Ensuring the timely and precise monitoring of severe liver diseases is crucial for guiding effective therapies and significantly extending overall quality of life.However,this remains a worldwide challenge,given the h...Ensuring the timely and precise monitoring of severe liver diseases is crucial for guiding effective therapies and significantly extending overall quality of life.However,this remains a worldwide challenge,given the high incidence rate and the presence of strong confounding clinical symptoms.Herein,we applied a convenient and high-yield method to prepare the magnetic mesoporous carbon(MMC-Fe),guided by a composite of resol and triblock copolymer.With the combination of MMC-Fe,high-throughput mass spectrometry,and a simple machine learning algorithm,we extracted N-glycan profiles from various serum samples,including healthy controls,liver cirrhosis,and liver cancer,and from which we screened specific N-glycans.Specifically,the selected N-glycans demonstrate exceptional performance with area under the curve(AUC)values ranging from 0.948 to 0.993 for the detection of liver diseases,including alpha fetoprotein(AFP)-negative liver cancer.Among them,five N-glycans holds potential in monitoring distinctions between liver cirrhosis and AFP-negative liver cancer(AUC values of 0.827–0.842).This study is expected to promote the glycan-based precise monitoring of diseases,not limited to liver disease.展开更多
As the most common pathological type of nephrotic syndrome,membranous nephropathy(MN)presents diversity in progression trends,facing severe complications.The precise discrimination of MN from healthy people,other type...As the most common pathological type of nephrotic syndrome,membranous nephropathy(MN)presents diversity in progression trends,facing severe complications.The precise discrimination of MN from healthy people,other types of nephrotic syndrome or those with therapeutic remission has always been huge challenge in clinics,not to mention comprehensive individualized monitoring relied on minimally invasive molecular detection means.Herein,we construct a functionalized pore architecture to couple with machine learning to aid all-round peptidome enrichment and data profiling from hundreds of human serum samples,and finally establish a set of defined peptide panel consisting of 12 specific feature signals.In addition to the realization of above-mentioned precise discrimination with more than 97%of sensitivity,88%of accuracy and f1 score,the simultaneously comprehensive individualized monitoring for MN can also be achieved,including conventionally screening diagnosis,congeneric distinction and prognostic evaluation.This work greatly advances the development of peptidome data-driven individualized monitoring means for complex diseases and undoubtedly inspire more devotion into molecular detection field.展开更多
Phosphorylation plays crucial parts in lenticular biological function.Getting knowledge of region-resolved phosphoproteome contributes to better comprehending the pathogenesis.Here,we prepared the hybrid metal organic...Phosphorylation plays crucial parts in lenticular biological function.Getting knowledge of region-resolved phosphoproteome contributes to better comprehending the pathogenesis.Here,we prepared the hybrid metal organic frameworks(HMOFs)for probing the region-resolved heterogeneity of phosphoproteome in human lens.1334 phosphosites corresponding to 564 phosphoproteins,1160 phosphosites corresponding to 316 phosphoproteins and 517 phosphosites corresponding to 205 phosphoproteins were identified in capsule,cortex and nucleus,respectively,providing the relatively extensive distribution mapping of phosphorylation in human lens for the first time.The label-free quantification experiments and principal component analysis presented differential expression of phopshoproteins in three subregions.For instance,α-crystallin,β-crystallin and fibrillin-1 closely associated with cataract and Marfan syndrome showed disparate spatial distribution.The preferential phosphoproteins in capsule,cortex and nucleus were involved in cytoskeleton organization,metabolic process and lens development in camera-type eye,respectively.This work first provided a general overview of region-resolved phosphoproteome of human lens.展开更多
Crohn's disease(CD)as a big issue to public health needs an accurate diagnosis urgently that is the common challenge among internal diseases.Herein,we design a mesoporous polydopamine with builtin metal-organic fr...Crohn's disease(CD)as a big issue to public health needs an accurate diagnosis urgently that is the common challenge among internal diseases.Herein,we design a mesoporous polydopamine with builtin metal-organic frameworks(dubbed MMP-b-MOFs)to combine with high-throughput mass spectrometry to extract serum peptide fingerprints from CD and healthy controls(HC).Benefitting by the sizeexclusion and strong hydrophilicity of MMP-b-MOFs,the extracted peptide fingerprints present extremely high quality.CD and HC are explicitly discriminated with orthogonal partial least squares discriminant analysis(OPLS-DA),the corresponding area under the curve(AUC)value is 1.000.Moreover,eight peptides with clear identity are screened out and achieve the accurate diagnosis and subtype classification of CD,with all AUC values up to 1.000.Moreover,the unsupervised model is also established to precisely classify HC and CD based on these eight clearly identified peptides.This work brings great benefits for clinical detection especially internal medicine.展开更多
Both glycosylation and phosphorylation exert crucial rule in multitudinous biological processes.For in-depth profiling of glycosylation and phosphorylation,a magnetic metal oxide is effectively coupled with inherently...Both glycosylation and phosphorylation exert crucial rule in multitudinous biological processes.For in-depth profiling of glycosylation and phosphorylation,a magnetic metal oxide is effectively coupled with inherently hydrophilic mesoporous channels(denoted as Fe_(3)O_(4)@TiO_(2)@mSiO_(2)-TSG).Based on the mechanism of hydrophilic interaction liquid chromatography(HILIC)and metal oxide affinity chromatography(MOAC),the Fe_(3)O_(4)@TiO_(2)@mSiO_(2)-TSG nanomaterial shows high capacity for simultaneously enriching glycopeptides and phosphopeptides.With human saliva collected in successive four days as practical biological sample,endogenous glycopeptides and phosphopeptides are efficiently enriched.Further gene ontology analysis reveals that the identified endogenous glycopeptides and phosphopeptides participate in diverse molecular functions and biological processes.This strategy is anticipated to promote variation analysis of salivary post-translational modifications.展开更多
Body fluids contain a large number of disease markers including proteins,exosomes and cells,the concentration of which indicates the health status of a body system and can be hence applied to predict the degree of ser...Body fluids contain a large number of disease markers including proteins,exosomes and cells,the concentration of which indicates the health status of a body system and can be hence applied to predict the degree of seriousness of a disease.However,the content of disease markers is relatively low.For solving this problem,a variety of pretreatment methods have been developed,among which aptamer-based nanomaterials hold great potential for biomarker capture because of various natural properties of nano-substrates such as high specific surface area,as well as the high affinity of aptamer towards target and the higher stability than antibody.In this review,we summarized the recent aptamer-based nanomaterials for the separation and analysis of different biomarkers including proteins,exosomes and cells.More specifically,the standard of classification description was based on the applied substrates including magnetic substrates and non-magnetic substrates.Moreover,the perspective of aptamer-based nanomaterials was discussed.展开更多
Exosome and inclusive cargoes have manifested significant function in different biological events. In particular, glycopeptides in exosome are closely associated with occurrence and development of various diseases. De...Exosome and inclusive cargoes have manifested significant function in different biological events. In particular, glycopeptides in exosome are closely associated with occurrence and development of various diseases. Developing advanced tools is highly desired to enrich glycopeptides from exosomes, and enrich exosomes from complex biological samples as well. In this work, integration of L-cysteine and titania onto the surface of magnetic nanoparticles is designed to realize the coefficient affinity towards exosomes and inclusive glycopeptides. Benefiting from the synergistic affinity, we separate exosomes from human urine concentrate directly, which was proved by the detection of three typical antigen markers of exosomes. Furthermore, hardly any exosomes remained on materials after ultrasonication, which confirmed the good capture performance of Fe_(3)O_(4)@TiO_(2)@L-Cys and high release effect of direct lysis.Moreover, 146 glycopeptides corresponding to 77 glycoproteins were successfully identified from captured exosomes. These satisfactory results will inspire more efforts to be devoted to this field and will be extremely helpful to in-depth information excavation of biological markers, especially disease-related ones, through exosomes and inclusive glycopeptides.展开更多
Human health is always under global spotlight, but now it suffers from severe environmental issue and various diseases.Developing highly selective and effective extraction technique for environmental pollutant removal...Human health is always under global spotlight, but now it suffers from severe environmental issue and various diseases.Developing highly selective and effective extraction technique for environmental pollutant removal and target protein/peptide molecules conduces to the solution of environmental contamination and early disease detection, which will promise human health to a great degree. Metal-organic frameworks(MOFs) are typical porous nanomaterials featuring rigid structure, large specific surface area, thermal and chemical stability, numerous active sites and easy functionalization. Moreover, multitudinous combination of metal centers and organic ligands often endows MOFs with structure and function diversity. Owing to such splendid merits, MOFs are able to act as advanced adsorbents for sample-pretreatment in proteomics and environmental field,which indicates great efficiency, reproducibility, convenience and cost-effectiveness. In this review, the novel design of MOFs and their applications in proteomics and environmental research are roughly summarized. We first introduce the representative researches of functional MOFs in protein post-translational modifications including glycosylation and phosphorylation, mainly focusing on hydrophilic interaction liquid chromatography(HILIC) or metal-oxide affinity chromatography(MOAC). The important role of MOFs in enzyme immobilization is also covered. Then MOF-based adsorptive removal of diverse environmental contaminants embracing plasticizers, pesticides and varied water pollutants(pharmaceutical and personal care products,organic dyes and heavy metals), in which multiple chemical and non-chemical interactions play a vital role, is emphatically discussed. Finally, we analyze the existing problems and challenges in the way of wider practical applications and put forward prospective anticipation.展开更多
Due to inefficient diagnostic methods,inflammatory bowel disease(IBD)normally progresses into severe complications including cancer.Highly efficient extraction and identification of metabolic fingerprints are of signi...Due to inefficient diagnostic methods,inflammatory bowel disease(IBD)normally progresses into severe complications including cancer.Highly efficient extraction and identification of metabolic fingerprints are of significance for disease surveillance.In this work,we synthesized a layered titania nanosheet doped with graphitized carbon(2D-GC-mTNS)through a simple one-step assembly process for assisting laser desorption ionization mass spectrometry(LDI-MS)for metabolite analysis.Based on the synergistic effect of graphitized carbon and mesoporous titania,2D-GC-mTNS exhibits good extraction ability including high sensitivity(<1 fmolμL−1)and great repeatability toward metabolites.A total of 996 fingerprint spectra were collected from hundreds of native urine samples(including IBD patients and healthy controls),each of which contained 1220 m/z metabolite features.Diagnostic model was further established for precise discrimination of patients from healthy controls,with high area under the curve value of 0.972 and 0.981 toward discovery cohort and validation cohort,respectively.The 2D-GC-mTNS promotes LDI-MS to be close to clinical application,with rapid speed,minimum sample consumption and free of sample pretreatment.展开更多
基金supported by National Key R&D Program of China(No.2018YFA0507501)the National Natural Science Foundation of China(Nos.22074019,21425518,22004017)Shanghai Sailing Program(No.20YF1405300)。
文摘Ensuring the timely and precise monitoring of severe liver diseases is crucial for guiding effective therapies and significantly extending overall quality of life.However,this remains a worldwide challenge,given the high incidence rate and the presence of strong confounding clinical symptoms.Herein,we applied a convenient and high-yield method to prepare the magnetic mesoporous carbon(MMC-Fe),guided by a composite of resol and triblock copolymer.With the combination of MMC-Fe,high-throughput mass spectrometry,and a simple machine learning algorithm,we extracted N-glycan profiles from various serum samples,including healthy controls,liver cirrhosis,and liver cancer,and from which we screened specific N-glycans.Specifically,the selected N-glycans demonstrate exceptional performance with area under the curve(AUC)values ranging from 0.948 to 0.993 for the detection of liver diseases,including alpha fetoprotein(AFP)-negative liver cancer.Among them,five N-glycans holds potential in monitoring distinctions between liver cirrhosis and AFP-negative liver cancer(AUC values of 0.827–0.842).This study is expected to promote the glycan-based precise monitoring of diseases,not limited to liver disease.
基金financially supported by National Key R&D Program of China(No.2018YFA0507501)the National Natural Science Foundation of China(Nos.22074019,21425518,22004017)Shanghai Sailing Program(No.20YF1405300)。
文摘As the most common pathological type of nephrotic syndrome,membranous nephropathy(MN)presents diversity in progression trends,facing severe complications.The precise discrimination of MN from healthy people,other types of nephrotic syndrome or those with therapeutic remission has always been huge challenge in clinics,not to mention comprehensive individualized monitoring relied on minimally invasive molecular detection means.Herein,we construct a functionalized pore architecture to couple with machine learning to aid all-round peptidome enrichment and data profiling from hundreds of human serum samples,and finally establish a set of defined peptide panel consisting of 12 specific feature signals.In addition to the realization of above-mentioned precise discrimination with more than 97%of sensitivity,88%of accuracy and f1 score,the simultaneously comprehensive individualized monitoring for MN can also be achieved,including conventionally screening diagnosis,congeneric distinction and prognostic evaluation.This work greatly advances the development of peptidome data-driven individualized monitoring means for complex diseases and undoubtedly inspire more devotion into molecular detection field.
基金financially supported by National Key R&D Program of China(No.2018YFA0507501)the National Natural Science Foundation of China(Nos.22074019,21425518 and 22004017)Shanghai Sailing Program(No.20YF1405300)。
文摘Phosphorylation plays crucial parts in lenticular biological function.Getting knowledge of region-resolved phosphoproteome contributes to better comprehending the pathogenesis.Here,we prepared the hybrid metal organic frameworks(HMOFs)for probing the region-resolved heterogeneity of phosphoproteome in human lens.1334 phosphosites corresponding to 564 phosphoproteins,1160 phosphosites corresponding to 316 phosphoproteins and 517 phosphosites corresponding to 205 phosphoproteins were identified in capsule,cortex and nucleus,respectively,providing the relatively extensive distribution mapping of phosphorylation in human lens for the first time.The label-free quantification experiments and principal component analysis presented differential expression of phopshoproteins in three subregions.For instance,α-crystallin,β-crystallin and fibrillin-1 closely associated with cataract and Marfan syndrome showed disparate spatial distribution.The preferential phosphoproteins in capsule,cortex and nucleus were involved in cytoskeleton organization,metabolic process and lens development in camera-type eye,respectively.This work first provided a general overview of region-resolved phosphoproteome of human lens.
基金financially supported by National Key R&D Program of China(No.2018YFA0507501)the National Natural Science Foundation of China(Nos.22074019,21425518,22004017)Shanghai Sailing Program(No.20YF1405300)。
文摘Crohn's disease(CD)as a big issue to public health needs an accurate diagnosis urgently that is the common challenge among internal diseases.Herein,we design a mesoporous polydopamine with builtin metal-organic frameworks(dubbed MMP-b-MOFs)to combine with high-throughput mass spectrometry to extract serum peptide fingerprints from CD and healthy controls(HC).Benefitting by the sizeexclusion and strong hydrophilicity of MMP-b-MOFs,the extracted peptide fingerprints present extremely high quality.CD and HC are explicitly discriminated with orthogonal partial least squares discriminant analysis(OPLS-DA),the corresponding area under the curve(AUC)value is 1.000.Moreover,eight peptides with clear identity are screened out and achieve the accurate diagnosis and subtype classification of CD,with all AUC values up to 1.000.Moreover,the unsupervised model is also established to precisely classify HC and CD based on these eight clearly identified peptides.This work brings great benefits for clinical detection especially internal medicine.
基金supported by National Key R&D Program of China(No.2018YFA0507501)the National Science Foundation for Distinguished Young Scholars of China(No.21425518)+1 种基金the National Natural Science Foundation of China(Nos.22074019,22004017)Shanghai Sailing Program(No.20YF1405300).
文摘Both glycosylation and phosphorylation exert crucial rule in multitudinous biological processes.For in-depth profiling of glycosylation and phosphorylation,a magnetic metal oxide is effectively coupled with inherently hydrophilic mesoporous channels(denoted as Fe_(3)O_(4)@TiO_(2)@mSiO_(2)-TSG).Based on the mechanism of hydrophilic interaction liquid chromatography(HILIC)and metal oxide affinity chromatography(MOAC),the Fe_(3)O_(4)@TiO_(2)@mSiO_(2)-TSG nanomaterial shows high capacity for simultaneously enriching glycopeptides and phosphopeptides.With human saliva collected in successive four days as practical biological sample,endogenous glycopeptides and phosphopeptides are efficiently enriched.Further gene ontology analysis reveals that the identified endogenous glycopeptides and phosphopeptides participate in diverse molecular functions and biological processes.This strategy is anticipated to promote variation analysis of salivary post-translational modifications.
基金supported by the National Key R&D Program of China(2018YFA0507501)the National Natural Science Foundation of China(22074019,22004017)Shanghai Sailing Program(20YF1405300)。
文摘Body fluids contain a large number of disease markers including proteins,exosomes and cells,the concentration of which indicates the health status of a body system and can be hence applied to predict the degree of seriousness of a disease.However,the content of disease markers is relatively low.For solving this problem,a variety of pretreatment methods have been developed,among which aptamer-based nanomaterials hold great potential for biomarker capture because of various natural properties of nano-substrates such as high specific surface area,as well as the high affinity of aptamer towards target and the higher stability than antibody.In this review,we summarized the recent aptamer-based nanomaterials for the separation and analysis of different biomarkers including proteins,exosomes and cells.More specifically,the standard of classification description was based on the applied substrates including magnetic substrates and non-magnetic substrates.Moreover,the perspective of aptamer-based nanomaterials was discussed.
基金supported by National Key R&D Program of China (No. 2018YFA0507501)the National Science Foundation for Distinguished Young Scholars of China (No. 21425518)+1 种基金the National Natural Science Foundation of China (Nos. 22074019, 22004017)Shanghai Sailing Program (No. 20YF1405300)。
文摘Exosome and inclusive cargoes have manifested significant function in different biological events. In particular, glycopeptides in exosome are closely associated with occurrence and development of various diseases. Developing advanced tools is highly desired to enrich glycopeptides from exosomes, and enrich exosomes from complex biological samples as well. In this work, integration of L-cysteine and titania onto the surface of magnetic nanoparticles is designed to realize the coefficient affinity towards exosomes and inclusive glycopeptides. Benefiting from the synergistic affinity, we separate exosomes from human urine concentrate directly, which was proved by the detection of three typical antigen markers of exosomes. Furthermore, hardly any exosomes remained on materials after ultrasonication, which confirmed the good capture performance of Fe_(3)O_(4)@TiO_(2)@L-Cys and high release effect of direct lysis.Moreover, 146 glycopeptides corresponding to 77 glycoproteins were successfully identified from captured exosomes. These satisfactory results will inspire more efforts to be devoted to this field and will be extremely helpful to in-depth information excavation of biological markers, especially disease-related ones, through exosomes and inclusive glycopeptides.
基金supported by the National Key R&D Program of China(2018YFA0507501)the National Natural Science Foundation of China(22074019,21425518,22004017)Shanghai Sailing Program(20YF1405300)。
文摘Human health is always under global spotlight, but now it suffers from severe environmental issue and various diseases.Developing highly selective and effective extraction technique for environmental pollutant removal and target protein/peptide molecules conduces to the solution of environmental contamination and early disease detection, which will promise human health to a great degree. Metal-organic frameworks(MOFs) are typical porous nanomaterials featuring rigid structure, large specific surface area, thermal and chemical stability, numerous active sites and easy functionalization. Moreover, multitudinous combination of metal centers and organic ligands often endows MOFs with structure and function diversity. Owing to such splendid merits, MOFs are able to act as advanced adsorbents for sample-pretreatment in proteomics and environmental field,which indicates great efficiency, reproducibility, convenience and cost-effectiveness. In this review, the novel design of MOFs and their applications in proteomics and environmental research are roughly summarized. We first introduce the representative researches of functional MOFs in protein post-translational modifications including glycosylation and phosphorylation, mainly focusing on hydrophilic interaction liquid chromatography(HILIC) or metal-oxide affinity chromatography(MOAC). The important role of MOFs in enzyme immobilization is also covered. Then MOF-based adsorptive removal of diverse environmental contaminants embracing plasticizers, pesticides and varied water pollutants(pharmaceutical and personal care products,organic dyes and heavy metals), in which multiple chemical and non-chemical interactions play a vital role, is emphatically discussed. Finally, we analyze the existing problems and challenges in the way of wider practical applications and put forward prospective anticipation.
基金This work was financially supported by National Key R&D Program of China(2018YFA0507501)the National Natural Science Foundation of China(22074019,21425518,22004017)Shanghai Sailing Program(20YF1405300).
文摘Due to inefficient diagnostic methods,inflammatory bowel disease(IBD)normally progresses into severe complications including cancer.Highly efficient extraction and identification of metabolic fingerprints are of significance for disease surveillance.In this work,we synthesized a layered titania nanosheet doped with graphitized carbon(2D-GC-mTNS)through a simple one-step assembly process for assisting laser desorption ionization mass spectrometry(LDI-MS)for metabolite analysis.Based on the synergistic effect of graphitized carbon and mesoporous titania,2D-GC-mTNS exhibits good extraction ability including high sensitivity(<1 fmolμL−1)and great repeatability toward metabolites.A total of 996 fingerprint spectra were collected from hundreds of native urine samples(including IBD patients and healthy controls),each of which contained 1220 m/z metabolite features.Diagnostic model was further established for precise discrimination of patients from healthy controls,with high area under the curve value of 0.972 and 0.981 toward discovery cohort and validation cohort,respectively.The 2D-GC-mTNS promotes LDI-MS to be close to clinical application,with rapid speed,minimum sample consumption and free of sample pretreatment.
