-mediated modified pesticides are vital for reducing pesticide dosage and increasing utilization,yet it remains a great challenge due to limited insights into plant translocation mechani...Design and discovery of carrier-mediated modified pesticides are vital for reducing pesticide dosage and increasing utilization,yet it remains a great challenge due to limited insights into plant translocation mechanisms.Nanostructure/nanoparticle assisted laser desorption/ionization strategy has established itself as a preferential analytical tool for biological tissue analysis,whereas potential applications in plant sciences are hindered with regard to the inability to slice plant leaves and petals.Herein,we report gold nanoparticle(AuNP)-immersed paper imprinting mass spectrometry imaging(MSI)for the spatiotemporal visualization of pesticide translocation in plant leaves.This approach plays a dual role in preserving spatial information and improving ionization efficiency for pesticides regardless of imaging artifacts due to homogenous AuNP deposition.Using this MSI platform,we proposed the elaborate plant translocation mechanism of agrochemicals for the first time,which is currently poorly understood.The dynamic processes of carrier-mediated pesticides can be clearly visualized,including crossing of plasma membranes by transporters,translocation downward in stems through the phloem,diffusion to the xylem and,conversely,accumulation at margins of the treated leaves.Moreover,this AuNP-assisted paper imprinting method could be highly compatible with laser-based MSI instruments,expediting researches across a broad range of fields,especially in nanomaterial development and life sciences.展开更多
Thyroid carcinoma is one of the most common endocrine malignant diseases worldwide.With the rapid development of medical technology,early and effective diagnostic methods could be able to improve the survival rate and...Thyroid carcinoma is one of the most common endocrine malignant diseases worldwide.With the rapid development of medical technology,early and effective diagnostic methods could be able to improve the survival rate and quality of life of patients suffering from the disease.Considering the complexity of cancer,some specific detection method is desired for diagnosis and treatment.Mass spectrometry imaging(MSI)is an emerging technique for acquiring molecular information from biological tissues without staining and labeling,including qualitative,quantitative and spatial distribution information.Over the past several decades,MSI has been widely used for pharmacological monitoring,biomolecular imaging of cells and tissues.In this review,we introduce the tumor progression and histological characteristics of thyroid cancer,and focus mainly on the preparation of biological specimens for MSI and mass spectrometry(MS)analysis,as well as the recent progress in MS and MSI-based thyroid cancer research.This review thoroughly discusses the importance of MS and MSI for clinical diagnosis,identification and prognosis of thyroid cancer,and provides some new clues for molecular mechanisms research and tumor metastasis.展开更多
The imaging mass spectrometry（IMS） technology has experienced a rapid development in recent years.A new IMS technology which is based on air flow assisted ionization（AFAI） was reported.It allows for the convenient...The imaging mass spectrometry（IMS） technology has experienced a rapid development in recent years.A new IMS technology which is based on air flow assisted ionization（AFAI） was reported.It allows for the convenient pretreatment of the samples and can image a large area of sample in a single measurement with high sensitivity.The AFAI in DESI mode was used as the ion source in this paper.The new IMS method is named AFADESI-IMS.The adoption of assisted air flow makes the sample pretreatment easy and convenient.An optimization of the distance between the ion transport tube and MS orifice increases the sensitivity of the system.For data processing,a program based on MATLAB with the function of numerical analysis was developed.A theoretical imaging resolution of a few hundred microns can be achieved.The composite AFAI-IMS images of different target analytes were imaged with high sensitivity.A typical AFAI-IMS image of the whole-body section of a rat was obtained in a single analytical measurement.The ability to image a large area for relevant samples in a single measurement with high sensitivity and repeatability is a significant advantage.The method has enormous potentials in the MS imaging of large and complicated samples.展开更多
A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry（IMS） techniques is reported.The strategy divides the whole datacube of the sample into several subs...A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry（IMS） techniques is reported.The strategy divides the whole datacube of the sample into several subsets and analyses them one by one to obtain the results.Instead of analyzing the whole datacube at one time,the strategy makes the analysis easier and decreases the computation time greatly.In this report,the IMS data are produced by the air flow-assisted ionization IMS（AFAI-IMS）.The strategy can be used in combination with most multivariate statistical analysis methods.In this paper,the strategy was combined with the principal component analysis（PCA） and partial least square analysis（PLS）.It was proven to be effective by analyzing the handwriting sample.By using the strategy,the m/z corresponding to the specific lipids in rat brain tissue were distinguished successfully.Moreover the analysis time grew linearly instead of exponentially as the size of sample increased.The strategy developed in this study has enormous potential for searching for the mjz of potential biomarkers quickly and effectively.展开更多
文摘From the point of view of design requirements, influence of the width of the output image of an imaging subsystem in a tomographic imaging spectrometer, namely width of the slit, the grating and the size of the CCD pixel are analyzed. For the tomographic imaging spectrometry, if the amplification ratio of the imaging subsystem is not high enough to make the whole object to be compressed within the slit, then either the slit width should be increased or the slit width kept unchanged but scanned to receive information of the object. While the width-increase method reduces the spectral resolving power and the SNR; the scanning method reduces the SNR. Analysis of the two cases and computer simulation results are given.
基金funded by the National Natural Science Foundation of China(Grant No.:21874156)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(Grant No.:2021-1-I2M-028).
文摘Three-dimensional(3D)cell spheroid models combined with mass spectrometry imaging(MSI)enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions.Herein,airflow-assisted desorption electrospray ionization-MSI(AFADESI-MSI)was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone(AMI).High-coverage imaging of>1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI.Following AMI treatment at different times,15 metabolites of AMI involved in Ndesethylation,hydroxylation,deiodination,and desaturation metabolic reactions were identified,and according to their spatiotemporal dynamics features,the metabolic pathways of AMI were proposed.Subsequently,the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis.The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism,providing considerable evidence for the mechanism of AMI hepatotoxicity.In addition,a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI.The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs,drug metabolites,and endogenous metabolites after AMI treatment,providing an effective tool for in vitro drug hepatotoxicity evaluation.
基金supported by the National Natural Science Foundation of China(Grant Nos.:21927808 and 81803483).
文摘Diabetic cardiomyopathy(DCM)is a metabolic disease and a leading cause of heart failure among people with diabetes.Mass spectrometry imaging(MSI)is a versatile technique capable of combining the molecular specificity of mass spectrometry(MS)with the spatial information of imaging.In this study,we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity.We optimized the air flow-assisted desorption electrospray ionization(AFADESI)-MSI platform to detect a wide range of metabolites,and then used matrix-assisted laser desorption ionization(MALDI)-MSI for increasing metabolic coverage and improving localization resolution.AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections,respectively,while MALDI-MSI detected 61 metabolites in negative analysis.Our study revealed the heterogenous metabolic profile of the heart in a DCM model,with over 105 region-specific changes in the levels of a wide range of metabolite classes,including carbohydrates,amino acids,nucleotides,and their derivatives,fatty acids,glycerol phospholipids,carnitines,and metal ions.The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model.Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.
基金the National Basic Research Program of China on Global Change(Grant No.2010CB950701,2010CB833503)the Chinese Academy of Sciences for Strategic Priority Research Program(Grant No.XDA05050602-1)National Natural Science Foundation of China(Grant No.31070438)
文摘Canopy foliar Nitrogen Concentration （CNC） is one of the most important parameters influencing vegetation productivity in forest ecosystems. In this study, we explored the potential of imaging spectrometry （hyperspectral） remote sensing of CNC in conifer plantations in China’s subtropical red soil hilly region. Our analysis included data from 57 field plots scattered across two transects covered by Hyperion images. Single regression and partial least squares regression （PLSR） were used to explore the relationships between CNC and hyperspectral data. The correlations between CNC and nearinfrared relfectance （NIR） were consistent in three data subsets （subsets A-C）. For all subsets, CNC was signiifcantly positively correlated with NIR in the two transects （R2=0.29, 0.33 and 0.36, P＆lt;0.05 or P＆lt;0.01, respectively）. It suggested that the NIR-CNC relationship exist despite a weak one, and the relationship may be weakened by the single canopy structure. Besides, we also applied a shortwave infrared （SWIR） index - Normalized Difference Nitrogen Index （NDNI） to estimate CNC variation. NDNI presented a signiifcant positive correlation with CNC in different subsets, but like NIR, it was also with low coefifcient of determination （R2=0.38, 0.20 and 0.17, P＆lt;0.01, respectively）. Also, the correlations between CNC and the entire spectrum reflectance （or its derivative and logarithmic transformation） by PLSR owned different signiifcance in various subsets. We did not ifnd the very robust relationship like previous literatures, so the data we used were checked again. The paired T-test was applied to estimate the inlfuence of inter-annual variability of FNC on the relationships between CNC and Hyperion data. The inter-annual mismatch between period of ifeldwork and Hyperion acquisition had no inlfuence on the correlations of CNC-Hyperion data. Meanwhile, we pointed out that the lack of the canopy structure variation in conifer plantation area may lead to these weak relationships.
基金supported by the General Research Fund(grant no.12302122)of the Research Grants CouncilHong Kong Special Administrative Region,China,the Start-up Grant from Hong Kong Baptist University,and the State Key Laboratory of Environmental and Biological Analysis Research Grant(grant no.SKLP_2021_P04)。
文摘A novel method for enhanced resolution,termed expansion mass spectrometry imaging,has been developed for lipid mass spectrometry imaging,utilizing existing commercially available mass spectrometers without necessitating modifications.This approach involves embedding tissue sections in a swellable polyelectrolyte gel,with the target biomolecules indirectly anchored to the gel network.By employing matrix-assisted laser desorption ionization mass spectrometry imaging,the method has realized an enhanced spatial resolution that surpasses the conventional resolution limits of commercial instruments by approximately 4.5 fold.This enhancement permits the detailed visualization of intricate structures within the mouse brain at a subcellular level,with a lateral resolution nearing 1μm.As a physical technique for achieving resolution beyond standard capabilities,this readily adaptable approach presents a powerful tool for high-definition imaging in biological research.
基金the National Natural Science Foundation of China,No. 30972197 and 31072148Science and Technology Plan Program of Jilin Province,No. 201105038
文摘Differentialiy expressed polypeptides in the brain of a BALB/c mouse model infected with scrapie strain 22L were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that 21 peptides were down-regulated, with peptides of mass-to-charge ratio 758.772 5 and mass-to-charge ratio 5 432.206 9, demonstrating the most significant decreases. These finding suggest that these peptides are candidate biomarkers and may play an important role in the pathogenesis of prion disease.
文摘Overlapping latent fingermarks constitute a serious challenge to database related recognition and matching algorithms in biometry, forensic and crime scene investigations. Mass spectrometry imaging (MSI) is a powerful tool for deciphering and analyzing overlapping fingermarks based on the individual chemical information of each deposit. Fingermark MSI in practice still requires a subjective judgment of an MSI expert, such that rapid analysis, automation, standardization, and a quantitative evaluation of the complete detection and separation process of overlapped fingermarks from MSI data sets is the ultimate goal and will be necessary to become an accepted process in criminal investigations and law enforcement. Here we investigated the feasibility and efficiency of different statistical approaches for the separation of overlapped latent fingermarks based on MSI data. Entropy analysis of generated m/z-images was used to evaluate the results obtained from the statistical analysis. Furthermore, we demonstrate and discuss the opportunity to reconstitute and separate overlapping fingermarks by discrete scanning at selected x,y-positions defined from a previous image analysis using a more simple schema based on visible and therefore optical distinguishable overlapped ink-based fingermarks. The overlapped latent fingermarks were developed by rapid gold sputter coating and analyzed by laser based MSI, without (organic) matrix preparation. Latent finger marks can be transferred from the substrate/surface with and conserved on a soft gold sputtered soft membrane at low temperatures.
基金supported by the National Natural Science Foundation of China(No.21927808)the Chinese Academy of Medical Science(CAMS)Innovation Fund for Medical Sciences(CIFMS,Nos.2022-I2M-2-002 and 2021-1-I2M-028).
文摘On-tissue chemical derivatization(OTCD)effectively enhances ionization efficiency of low abundant and poorly ionized functional molecules to improve detection sensitivity and coverage of mass spectrometry imaging(MSI).Combination OTCD and MSI provides a novel strategy for visualizing previously undisclosed metabolic heterogeneity in tumor.Herein,we present a method to visualize heterogeneous metabolism of oxylipins within tumor by coupling OTCD with airflow-assisted desorption electrospray ionization(AFADESI)-MSI.Taking Girard’s P as a derivatization reagent,easily ionized hydrazide and quaternary amine groups were introduced into the structure of carbonyl metabolites via condensation reaction.Oxylipins,including 127 fatty aldehydes(FALs)and 71 oxo fatty acids(FAs),were detected and imaged in esophageal cancer xenograft with AFADESI-MSI after OTCD.Then t-distributed stochastic neighbor embedding and random forest were exploited to precisely locate the distribution of oxylipins in heterogeneous tumor tissue.With this method,we surprisingly found almost all FALs and oxo FAs significantly accumulated in the core region of tumor,and exhibited a gradual increase trend in tumor over time.These results reveal spatiotemporal heterogeneity of oxylipins in tumor progression,highlighting the value of OTCD combined with MSI to gain deeper insights into understanding tumor metabolism.
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(No.2019YFC1605600)the National Natural Science Foundation of China(No.21804024)+2 种基金Guangdong Provincial Key Laboratory of Quality&Safety Risk Assessment for Agro-Products(2019)(No.2019B121203009)the Special Fund for Science and Technology Innovation Strategy(Construction of High-Level Academy of Agricultural Sciences of Guangdong Province)the Natural Science Foundation of Guangzhou(No.2023A04J0787),China.
文摘Background:Cowpea(Vigna unguiculata L.Walp.)is an economically important crop.It is nutritious and popular with consumers.However,it has been listed as one of the agricultural products of critical concern about safety in China and cyromazine is the major risk factor.Objectives:This study analyzed the dissipation and permeation kinetics of cyromazine residue in cowpea,to offer a scientific basis for the rational use of pesticide and ensure the safety of agricultural products.Materials and methods:The dissipation and residue level of the systemic insecticide cyromazine on cowpea under field and stored conditions were investigated.Subsequently,the spatial distribution of cyromazine was studied using mass spectrometry imaging to visualize the dynamic processes of permeation and migration in the tissues post pesticide application.Results:The dissipation processing of cyromazine in cowpea was shown to follow the first-order kinetics and half-life was 7.76 d in the field.In cowpea,the permeation and migration rate of cyromazine was faster than that in kidney beans and accumulation was mainly in the pulp.It is not safe to apply cyromazine to cowpeas with reference to the application method on kidney beans.Conclusions:These findings present vital data for the determination of risks linked with cowpea consumption and pesticide intake.
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the National Natural Science Foundation of China(Nos.31901911 and 21904142)the Natural Science Foundation of Guangdong Province(Nos.2019A1515011521 and 2022A1515011385)supported by the Young Talent Support Project of Guangzhou Association for Science and Technology(No.QT20220101031).
文摘Mass spectrometry imaging(MSI)has made the spatio-chemical characterization of a broad range of small-molecule metabolites within biological tissues possible.However,available matrix-assisted laser desorption/ionization mass spectrometry(MALDI-MS)suffers from severe background interferences in low-mass ranges and inhomogeneous matrix deposition.Thus,surface-assisted LDI-MS(SALDI-MS)has been an attractive alternative for high-sensitivity detection and imaging of small biomolecules.In this study,we construct a new composite substrate,hydrophobic polydopamine(hPDA)-modified TiO_(2)nanotube(TDNT)coated with plasmonic gold nanoparticle(AuNP-hPDA-TDNT),as a dual-polarity SALDI substrate using an easy and cost-effective fabrication approach.Benefitting from the synergistic effects of TDNT semiconductor and plasmonic PDA modification,this SALDI substrate exhibits superior performance for dual-polarity detection of a vast diversity of small molecules.Highly reduced background interferences,lower detection limits,and spot-to-spot repeatability can be achieved using AuNP-hPDA-TDNT substrates.Due to its unique imprinting performance,various metabolites and lipids can be visualized within jatropha integerrima petals,ginkgo leaves,strawberry fruits,and latent fingerprints.More valuably,the universality of this matrix-free substrate is demonstrated for mapping spatial distribution of lipids within mouse brain tissue sections.Considered together,this AuNP-hPDA-TDNT material is expected to be a promising SALDI substrate in various fields,especially in nanomaterial development and life sciences.
基金supported by the National Natural Science Foundation of China (Nos.22036001, 22276034 and 22106130)。
文摘Cancer cell spheroids(CCS) are a valuable three-dimensional cell model in cancer studies because they could replicate numerous characteristics of solid tumors. Increasing researches have used matrix-assisted laser desorption/ionization mass spectrometry imaging(MALDI-MSI) to investigate the spatial distribution of endogenous compounds(e.g., lipids) in CCS. However, only limited lipid species can be detected owing to a low ion yield by using MALDI. Besides, it is still challenging to fully characterize the structural diversity of lipids due to the existence of isomeric/isobaric species. Here, we carried out the initial application of MALDI coupled with laser-postionization(MALDI-2) and trapped ion mobility spectrometry(TIMS) imaging in HCT116 colon CCS to address these challenges. We demonstrated that MALDI-2 is capable of detecting more number and classes of lipids in HCT116 colon CCS with higher signal intensities than MALDI. TIMS could successfully separate numerous isobaric/isomeric species of lipids in CCS. Interestingly, we found that some isomeric/isobaric species have totally different spatial distributions in colon CCS. Further MS/MS imaging analysis was employed to determine the compositions of fatty acid chains for isomeric species by examining disparities in signal intensities and spatial distributions of product ions. This work stresses the robust ability of TIMS and MALDI-2 imaging in analyzing endogenous lipids in CCS, which could potentially become powerful tools for future cancer studies.
文摘Imaging mass spectrometry (IMS) methodology for biological tissue component distribution map using MALDI-TOF MS and MALDI-TOF/TOF MS was established.Peak density distribution was probed to be quite useful for MS image classification.More than 40 000 spectra from 200 tissue sections were acquired and reproducibility between various of species groups was great than 80%.Tens of differentiately expressed components were detected by t-test (P<0.01).Classification modeling was created based on the differentiate components,blind species were analyzed for model validation,accuracy was above 90%.
基金supported by the National Key Research and Development Program of China(No.2017YFC1704000)Outstanding Talent Support Program of Beijing,China(No.2017000020124G272)
文摘Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development.Herein,an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging(AFADESI-MSI)was established for direct analysis of metabolites in renal tissue sections.This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I,a known nephrotoxic drug,aimed to discover metabolites associated with nephrotoxicity.As a result,38 metabolites related to the arginine-creatinine metabolic pathway,the urea cycle,the serine synthesis pathway,metabolism of lipids,choline,histamine,lysine,and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I.These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions.This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.
基金supported by the National Natural Science Foundation of China(No.81803483,No.21927808)National Key Research and Development Program of China(No.2017YFC1704006)。
文摘Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy(DN)is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies.In the present study,a spatial-resolved metabolomics approach based on air flowassisted desorption electrospray ionization(AFADESI)and matrix-assisted laser desorption ionization(MALDI)integrated mass spectrometry imaging(MSI)was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin(STZ)-treated DN rats and the therapeutic effect of astragalosideⅣ,a potential anti-diabetic drug,against DN.As a result,a wide range of functional metabolites including sugars,amino acids,nucleotides and their derivatives,fatty acids,phospholipids,sphingolipids,glycerides,carnitine and its derivatives,vitamins,peptides,and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution.These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside Ⅳ(100 mg/kg)for 12 weeks.This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats.These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.
基金support from the National Natural Science Foundation of China(Nos.31901911 and 21904142)the National Key R&D Program of China(No.2018YFD0200300)+1 种基金the Natural Science Foundation of Guangdong Province(No.2018A030310215)This work is also supported by the project funded by the National Postdoctoral Program for Innovative Talents(No.BX20180399).
文摘Design and discovery of carrier-mediated modified pesticides are vital for reducing pesticide dosage and increasing utilization,yet it remains a great challenge due to limited insights into plant translocation mechanisms.Nanostructure/nanoparticle assisted laser desorption/ionization strategy has established itself as a preferential analytical tool for biological tissue analysis,whereas potential applications in plant sciences are hindered with regard to the inability to slice plant leaves and petals.Herein,we report gold nanoparticle(AuNP)-immersed paper imprinting mass spectrometry imaging(MSI)for the spatiotemporal visualization of pesticide translocation in plant leaves.This approach plays a dual role in preserving spatial information and improving ionization efficiency for pesticides regardless of imaging artifacts due to homogenous AuNP deposition.Using this MSI platform,we proposed the elaborate plant translocation mechanism of agrochemicals for the first time,which is currently poorly understood.The dynamic processes of carrier-mediated pesticides can be clearly visualized,including crossing of plasma membranes by transporters,translocation downward in stems through the phloem,diffusion to the xylem and,conversely,accumulation at margins of the treated leaves.Moreover,this AuNP-assisted paper imprinting method could be highly compatible with laser-based MSI instruments,expediting researches across a broad range of fields,especially in nanomaterial development and life sciences.
基金The Natural Science Foundation of Guangdong Province,China(2021A1515010171)Natural Science Foundation of Shanxi Province of China(201901D111210)+2 种基金2019 Platform Base Special Project of Shanxi Province(201905D121002)Shanxi Medical University Innovation and Entrepreneurship Fund for College Students(2020181)Shenzhen Science and Technology Innovation Commission(KCXFZ202002011008124)
文摘Thyroid carcinoma is one of the most common endocrine malignant diseases worldwide.With the rapid development of medical technology,early and effective diagnostic methods could be able to improve the survival rate and quality of life of patients suffering from the disease.Considering the complexity of cancer,some specific detection method is desired for diagnosis and treatment.Mass spectrometry imaging(MSI)is an emerging technique for acquiring molecular information from biological tissues without staining and labeling,including qualitative,quantitative and spatial distribution information.Over the past several decades,MSI has been widely used for pharmacological monitoring,biomolecular imaging of cells and tissues.In this review,we introduce the tumor progression and histological characteristics of thyroid cancer,and focus mainly on the preparation of biological specimens for MSI and mass spectrometry(MS)analysis,as well as the recent progress in MS and MSI-based thyroid cancer research.This review thoroughly discusses the importance of MS and MSI for clinical diagnosis,identification and prognosis of thyroid cancer,and provides some new clues for molecular mechanisms research and tumor metastasis.
基金financially supported by the National Instrumentation Program (No. 2011YQ17006702)the National Natural Science Foundation of China (No. 21027013 and No. 81102413)Fundamental Research Program of Shenzhen (No. JC201005280634A)
文摘The imaging mass spectrometry（IMS） technology has experienced a rapid development in recent years.A new IMS technology which is based on air flow assisted ionization（AFAI） was reported.It allows for the convenient pretreatment of the samples and can image a large area of sample in a single measurement with high sensitivity.The AFAI in DESI mode was used as the ion source in this paper.The new IMS method is named AFADESI-IMS.The adoption of assisted air flow makes the sample pretreatment easy and convenient.An optimization of the distance between the ion transport tube and MS orifice increases the sensitivity of the system.For data processing,a program based on MATLAB with the function of numerical analysis was developed.A theoretical imaging resolution of a few hundred microns can be achieved.The composite AFAI-IMS images of different target analytes were imaged with high sensitivity.A typical AFAI-IMS image of the whole-body section of a rat was obtained in a single analytical measurement.The ability to image a large area for relevant samples in a single measurement with high sensitivity and repeatability is a significant advantage.The method has enormous potentials in the MS imaging of large and complicated samples.
基金supported by the National Instrumentation Programmme(Nos.2011YQ17006702 and 2011YQ14015010)the National Natural Science Foundation of China(Nos.81102413 and 21175121)Fundamental Research Program of Shenzhen (No.JC201005280634A).
文摘A new multivariate statistical strategy for analyzing large datasets that are produced by imaging mass spectrometry（IMS） techniques is reported.The strategy divides the whole datacube of the sample into several subsets and analyses them one by one to obtain the results.Instead of analyzing the whole datacube at one time,the strategy makes the analysis easier and decreases the computation time greatly.In this report,the IMS data are produced by the air flow-assisted ionization IMS（AFAI-IMS）.The strategy can be used in combination with most multivariate statistical analysis methods.In this paper,the strategy was combined with the principal component analysis（PCA） and partial least square analysis（PLS）.It was proven to be effective by analyzing the handwriting sample.By using the strategy,the m/z corresponding to the specific lipids in rat brain tissue were distinguished successfully.Moreover the analysis time grew linearly instead of exponentially as the size of sample increased.The strategy developed in this study has enormous potential for searching for the mjz of potential biomarkers quickly and effectively.
