Ossifying fibroma(OF)and fibrous dysplasia(FD)are two fibro-osseous lesions with overlapping clinicopathological features,making diagnosis challenging.In this study,we applied a whole-genome shallow sequencing approac...Ossifying fibroma(OF)and fibrous dysplasia(FD)are two fibro-osseous lesions with overlapping clinicopathological features,making diagnosis challenging.In this study,we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations(CNAs)using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples.Freshly frozen tissue specimens from OF(n=29)and FD(n=28)patients were obtained for analysis.Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection(LCM),with~30–50 cells(5000–10000µm2)per sample.We found that the rate of recurrent CNAs in OF cases was much higher(44.8%,13 of 29)than that in FD cases(3.6%,1 of 28).Sixty-nine percent(9 of 13)of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and 12.We also identified eight CNA-associated genes(HILPDA,CALD1,C1GALT1,MICALL2,PHF14,AIMP2,MDM2,and CDK4)with amplified expression,which was consistent with the copy number changes.We further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA profile.Moreover,analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery,recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points,suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant potential.Overall,CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.展开更多
Matrix-assisted laser desorption/ionization(MALDI)mass spectrometry(MS)plays an indispensable role in analyzing protein covalent structures.The reliable identification of amino acid residues and modifications relies o...Matrix-assisted laser desorption/ionization(MALDI)mass spectrometry(MS)plays an indispensable role in analyzing protein covalent structures.The reliable identification of amino acid residues and modifications relies on the mass accuracy,which is highly dependent on calibration.However,the accuracy provided by the currently available calibrants still needs further improvement in terms of compatibility with multiple tandem MS modes or ion polarity modes,calibratable range,and minimizing suppression of and interference with analyte signals.Here aiming at developing a versatile calibrant to solve these problem,we designed a synthetic peptide format of calibrant R_x(GDP_n)_m(referred to as“Gly-Asp-Pro,GDP”)according to the chemical natures of amino acids and polypeptide fragmentation rules in tandem MS.With four types of amino acid residues selected and arranged through rational designs,a GDP peptide produces highly regulated fragments that give rise to evenly spaced signals in each tandem MS mode and is compatible with both positive and negative ion modes.In internal calibration,its regulated fragmentation pattern minimizes interference with analyte signals,and using a single peptide as the input minimizes suppression of the analyte signals.As demonstrated by analyses of proteins including monoclonal antibody and Aβ-42,these features allowed significant increase of the mass accuracy and precision,which improved sequence coverage and sequence resolution in sequence analyses(including de novo sequencing).This rational design strategy may also inspire further development of synthetic calibrants that benefit structural analysis of biomolecules.展开更多
White organic light-emitting diodes(WOLEDs)is a new generation of lighting technology and has stimulated wide-ranging studies.Despite the advantage of simple device structure,single-emitting-layer WOLEDs(SEL-WOLEDs)st...White organic light-emitting diodes(WOLEDs)is a new generation of lighting technology and has stimulated wide-ranging studies.Despite the advantage of simple device structure,single-emitting-layer WOLEDs(SEL-WOLEDs)still face the challenges of difficult material screening and fine energy level regulation.Herein,we report efficient SEL-WOLEDs with a sky-blue emitting cerium(Ⅲ)complex Ce-TBO2Et and an orange-red emitting europium(Ⅱ)complex Eu(Tp2Et)2 as the emitters,showing a maximum external quantum efficiency of 15.9%and Commission Internationale de l'Eclairage coordinates of(0.33,0.39)at various luminances.Most importantly,the electroluminescence mechanism of direct hole capture and hindered energy transfer between the two emitters facilitate a manageable weight doping concentration of 5%for Eu(Tp2Et)2,avoiding the low concentration(<1%)of the low-energy emitter in typical SEL-WOLEDs.Our results indicate that d-f transition emitters may circumvent fine energy level regulation and provide development potential for SEL-WOLEDs.展开更多
Chemistry,a fundamental scientific discipline,plays a significant role in various fields,including medical science.Its ability to break down human cells into constituent biomolecules,such as nucleic acids,proteins,car...Chemistry,a fundamental scientific discipline,plays a significant role in various fields,including medical science.Its ability to break down human cells into constituent biomolecules,such as nucleic acids,proteins,carbohydrates and lipids,has been a valuable resource for studying fundamental building blocks at the atomic level.By studying the functions of these biomolecules,chemists can gain insights into the underlying mechanisms of various diseases.The integration of chemistry and medical science has facilitated advancements in diagnostic,therapeutic and translational research,leading to fruitful collaborations between these two fields.As a result,this interdisciplinary approach has yielded cutting-edge research with implications for the improvement of human health.展开更多
Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma.However,a predictor of oral leukoplakia prognosis has not yet been ide...Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma.However,a predictor of oral leukoplakia prognosis has not yet been identified.We investigated whether copy number alteration patterns may effectively predict the prognostic outcomes of oral leukoplakia using routinely processed paraffin sections.Comparison of copy number alteration patterns between oral leukoplakia with hyperplasia(HOL,n=22)and dysplasia(DOL,n=21)showed that oral leukoplakia with dysplasia had a higher copy number alteration rate(86%)than oral leukoplakia with hyperplasia(46%).Oral leukoplakia with dysplasia exhibited a wider range of genomic variations across all chromosomes compared with oral leukoplakia with hyperplasia.We also examined a retrospective cohort of 477 patients with oral leukoplakia with hyperplasia with detailed follow-up information.The malignant transformation(MT,n=19)and leukoplakia recurrence(LR,n=253)groups had higher frequencies of aneuploidy events and copy number loss rate than the free of disease(FD,n=205)group.Together,our results revealed the association between the degree of copy number alterations and the histological grade of oral leukoplakia and demonstrated that copy number alteration may be effective for prognosis prediction in oral leukoplakia patients with hyperplasia.展开更多
Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nuc...Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.展开更多
We described a novel single-cell RNA-seq technique called MR-seq(measure a single-cell transcriptome repeatedly),which permits statistically assessing the technical variation and identifying the differentially express...We described a novel single-cell RNA-seq technique called MR-seq(measure a single-cell transcriptome repeatedly),which permits statistically assessing the technical variation and identifying the differentially expressed genes between just two single cells by measuring each single cell twice. We demonstrated that MR-seq gave sensitivity and reproducibility similar to the standard single-cell RNA-seq and increased the positive predicate value. Application of MR-seq to early mouse embryos identified hundreds of candidate intra-embryonic heterogeneous genes among mouse 2-,4-and 8-cell stage embryos. MR-seq should be useful for detecting differentially expressed genes among a small number of cells.展开更多
Dear Editor,Since its invention,next generation sequencing(NGS)has greatly facilitated biomedical research and clinical diagnosis(Sikkema-Raddatz et al.,2013).Continuous dropping of the cost further accelerated the ad...Dear Editor,Since its invention,next generation sequencing(NGS)has greatly facilitated biomedical research and clinical diagnosis(Sikkema-Raddatz et al.,2013).Continuous dropping of the cost further accelerated the adaptation of sequencing as a standard analytical tool,from identification of drug candidates(Walker et al.,2015)to deciphering the complex biological systems(McConnell et al.,2013).展开更多
As anconversion of essential cofactor for lipid biosynthesisand antioxidant defense, reduced nicotinamideadenine dinucleotide phosphate (NADPH) isproduced via various pathways, including the oxidativepentose phosphate...As anconversion of essential cofactor for lipid biosynthesisand antioxidant defense, reduced nicotinamideadenine dinucleotide phosphate (NADPH) isproduced via various pathways, including the oxidativepentose phosphate pathway (oxPPP) and themalic enzyme 1 (ME1)-catalyzed conversion of malateto pyruvate. Live-cell detection of NADPH productionroutes remains challenging. Here, we reporttracing hydrides into lipid droplets (THILD), achemical imaging strategy for the detection ofpathway-specific NADPH generation in live cells. Thisstrategy exploits deuterium (2H)-labeled glucose([2H]Glc) tracers that transfer deuterides to NADPHvia specific pathways. The NADP^(2)H, in turn, transfersdeuterides to lipids, resulting in accumulation of C-2Hbonds in lipid droplets, which can be visualized bybioorthogonal stimulated Raman scattering (SRS)microscopy. We used this concept to demonstratethe imaging of oxPPP-produced NADPH using theoxPPP-specific tracer, [3-2H]Glc. Furthermore, the“switch on” of NADPH production by ME1 in differentiatingadipocytes was imaged by [4-2H]Glc. Finally,comparison of [3-2H]Glc and [4-2H]Glc THILDimaging of adipocytes showed that hypoxia inducessuppression of ME1-mediated NADPH productionand oxPPP-produced NADPH becomes the mainsource.展开更多
基金This research was supported by research grants from the National Natural Science Foundation of China(81671006,81700994,22050002,22050004)and CAMS Innovation Fund for Medical Sciences(2019-I2M-5-038).
文摘Ossifying fibroma(OF)and fibrous dysplasia(FD)are two fibro-osseous lesions with overlapping clinicopathological features,making diagnosis challenging.In this study,we applied a whole-genome shallow sequencing approach to facilitate differential diagnosis via precise profiling of copy number alterations(CNAs)using minute amounts of DNA extracted from morphologically correlated microdissected tissue samples.Freshly frozen tissue specimens from OF(n=29)and FD(n=28)patients were obtained for analysis.Lesion fibrous tissues and surrounding normal tissues were obtained by laser capture microdissection(LCM),with~30–50 cells(5000–10000µm2)per sample.We found that the rate of recurrent CNAs in OF cases was much higher(44.8%,13 of 29)than that in FD cases(3.6%,1 of 28).Sixty-nine percent(9 of 13)of the CNA-containing OF cases involved segmental amplifications and deletions on Chrs 7 and 12.We also identified eight CNA-associated genes(HILPDA,CALD1,C1GALT1,MICALL2,PHF14,AIMP2,MDM2,and CDK4)with amplified expression,which was consistent with the copy number changes.We further confirmed a jaw lesion with a previous uncertain diagnosis due to its ambiguous morphological features and the absence of GNAS mutation as OF based on the typical Chr 12 amplification pattern in its CNA profile.Moreover,analysis of a set of longitudinal samples collected from an individual with a cellular lesion in suspicion of OF at the first surgery,recurrence and the latest malignant transformation revealed identical CNA patterns at the three time points,suggesting that copy number profiling can be used as an important tool to identify borderline lesions or lesions with malignant potential.Overall,CNA profiling of fibro-osseous lesions can greatly improve differential diagnosis between OF and FD and help predict disease progression.
基金supported by grants from the National Natural Science Foundation of China(No.21974069)Open Fund Programs of Shenzhen Bay Laboratory(No.SZBL2020090501001)。
文摘Matrix-assisted laser desorption/ionization(MALDI)mass spectrometry(MS)plays an indispensable role in analyzing protein covalent structures.The reliable identification of amino acid residues and modifications relies on the mass accuracy,which is highly dependent on calibration.However,the accuracy provided by the currently available calibrants still needs further improvement in terms of compatibility with multiple tandem MS modes or ion polarity modes,calibratable range,and minimizing suppression of and interference with analyte signals.Here aiming at developing a versatile calibrant to solve these problem,we designed a synthetic peptide format of calibrant R_x(GDP_n)_m(referred to as“Gly-Asp-Pro,GDP”)according to the chemical natures of amino acids and polypeptide fragmentation rules in tandem MS.With four types of amino acid residues selected and arranged through rational designs,a GDP peptide produces highly regulated fragments that give rise to evenly spaced signals in each tandem MS mode and is compatible with both positive and negative ion modes.In internal calibration,its regulated fragmentation pattern minimizes interference with analyte signals,and using a single peptide as the input minimizes suppression of the analyte signals.As demonstrated by analyses of proteins including monoclonal antibody and Aβ-42,these features allowed significant increase of the mass accuracy and precision,which improved sequence coverage and sequence resolution in sequence analyses(including de novo sequencing).This rational design strategy may also inspire further development of synthetic calibrants that benefit structural analysis of biomolecules.
基金This work was supported by the National Natural Science Foundation of China(22071003,62104013,and 92156016)the National Key R&D PProgramof China(2021YFB3500400,2021YFB3501800,and 2022YFB3503702)the Beijing Natural Science Foundation(2202015).
文摘White organic light-emitting diodes(WOLEDs)is a new generation of lighting technology and has stimulated wide-ranging studies.Despite the advantage of simple device structure,single-emitting-layer WOLEDs(SEL-WOLEDs)still face the challenges of difficult material screening and fine energy level regulation.Herein,we report efficient SEL-WOLEDs with a sky-blue emitting cerium(Ⅲ)complex Ce-TBO2Et and an orange-red emitting europium(Ⅱ)complex Eu(Tp2Et)2 as the emitters,showing a maximum external quantum efficiency of 15.9%and Commission Internationale de l'Eclairage coordinates of(0.33,0.39)at various luminances.Most importantly,the electroluminescence mechanism of direct hole capture and hindered energy transfer between the two emitters facilitate a manageable weight doping concentration of 5%for Eu(Tp2Et)2,avoiding the low concentration(<1%)of the low-energy emitter in typical SEL-WOLEDs.Our results indicate that d-f transition emitters may circumvent fine energy level regulation and provide development potential for SEL-WOLEDs.
文摘Chemistry,a fundamental scientific discipline,plays a significant role in various fields,including medical science.Its ability to break down human cells into constituent biomolecules,such as nucleic acids,proteins,carbohydrates and lipids,has been a valuable resource for studying fundamental building blocks at the atomic level.By studying the functions of these biomolecules,chemists can gain insights into the underlying mechanisms of various diseases.The integration of chemistry and medical science has facilitated advancements in diagnostic,therapeutic and translational research,leading to fruitful collaborations between these two fields.As a result,this interdisciplinary approach has yielded cutting-edge research with implications for the improvement of human health.
基金supported by the National Natural Science Foundation of China(81671006,81300894,22050002,22050004)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M-5-038)。
文摘Oral leukoplakia is the most common type of oral potentially malignant disorders and considered a precursor lesion to oral squamous cell carcinoma.However,a predictor of oral leukoplakia prognosis has not yet been identified.We investigated whether copy number alteration patterns may effectively predict the prognostic outcomes of oral leukoplakia using routinely processed paraffin sections.Comparison of copy number alteration patterns between oral leukoplakia with hyperplasia(HOL,n=22)and dysplasia(DOL,n=21)showed that oral leukoplakia with dysplasia had a higher copy number alteration rate(86%)than oral leukoplakia with hyperplasia(46%).Oral leukoplakia with dysplasia exhibited a wider range of genomic variations across all chromosomes compared with oral leukoplakia with hyperplasia.We also examined a retrospective cohort of 477 patients with oral leukoplakia with hyperplasia with detailed follow-up information.The malignant transformation(MT,n=19)and leukoplakia recurrence(LR,n=253)groups had higher frequencies of aneuploidy events and copy number loss rate than the free of disease(FD,n=205)group.Together,our results revealed the association between the degree of copy number alterations and the histological grade of oral leukoplakia and demonstrated that copy number alteration may be effective for prognosis prediction in oral leukoplakia patients with hyperplasia.
文摘Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.
基金supported by grants from the Beijing Municipal Science and Technology Commission (D15110700240000)
文摘We described a novel single-cell RNA-seq technique called MR-seq(measure a single-cell transcriptome repeatedly),which permits statistically assessing the technical variation and identifying the differentially expressed genes between just two single cells by measuring each single cell twice. We demonstrated that MR-seq gave sensitivity and reproducibility similar to the standard single-cell RNA-seq and increased the positive predicate value. Application of MR-seq to early mouse embryos identified hundreds of candidate intra-embryonic heterogeneous genes among mouse 2-,4-and 8-cell stage embryos. MR-seq should be useful for detecting differentially expressed genes among a small number of cells.
基金National Natural Science Foundation of China(21327808,21525521 to Yanyi Huang and 21675098 to Jianbin Wang)Ministry of Science and Tech no logy of China(2015AA0200601 to Yuhong Pang and 2016YFC0900100 to Jianbin Wang and Yuhong Pang)Beijing Advaneed Inn ovation Center for Genomics.
文摘Dear Editor,Since its invention,next generation sequencing(NGS)has greatly facilitated biomedical research and clinical diagnosis(Sikkema-Raddatz et al.,2013).Continuous dropping of the cost further accelerated the adaptation of sequencing as a standard analytical tool,from identification of drug candidates(Walker et al.,2015)to deciphering the complex biological systems(McConnell et al.,2013).
基金This project is supported by the National Natural Science Foundation of China(nos.91753206 and 21521003 to X.Cnos.21327808 and 21525521 to Y.H.),the National Key R&D Program of China(no.2018YFA0507600 to X.C.and no.2018YFA0108100 to Y.H.),the 2018 Beijing Brain Initiation(no.Z181100001518004 to Y.H.),the Beijing Advanced Innovation Center for Genomics(Y.H.),the US National Institutes of Health(no.R01CA163591 to J.D.R.),and the China Postdoctoral Science Foundation(no.2015M580009 to S.H.).
文摘As anconversion of essential cofactor for lipid biosynthesisand antioxidant defense, reduced nicotinamideadenine dinucleotide phosphate (NADPH) isproduced via various pathways, including the oxidativepentose phosphate pathway (oxPPP) and themalic enzyme 1 (ME1)-catalyzed conversion of malateto pyruvate. Live-cell detection of NADPH productionroutes remains challenging. Here, we reporttracing hydrides into lipid droplets (THILD), achemical imaging strategy for the detection ofpathway-specific NADPH generation in live cells. Thisstrategy exploits deuterium (2H)-labeled glucose([2H]Glc) tracers that transfer deuterides to NADPHvia specific pathways. The NADP^(2)H, in turn, transfersdeuterides to lipids, resulting in accumulation of C-2Hbonds in lipid droplets, which can be visualized bybioorthogonal stimulated Raman scattering (SRS)microscopy. We used this concept to demonstratethe imaging of oxPPP-produced NADPH using theoxPPP-specific tracer, [3-2H]Glc. Furthermore, the“switch on” of NADPH production by ME1 in differentiatingadipocytes was imaged by [4-2H]Glc. Finally,comparison of [3-2H]Glc and [4-2H]Glc THILDimaging of adipocytes showed that hypoxia inducessuppression of ME1-mediated NADPH productionand oxPPP-produced NADPH becomes the mainsource.